α晶体蛋白对视神经损伤微环境中视网膜小胶质细胞的作用研究
|
摘要
α晶体蛋白是晶状体来源的“神经保护性物质”之一,它能有效的保护视神经损伤后RGCs细胞并促进轴突的再生;近年来损伤后RGCs周围的小胶质细胞在其再生和修复中的作用受到人们的关注。已有研究表明,中枢神经系统的小胶质细胞在炎症、缺血、变性疾病及损伤后可被激活,一方面产生大量的超氧阴离子、一氧化氮、花生四烯酸衍生物、兴奋性氨基酸以及其它一些潜在的神经毒素,导致神经元死亡,从而加重中枢神经系统的病理损伤;另一方面可以吞噬死亡的神经元碎屑,起到清除的作用。在既往研究中我们意外观察到,α晶体蛋白在保护RGCs的同时,可以抑制视神经钳夹伤模型中吞噬荧光金的小胶质细胞,那么这种作用是直接还是间接的,小胶质细胞的减少对RGCs的保护是否有益?目前尚不清楚。
目的
通过离体实验和在体模型,观察α晶体蛋白对视网膜小胶质细胞的增殖、活化以及分布的影响,并在蛋白和mRNA水平检测α晶体蛋白对小胶质细胞激活时分泌的TNF-α和iNOS表达的影响,分析α晶体蛋白对视网膜小胶质细胞与RGCs变化的相关性,为α晶体蛋白对视神经损伤后RGCs的保护提供新的理论依据,为临床治疗探索可行性方法。
方法
1.通过视网膜混合细胞培养和恒温摇床震荡分离的方法培养视网膜小胶质细胞,并通过免疫组化、扫描电镜、流式细胞仪鉴定细胞纯度。
2.离体实验:以离体培养的小胶质细胞为对象,用不同浓度LPS和α晶体蛋白干预,通过MTT分析,细胞计数法摸索合适的LPS、α晶体蛋白工作浓度,研究α晶体蛋白对小胶质细胞的增殖、活化的影响;并通过RT-PCR,ELISA、荧光定量PCR等方法,分析小胶质细胞分泌的TNF-α,iNOS的表达变化。
3.在体实验:以成年Long Evans大鼠为研究对象,建立视神经钳夹损伤模型,玻璃体腔注射10-4g/Lα晶体蛋白,并设立牛血清白蛋白注射为阴性对照;通过视网膜组织切片和全视网膜铺片免疫组化的方法,在损伤后1、2、3、4、6、8周观察α晶体蛋白对小胶质细胞的形态、分布、数量的影响,并分析其与RGCs变化的相互关系。另外,在伤后3周时重复注射α晶体蛋白了解重复注射是否可以抑制视神经损伤4-8周的小胶质细胞,保护RGCs;并通过werstern blot分析各组在损伤后1、2、4、8周视网膜TNF-α,iNOS蛋白释放的情况。
结果
1.通过视网膜混合细胞培养和恒温摇床震荡分离的方法,成功原代培养并鉴定Long-Evans大鼠的视网膜小胶质细胞:应用GSA- IB4与CD11b细胞化学、流式细胞鉴定小胶质细胞的纯度分别为94.5%、95.8%和91.7%,并且在扫描电镜观察细胞表面呈树突样外观,表明本培养方法可以得到纯度较高的小胶质细胞。
2.与正常对照组相比,浓度为10-2g/L至10-6g/L LPS均可刺激视网膜小胶质细胞的增殖和活化(P<0.01-0.05),10-4 g/Lα晶体蛋白可以抑制10-6 g/L LPS对视网膜小胶质细胞的增殖和活化(P<0.05)。
3.α晶体蛋白可以降低小胶质细胞激活时细胞上清中TNF-α蛋白的浓度(P<0.01-0.05),减少NO的释放(P<0.05);并降低小胶质细胞激活时TNF-α、iNOS mRNA的表达。
4.玻璃体腔注射10-4 g/L的α晶体蛋白,与牛血清白蛋白注射组比较,在损伤后1-4周可显著减少视网膜小胶质细胞的数量(p<0.05),抑制小胶质细胞的迁移和向活化阿米巴样形态的转变,而在损伤后6-8周α晶体蛋白对小胶质细胞的作用不明显。在损伤3周重复注射α晶体蛋白,与单次注射组比较,小胶质细胞的形态无明显改变;但在伤后4周小胶质细胞的数量明显减少(p<0.05),伤后6-8周两组间比较无显著统计学差异(p>0.05)。
5.在伤后1-4周,α晶体蛋白可显著减少视网膜小胶质细胞数量(p<0.05),同时增加RGCs细胞的数量,相关性分析发现在视神经损伤后α晶体蛋白对两种细胞的影响存在直线相关。
6.与牛血清白蛋白组比较,损伤后1-4周α晶体蛋白可以降低视网膜TNF-α,iNOS的蛋白的表达(P<0.01-0.05),损伤后8周,两组间比较无统计学意义(p>0.05)。
结论
1.通过视网膜混合细胞培养和恒温摇床震荡分离的方法,可以成功培养出纯度高的视网膜小胶质细胞。
2.α晶体蛋白可以直接抑制离体培养视网膜小胶质细胞的增殖和活化,并降低细胞上清中TNF-α、iNOS蛋白的浓度及mRNA的表达,提示可能在病理的情况下,α晶体蛋白可以通过抑制小胶质细胞产生TNF-α、iNOS,减轻其对RGCs的损害。
3.α晶体蛋白对视网膜小胶质细胞的抑制作用主要在1-4周,其作用发挥与小胶质细胞的功能状态有关;α晶体蛋白不仅可以抑制视网膜小胶质细胞的增殖、迁移及活化,也能抑制视网膜TNF-α,iNOS的释放,减轻小胶质细胞对RGCs的过度吞噬和继发性损害,可能是视神经损伤后α晶体蛋白间接保护RGCs存活的另一机制。
As one of lentogenic factors, alpha-crystallin can promote axon regeneration after optic nerve injury. The microenviroment around RGC cells is also important. Microglia cells are actived when there are inflammation, injury and degeneration diseases in CNS. They secret some nervous poison matter, such as NO、TNF-α、IL-6, which destroy neurons and clear dead neuron debris. Our group had found that alpha-crystallin could inhibit microglial cells proliferation and protect RGC cells in optic nerve injury rats. However, the effect of alpha-crystallin on retinal microglia of optic nerve injury rat is not clear. Objective
After culture and characterization of Long-evans neonate rat retinal microglia cells, we investigated the effect of alpha-Crystallin on the activity and the expression of TNF-αand iNOS of rat retinal microglia cells stimulated with lipopolysaccharides in vitro. In addition, the distribution, morphous and number of microglia cells and TNF-α, iNOS expression of retina was also performed with or without alpha-Crystallin in optic nerve injury rat model.
Methods
1. Mixed microglia of Long Evans rats were cultured for 10-12days, then retinal microglia cells were purified by shaking in 37°C swing bed.The retinal microglia cells were identified by specific microglia marker GSA-IB4 and CD11b, and cell surface of retinal microglia cells were observed by scanning electron micrograph.
2. In vitro: The number and proliferation of microglia cell were performed by cell counting and MTT. The mRNA and protein expression of TNF-α, iNOS were dectected the by ELISA kit, RT-PCR and fluorescent quantitation PCR in different groups treated with alpha-Crystallin or not.
3. In vivo: After the optic nerve injury rat model was established, microglia cell numbers of different groups were analyzed by rentina flat counting and immunohistochemistry. In addition, the expression of TNF-αand iNOS were evaluated by western blot.
Results
1. Retinal microglia cells were cultured successfully by mixed culture and swing bed shaking.Purity of microglial cells was 94.5% and 95.8% by cell immunochemistry identification of IB4 and CD11b, 91.7% by FCM. Spinous processes Cell surface indicated microglial cells, contrasting the smooth surfaces of macrophages.
2. The proliferation and activation of microglia cells could be stimulated by 10-2g/L to 10-8g/L LPS. 10-4g/L alpha-Crystallin could inhibit proliferation and activation of microglia cells stimulated by LPS which indicated 10-4g/L alpha-Crystallin was suitable for further experiment.
3.10-4g/L alpha-Crystallin could decreased the expression of mRNA and protein of TNF-α, iNOS (P<0.01-0.05) which suggested that alpha-Crystallin could relieve the damage to RGCs by inhibition of the expression of TNF-α, iNOS.
4. Compare to BSA injection group, alpha-Crystallin could inhibit the number of microglia cells (p<0.05) and reduce the immigration and activation1-4 weeks after injury. However, the difference between two group was not significant 6-8 weeks after injury (p>0.05).
5. The correlation analyse indicated the inhibition of microglia cells and the protection of RGCs by alpha–Crystallin had linear relationship.
6. Compare to BSA injection group, alpha-Crystallin could reduce the expression of TNF-αand iNOS(P<0.01-0.05)1-4 weeks after injury. On the other hand, the difference between two group was not significant(p>0.05)6-8 weeks after injury.
Conclusions
1. High purify retinal microglia cells can be successfully obtained by mixed glial cell culture and swing bed shaking.
2. Alpha-Crystallin directly inhibits proliferation and activation of microglia cells stimulated by LPS, and reduces the expression of retinal TNF-αand iNOS in cells supernatant, indicating alpha–Crystallin can lessen the damage of RGCs by the inhibition of TNF-αand iNOS.
3. Alpha-Crystallin inhibits the activation, immigration and reduce the number of microglia cells 1-4 weeks after optic nerve injury, at the same time, it protects RGCs. Otherwise, it didn't work 6-8 weeks after injury. Alpha–Crystallin also can diminish the expression of retinal TNF-αand iNOS which may contribute to the protection of alpha -Crystallin on RGCs.
目的
通过离体实验和在体模型,观察α晶体蛋白对视网膜小胶质细胞的增殖、活化以及分布的影响,并在蛋白和mRNA水平检测α晶体蛋白对小胶质细胞激活时分泌的TNF-α和iNOS表达的影响,分析α晶体蛋白对视网膜小胶质细胞与RGCs变化的相关性,为α晶体蛋白对视神经损伤后RGCs的保护提供新的理论依据,为临床治疗探索可行性方法。
方法
1.通过视网膜混合细胞培养和恒温摇床震荡分离的方法培养视网膜小胶质细胞,并通过免疫组化、扫描电镜、流式细胞仪鉴定细胞纯度。
2.离体实验:以离体培养的小胶质细胞为对象,用不同浓度LPS和α晶体蛋白干预,通过MTT分析,细胞计数法摸索合适的LPS、α晶体蛋白工作浓度,研究α晶体蛋白对小胶质细胞的增殖、活化的影响;并通过RT-PCR,ELISA、荧光定量PCR等方法,分析小胶质细胞分泌的TNF-α,iNOS的表达变化。
3.在体实验:以成年Long Evans大鼠为研究对象,建立视神经钳夹损伤模型,玻璃体腔注射10-4g/Lα晶体蛋白,并设立牛血清白蛋白注射为阴性对照;通过视网膜组织切片和全视网膜铺片免疫组化的方法,在损伤后1、2、3、4、6、8周观察α晶体蛋白对小胶质细胞的形态、分布、数量的影响,并分析其与RGCs变化的相互关系。另外,在伤后3周时重复注射α晶体蛋白了解重复注射是否可以抑制视神经损伤4-8周的小胶质细胞,保护RGCs;并通过werstern blot分析各组在损伤后1、2、4、8周视网膜TNF-α,iNOS蛋白释放的情况。
结果
1.通过视网膜混合细胞培养和恒温摇床震荡分离的方法,成功原代培养并鉴定Long-Evans大鼠的视网膜小胶质细胞:应用GSA- IB4与CD11b细胞化学、流式细胞鉴定小胶质细胞的纯度分别为94.5%、95.8%和91.7%,并且在扫描电镜观察细胞表面呈树突样外观,表明本培养方法可以得到纯度较高的小胶质细胞。
2.与正常对照组相比,浓度为10-2g/L至10-6g/L LPS均可刺激视网膜小胶质细胞的增殖和活化(P<0.01-0.05),10-4 g/Lα晶体蛋白可以抑制10-6 g/L LPS对视网膜小胶质细胞的增殖和活化(P<0.05)。
3.α晶体蛋白可以降低小胶质细胞激活时细胞上清中TNF-α蛋白的浓度(P<0.01-0.05),减少NO的释放(P<0.05);并降低小胶质细胞激活时TNF-α、iNOS mRNA的表达。
4.玻璃体腔注射10-4 g/L的α晶体蛋白,与牛血清白蛋白注射组比较,在损伤后1-4周可显著减少视网膜小胶质细胞的数量(p<0.05),抑制小胶质细胞的迁移和向活化阿米巴样形态的转变,而在损伤后6-8周α晶体蛋白对小胶质细胞的作用不明显。在损伤3周重复注射α晶体蛋白,与单次注射组比较,小胶质细胞的形态无明显改变;但在伤后4周小胶质细胞的数量明显减少(p<0.05),伤后6-8周两组间比较无显著统计学差异(p>0.05)。
5.在伤后1-4周,α晶体蛋白可显著减少视网膜小胶质细胞数量(p<0.05),同时增加RGCs细胞的数量,相关性分析发现在视神经损伤后α晶体蛋白对两种细胞的影响存在直线相关。
6.与牛血清白蛋白组比较,损伤后1-4周α晶体蛋白可以降低视网膜TNF-α,iNOS的蛋白的表达(P<0.01-0.05),损伤后8周,两组间比较无统计学意义(p>0.05)。
结论
1.通过视网膜混合细胞培养和恒温摇床震荡分离的方法,可以成功培养出纯度高的视网膜小胶质细胞。
2.α晶体蛋白可以直接抑制离体培养视网膜小胶质细胞的增殖和活化,并降低细胞上清中TNF-α、iNOS蛋白的浓度及mRNA的表达,提示可能在病理的情况下,α晶体蛋白可以通过抑制小胶质细胞产生TNF-α、iNOS,减轻其对RGCs的损害。
3.α晶体蛋白对视网膜小胶质细胞的抑制作用主要在1-4周,其作用发挥与小胶质细胞的功能状态有关;α晶体蛋白不仅可以抑制视网膜小胶质细胞的增殖、迁移及活化,也能抑制视网膜TNF-α,iNOS的释放,减轻小胶质细胞对RGCs的过度吞噬和继发性损害,可能是视神经损伤后α晶体蛋白间接保护RGCs存活的另一机制。
As one of lentogenic factors, alpha-crystallin can promote axon regeneration after optic nerve injury. The microenviroment around RGC cells is also important. Microglia cells are actived when there are inflammation, injury and degeneration diseases in CNS. They secret some nervous poison matter, such as NO、TNF-α、IL-6, which destroy neurons and clear dead neuron debris. Our group had found that alpha-crystallin could inhibit microglial cells proliferation and protect RGC cells in optic nerve injury rats. However, the effect of alpha-crystallin on retinal microglia of optic nerve injury rat is not clear. Objective
After culture and characterization of Long-evans neonate rat retinal microglia cells, we investigated the effect of alpha-Crystallin on the activity and the expression of TNF-αand iNOS of rat retinal microglia cells stimulated with lipopolysaccharides in vitro. In addition, the distribution, morphous and number of microglia cells and TNF-α, iNOS expression of retina was also performed with or without alpha-Crystallin in optic nerve injury rat model.
Methods
1. Mixed microglia of Long Evans rats were cultured for 10-12days, then retinal microglia cells were purified by shaking in 37°C swing bed.The retinal microglia cells were identified by specific microglia marker GSA-IB4 and CD11b, and cell surface of retinal microglia cells were observed by scanning electron micrograph.
2. In vitro: The number and proliferation of microglia cell were performed by cell counting and MTT. The mRNA and protein expression of TNF-α, iNOS were dectected the by ELISA kit, RT-PCR and fluorescent quantitation PCR in different groups treated with alpha-Crystallin or not.
3. In vivo: After the optic nerve injury rat model was established, microglia cell numbers of different groups were analyzed by rentina flat counting and immunohistochemistry. In addition, the expression of TNF-αand iNOS were evaluated by western blot.
Results
1. Retinal microglia cells were cultured successfully by mixed culture and swing bed shaking.Purity of microglial cells was 94.5% and 95.8% by cell immunochemistry identification of IB4 and CD11b, 91.7% by FCM. Spinous processes Cell surface indicated microglial cells, contrasting the smooth surfaces of macrophages.
2. The proliferation and activation of microglia cells could be stimulated by 10-2g/L to 10-8g/L LPS. 10-4g/L alpha-Crystallin could inhibit proliferation and activation of microglia cells stimulated by LPS which indicated 10-4g/L alpha-Crystallin was suitable for further experiment.
3.10-4g/L alpha-Crystallin could decreased the expression of mRNA and protein of TNF-α, iNOS (P<0.01-0.05) which suggested that alpha-Crystallin could relieve the damage to RGCs by inhibition of the expression of TNF-α, iNOS.
4. Compare to BSA injection group, alpha-Crystallin could inhibit the number of microglia cells (p<0.05) and reduce the immigration and activation1-4 weeks after injury. However, the difference between two group was not significant 6-8 weeks after injury (p>0.05).
5. The correlation analyse indicated the inhibition of microglia cells and the protection of RGCs by alpha–Crystallin had linear relationship.
6. Compare to BSA injection group, alpha-Crystallin could reduce the expression of TNF-αand iNOS(P<0.01-0.05)1-4 weeks after injury. On the other hand, the difference between two group was not significant(p>0.05)6-8 weeks after injury.
Conclusions
1. High purify retinal microglia cells can be successfully obtained by mixed glial cell culture and swing bed shaking.
2. Alpha-Crystallin directly inhibits proliferation and activation of microglia cells stimulated by LPS, and reduces the expression of retinal TNF-αand iNOS in cells supernatant, indicating alpha–Crystallin can lessen the damage of RGCs by the inhibition of TNF-αand iNOS.
3. Alpha-Crystallin inhibits the activation, immigration and reduce the number of microglia cells 1-4 weeks after optic nerve injury, at the same time, it protects RGCs. Otherwise, it didn't work 6-8 weeks after injury. Alpha–Crystallin also can diminish the expression of retinal TNF-αand iNOS which may contribute to the protection of alpha -Crystallin on RGCs.
引文
1. Richardson P, McGinness U, Aguayo A. Axon from CNS neurons regenerate into PNS grafts. Nature, 2002; 284: 264 - 265.
2. Robaey MS, Clarke DB, Wang YC, et al. Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells. Proc Natl Acad Sci USA,1994 ;91: 1632–1636
3. Fischer D, Pavlidis M, Thanos S. Cataractogenic lens injury prevents traumatic ganglion cell death and promotes axonal regeneration both in vivo and in culture. Invest Ophthalmol Vis Sci ,2000 ;41 (12): 3943-3954
4. Leon S, Yin YQ, Nguyen J, et al. Lens Injury Stimulates Axon Regeneration in the Mature Rat Optic Nerve. Journal of Neuroscience, 2000, 20(12):4615-4626
5.王艳华,王一。晶体蛋白对离体培养的大鼠视网膜神经节细胞的作用。中华创伤杂志,2005,21(2):98-103
6.刘康,王一,王艳华等。晶状体蛋白促大鼠视网膜神经节细胞存活和突起生长的体外研究。中华创伤杂志,2007,23(1):41-46
7.王晓芹,王一等。α晶体蛋白与视网膜神经节细胞结合的细胞定位研究。中华创伤杂志,2007,23(12):1-6
8.刘志敏,王一。混合晶状体蛋白对大鼠视神经损伤后视网膜神经节细胞的保护作用。中华创伤杂志,2006,22(12):926-929
9.张莉,王一,张辰星。α-晶状体蛋白对视神经损伤后视网膜神经节细胞保护作用的研究。中华创伤杂志,2007;23(3): 344-348.
10. Sasaki A, Yokoo H, Naito M, et al. Effects of macrophage-colony-stimulating factor deficiency on the maturation of microglia and brain macrophages and on their expression of scavenger receptor, Neuropathology 2000 ;20:134– 142.
11. Raivich G., Bohatschek M., Kloss CU, et al. Neuroglial activation repertoire in the injured brain:graded response, molecular mechanisms and cues to physiological function, Brain Res,1999 ;30:77– 105.
12. Kato H, Takahashi A, Itoyama Y. Cell cycle protein expression in proliferating microglia and astrocytes following transient global cerebral ischemia in the rat, BrainRes. Bull. 2003 ;60:215-221.
13. Compston A, Coles A. Multiple sclerosis. Lancet. 2002; 359: 1221-1231
14. Wenk GL. Neuropathologic changes in Alzheimer's disease. J Clin Psychiatry 2003; 64 suppl 9:7-10.
15. Wersinger C, Sidhu A. Inflammation and Parkinson's disease. Curr Drug Targets Inflamm Allergy .2002; 1:221-242.
16. Gupta N, Kimberly EB, Milam AH. Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration. Experimental Eye Research 2003;76 :463–471
17. Zeiss CJ, Johnson EA. Proliferation of Microglia, but not Photoreceptors, in the Outer Nuclear Layer of the rd-1 Mouse. Investigative Ophthalmology Visual Science, 2004; 45:971-976
18. Raibon E, Sauve Y, Carter DA, et al. Microglial changes accompanying the promotion of retinal ganglion cell axonal regeneration into peripheral nerve grafts. Journal of Neurocytology 2002;31:57-71
19. Watanabe, M, Fukuda, Y. Survival and axonal regeneration of retinal ganglion cells in adult cats. Prog. Retinal Eye Res. 2002,21:529-553
20. Fischer, D, Heiduschka, P, Thanos S. Lens-injury-stimulated axonal regeneration throughout the optic pathway of adult rats. Exp. Neurol. 2001. 172, 257-272.
21. Glenn Y, He ZG. Signaling mechanisms of the myelin inhibitors of axon regeneration. Current Opinoin in Neurobiology. 2003;13:545-551
22. Tikka T, Fiebich BL, Goldsteins G, et al. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci 2001, 21(8): 2580-2588.
23. Galiano M, Liu ZQ, Kalla R,et al. Interleukin-6 (IL-6) and cellular response to facial nerve injury:effects on lymphocyte recruitment,early microglial activation and axonal outgrowth in IL6-deficient mice. Eur J Neurosci,2001,14(2):327-341.
24. Yuan L,Neufeld AH.Tumor necrosis factor-alpha:a potentially neurodestructive cytokine produced by gila in the human glaucomatous optic nerve head.Glia,2000,32:42-50.
25. Raivich G, Bohatschek M, Kloss CU, et al. Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function, Brain Res. Rev. 1999;30:77–105.
26. Giulian D, Baker TJ. Characterization of amoeboid microglia isolated from developing mammalian brain.J Neurosci 1986,6:2163-78
27.杨忠,何家全,蔡文琴。一种改良的小胶质细胞培养方法及初步研究。创伤外科杂志2001,3(3):239-240
28.蔡文琴.现代实用细胞与分子生物学实验技术.北京.人民军医出版社。2003:115-138
29.朱长庚主编。神经解剖学人民卫生出版社,2002年3月第一版: 412-414
30. Chen L, Yang P,Istra KA. Distribution, markers,and functions of retinal microglia.Ocul Immunol Inflamm,2002,10:27-39.
31.张敏,魏桂荣等.一种高产量的小胶质细胞培养及其鉴定方法.卒中与神经疾病2005,12(4): 224-226
32. Navascues J,Moujahid A,Almendros A, et a1. Origin of microglia in the quail retina:central-to-peripheral and vitreal-to-scleral migration of microglial precursors during development.J Comp Neurol 1995,354:209-228.
33. Alejandro MS, Mary H, Michael JF, et al. Effect of a short-term in vitro exposure to the marine toxin domoicacid on viability, tumor necrosis factor-alpha, matrixmetalloproteinase-9 and superoxide anion release by rat neonatal microglia. BMC Pharmacology ,2001, 7:1471-1484
34. Rune L, Martin W, Bente F, et al. Microglial cell population dynamics in the injured adult central nervous system. Brain Research Reviews 2005,48: 196-206
35. Aldskogius H, Kozlova EN, Central neuron-glial and glial-glial interactions following axon injury, Prog. Neurobiol. 1998, 55:1-26
36. Neufeld AH. Microglia in the optic nerve head and the region of parapapillary chorioretinal atrophy in glaucoma. Arch Ophthalmol 1999,117:1050-1056.
37. Yuan L, Neufeld AH .Activated microglia in the human glaucomatous optic nerve head. J Neurosci Res 2001,64:523-532
38. Gilles JG, Bruce JB. Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification. Journal of Leukocyte Biology 2004;75:388-397.
39. Giulian D, Li J, Bartel S, et al. Cell Surface Morphology Identifies Microglia as a Distinct Class of Mononuclear Phagocyte. Journal of Neuroscience, November 1995, 15(11): 7712-7726
40. Gonzalez SF, Blatuch G. Microglia as mediators of inflammatory and degenerative diseases. Annu Rev Neurosci 1999,22:222-240
41. Mofoika T, Kalehua, ANN, Streit WJ. The imbroglio reaction in the rat dorsal hippocampus following transient forebrain schema. J Cereb Blood Flow Metablo 1991,11:966-973
42. Suraj PB.Transparency and non-refractive functionsof crystallins-a proposal. Experimental Eye Research 79 (2004) 809–816.
43. Hans B, Christine S, et al. Ageing and vision: structure, stability and function of lens crystallins Progress in Biophysics & Molecular Biology 86 (2004) 407–48.
44.刘康,王一。α-晶状体蛋白的研究进展[J]。眼科新进展2005;25(2):86-89.
45. Derham BK.Harding JJ.Effect of aging on the chaperone-like function of human -crystallin assessed by three methods.Biochem J,1997,328:763-768.
46. Lampi KJ, Shih M, Ueda Y, et a1. Lens proteomics:analysis of rat crystallin sequences and two-dimensional electrophoresis map.Invest Ophthalmol Vis Sci,2002,43:216-224.
47.严宏,惠延年,李明勇。阿司匹林类药物和α-晶状体蛋白保护酯酶的失活。第四军医大学学报2002;23(5):476-479.
48. Horwitz J. A1pha-crystallin.Exp Eye Res 2003;76: 145-153
49. Vanhoudt J, Aerts T, Abgar S, et al. Native quaternary structure of bovine alpha- crystallin. Biochemistry 2000;39:4483-4492
50. Reddy GB,Reddy PY. AlphaA-and alphaB-crystallins protect glucose-6-phosphate dehydrogenase against UVB irradiation induced inactivation. Biochim Biophys Res Commun,2002,282:712-716.
51. Kamradt MC, Chen F, Cryns VL. The small heat shock protein alpha B crystallin negatively regulates cytochrome c and caspase-8 dependent activation of caspase-3 by inhibiting its autoproteolytic maturation.J Biol Chem,2001,276:16059-l6063.
52. Alge CS,Priglinger SG,Neubauer AS,et a1. Retinal pigment epithelium is protected against apoptosis by alphaB-crystallin.Invest Ophthalmol Vis Sic,2002,43:3575-3582.
53. Machida S,Chaudhry P,Shinohara T, et al. Lens epithelium derived growth factor promotes photoreceptor survival in light damaged and RCS rats.Invest Ophthalmol Vis Sic 200142:1087-l095.
54. Andley UP,Song Z,Wawrousek EF, et a1.Differential protective activity of alpha A -and alpha B-crystallin in lens epithelial cells.J Biol Chem 2000,275:36823-36831.
55. Eaton P, Fuller W, Bell JR, et a1. Alpha B crystallin translocation and phosphorylation:signal transduction pathways and preconditioning in the isolated rat heart.J Mol Cell Cardiol 2001,33: 1659-1671.
56. Hou Y, Wu CF, Yang JY, et al. Effects of clozapine, olanzapine and haloperidol on nitric oxide production by lipopolysaccharide activated N9 cells. Prog Neuropsychopharmacol Biol Psychiatry 2006;23:1-6
57. Weinsteirt SL, Sanhera JS, Lemke K, et al. Bacterial lipopolysaccharide induces tyrosine phosphory1ation and activation of mitogen-activated protein kinase in macrophages.J Biol Chem 1992;267 :14955-14962.
58. Seg R, Kreb EG. The MAPK signaling cascade.FASEB J.1995,9:726-7
59. Takeshi O, Ichikawa M, et al. Intravitreal macrophage activation enables cat retinal ganglion cells toregenerate injured axons into the mature optic nerve. Experimental Neurology 2005,196:153-163
60. Chen A, Kumar SM, Sahley CL, et a1. Nitric oxide influences injury induced microglial migration and accumulation in the CNS.J Neurosci,2000;20:1036-1043.
61. Dalmau I, Vela JM, Gonzalez B, et al. Dynamics of microglia in the developing rat brain, J. Comp. Neurol. 2003;458 :144-157.
62. Drojdahl N, Fenger C, Finsen B, et al. Dynamics of microlgia responses to anterograde axonal and terminal degeneration in normal and TNF-transgenic mice, J. Neurosci. Res. 75 (2004) 203–217.
63. Rao NA,Kimoto T,Zarnir E.Pathogenic role of retinal microglia in experimental uveoretinitis.Invest Ophthalmol Vis Sci,2003,44:22-31.
64. Neufeld AH.Microglia in the optic nerve head and the region of parapapilary chorioretinal atrophy in glaucoma.Arch Ophthalmol,1999,117:1050-1056
65. Watanabe M, Tokita Y, Kato M, et a1. Intravitreal injections of neurotrophic factors and forskolin enhance surviva1 and axonal regeneration of axotomized beta ganglion cells in cat retina.Neuroscience,2003,116:733-742.
66. Ander S,Stoll G. Role of NMDA receptor signaling in the regulation of inflammatory gene expression after focal brain ischemia. Journal of Neuroimmunology 2000 ; 109: 181-187
67. Chao CC, Hu S. Tumor necrosis factor-αpotentiates qlutamate neurotoxicity in human fetal brain cell cultures. Dev Neurosci, 1994, 16:172-179
68. Mizuno T, Kurotani T, Komatsu Y,et al. Neuroprotective role of phosphodiesterase inhibitor ibudilast on neuronal cell death induced by activated microglia Neuropharmacology, 2004, 46: 404-411
69. Tezel, G, Wax, MB. Increased production of tumor necrosis factor-alpha by glial cells exposed to simulated ischemia or elevated hydrostatic pressure induces apoptosis in cocultured retinal ganglion cells. Neurosci 2000b ; 20, 8693–8700.
70. Kim JS, Lee HJ, Lee MH. Luteolin inhibits LPS-stimulated inducible nitric oxide synthase expression in BV-2 microglial cells. Planta Med. 2006;72:65-8.
71. Calapai G, Marcinom C, Corica F, et a1.Erythmpoietin protects against brain ischemic injury by inhibition of nitric oxide formation.Eur J Pharmacol,2000;401:349-356.
72. Liu B, Hong JS. Role of microglia in inflammation mediated neurodegenerative diseases:mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther,2003,304(1):1 -7.
73. Combs CK, Karlo JC, Kao SC, et al. beta-Amyloid stimulation of microglia and monocytes results in TNF alpha dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J Neurosci,2001,21:1179-1188
74. Levkovitch VH, Quigley HA, Kesrigan BLA.Optic nerve transtection in monkeys may result in secondary degeneration of retinal ganglion cells. Invest Ophthalmol Vis Sci. 2001;42:975-982.
75. Levkovitch VH, Quigley HA, Martin KRG, et al. A model to study differences betweenprimary andsecondary degeneration of retinal ganglion cells in rats by partialoptic nerve transaction. Invest Ophthalmol Vis Sci. 2003;44:3388–3393.
76.史剑波,徐锦堂,夏潮勇。视神经损伤对视网膜结构的形态学研究。眼外伤职业眼病杂志,1998;20(4):283-285
77. Milligan CE, Levitt P, Cunningham TJ. Brain macrophages and microglia respond differently to lesions of the developing and adult visual system. J Comp Neurol 1991; 314:136-46.
78. Kaur C, Hao AJ, Wu CH, et al. Origin of microglia. Microsc Res Tech 2001; 54:2-9.
79. Pearson HE, Payne BR, Cunningham TJ. Microglial invasion and activation in response to naturally occurring neuronal degeneration in the ganglion cell layer of the postnatal cat retina.Brain Res Dev Brain Res 1993; 76:249-55.
80. Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996; 19: 312-318.
81. Kempennann G, Neumann H. Microglia: The Enemy Within? Science. 2003; 302 : 1689-1690
82. Qin L, Liu Y, Wang T, Wei SJ, et al. NADPH oxidase mediates LPS-induced neurotoxicity and pro-inflammatory gene expression in activated microglia.J Biol Chem. 2004;279:1415-21
83. Schwab JM, Schluesener HJ. Microglia rules: insights into micoglial neuronal Signaling.Cell Death and Differentiation, 2004, 11:1245-1246.
84. Ralf E, Daniela C, Annett B, et al. A different retinal glia response to optic nerve injury /lipopolysaccharide administration in hooded and albino rats Brain Research 2001;889:251–255
85. Schuetz E, Thanos S. Neuro-glial interactions in the adult rat retina after reaxotomy of ganglion cells: examination of neuron survival and phagocytic microglia using fluorescent tracers Brain Research Bulletin 2004;62 :391-396
86. Madigan MC, Sadun AA, Rao NS, et al. Tumor necrosis factor-alpha (TNF-alpha) induced optic neuropathyin rabbits. Neurol. Res. 1996;18:176-184.
87. Tezel G, Chauhan BC, LeBlanc RP, et al. Immunohistochemical assessment of the glial mitogen-activated protein kinase activation in glaucoma, Invest. Ophthalmol. VisualSci. 2003;44:3025–3033.
88. Liu T, Clark RK, McDonnell PC, et al. Increased production of tumor necrosis factoralpha by glial cells exposed to simulated ischemia or elevated hydrostatic pressure induces apoptosis in cocultured retinal ganglion cells. J Neurosci. 2000;20 : 8693-8700.
89. Tezel G, Yang XJ, Yang JJ, et al. Role of tumor necrosis factor receptor-1 in the death of retinal ganglion cells following optic nerve crush injury in mice. Brain Research 2004;996:202-212
90. Kim HS, Chan KP. Retinal ganglion cell death is delayed by activation of retinal intrinsic cell survival program.Brain Research 2005;1057: 17-28
91. Wong A, Luth HJ, Deuther CW, et a1. Advanced glycation endproducts co localize with inducible nitric oxide synthase in Alzheimer′s disease. Brain Res ,2001;920:32-40.
92. Golde S, Chandran S, Brown GC, et a1. Different pathways for iNOS mediated toxicity in vitro dependent on neuronal maturation and NMDA receptor expression. J Neurochem, 2002;82:269-282.
93. Merrill JE , Ignarro LJ , Sherman MP, et a1 . Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J Immunol,1993;151:2132-2141
94. Guzy RD,Schumacker PT. Oxygen sensing by mitochondria at complex III: The paradox of increased ROS during hypoxia. Exp Physiol 2006;91:07-819.
95. Wei T,Chen C,Zhao B,et al. EPC K1 attenuates peroxynitrite induced apoptosis in cerebellar granule cells. Biochem Mol Biol Int 1998;46:89-97
96. Villegas PM, Vidal SM, Rasminsky M, et al. Rapid and protracted phases of retinal ganglion cell loss follow axotomy in the optic nerve of adult rats. J Neurobio. 1993;24:23-36.
97. Aktan F. INOS mediated nitric oxide production and its regulation. Life Sciences,2004;75:639-653.
98. Tikka T, Fiebich BL, Goldstein G, et al. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci, 2001; 21: 2580-2588.
99. Liu B, Gao HM, Wang, JY, et al. Role of nitric oxide in inflammation mediated neurodegeneration. Annals of the New York Academy of Sciences,2002; 962:318- 331
100. Thanos S. Regenerating ganglion cell axons in the adult rat establish retinofugal topography and restore visual function. Exp-Brain-Res. 1997,114(3):483-91.
101. Stupp T, Thanos S. Can lenticular factors improve the posttrauma fate of neurons? Progress in Retinal and Eye Research 2005;24:241-257
102. Lorber B, Berry M, Logan A, et a1. Effect of lens lesion on neurite outgrowth of retinal ganglion cells in vitro.Mol Cell Neurosci,2002;21:301-3l1
103.王艳华。α晶体蛋白促进视网膜神经节细胞轴突再生的机制研究。2007年博士论文,P70。
1. Rune L, Martin W, Bente F. Microglial cell population dynamics in the injured adult central nervous system. Brain Research Reviews. 2005; 48:196-206
2. Kreutzberg G W. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996; 19: 312-318
3. McGeer PL, K Yasojima and EG McGeer. Association of interleukin-1 beta polymorphisms with idiopathic Parkinson's disease. Neurosci Lett.2002; 326:67-69.
4. Compston A , Coles A. Multiple sclerosis. Lancet. 2002; 359: 1221-1231
5. Wenk GL. Neuropathologic changes in Alzheimer's disease. J Clin Psychiatry 2003; 64 suppl 9:7-10.
6. Liu B, Hong JS. Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Therapy. 2003; 304: 1-7.
7. McGeer PL, Yasojima K ,McGeer . EG Inflammation in Parkinson's disease. Adv Neuro.2001;186: 83-89.
8. Liu B, Gao HM, Wang JY, Jeohn GH. Role of nitric oxide in inflammation-mediated neurodegeneration. Ann N Y Acad Sci. 2002; 962: 318-331.
9. McGeer PL and McGeer EG. Local neuromflammation and the progression of Alzheimer's disease. J Neurovirol 2002; 8: 529-538.
10. Wersinger C , Sidhu A. Inflammation and Parkinson's disease. Curr Drug Targets Inflamm Allergy .2002; 1:221-242.
11.朱长庚主编。神经解剖学人民卫生出版社,2002年3月第一版: 412-414
12. Kreutzberg G W. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996; 19: 312-318.
13. Kempennann G, Neumann H. Microglia: The Enemy Within? Science. 2003; 302 : 1689-1690
14. Qin L, Liu Y, Wang T, Wei SJ, Block ML, Wilson B, Liu B, Hong JS. (2004) NADPH oxidase mediates LPS-induced neurotoxicity and pro-inflammatory gene expression in activated microglia.J Biol Chem.279(2):1415-21
15. Yokoyama A, Yang L, Itoh S, Mori K, Tanaka J. Microglia, a potential source of neurons, astrocytes, and oligodendrocytes.Glia. 2004;45: 96-104.
16. Chen L, Yang P, Kijlstra A. Distribution, markers, and functions of retinal microglia. Ocul Immunol Inflamm, 2002, 10: 27-39
17. Katrin F, Helmut K. Physiology of microlglia cell. Brain research review, 2005; 48:133-143.
18. Nelson PT, Soma LA, Lavi E. Microglia in diseases of the central nervous system. Ann Med. 2002; 34:491-500.
19. Boucsein C, Kettenmann H, Nolte C. Electrophysiological properties of microglial cells in normal and pathologic rat brain slices. Eur. J Neurosci. 2000;12: 2049– 2058.
20. Brown H, kozlowski R, Perri H. The importance of ion channels for macrophage and microglial activation in vitro. Glia 1998,220:94-97
21. Kuho Y,Baldwin TJ,Jan YN, et al. Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature, 1993, 362:127-133
22. Schilling T, Quandt FN, Chexny VV, et al. Upregulation of K+ channels in microglia deactivated by TGF-beta. Am J Physiol, 2000, 279: 1123-1134.
23. Eder C,Heinemann U. Proton modulation of outward K+currents in interferon-activated microglia. Neurosci Lett, 1996,206:101-104.
24. Eder C,Klee R, Heinemann U. Pharmacological properties of Ca -activated K+ currents of ramified murine brain macrophages. Naunyn Schmiedebergs Arch Pharmacol,1996, 356:233-239.
25. Ishi TM, Si lvia C, Hirschberg B, et al. A human intermediate conductance calcium-activated potassium channel.Proc Natl Acad Sci,1997,94:11651-6.
26. Khanna R, Roy L, Zhu X, Schlichter LC. K channels and the microglial respiratory burst.Am J Physiol,2001, 280:796-806.
27. Zhou W,Cayabyab FS,Pennefather PS, et al. HERG like K+ channels in microglia. J Gen Physiol, 1998, 111:781-794.
28. Vilhardt F. Microglia: phagocyte and glia cell. Int J Biochem Cell Biol. 2005; 37: 17-21
29. Asheuer M, Pflumio F, Benhamida S, Cartier N, Human CD34+ cells differentiate into microglia and express recombinant therapeutic protein, Proc. Natl. Acad. Sci. U. S. A.2004;101: 3557-3562.
30. Choi C, Benveniste E.N., Fas ligand/Fas system in the brain:regulator of immune and apoptotic responses, Brain Res. Brain Res Rev. 2004; 44 :65-81.
31. N. Drojdahl, C. Fenger, H.H. Nielsen, T. Owens, B. Finsen. Dynamics of micorglia responses to anterograde axonal and terminal degeneration in normal and TNF-transgenic mice. Neurosci. Res. 2004; 75 :203–217.
32. M.B. Jensen, I.V. Hegelund, N.D. Lomholt, B. Finsen, T. Owens. IFN gamma enhances microglial reactions to hippocampal axonal degeneration, Neurosci, 2000; 20:3612-3621.
33. Cheng Zhang, Ji-kui Shen, Tim T. Lam, Mark O. M. Tso.Activation of microglia and chemokines in light-induced retinal Degeneration Molecular Vision 2005; 11:887-95
34. Qin L, Liu Y, Cooper C, Liu B, Wilson B, Hong JS. Microglia enhance beta-amyloid peptide-induced toxicity incortical and mesencephalic neurons by producing reactive oxygen species. J Neurochem. 2002; 83:973-983
35. Gayle DA, Ling Z, Carvey PM. Lipopolysaccharide (LPS)-induced dopamine cell loss in culture: roles of tumor necrosis factor-alpha, interleukin-lbeta, and nitric oxide. Brain Res Dev Brain Res. 2002; 133: 27-35
36. Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci 1996; 19:312-318.
37. Cui YH, Le Y, Gong Wang JM. Bacterial lipopolysaccharide selectively up-regulates the function of the chemotactic peptide receptor formyl peptide receptor 2 in murine mircroglial cells. Immunol. 2002; 168: 434-442
38. Andrea MR, Cole GM, Ard MD. The microglial phagocytic role with specific plaque types in the Alzheimer disease brain. Neurobiol Aging. 2004; 25: 675-683
39. Mun-Bryce S, Lukes A, Wallace J, Lukes-Marx M, Rosenberg GA. Stromelysin-1 and gelatinase A are upregulated before TNF-alpha in LPS-stimulated neuroinflammation. Brain Res. 2002; 933: 42-49
40. Gotilieb M, Matute C. Expression of inontropic glutamate receptor subunits in glia cells of the hippocampal CA1 area following transient forebrain isehemia. J Cereb Blood Flow Metab 1997;17:290-300.
41. WuYP,LingEA. Induction of microglia and astrocytic response in the adult rat lumbar spinal cord following MCV occlusion. Exp Brain Res,1998;118:235-242.
42. Sehroeter M,Jander S,Witte OW,Stoll G.. Heterogeneity of the microglia response in photochemically induced focal ischemia of the rat cerebral cortex. Neuroscience 1999;59:1367-1377.
43. Jochen Gehrmann,Yoh Matsuxnoto,Georg W Kreutzberg,Microglia : intrinsic immuneffector cell of the brain. Brain Res Brain Rev, 1995;20:269-287.
44. Zielasek J, Hartung HP. Molecular mechanisms of microglial activation. ADV Neuroimmunol,1991;6:191-222.
45. Planas AM,Soriano MA,Berruezo M,et,al. Induction of Stat3,a signal transducer and transcription factor,in reactive microglia following transient focal cerebral ischaemia. Eur J Neurosci,1996;8:2612-2618.
46. Wiessner C,Brink J,Lorenz P,et, al. CyclinD1 messenger RNA is induced in microglia rather than neurons following transient forebrain ischamia. Neuroscience ,1996,72:947-958.
47. Lambertsen KL, Gregersen R, Drojdal N, et al. A specidic and sensitive method for visualization of tumor necrosis factor in the murine central nervous system.Brain Res Brain Res Protoc 2001;7:175-191.
48. Paakkari I,Undsberg P. Nitric oxide in the CNS. Ann Med,1995;27:369-377.
49. Clemens JA,Stephenson DT,Smalstig EB,et al. Reactive glia express cytosolic phospholipase A2 after transient global forebrain ischemia in the rat. Stroke, 1996;27:527-535.
50. Wiessner C,Brink I,Lorenz P,et al. CyelinDl messenger RNA is induced in microglia rather than neurons following transient forebrain ischemia. Neuroscience 1996;72:947-958.
51. Stoll G,Jander S,Sehroeter M. Inflammation and glial responses in ischemia brain lesions. Prog Neurobiol,1998;56:149-171.
52. Schwab JM,Nguyen TD,Meyermann R,et al. Human focal cerebral infarctions induced differential lesional interleukin-16 expression confined to infiltrating granulocytes,CD8+T-lymphocytes and aetivated microglia/macrophages,J Neuroimmunol 200l;114:232-241.
53. Selmaj K,Raine CS,Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol, 1998;23:339-346.
54. Mitrovic B,Ignarro LJ,Vinters HV,et al. Nitric oxide induces necrotic but not apoptotic cell death in oligodendrocytes. Neuroscience,1995;65:531-539.
55. Nakajima K, Kohsaka S. Microglia: neuroprotective and neurotrophic cells in the central nervous system. Curr Drug Targets Cardiovasc Haematol Disord, 2004;4:65-84.
56. Minghetti L, Levi G. Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Prog Neurobiol, 1998;54:99-125.
57. Schwab JM, Schluesener HJ. Microglia rules: insights into micoglial neuronal Signaling.Cell Death and Differentiation, 2004, 11:1245-1246.
58. Franzen R, Schoenen J, Leprince P, et al. Effects of macrophage transplantation in the injured adult rat spinal cord: a combined immunocytochemical and biochemical study. J Neurosci Res, 1999; 51:316-327.
59. Li YQ, Wong CS.Radiation-induced apoptosis in the neonatal and adult rat spinal cord. Radiat Res.2000;154:268-276
60. Li Y, Field PM, Raisman G. Death of oligodendrocytes and microglial phagocytosis of myelin precede immigration of Schwann cells into the spinal cord. J Neurocytol. 1999; 28: 417-427
61. Thanos S, Mey J, Wild M. Treatment of the adult retina with microglia-suppressing factors retards axotomy-induced neuronal degradation and enhances axonal regeneration in vivo and in vitro. J Neurosci. 1993;13:455–466
62. Zhang C, Tso MO. Characterization of activated retinal microglia following optic axotomy. J Neurosci Res 2003;73:840-845
63. Gupta N,Brown KE,Milam AH.Activated microglia in human retinitis pigmentsosa, late-onset retinal degeneration, and age related macular degeneration.Exp Eye Res 2003; 76:463-471
64. Erik Schuetz, Solon Thanos. Neuro-glial interactions in the adult rat retina after reaxotomy of ganglion cells: examination of neuron survival and phagocytic microglia using fluorescent tracers Brain Research Bulletin 2004;62:391-396
65. Enrique GV, Sansar C Sharma, Ana Luisa Pi. Multilayered retinal microglial response to optic nerve transaction in rats. Molecular Vision 2005; 11:225-31
66. Raibon E, Sauve Y, Carter DA, Gallard F. Microglial changes accompanying the promotion of retinal ganglion cell axonal regeneration into peripheral nerve grafts. Journal of Neurocytology 2002;31:57–71
2. Robaey MS, Clarke DB, Wang YC, et al. Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells. Proc Natl Acad Sci USA,1994 ;91: 1632–1636
3. Fischer D, Pavlidis M, Thanos S. Cataractogenic lens injury prevents traumatic ganglion cell death and promotes axonal regeneration both in vivo and in culture. Invest Ophthalmol Vis Sci ,2000 ;41 (12): 3943-3954
4. Leon S, Yin YQ, Nguyen J, et al. Lens Injury Stimulates Axon Regeneration in the Mature Rat Optic Nerve. Journal of Neuroscience, 2000, 20(12):4615-4626
5.王艳华,王一。晶体蛋白对离体培养的大鼠视网膜神经节细胞的作用。中华创伤杂志,2005,21(2):98-103
6.刘康,王一,王艳华等。晶状体蛋白促大鼠视网膜神经节细胞存活和突起生长的体外研究。中华创伤杂志,2007,23(1):41-46
7.王晓芹,王一等。α晶体蛋白与视网膜神经节细胞结合的细胞定位研究。中华创伤杂志,2007,23(12):1-6
8.刘志敏,王一。混合晶状体蛋白对大鼠视神经损伤后视网膜神经节细胞的保护作用。中华创伤杂志,2006,22(12):926-929
9.张莉,王一,张辰星。α-晶状体蛋白对视神经损伤后视网膜神经节细胞保护作用的研究。中华创伤杂志,2007;23(3): 344-348.
10. Sasaki A, Yokoo H, Naito M, et al. Effects of macrophage-colony-stimulating factor deficiency on the maturation of microglia and brain macrophages and on their expression of scavenger receptor, Neuropathology 2000 ;20:134– 142.
11. Raivich G., Bohatschek M., Kloss CU, et al. Neuroglial activation repertoire in the injured brain:graded response, molecular mechanisms and cues to physiological function, Brain Res,1999 ;30:77– 105.
12. Kato H, Takahashi A, Itoyama Y. Cell cycle protein expression in proliferating microglia and astrocytes following transient global cerebral ischemia in the rat, BrainRes. Bull. 2003 ;60:215-221.
13. Compston A, Coles A. Multiple sclerosis. Lancet. 2002; 359: 1221-1231
14. Wenk GL. Neuropathologic changes in Alzheimer's disease. J Clin Psychiatry 2003; 64 suppl 9:7-10.
15. Wersinger C, Sidhu A. Inflammation and Parkinson's disease. Curr Drug Targets Inflamm Allergy .2002; 1:221-242.
16. Gupta N, Kimberly EB, Milam AH. Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration. Experimental Eye Research 2003;76 :463–471
17. Zeiss CJ, Johnson EA. Proliferation of Microglia, but not Photoreceptors, in the Outer Nuclear Layer of the rd-1 Mouse. Investigative Ophthalmology Visual Science, 2004; 45:971-976
18. Raibon E, Sauve Y, Carter DA, et al. Microglial changes accompanying the promotion of retinal ganglion cell axonal regeneration into peripheral nerve grafts. Journal of Neurocytology 2002;31:57-71
19. Watanabe, M, Fukuda, Y. Survival and axonal regeneration of retinal ganglion cells in adult cats. Prog. Retinal Eye Res. 2002,21:529-553
20. Fischer, D, Heiduschka, P, Thanos S. Lens-injury-stimulated axonal regeneration throughout the optic pathway of adult rats. Exp. Neurol. 2001. 172, 257-272.
21. Glenn Y, He ZG. Signaling mechanisms of the myelin inhibitors of axon regeneration. Current Opinoin in Neurobiology. 2003;13:545-551
22. Tikka T, Fiebich BL, Goldsteins G, et al. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci 2001, 21(8): 2580-2588.
23. Galiano M, Liu ZQ, Kalla R,et al. Interleukin-6 (IL-6) and cellular response to facial nerve injury:effects on lymphocyte recruitment,early microglial activation and axonal outgrowth in IL6-deficient mice. Eur J Neurosci,2001,14(2):327-341.
24. Yuan L,Neufeld AH.Tumor necrosis factor-alpha:a potentially neurodestructive cytokine produced by gila in the human glaucomatous optic nerve head.Glia,2000,32:42-50.
25. Raivich G, Bohatschek M, Kloss CU, et al. Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function, Brain Res. Rev. 1999;30:77–105.
26. Giulian D, Baker TJ. Characterization of amoeboid microglia isolated from developing mammalian brain.J Neurosci 1986,6:2163-78
27.杨忠,何家全,蔡文琴。一种改良的小胶质细胞培养方法及初步研究。创伤外科杂志2001,3(3):239-240
28.蔡文琴.现代实用细胞与分子生物学实验技术.北京.人民军医出版社。2003:115-138
29.朱长庚主编。神经解剖学人民卫生出版社,2002年3月第一版: 412-414
30. Chen L, Yang P,Istra KA. Distribution, markers,and functions of retinal microglia.Ocul Immunol Inflamm,2002,10:27-39.
31.张敏,魏桂荣等.一种高产量的小胶质细胞培养及其鉴定方法.卒中与神经疾病2005,12(4): 224-226
32. Navascues J,Moujahid A,Almendros A, et a1. Origin of microglia in the quail retina:central-to-peripheral and vitreal-to-scleral migration of microglial precursors during development.J Comp Neurol 1995,354:209-228.
33. Alejandro MS, Mary H, Michael JF, et al. Effect of a short-term in vitro exposure to the marine toxin domoicacid on viability, tumor necrosis factor-alpha, matrixmetalloproteinase-9 and superoxide anion release by rat neonatal microglia. BMC Pharmacology ,2001, 7:1471-1484
34. Rune L, Martin W, Bente F, et al. Microglial cell population dynamics in the injured adult central nervous system. Brain Research Reviews 2005,48: 196-206
35. Aldskogius H, Kozlova EN, Central neuron-glial and glial-glial interactions following axon injury, Prog. Neurobiol. 1998, 55:1-26
36. Neufeld AH. Microglia in the optic nerve head and the region of parapapillary chorioretinal atrophy in glaucoma. Arch Ophthalmol 1999,117:1050-1056.
37. Yuan L, Neufeld AH .Activated microglia in the human glaucomatous optic nerve head. J Neurosci Res 2001,64:523-532
38. Gilles JG, Bruce JB. Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification. Journal of Leukocyte Biology 2004;75:388-397.
39. Giulian D, Li J, Bartel S, et al. Cell Surface Morphology Identifies Microglia as a Distinct Class of Mononuclear Phagocyte. Journal of Neuroscience, November 1995, 15(11): 7712-7726
40. Gonzalez SF, Blatuch G. Microglia as mediators of inflammatory and degenerative diseases. Annu Rev Neurosci 1999,22:222-240
41. Mofoika T, Kalehua, ANN, Streit WJ. The imbroglio reaction in the rat dorsal hippocampus following transient forebrain schema. J Cereb Blood Flow Metablo 1991,11:966-973
42. Suraj PB.Transparency and non-refractive functionsof crystallins-a proposal. Experimental Eye Research 79 (2004) 809–816.
43. Hans B, Christine S, et al. Ageing and vision: structure, stability and function of lens crystallins Progress in Biophysics & Molecular Biology 86 (2004) 407–48.
44.刘康,王一。α-晶状体蛋白的研究进展[J]。眼科新进展2005;25(2):86-89.
45. Derham BK.Harding JJ.Effect of aging on the chaperone-like function of human -crystallin assessed by three methods.Biochem J,1997,328:763-768.
46. Lampi KJ, Shih M, Ueda Y, et a1. Lens proteomics:analysis of rat crystallin sequences and two-dimensional electrophoresis map.Invest Ophthalmol Vis Sci,2002,43:216-224.
47.严宏,惠延年,李明勇。阿司匹林类药物和α-晶状体蛋白保护酯酶的失活。第四军医大学学报2002;23(5):476-479.
48. Horwitz J. A1pha-crystallin.Exp Eye Res 2003;76: 145-153
49. Vanhoudt J, Aerts T, Abgar S, et al. Native quaternary structure of bovine alpha- crystallin. Biochemistry 2000;39:4483-4492
50. Reddy GB,Reddy PY. AlphaA-and alphaB-crystallins protect glucose-6-phosphate dehydrogenase against UVB irradiation induced inactivation. Biochim Biophys Res Commun,2002,282:712-716.
51. Kamradt MC, Chen F, Cryns VL. The small heat shock protein alpha B crystallin negatively regulates cytochrome c and caspase-8 dependent activation of caspase-3 by inhibiting its autoproteolytic maturation.J Biol Chem,2001,276:16059-l6063.
52. Alge CS,Priglinger SG,Neubauer AS,et a1. Retinal pigment epithelium is protected against apoptosis by alphaB-crystallin.Invest Ophthalmol Vis Sic,2002,43:3575-3582.
53. Machida S,Chaudhry P,Shinohara T, et al. Lens epithelium derived growth factor promotes photoreceptor survival in light damaged and RCS rats.Invest Ophthalmol Vis Sic 200142:1087-l095.
54. Andley UP,Song Z,Wawrousek EF, et a1.Differential protective activity of alpha A -and alpha B-crystallin in lens epithelial cells.J Biol Chem 2000,275:36823-36831.
55. Eaton P, Fuller W, Bell JR, et a1. Alpha B crystallin translocation and phosphorylation:signal transduction pathways and preconditioning in the isolated rat heart.J Mol Cell Cardiol 2001,33: 1659-1671.
56. Hou Y, Wu CF, Yang JY, et al. Effects of clozapine, olanzapine and haloperidol on nitric oxide production by lipopolysaccharide activated N9 cells. Prog Neuropsychopharmacol Biol Psychiatry 2006;23:1-6
57. Weinsteirt SL, Sanhera JS, Lemke K, et al. Bacterial lipopolysaccharide induces tyrosine phosphory1ation and activation of mitogen-activated protein kinase in macrophages.J Biol Chem 1992;267 :14955-14962.
58. Seg R, Kreb EG. The MAPK signaling cascade.FASEB J.1995,9:726-7
59. Takeshi O, Ichikawa M, et al. Intravitreal macrophage activation enables cat retinal ganglion cells toregenerate injured axons into the mature optic nerve. Experimental Neurology 2005,196:153-163
60. Chen A, Kumar SM, Sahley CL, et a1. Nitric oxide influences injury induced microglial migration and accumulation in the CNS.J Neurosci,2000;20:1036-1043.
61. Dalmau I, Vela JM, Gonzalez B, et al. Dynamics of microglia in the developing rat brain, J. Comp. Neurol. 2003;458 :144-157.
62. Drojdahl N, Fenger C, Finsen B, et al. Dynamics of microlgia responses to anterograde axonal and terminal degeneration in normal and TNF-transgenic mice, J. Neurosci. Res. 75 (2004) 203–217.
63. Rao NA,Kimoto T,Zarnir E.Pathogenic role of retinal microglia in experimental uveoretinitis.Invest Ophthalmol Vis Sci,2003,44:22-31.
64. Neufeld AH.Microglia in the optic nerve head and the region of parapapilary chorioretinal atrophy in glaucoma.Arch Ophthalmol,1999,117:1050-1056
65. Watanabe M, Tokita Y, Kato M, et a1. Intravitreal injections of neurotrophic factors and forskolin enhance surviva1 and axonal regeneration of axotomized beta ganglion cells in cat retina.Neuroscience,2003,116:733-742.
66. Ander S,Stoll G. Role of NMDA receptor signaling in the regulation of inflammatory gene expression after focal brain ischemia. Journal of Neuroimmunology 2000 ; 109: 181-187
67. Chao CC, Hu S. Tumor necrosis factor-αpotentiates qlutamate neurotoxicity in human fetal brain cell cultures. Dev Neurosci, 1994, 16:172-179
68. Mizuno T, Kurotani T, Komatsu Y,et al. Neuroprotective role of phosphodiesterase inhibitor ibudilast on neuronal cell death induced by activated microglia Neuropharmacology, 2004, 46: 404-411
69. Tezel, G, Wax, MB. Increased production of tumor necrosis factor-alpha by glial cells exposed to simulated ischemia or elevated hydrostatic pressure induces apoptosis in cocultured retinal ganglion cells. Neurosci 2000b ; 20, 8693–8700.
70. Kim JS, Lee HJ, Lee MH. Luteolin inhibits LPS-stimulated inducible nitric oxide synthase expression in BV-2 microglial cells. Planta Med. 2006;72:65-8.
71. Calapai G, Marcinom C, Corica F, et a1.Erythmpoietin protects against brain ischemic injury by inhibition of nitric oxide formation.Eur J Pharmacol,2000;401:349-356.
72. Liu B, Hong JS. Role of microglia in inflammation mediated neurodegenerative diseases:mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther,2003,304(1):1 -7.
73. Combs CK, Karlo JC, Kao SC, et al. beta-Amyloid stimulation of microglia and monocytes results in TNF alpha dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J Neurosci,2001,21:1179-1188
74. Levkovitch VH, Quigley HA, Kesrigan BLA.Optic nerve transtection in monkeys may result in secondary degeneration of retinal ganglion cells. Invest Ophthalmol Vis Sci. 2001;42:975-982.
75. Levkovitch VH, Quigley HA, Martin KRG, et al. A model to study differences betweenprimary andsecondary degeneration of retinal ganglion cells in rats by partialoptic nerve transaction. Invest Ophthalmol Vis Sci. 2003;44:3388–3393.
76.史剑波,徐锦堂,夏潮勇。视神经损伤对视网膜结构的形态学研究。眼外伤职业眼病杂志,1998;20(4):283-285
77. Milligan CE, Levitt P, Cunningham TJ. Brain macrophages and microglia respond differently to lesions of the developing and adult visual system. J Comp Neurol 1991; 314:136-46.
78. Kaur C, Hao AJ, Wu CH, et al. Origin of microglia. Microsc Res Tech 2001; 54:2-9.
79. Pearson HE, Payne BR, Cunningham TJ. Microglial invasion and activation in response to naturally occurring neuronal degeneration in the ganglion cell layer of the postnatal cat retina.Brain Res Dev Brain Res 1993; 76:249-55.
80. Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996; 19: 312-318.
81. Kempennann G, Neumann H. Microglia: The Enemy Within? Science. 2003; 302 : 1689-1690
82. Qin L, Liu Y, Wang T, Wei SJ, et al. NADPH oxidase mediates LPS-induced neurotoxicity and pro-inflammatory gene expression in activated microglia.J Biol Chem. 2004;279:1415-21
83. Schwab JM, Schluesener HJ. Microglia rules: insights into micoglial neuronal Signaling.Cell Death and Differentiation, 2004, 11:1245-1246.
84. Ralf E, Daniela C, Annett B, et al. A different retinal glia response to optic nerve injury /lipopolysaccharide administration in hooded and albino rats Brain Research 2001;889:251–255
85. Schuetz E, Thanos S. Neuro-glial interactions in the adult rat retina after reaxotomy of ganglion cells: examination of neuron survival and phagocytic microglia using fluorescent tracers Brain Research Bulletin 2004;62 :391-396
86. Madigan MC, Sadun AA, Rao NS, et al. Tumor necrosis factor-alpha (TNF-alpha) induced optic neuropathyin rabbits. Neurol. Res. 1996;18:176-184.
87. Tezel G, Chauhan BC, LeBlanc RP, et al. Immunohistochemical assessment of the glial mitogen-activated protein kinase activation in glaucoma, Invest. Ophthalmol. VisualSci. 2003;44:3025–3033.
88. Liu T, Clark RK, McDonnell PC, et al. Increased production of tumor necrosis factoralpha by glial cells exposed to simulated ischemia or elevated hydrostatic pressure induces apoptosis in cocultured retinal ganglion cells. J Neurosci. 2000;20 : 8693-8700.
89. Tezel G, Yang XJ, Yang JJ, et al. Role of tumor necrosis factor receptor-1 in the death of retinal ganglion cells following optic nerve crush injury in mice. Brain Research 2004;996:202-212
90. Kim HS, Chan KP. Retinal ganglion cell death is delayed by activation of retinal intrinsic cell survival program.Brain Research 2005;1057: 17-28
91. Wong A, Luth HJ, Deuther CW, et a1. Advanced glycation endproducts co localize with inducible nitric oxide synthase in Alzheimer′s disease. Brain Res ,2001;920:32-40.
92. Golde S, Chandran S, Brown GC, et a1. Different pathways for iNOS mediated toxicity in vitro dependent on neuronal maturation and NMDA receptor expression. J Neurochem, 2002;82:269-282.
93. Merrill JE , Ignarro LJ , Sherman MP, et a1 . Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J Immunol,1993;151:2132-2141
94. Guzy RD,Schumacker PT. Oxygen sensing by mitochondria at complex III: The paradox of increased ROS during hypoxia. Exp Physiol 2006;91:07-819.
95. Wei T,Chen C,Zhao B,et al. EPC K1 attenuates peroxynitrite induced apoptosis in cerebellar granule cells. Biochem Mol Biol Int 1998;46:89-97
96. Villegas PM, Vidal SM, Rasminsky M, et al. Rapid and protracted phases of retinal ganglion cell loss follow axotomy in the optic nerve of adult rats. J Neurobio. 1993;24:23-36.
97. Aktan F. INOS mediated nitric oxide production and its regulation. Life Sciences,2004;75:639-653.
98. Tikka T, Fiebich BL, Goldstein G, et al. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci, 2001; 21: 2580-2588.
99. Liu B, Gao HM, Wang, JY, et al. Role of nitric oxide in inflammation mediated neurodegeneration. Annals of the New York Academy of Sciences,2002; 962:318- 331
100. Thanos S. Regenerating ganglion cell axons in the adult rat establish retinofugal topography and restore visual function. Exp-Brain-Res. 1997,114(3):483-91.
101. Stupp T, Thanos S. Can lenticular factors improve the posttrauma fate of neurons? Progress in Retinal and Eye Research 2005;24:241-257
102. Lorber B, Berry M, Logan A, et a1. Effect of lens lesion on neurite outgrowth of retinal ganglion cells in vitro.Mol Cell Neurosci,2002;21:301-3l1
103.王艳华。α晶体蛋白促进视网膜神经节细胞轴突再生的机制研究。2007年博士论文,P70。
1. Rune L, Martin W, Bente F. Microglial cell population dynamics in the injured adult central nervous system. Brain Research Reviews. 2005; 48:196-206
2. Kreutzberg G W. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996; 19: 312-318
3. McGeer PL, K Yasojima and EG McGeer. Association of interleukin-1 beta polymorphisms with idiopathic Parkinson's disease. Neurosci Lett.2002; 326:67-69.
4. Compston A , Coles A. Multiple sclerosis. Lancet. 2002; 359: 1221-1231
5. Wenk GL. Neuropathologic changes in Alzheimer's disease. J Clin Psychiatry 2003; 64 suppl 9:7-10.
6. Liu B, Hong JS. Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Therapy. 2003; 304: 1-7.
7. McGeer PL, Yasojima K ,McGeer . EG Inflammation in Parkinson's disease. Adv Neuro.2001;186: 83-89.
8. Liu B, Gao HM, Wang JY, Jeohn GH. Role of nitric oxide in inflammation-mediated neurodegeneration. Ann N Y Acad Sci. 2002; 962: 318-331.
9. McGeer PL and McGeer EG. Local neuromflammation and the progression of Alzheimer's disease. J Neurovirol 2002; 8: 529-538.
10. Wersinger C , Sidhu A. Inflammation and Parkinson's disease. Curr Drug Targets Inflamm Allergy .2002; 1:221-242.
11.朱长庚主编。神经解剖学人民卫生出版社,2002年3月第一版: 412-414
12. Kreutzberg G W. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996; 19: 312-318.
13. Kempennann G, Neumann H. Microglia: The Enemy Within? Science. 2003; 302 : 1689-1690
14. Qin L, Liu Y, Wang T, Wei SJ, Block ML, Wilson B, Liu B, Hong JS. (2004) NADPH oxidase mediates LPS-induced neurotoxicity and pro-inflammatory gene expression in activated microglia.J Biol Chem.279(2):1415-21
15. Yokoyama A, Yang L, Itoh S, Mori K, Tanaka J. Microglia, a potential source of neurons, astrocytes, and oligodendrocytes.Glia. 2004;45: 96-104.
16. Chen L, Yang P, Kijlstra A. Distribution, markers, and functions of retinal microglia. Ocul Immunol Inflamm, 2002, 10: 27-39
17. Katrin F, Helmut K. Physiology of microlglia cell. Brain research review, 2005; 48:133-143.
18. Nelson PT, Soma LA, Lavi E. Microglia in diseases of the central nervous system. Ann Med. 2002; 34:491-500.
19. Boucsein C, Kettenmann H, Nolte C. Electrophysiological properties of microglial cells in normal and pathologic rat brain slices. Eur. J Neurosci. 2000;12: 2049– 2058.
20. Brown H, kozlowski R, Perri H. The importance of ion channels for macrophage and microglial activation in vitro. Glia 1998,220:94-97
21. Kuho Y,Baldwin TJ,Jan YN, et al. Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature, 1993, 362:127-133
22. Schilling T, Quandt FN, Chexny VV, et al. Upregulation of K+ channels in microglia deactivated by TGF-beta. Am J Physiol, 2000, 279: 1123-1134.
23. Eder C,Heinemann U. Proton modulation of outward K+currents in interferon-activated microglia. Neurosci Lett, 1996,206:101-104.
24. Eder C,Klee R, Heinemann U. Pharmacological properties of Ca -activated K+ currents of ramified murine brain macrophages. Naunyn Schmiedebergs Arch Pharmacol,1996, 356:233-239.
25. Ishi TM, Si lvia C, Hirschberg B, et al. A human intermediate conductance calcium-activated potassium channel.Proc Natl Acad Sci,1997,94:11651-6.
26. Khanna R, Roy L, Zhu X, Schlichter LC. K channels and the microglial respiratory burst.Am J Physiol,2001, 280:796-806.
27. Zhou W,Cayabyab FS,Pennefather PS, et al. HERG like K+ channels in microglia. J Gen Physiol, 1998, 111:781-794.
28. Vilhardt F. Microglia: phagocyte and glia cell. Int J Biochem Cell Biol. 2005; 37: 17-21
29. Asheuer M, Pflumio F, Benhamida S, Cartier N, Human CD34+ cells differentiate into microglia and express recombinant therapeutic protein, Proc. Natl. Acad. Sci. U. S. A.2004;101: 3557-3562.
30. Choi C, Benveniste E.N., Fas ligand/Fas system in the brain:regulator of immune and apoptotic responses, Brain Res. Brain Res Rev. 2004; 44 :65-81.
31. N. Drojdahl, C. Fenger, H.H. Nielsen, T. Owens, B. Finsen. Dynamics of micorglia responses to anterograde axonal and terminal degeneration in normal and TNF-transgenic mice. Neurosci. Res. 2004; 75 :203–217.
32. M.B. Jensen, I.V. Hegelund, N.D. Lomholt, B. Finsen, T. Owens. IFN gamma enhances microglial reactions to hippocampal axonal degeneration, Neurosci, 2000; 20:3612-3621.
33. Cheng Zhang, Ji-kui Shen, Tim T. Lam, Mark O. M. Tso.Activation of microglia and chemokines in light-induced retinal Degeneration Molecular Vision 2005; 11:887-95
34. Qin L, Liu Y, Cooper C, Liu B, Wilson B, Hong JS. Microglia enhance beta-amyloid peptide-induced toxicity incortical and mesencephalic neurons by producing reactive oxygen species. J Neurochem. 2002; 83:973-983
35. Gayle DA, Ling Z, Carvey PM. Lipopolysaccharide (LPS)-induced dopamine cell loss in culture: roles of tumor necrosis factor-alpha, interleukin-lbeta, and nitric oxide. Brain Res Dev Brain Res. 2002; 133: 27-35
36. Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci 1996; 19:312-318.
37. Cui YH, Le Y, Gong Wang JM. Bacterial lipopolysaccharide selectively up-regulates the function of the chemotactic peptide receptor formyl peptide receptor 2 in murine mircroglial cells. Immunol. 2002; 168: 434-442
38. Andrea MR, Cole GM, Ard MD. The microglial phagocytic role with specific plaque types in the Alzheimer disease brain. Neurobiol Aging. 2004; 25: 675-683
39. Mun-Bryce S, Lukes A, Wallace J, Lukes-Marx M, Rosenberg GA. Stromelysin-1 and gelatinase A are upregulated before TNF-alpha in LPS-stimulated neuroinflammation. Brain Res. 2002; 933: 42-49
40. Gotilieb M, Matute C. Expression of inontropic glutamate receptor subunits in glia cells of the hippocampal CA1 area following transient forebrain isehemia. J Cereb Blood Flow Metab 1997;17:290-300.
41. WuYP,LingEA. Induction of microglia and astrocytic response in the adult rat lumbar spinal cord following MCV occlusion. Exp Brain Res,1998;118:235-242.
42. Sehroeter M,Jander S,Witte OW,Stoll G.. Heterogeneity of the microglia response in photochemically induced focal ischemia of the rat cerebral cortex. Neuroscience 1999;59:1367-1377.
43. Jochen Gehrmann,Yoh Matsuxnoto,Georg W Kreutzberg,Microglia : intrinsic immuneffector cell of the brain. Brain Res Brain Rev, 1995;20:269-287.
44. Zielasek J, Hartung HP. Molecular mechanisms of microglial activation. ADV Neuroimmunol,1991;6:191-222.
45. Planas AM,Soriano MA,Berruezo M,et,al. Induction of Stat3,a signal transducer and transcription factor,in reactive microglia following transient focal cerebral ischaemia. Eur J Neurosci,1996;8:2612-2618.
46. Wiessner C,Brink J,Lorenz P,et, al. CyclinD1 messenger RNA is induced in microglia rather than neurons following transient forebrain ischamia. Neuroscience ,1996,72:947-958.
47. Lambertsen KL, Gregersen R, Drojdal N, et al. A specidic and sensitive method for visualization of tumor necrosis factor in the murine central nervous system.Brain Res Brain Res Protoc 2001;7:175-191.
48. Paakkari I,Undsberg P. Nitric oxide in the CNS. Ann Med,1995;27:369-377.
49. Clemens JA,Stephenson DT,Smalstig EB,et al. Reactive glia express cytosolic phospholipase A2 after transient global forebrain ischemia in the rat. Stroke, 1996;27:527-535.
50. Wiessner C,Brink I,Lorenz P,et al. CyelinDl messenger RNA is induced in microglia rather than neurons following transient forebrain ischemia. Neuroscience 1996;72:947-958.
51. Stoll G,Jander S,Sehroeter M. Inflammation and glial responses in ischemia brain lesions. Prog Neurobiol,1998;56:149-171.
52. Schwab JM,Nguyen TD,Meyermann R,et al. Human focal cerebral infarctions induced differential lesional interleukin-16 expression confined to infiltrating granulocytes,CD8+T-lymphocytes and aetivated microglia/macrophages,J Neuroimmunol 200l;114:232-241.
53. Selmaj K,Raine CS,Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol, 1998;23:339-346.
54. Mitrovic B,Ignarro LJ,Vinters HV,et al. Nitric oxide induces necrotic but not apoptotic cell death in oligodendrocytes. Neuroscience,1995;65:531-539.
55. Nakajima K, Kohsaka S. Microglia: neuroprotective and neurotrophic cells in the central nervous system. Curr Drug Targets Cardiovasc Haematol Disord, 2004;4:65-84.
56. Minghetti L, Levi G. Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Prog Neurobiol, 1998;54:99-125.
57. Schwab JM, Schluesener HJ. Microglia rules: insights into micoglial neuronal Signaling.Cell Death and Differentiation, 2004, 11:1245-1246.
58. Franzen R, Schoenen J, Leprince P, et al. Effects of macrophage transplantation in the injured adult rat spinal cord: a combined immunocytochemical and biochemical study. J Neurosci Res, 1999; 51:316-327.
59. Li YQ, Wong CS.Radiation-induced apoptosis in the neonatal and adult rat spinal cord. Radiat Res.2000;154:268-276
60. Li Y, Field PM, Raisman G. Death of oligodendrocytes and microglial phagocytosis of myelin precede immigration of Schwann cells into the spinal cord. J Neurocytol. 1999; 28: 417-427
61. Thanos S, Mey J, Wild M. Treatment of the adult retina with microglia-suppressing factors retards axotomy-induced neuronal degradation and enhances axonal regeneration in vivo and in vitro. J Neurosci. 1993;13:455–466
62. Zhang C, Tso MO. Characterization of activated retinal microglia following optic axotomy. J Neurosci Res 2003;73:840-845
63. Gupta N,Brown KE,Milam AH.Activated microglia in human retinitis pigmentsosa, late-onset retinal degeneration, and age related macular degeneration.Exp Eye Res 2003; 76:463-471
64. Erik Schuetz, Solon Thanos. Neuro-glial interactions in the adult rat retina after reaxotomy of ganglion cells: examination of neuron survival and phagocytic microglia using fluorescent tracers Brain Research Bulletin 2004;62:391-396
65. Enrique GV, Sansar C Sharma, Ana Luisa Pi. Multilayered retinal microglial response to optic nerve transaction in rats. Molecular Vision 2005; 11:225-31
66. Raibon E, Sauve Y, Carter DA, Gallard F. Microglial changes accompanying the promotion of retinal ganglion cell axonal regeneration into peripheral nerve grafts. Journal of Neurocytology 2002;31:57–71