氯化锂抑制血管平滑肌细胞增殖和迁移以及抗神经细胞损伤的分子机制研究
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摘要
作为化学元素周期表中最轻的元素之一,锂离子用于治疗精神疾病的历史已过百年。锂离子既能有效控制急性躁狂和急性抑郁,又能预防躁狂和抑郁反复发作,因此是治疗双相和单相抑郁性障碍的首选药物之一。
血管平滑肌细胞(vascular smooth muscle cells,VSMCs)的病理性增殖和迁移是导致诸多心血管病变的重要诱因,同时也是发生支架内再狭窄的独立风险性因素。近年来的研究显示,锂离子对心血管系统同样具有保护作用。然而,目前有关这方面的报道还主要停留在现象的描述上,缺乏深入细致的机制探讨。
转录共激活因子PGC-1α(peroxisome proliferator activated receptor y coactivator1α)是近年来发现的最为重要的能量代谢调节因子。近期我们注意到,PGC-1α在调控VSMCs功能方面同样有着活跃的表现,提高PGC-1α的表达对内膜增生的治疗具有重要的应用价值。
我们通过实验发现,预孵氯化锂(lithium chloride, LiCl)可以剂量依赖性地提高PGC1α的蛋白表达量以及核定位。四甲基偶氮唑盐(MTT)法和乙炔脱氧尿嘧啶核苷(EdU)法证明LiCl可以抑制血清诱导的VSMCs增殖。相似地,划痕癒合(wound healing)实验和迁移小室(Transwell)实验证实LiCl可以抑制血清诱导的VSMCs迁移。LiC1同样可以阻滞血清诱导的氧自由基(reactive oxygen species, ROS)产生和细胞周期的病理性进程。在分子水平上,LiC能够减少细胞重新进入细胞周期、粘附、炎症和迁移所需的蛋白表达量。此外,在体内水平,大鼠接受连续14天的LiCl灌胃,减缓了球囊损伤模型后内膜增生的病理性变化。更为重要的是,通过PGC-1α siRNA干扰PGC-1α的表达,能够明显削弱LiCl在体内体外水平上对于VSMCs的保护效果。
局部麻醉对于脊椎麻醉和病痛缓解有着至关重要的作用。但是,运用局部麻醉可能会引起神经毒性并导致手术后病人神经学上的并发症。我们探索了LiCl对于神经毒性的保护作用。在我们的研究中采用体外培养的小鼠神经母细胞瘤细胞株(mouse neuroblastoma neuro2a, N2a),探讨LiCl对其突触生长的影响及其机制。结果显示,预孵LiCl可以减少布比卡因引起的N2a细胞损伤,其作用逆转了布比卡因所导致的Akt (threonine-serine protein kinase B)以及ERKs (extracellular-signal regulated kinases)信号通路的下降并阻滞线粒体膜电位的降低。我们还观察到,Akt以及ERKs信号通路的抑制剂可以削弱LiCl对于布比卡因所致神经损伤的保护作用。
综上所述,我们的研究表明,LiCl对于体外水平的VSMCs增殖和迁移,以及体内水平的内膜增生病理模型有着重要的保护意义。另外,LiCL可以同时激活N2a细胞内Akt以及ERKs信号通路。LiCl主要通过Akt以及ERKs信号通路保护N2a细胞神经突触免受布比卡因的细胞毒性。
As one of the lightest solid elements, lithium has been used as a mood stabilizer for more than one century. Studies in recent years have shown that lithium also plays a protective role on the cardiovascular system.
The proliferation and migration of vascular smooth muscle cells (VSMCs) is a major pathophysiological process leading to various cardiovascular disorders such as in-stent restenosis. However, previous studies stay in the descriptive stage and the direct molecular target responsible for the beneficial action of lithium in cardiovascular system remains unknown.
Peroxisome proliferator-activated receptor coactivator-la (PGC-la) is a transcriptional coactivator intensively involved in the regulation of cellular energy metabolism. Recently, We have noted that PGC-la could negatively regulate the pathological activation of VSMCs and increase of PGC-la expression may have great potentials to treat restenosis.
We found that pretreatment of LiCl increased PGC-laprotein expression and nuclear translocation in a dose-dependent manner. MTT and EdU incorporation assays indicated that LiCl inhibited serum-induced VSMC proliferation. Similarly, deceleration of VSMC migration was confirmed by wound healing and transwell assays. LiCl also suppressed serum-induced ROS generation and cell cycle progression. At the molecular level, LiCl reduced the protein which involved in the cell cycle re-entry, adhesion, inflammation and motility. In addition, in vivo administration of LiCl alleviated the pathophysiological changes in balloon injury-induced neointima hyperplasia. More importantly, knockdown of PGC-laby siRNA significantly attenuated the beneficial effects of LiCl on VSMCs both in vitro and in vivo.
Local anesthetics (LAs) are necessary for the regional anesthesia, spinal anesthesia, and pain management. However, the application of LAs may cause neurotoxicity and result in postoperative neurological complications. In the second part, we evaluated the effects of LiCl on bupivacaine (a frequently used LAs) induced injury in mouse neuroblastoma neuro2a(N2a) cells. Pretreatment of N2a cells with LiCl significantly attenuated bupivacaine-induced cell injury. LiCl pretreatment completely reversed the suppression of Akt and ERKs signalings and significantly prevented the decline of transmembrane potentialin N2a cells after bupivacaine treatment. More importantly, pharmacological inhibition of Akt and ERKs diminished the protective effect of LiCl against bupivacaine-induced neuronal death.
In conclusion, our research shows that LiCl has great potentials on the prevention and treatment of cardiovascular diseases related to VSMC abnormal proliferation and migration. In addition, LiCl increases the phosphorylation of ERKs and Akt. LiCl pretreatment provides a protective effect on bupivacaine induced neuronal cell injury. This action of LiCl is mediated through, at least in part, the activating of Akt-and ERKs-dependent mechanisms.
血管平滑肌细胞(vascular smooth muscle cells,VSMCs)的病理性增殖和迁移是导致诸多心血管病变的重要诱因,同时也是发生支架内再狭窄的独立风险性因素。近年来的研究显示,锂离子对心血管系统同样具有保护作用。然而,目前有关这方面的报道还主要停留在现象的描述上,缺乏深入细致的机制探讨。
转录共激活因子PGC-1α(peroxisome proliferator activated receptor y coactivator1α)是近年来发现的最为重要的能量代谢调节因子。近期我们注意到,PGC-1α在调控VSMCs功能方面同样有着活跃的表现,提高PGC-1α的表达对内膜增生的治疗具有重要的应用价值。
我们通过实验发现,预孵氯化锂(lithium chloride, LiCl)可以剂量依赖性地提高PGC1α的蛋白表达量以及核定位。四甲基偶氮唑盐(MTT)法和乙炔脱氧尿嘧啶核苷(EdU)法证明LiCl可以抑制血清诱导的VSMCs增殖。相似地,划痕癒合(wound healing)实验和迁移小室(Transwell)实验证实LiCl可以抑制血清诱导的VSMCs迁移。LiC1同样可以阻滞血清诱导的氧自由基(reactive oxygen species, ROS)产生和细胞周期的病理性进程。在分子水平上,LiC能够减少细胞重新进入细胞周期、粘附、炎症和迁移所需的蛋白表达量。此外,在体内水平,大鼠接受连续14天的LiCl灌胃,减缓了球囊损伤模型后内膜增生的病理性变化。更为重要的是,通过PGC-1α siRNA干扰PGC-1α的表达,能够明显削弱LiCl在体内体外水平上对于VSMCs的保护效果。
局部麻醉对于脊椎麻醉和病痛缓解有着至关重要的作用。但是,运用局部麻醉可能会引起神经毒性并导致手术后病人神经学上的并发症。我们探索了LiCl对于神经毒性的保护作用。在我们的研究中采用体外培养的小鼠神经母细胞瘤细胞株(mouse neuroblastoma neuro2a, N2a),探讨LiCl对其突触生长的影响及其机制。结果显示,预孵LiCl可以减少布比卡因引起的N2a细胞损伤,其作用逆转了布比卡因所导致的Akt (threonine-serine protein kinase B)以及ERKs (extracellular-signal regulated kinases)信号通路的下降并阻滞线粒体膜电位的降低。我们还观察到,Akt以及ERKs信号通路的抑制剂可以削弱LiCl对于布比卡因所致神经损伤的保护作用。
综上所述,我们的研究表明,LiCl对于体外水平的VSMCs增殖和迁移,以及体内水平的内膜增生病理模型有着重要的保护意义。另外,LiCL可以同时激活N2a细胞内Akt以及ERKs信号通路。LiCl主要通过Akt以及ERKs信号通路保护N2a细胞神经突触免受布比卡因的细胞毒性。
As one of the lightest solid elements, lithium has been used as a mood stabilizer for more than one century. Studies in recent years have shown that lithium also plays a protective role on the cardiovascular system.
The proliferation and migration of vascular smooth muscle cells (VSMCs) is a major pathophysiological process leading to various cardiovascular disorders such as in-stent restenosis. However, previous studies stay in the descriptive stage and the direct molecular target responsible for the beneficial action of lithium in cardiovascular system remains unknown.
Peroxisome proliferator-activated receptor coactivator-la (PGC-la) is a transcriptional coactivator intensively involved in the regulation of cellular energy metabolism. Recently, We have noted that PGC-la could negatively regulate the pathological activation of VSMCs and increase of PGC-la expression may have great potentials to treat restenosis.
We found that pretreatment of LiCl increased PGC-laprotein expression and nuclear translocation in a dose-dependent manner. MTT and EdU incorporation assays indicated that LiCl inhibited serum-induced VSMC proliferation. Similarly, deceleration of VSMC migration was confirmed by wound healing and transwell assays. LiCl also suppressed serum-induced ROS generation and cell cycle progression. At the molecular level, LiCl reduced the protein which involved in the cell cycle re-entry, adhesion, inflammation and motility. In addition, in vivo administration of LiCl alleviated the pathophysiological changes in balloon injury-induced neointima hyperplasia. More importantly, knockdown of PGC-laby siRNA significantly attenuated the beneficial effects of LiCl on VSMCs both in vitro and in vivo.
Local anesthetics (LAs) are necessary for the regional anesthesia, spinal anesthesia, and pain management. However, the application of LAs may cause neurotoxicity and result in postoperative neurological complications. In the second part, we evaluated the effects of LiCl on bupivacaine (a frequently used LAs) induced injury in mouse neuroblastoma neuro2a(N2a) cells. Pretreatment of N2a cells with LiCl significantly attenuated bupivacaine-induced cell injury. LiCl pretreatment completely reversed the suppression of Akt and ERKs signalings and significantly prevented the decline of transmembrane potentialin N2a cells after bupivacaine treatment. More importantly, pharmacological inhibition of Akt and ERKs diminished the protective effect of LiCl against bupivacaine-induced neuronal death.
In conclusion, our research shows that LiCl has great potentials on the prevention and treatment of cardiovascular diseases related to VSMC abnormal proliferation and migration. In addition, LiCl increases the phosphorylation of ERKs and Akt. LiCl pretreatment provides a protective effect on bupivacaine induced neuronal cell injury. This action of LiCl is mediated through, at least in part, the activating of Akt-and ERKs-dependent mechanisms.
引文
1. Lin, J., C. Handschin, and B.M. Spiegelman, Metabolic control through the PGC-1 family of transcription coactivators. Cell metabolism,2005.1(6):p.361-370.
2. Chang, M.W., et al., Adenovirus-mediated over-expression of the cyclin/cyclin-dependent kinase inhibitor, p21 inhibits vascular smooth muscle cell proliferation and neointima formation in the rat carotid artery model of balloon angioplasty. Journal of Clinical Investigation,1995.96(5):p.2260.
3. Chang, M., et al., Adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene inhibits vascular smooth muscle cell proliferation and neointima formation following balloon angioplasty of the rat carotid artery. Molecular Medicine,1995.1(2):p.172.
4. Thyberg, J., et al., Regulation of differentiated properties and proliferation of arterial smooth muscle cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 1990.10(6):p.966-990.
5. Werry, T.D., P.M. Sexton, and A. Christopoulos,'Ins and outs'of seven-transmembrane receptor signalling to ERK. Trends in Endocrinology & Metabolism,2005.16(1):p.26-33.
6. Macleod, K., D. Leprince, and D. Stehelin, The< i> ets gene family. Trends in biochemical sciences,1992.17(7):p.251-256.
7. Harbour, J.W. and D.C. Dean, Rb function in cell-cycle regulation and apoptosis. Nature Cell Biology,2000.2(4):p. E65-E67.
8. Sherr, C.J. and J.M. Roberts, CDK inhibitors:positive and negative regulators of G1-phase progression. Genes & development,1999.13(12):p.1501-1512.
9. Fernandez, C, et al., Regulation of the extracellular ligand binding activity of integrins. Front. Biosci,1998.3:p.684-700.
10. Klemke, R.L., et al., Regulation of cell motility by mitogen-activated protein kinase. The Journal of cell biology,1997.137(2):p.481-492.
11. Goetze, S., et al., PPARy-ligands inhibit migration mediated by multiple chemoattractants in vascular smooth muscle cells. Journal of cardiovascular pharmacology,1999.33(5):p.798-806.
12. Cai, H. and D.G. Harrison, Endothelial dysfunction in cardiovascular diseases:the role of oxidant stress. Circulation research,2000.87(10):p.840-844.
13. Pou, S., et al., Generation of superoxide by purified brain nitric oxide synthase. Journal of Biological Chemistry,1992.267(34):p.24173-24176.
14. Harrison, D., Endothelial function and oxidant stress. Clinical cardiology,1997. 20(11 Suppl 2):p. Ⅱ-11-7.
15. Rubanyi, G. and P. Vanhoutte, Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. American Journal of Physiology-Heart and Circulatory Physiology,1986.250(5):p. H822-H827.
16. Thomson, L., et al., Kinetics of cytochrome C2+oxidation by peroxynitrite: implications for superoxide measurements in nitric oxide-producing biological-systems. Archives of biochemistry and biophysics,1995.319(2):p. 491-497.
17. Minor Jr, R.L., et al., Diet-induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta. Journal of Clinical Investigation,1990.86(6):p.2109.
18. INVALID CITATION!!!
19. Nakazono, K., et al., Does superoxide underlie the pathogenesis of hypertension? Proceedings of the National Academy of Sciences,1991.88(22):p.10045-10048.
20. Suzuki, H., et al., In vivo evidence for microvascular oxidative stress in spontaneously hypertensive rats Hydroethidine microfluorography. Hypertension, 1995.25(5):p.1083-1089.
21. De Keulenaer, GW., et al., Oscillatory and steady laminar shear stress differentially affect human endothelial redox state role of a superoxide-producing NADH oxidase. Circulation research,1998.82(10):p.1094-1101.
22. Rajagopalan, S., et al., Angiotensin Ⅱ-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. Journal of Clinical Investigation,1996. 97(8):p.1916.
23. Bauersachs, J., et al., Endothelial Dysfunction in Chronic Myocardial Infarction Despite Increased Vascular Endothelial Nitric Oxide Synthase and Soluble Guanylate Cyclase Expression Role of Enhanced Vascular Superoxide Production. Circulation,1999.100(3):p.292-298.
24. Kerr, S., et al., Superoxide anion production is increased in a model of genetic hypertension role of the endothelium. Hypertension,1999.33(6):p.1353-1358.
25. Canevari, L., et al., Stimulation of the Brain NO/Cyclic GMP Pathway by Peripheral Administration of Tetrahydrobiopterin in the hph-1 Mouse. Journal of neurochemistry,1999.73(6):p.2563-2568.
26. Valle, I., et al., PGC-1α regulates the mitochondrial antioxidant defense system in vascular endothelial cells. Cardiovascular research,2005.66(3):p.562-573.
27. Taniyama, Y. and K.K. Griendling, Reactive oxygen species in the vasculature molecular and cellular mechanisms. Hypertension,2003.42(6):p.1075-1081.
28. Won, J.C., et al., Peroxisome proliferator-activated receptor-y coactivator 1-a overexpression prevents endothelial apoptosis by increasing ATP/ADP translocase activity. Arteriosclerosis, thrombosis, and vascular biology,2010.30(2):p.290-297.
29. Fuster, J.J., et al., Control of cell proliferation in atherosclerosis:insights from animal models and human studies. Cardiovascular research,2010.86(2):p.254-264.
30. Nathe, T.J., et al., Interleukin-1/3 inhibits expression of p21 (WAFI/C1P1) and p27 (KIPI) and enhances proliferation in response to platelet-derived growth factor-BB in smooth muscle cells. Arteriosclerosis, thrombosis, and vascular biology,2002. 22(8):p.1293-1298.
31. Takahashi, A., et al., Tranilast inhibits vascular smooth muscle cell growth and intimal hyperplasia by induction ofp21waf1/cipl/sdil and p53. Circulation research, 1999.84(5):p.543-550.
32. Otterbein, L.E., et al., Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nature medicine, 2003.9(2):p.183-190.
33. Akimoto, S., et al., Laminar shear stress inhibits vascular endothelial cell proliferation by inducing cyclin-dependent kinase inhibitor p21Sdi1/Cip1/Waf1. Circulation research,2000.86(2):p.185-190.
34. Seasholtz, T.M., et al., Increased expression and activity of RhoA are associated with increased DNA synthesis and reduced p27Kip1 expression in the vasculature of hypertensive rats. Circulation research,2001.89(6):p.488-495.
35. Ihling, C., et al., Topographical association between the cyclin-dependent kinases inhibitor P21, p53 accumulation, and cellular proliferation in human atherosclerotic tissue. Arteriosclerosis, thrombosis, and vascular biology,1997.17(10):p. 2218-2224.
36. Olson, N.E., J. Kozlowski, and M.A. Reidy, Proliferation of Intimal Smooth Muscle Cells ATTENUATION OF BASIC FIBROBLAST GROWTH FACTOR 2-STIMULATED PROLIFERATION IS ASSOCIATED WITH INCREASED EXPRESSION OF CELL CYCLE INHIBITORS. Journal of Biological Chemistry, 2000.275(15):p.11270-11277.
37. Fukui, R., et al., Increased migration in late G1 phase in cultured smooth muscle cells. American Journal of Physiology-Cell Physiology,2000.279(4):p. C999-C1007.
38. Reshetnikova, G, et al., Disruption of the actin cytoskeleton leads to inhibition of mitogen-induced cyclin E expression, Cdk2 phosphorylation, and nuclear accumulation of the retinoblastoma protein-related p107 protein. Experimental cell research,2000.259(1):p.35-53.
39. Sun, J., et al., Role for p27Kip1 in vascular smooth muscle cell migration. Circulation,2001.103(24):p.2967-2972.
40. Humbert, S., R. Dhavan, and L. Tsai, p39 activates cdk5 in neurons, and is associated with the actin cytoskeleton. Journal of cell science,2000.113(6):p. 975-983.
41. Koyama, H., et al., Fibrillar collagen inhibits arterial smooth muscle proliferation through regulation of Cdk2 inhibitors. Cell,1996.87(6):p.1069-1078.
42. Diez-Juan, A. and V. Andres, Coordinate control of proliferation and migration by the p27Kipl/cyclin-dependent kinase/retinoblastoma pathway in vascular smooth muscle cells and fibroblasts. Circulation research,2003.92(4):p.402-410.
43. Zhan, Y, et al., Role of JNK, p38, and ERK in platelet-derived growth factor-induced vascular proliferation, migration, and gene expression. Arteriosclerosis, thrombosis, and vascular biology,2003.23(5):p.795-801.
44. Wakino, S., et al., Peroxisome proliferator-activated receptor y ligands inhibit retinoblastoma phosphorylation and G1→S transition in vascular smooth muscle cells. Journal of Biological Chemistry,2000.275(29):p.22435-22441.
45. Zhang, Y., et al., PGC-la inhibits oleic acid induced proliferation and migration of rat vascular smooth muscle cells. PLoS One,2007.2(11):p. e1137.
46. Jiang, X., et al.,17β-Estradiol inhibits oleic acid-induced rat VSMC Proliferation and migration by restoring PGC-1α expression. Molecular and cellular endocrinology,2010.315(1):p.74-80.
47. Forstermann, U., Oxidative stress in vascular disease:causes, defense mechanisms and potential therapies. Nature clinical practice Cardiovascular medicine,2008.5(6): p.338-349.
48. Qu, A., et al., PGC-1α attenuates neointimal formation via inhibition of vascular smooth muscle cell migration in the injured rat carotid artery. American Journal of Physiology-Cell Physiology,2009.297(3):p. C645-C653.
49. Mitra, A. and D. Agrawal, In stent restenosis:bane of the stent era. Journal of clinical pathology,2006.59(3):p.232-239.
50. McEver, R.P., GMP-140:A receptor for neutrophils and monocytes on activated platelets and endothelium. Journal of cellular biochemistry,1991.45(2):p.156-161.
51. Hayashi, S.-i., et al., Roles of P-selectin in inflammation, neointimal formation, and vascular remodeling in balloon-injured rat carotid arteries. Circulation,2000. 102(14):p.1710-1717.
52. Spertini, O., et al., P-selectin glycoprotein ligand 1 is a ligand for L-selectin on neutrophils, monocytes, and CD34+hematopoietic progenitor cells. The Journal of cell biology,1996.135(2):p.523-531.
53. Walcheck, B., et al., Neutrophil-neutrophil interactions under hydrodynamic shear stress involve L-selectin and PSGL-1. A mechanism that amplifies initial leukocyte accumulation of P-selectin in vitro. Journal of Clinical Investigation,1996.98(5):p. 1081.
54. Manka, D.R., et al., Arterial Injury Increases Expression of Inflammatory Adhesion Molecules in the Carotid Arteries of Apolipoprotein-E-Deficient Micel. Journal of vascular research,1999.36(5):p.372-378.
55. Collins, T. and M.I. Cybulsky, NF-κB:pivotal mediator or innocent bystander in atherogenesis? Journal of Clinical Investigation,2001.107(3):p.255-264.
56. Welt, F.G, et al., Neutrophil, not macrophage, infiltration precedes neointimal thickening in balloon-injured arteries. Arteriosclerosis, thrombosis, and vascular biology,2000.20(12):p.2553-2558.
57. Kim, H.-J., et al., Effects of PGC-1α on TNF-α-induced MCP-1 and VCAM-1 expression and NF-κB activation in human aortic smooth muscle and endothelial cells. Antioxidants & redox signaling,2007.9(3):p.301-307.
58. Stein, S., et al., ApoE-/- PGC-1α-/- mice display reduced IL-18 levels and do not develop enhanced atherosclerosis. PloS one,2010.5(10):p. e13539.
59. Qi, X., et al., Effect of PGC-1α on Proliferation, Migration, and Transdifferentiation of Rat Vascular Smooth Muscle Cells Induced by High Glucose. BioMed Research International,2012.2012.
60. Cade, J.F., Lithium salts in the treatment of psychotic excitement. BULLETIN-WORLD HEALTH ORGANIZATION,2000.78(4):p.518-520.
61. Morgan, T.H., The relation between normal and abnormal development of the embryo of the frog, as determined by injury to the yolk-portion of the egg. Archiv fur Entwicklungsmechanik der Organismen,1902.15(2):p.238-313.
62. Jamison, K., Manic-depressive illness and accomplishment:Creativity, leadership, and social class. Manic-depressive illness,1990:p.332-367.
63. MAEDA, Y., Influence of ionic conditions on cell differentiation and morphogenesis of the cellular slime molds. Development, growth & differentiation,1970.12(3):p. 217-227.
64. Van Lookeren Campagne, M.M., et al., Lithium respecifiescyclic-AMP-Induced cell-type specific gene expression in Dictyostelium. Developmental genetics,1988. 9(4-5):p.589-596.
65. Davies, J.A. and D.R. Garrod, Induction of early stages of kidney tubule differentiation by lithium ions. Developmental biology,1995.167(1):p.50-60.
66. Ptashne, K., F.E. Stockdale, and S. Conlon, Initiation of DNA synthesis in mammary epithelium and mammary tumors by lithium ions. Journal of cellular physiology, 1980.103(1):p.41-46.
67. Nestler, E.J., R.Z. Terwilliger, and R.S. Duman, Regulation of Endogenous ADP Ribosylation by Acute and Chronic Lithium in Rat Brain. Journal of neurochemistry, 1995.64(5):p.2319-2324.
68. Jope, R.S. and M.B. Williams, Lithium and brain signal transduction systems. Biochemical pharmacology,1994.47(3):p.429-441.
69. Avissar, S., et al., Lithium inhibits adrenergic and cholinergic increases in GTP binding in rat cortex.1988.
70. Phiel, C.J. and P.S. Klein, Molecular targets of lithium action. Annual review of pharmacology and toxicology,2001.41(1):p.789-813.
71. Berridge, M.J., C.P. Downes, and M.R. Hanley, Neural and developmental actions of lithium:a unifying hypothesis. Cell,1989.59(3):p.411-419.
72. York, J.D., J.W. Ponder, and P.W. Majerus, Definition of a metal-dependent/Li (+)-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core structure. Proceedings of the National Academy of Sciences, 1995.92(11):p.5149-5153.
73. Klein, P.S. and D.A. Melton, A molecular mechanism for the effect of lithium on development. Proceedings of the National Academy of Sciences,1996.93(16):p. 8455-8459.
74. COHEN, P., et al., Separation and characterisation of glycogen synthase kinase 3, glycogen synthase kinase 4 and glycogen synthase kinase 5 from rabbit skeletal muscle. European Journal of Biochemistry,1982.124(1):p.21-35.
75. Plyte, S.E., et al., Glycogen synthase kinase-3:functions in oncogenesis and development. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer,1992. 1114(2):p.147-162.
76. Woodgett, J.R., Molecular cloning and expression of glycogen synthase kinase-Vfactor A. The EMBO journal,1990.9(8):p.2431.
77. Stambolic, V., L. Ruel, and J.R. Woodgett, Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Current Biology, 1996.6(12):p.1664-1669.
78. Harwood, A., et al., Glycogen synthase kinase 3 regulates cell fate in Dictyostelium. Cell,1995.80(1):p.139-148.
79. Nusse, R., et al., Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15.1984.
80. Peifer, M. and P. Polakis, Wnt signaling in oncogenesis and embryogenesis--α look outside the nucleus. Science,2000.287(5458):p.1606-1609.
81. Polakis, P., Wnt signaling and cancer. Genes & development,2000.14(15):p. 1837-1851.
82. Hall, A.C., F.R. Lucas, and P.C. Salinas, Axonal remodeling and synoptic differentiation in the cerebellum is regulated by WNT-7a signaling. Cell,2000. 100(5):p.525-535.
83. Kikuchi, A., Modulation of Wnt signaling by Axin and Axil. Cytokine& growth factor reviews,1999.10(3):p.255-265.
84. Riggleman, B., P. Schedl, and E. Wieschaus, Spatial expression of the Drosophila segment polarity gene< i> armadillo is posttranscriptionally regulated by< i> wingless. Cell,1990.63(3):p.549-560.
85. Nelson, R.W. and B.M. Gumbiner, A cell-free assay system for β-catenin signaling that recapitulates direct inductive events in the early Xenopus laevis embryo. The Journal of cell biology,1999.147(2):p.367-374.
86. Rogers, I. and S. Varmuza, LiCl disrupts axial development in mouse but does not act through the β-catenin/Lef-1 pathway. Molecular reproduction and development,2000.55(4):p.387-392.
87. Singh, L.P. and E.D. Crook, The effects of glucose and the hexosamine biosynthesis pathway on glycogen synthase kinase-3 and other protein kinases that regulate glycogen synthase activity. Journal of investigative medicine:the official publication of the American Federation for Clinical Research,2000.48(4):p.251-258.
88. Hoeflich, K.P., et al., Requirement for glycogen synthase kinase-3β in cell survival and NF-κB activation. Nature,2000.406(6791):p.86-90.
89. Kim, Y.R., et al., Functional MRI of delayed chronic lithium treatment in rat focal cerebral ischemia. Stroke,2008.39(2):p.439-447.
90. Chuang, D.M., et al., Neuroprotective effects of lithium in cultured cells and animal models of diseases. Bipolar disorders,2002.4(2):p.129-136.
91. Kaga, S., et al., Glycogen synthase kinase-3β/β-catenin promotes angiogenic and anti-apoptotic signaling through the induction of VEGF, Bcl-2 and survivin expression in rat ischemic preconditioned myocardium. Journal of molecular and cellular cardiology,2006.40(1):p.138-147.
92. Guo, S., et al., Lithium upregulates vascular endothelial growth factor in brain endothelial cells and astrocytes. Stroke,2009.40(2):p.652-655.
93. Pardo, R., et al., Opposed effects of lithium on the MEK-ERK pathway in neural cells:inhibition in astrocytes and stimulation in neurons by GSK3 independent mechanisms. Journal of neurochemistry,2003.87(2):p.417-426.
94. Silva, R., et al., Lithium prevents stress-induced reduction of vascular endothelium growth factor levels. Neuroscience letters,2007.429(1):p.33-38.
95. Hashimoto, R., et al., Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons:an essential step for neuroprotection against glutamate excitotoxicity. Neuropharmacology,2002.43(7):p.1173-1179.
96. Zahler, S., et al., Anti-angiogenic potential of small molecular inhibitors of cyclin dependent kinases in vitro. Angiogenesis,2010.13(3):p.239-249.
97. Rossig, L., et al., Glycogen synthase kinase-3 couples AKT-dependent signaling to the regulation of p21Cip1. degradation. Journal of Biological Chemistry,2002. 277(12):p.9684-9689.
98. Cheng, C.-w., S.K. Smith, and D.S. Charnock-Jones, Wnt-1 signaling inhibits human umbilical vein endothelial cell proliferation and alters cell morphology. Experimental cell research,2003.291(2):p.415-425.
99. Choi, S.-E., et al., Atherosclerosis induced by a high-fat diet is alleviated by lithium chloride via reduction of VCAM expression in ApoE-deficient mice. Vascular pharmacology,2010.53(5):p.264-272.
100. Bowes, A.J., et al., Valproate attenuates accelerated atherosclerosis in hyperglycemic apoE-deficient mice:evidence in support of a role for endoplasmic reticulum stress and glycogen synthase kinase-3 in lesion development and hepatic steatosis. The American journal of pathology,2009.174(1):p.330-342.
101. Raghavendra, P.B., E. Lee, and N. Parameswaran, Regulation of Macrophage Biology by Lithium:A New Look at an Old Drug. Journal of Neuroimmune Pharmacology,2013:p.1-8.
102. Whittle, B.J., et al., Reduction of experimental colitis in the rat by inhibitors of glycogen synthase kinase-3/3. British journal of pharmacology,2006.147(5):p. 575-582.
103. Zhang, P., J. Katz, and S.M. Michalek, Glycogen synthase kinase-3β (GSK3β) inhibition suppresses the inflammatory response to< i> Francisella infection and protects against tularemia in mice. Molecular immunology,2009.46(4):p. 677-687.
104. De Meyer, I., et al., Inhibition of inositol monophosphatase by lithium chloride induces selective macrophage apoptosis in atherosclerotic plaques. British journal of pharmacology,2011.162(6):p.1410-1423.
105. Hodgson, P.S., et al., The neurotoxicity of drugs given intrathecally (spinal). Anesthesia & Analgesia,1999.88(4):p.797-809.
106. Phillips, O.C., et al., Neurologic Complications Following Spinal Anesthesia with Lidocaine:A Prospective Revieiv of 10,440 Cases. Anesthesiology,1969.30(3):p. 284-289.
107. Vandam, L.D.and R.D. Dripps, Long-term follow-up of patients who received 10,098 spinal anesthetics:syndrome of decreased intracranial pressure (headache and ocular and auditory difficulties). Journal of the American medical association, 1956.161(7):p:586-591.
108. Horlocker, T.T., et al., A retrospective review of 4767 consecutive spinal anesthetics: central nervous system complications. Anesthesia & Analgesia,1997.84(3):p. 578-584.
109. Polaner, D.M., et al., Pediatric Regional Anesthesia Network (PRAN):a multi-institutional study of the use and incidence of complications of pediatric regional anesthesia. Anesthesia & Analgesia,2012.115(6):p.1353-1364.
110. Pollock, J.E., Transient Neurologic. Complications in Regional Anesthesia and Pain Medicine,2012:p.144.
111. Wong, C.A., Nerve injuries after neuraxial anaesthesia and their medicolegal implications. Best Practice & Research Clinical Obstetrics & Gynaecology,2010. 24(3):p.367-381.
112. Werdehausen, R., et al., Lipophilicity but not stereospecijicity is a major determinant of local anaesthetic-induced cytotoxicily in human T-lymphoma cells. European Journal of Anaesthesiology (EJA),2012.29(1):p.35-41.
113. Cherng, C.-H., et al., Glutamate release and neurologic impairment after intrathecal administration of lidocaine and bupivacaine in the rat. Regional anesthesia and pain medicine,2011.36(5):p.452-456.
114. Brastianos, P.K., et al., The toxicity of intrathecal bevacizumab in a rabbit model of leptomeningeal carcinomatosis. Journal of neuro-oncofogy,2012.106(1):p.81-88.
115. Lundy, J.S., H.E. ESSEX, and J.W. KERNOHAN, Experiments with Anesthetics:Ⅳ. Lesions Produced in the Spinal Cord of Dogs by a Dose of Procaine Hydrochloride Sufficient to Cause Permanent and Fatal Paralysis. Journal of the American Medical Association,1933.101(20):p.1546-1550.
116. Lambert, L.A., D.H. Lambert, and G.R. Strichartz, Irreversible conduction block in isolated nerve by high concentrations of local anesthetics. Anesthesiology,1994. 80(5):p.1082-1093.
117. Bainton, C.R. and G.R. Strichartz, Concentration dependence of lidocaine-induced irreversible conduction loss in frog nerve. Anesthesiology,1994.81(3):p.657-667.
118. Kanai, Y., H. Katsuki, and M. Takasaki, Graded, irreversible changes in crayfish giant axon as manifestations of lidocaine neurotoxicity in vitro. Anesthesia & Analgesia,1998.86(3):p.569-573.
119. Johnson, M.E. and C.B. Uhl, Toxic elevation of cytoplasmic calcium by high dose lidocaine in a neuronal cell line. Regional Anesthesia and Pain Medicine,1997. 22(2):p.68.
120. Radwan, I.A., S. Saito, and F. Goto, The neurotoxicity of local anesthetics on growing neurons:a comparative study of lidocaine, bupivacaine, mepivacaine, and ropivacaine. Anesthesia & Analgesia,2002.94(2):p.319-324.
121. Hillerup, S., R.H. Jensen, and B.K. Ersboll, Trigeminal nerve injury associated with injection of local anesthetics Needle lesion or neurotoxicity? The Journal of the American Dental Association,2011.142(5):p.531-539.
122. Chabal, C., L. Jacobson, and J. Little, Effects of intrathecal fentanyl and lidocaine on somatosensory-evoked potentials, the H-reflex, and clinical responses. Anesthesia & Analgesia,1988.67(6):p.509-513.
123. Liu, S., D.J. Kopacz, and R.L. Carpenter, Quantitative assessment of differential sensory nerve block after lidocaine spinal anesthesia. Anesthesiology,1995.82(1):p. 60-63.
2. Chang, M.W., et al., Adenovirus-mediated over-expression of the cyclin/cyclin-dependent kinase inhibitor, p21 inhibits vascular smooth muscle cell proliferation and neointima formation in the rat carotid artery model of balloon angioplasty. Journal of Clinical Investigation,1995.96(5):p.2260.
3. Chang, M., et al., Adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene inhibits vascular smooth muscle cell proliferation and neointima formation following balloon angioplasty of the rat carotid artery. Molecular Medicine,1995.1(2):p.172.
4. Thyberg, J., et al., Regulation of differentiated properties and proliferation of arterial smooth muscle cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 1990.10(6):p.966-990.
5. Werry, T.D., P.M. Sexton, and A. Christopoulos,'Ins and outs'of seven-transmembrane receptor signalling to ERK. Trends in Endocrinology & Metabolism,2005.16(1):p.26-33.
6. Macleod, K., D. Leprince, and D. Stehelin, The< i> ets gene family. Trends in biochemical sciences,1992.17(7):p.251-256.
7. Harbour, J.W. and D.C. Dean, Rb function in cell-cycle regulation and apoptosis. Nature Cell Biology,2000.2(4):p. E65-E67.
8. Sherr, C.J. and J.M. Roberts, CDK inhibitors:positive and negative regulators of G1-phase progression. Genes & development,1999.13(12):p.1501-1512.
9. Fernandez, C, et al., Regulation of the extracellular ligand binding activity of integrins. Front. Biosci,1998.3:p.684-700.
10. Klemke, R.L., et al., Regulation of cell motility by mitogen-activated protein kinase. The Journal of cell biology,1997.137(2):p.481-492.
11. Goetze, S., et al., PPARy-ligands inhibit migration mediated by multiple chemoattractants in vascular smooth muscle cells. Journal of cardiovascular pharmacology,1999.33(5):p.798-806.
12. Cai, H. and D.G. Harrison, Endothelial dysfunction in cardiovascular diseases:the role of oxidant stress. Circulation research,2000.87(10):p.840-844.
13. Pou, S., et al., Generation of superoxide by purified brain nitric oxide synthase. Journal of Biological Chemistry,1992.267(34):p.24173-24176.
14. Harrison, D., Endothelial function and oxidant stress. Clinical cardiology,1997. 20(11 Suppl 2):p. Ⅱ-11-7.
15. Rubanyi, G. and P. Vanhoutte, Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. American Journal of Physiology-Heart and Circulatory Physiology,1986.250(5):p. H822-H827.
16. Thomson, L., et al., Kinetics of cytochrome C2+oxidation by peroxynitrite: implications for superoxide measurements in nitric oxide-producing biological-systems. Archives of biochemistry and biophysics,1995.319(2):p. 491-497.
17. Minor Jr, R.L., et al., Diet-induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta. Journal of Clinical Investigation,1990.86(6):p.2109.
18. INVALID CITATION!!!
19. Nakazono, K., et al., Does superoxide underlie the pathogenesis of hypertension? Proceedings of the National Academy of Sciences,1991.88(22):p.10045-10048.
20. Suzuki, H., et al., In vivo evidence for microvascular oxidative stress in spontaneously hypertensive rats Hydroethidine microfluorography. Hypertension, 1995.25(5):p.1083-1089.
21. De Keulenaer, GW., et al., Oscillatory and steady laminar shear stress differentially affect human endothelial redox state role of a superoxide-producing NADH oxidase. Circulation research,1998.82(10):p.1094-1101.
22. Rajagopalan, S., et al., Angiotensin Ⅱ-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. Journal of Clinical Investigation,1996. 97(8):p.1916.
23. Bauersachs, J., et al., Endothelial Dysfunction in Chronic Myocardial Infarction Despite Increased Vascular Endothelial Nitric Oxide Synthase and Soluble Guanylate Cyclase Expression Role of Enhanced Vascular Superoxide Production. Circulation,1999.100(3):p.292-298.
24. Kerr, S., et al., Superoxide anion production is increased in a model of genetic hypertension role of the endothelium. Hypertension,1999.33(6):p.1353-1358.
25. Canevari, L., et al., Stimulation of the Brain NO/Cyclic GMP Pathway by Peripheral Administration of Tetrahydrobiopterin in the hph-1 Mouse. Journal of neurochemistry,1999.73(6):p.2563-2568.
26. Valle, I., et al., PGC-1α regulates the mitochondrial antioxidant defense system in vascular endothelial cells. Cardiovascular research,2005.66(3):p.562-573.
27. Taniyama, Y. and K.K. Griendling, Reactive oxygen species in the vasculature molecular and cellular mechanisms. Hypertension,2003.42(6):p.1075-1081.
28. Won, J.C., et al., Peroxisome proliferator-activated receptor-y coactivator 1-a overexpression prevents endothelial apoptosis by increasing ATP/ADP translocase activity. Arteriosclerosis, thrombosis, and vascular biology,2010.30(2):p.290-297.
29. Fuster, J.J., et al., Control of cell proliferation in atherosclerosis:insights from animal models and human studies. Cardiovascular research,2010.86(2):p.254-264.
30. Nathe, T.J., et al., Interleukin-1/3 inhibits expression of p21 (WAFI/C1P1) and p27 (KIPI) and enhances proliferation in response to platelet-derived growth factor-BB in smooth muscle cells. Arteriosclerosis, thrombosis, and vascular biology,2002. 22(8):p.1293-1298.
31. Takahashi, A., et al., Tranilast inhibits vascular smooth muscle cell growth and intimal hyperplasia by induction ofp21waf1/cipl/sdil and p53. Circulation research, 1999.84(5):p.543-550.
32. Otterbein, L.E., et al., Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nature medicine, 2003.9(2):p.183-190.
33. Akimoto, S., et al., Laminar shear stress inhibits vascular endothelial cell proliferation by inducing cyclin-dependent kinase inhibitor p21Sdi1/Cip1/Waf1. Circulation research,2000.86(2):p.185-190.
34. Seasholtz, T.M., et al., Increased expression and activity of RhoA are associated with increased DNA synthesis and reduced p27Kip1 expression in the vasculature of hypertensive rats. Circulation research,2001.89(6):p.488-495.
35. Ihling, C., et al., Topographical association between the cyclin-dependent kinases inhibitor P21, p53 accumulation, and cellular proliferation in human atherosclerotic tissue. Arteriosclerosis, thrombosis, and vascular biology,1997.17(10):p. 2218-2224.
36. Olson, N.E., J. Kozlowski, and M.A. Reidy, Proliferation of Intimal Smooth Muscle Cells ATTENUATION OF BASIC FIBROBLAST GROWTH FACTOR 2-STIMULATED PROLIFERATION IS ASSOCIATED WITH INCREASED EXPRESSION OF CELL CYCLE INHIBITORS. Journal of Biological Chemistry, 2000.275(15):p.11270-11277.
37. Fukui, R., et al., Increased migration in late G1 phase in cultured smooth muscle cells. American Journal of Physiology-Cell Physiology,2000.279(4):p. C999-C1007.
38. Reshetnikova, G, et al., Disruption of the actin cytoskeleton leads to inhibition of mitogen-induced cyclin E expression, Cdk2 phosphorylation, and nuclear accumulation of the retinoblastoma protein-related p107 protein. Experimental cell research,2000.259(1):p.35-53.
39. Sun, J., et al., Role for p27Kip1 in vascular smooth muscle cell migration. Circulation,2001.103(24):p.2967-2972.
40. Humbert, S., R. Dhavan, and L. Tsai, p39 activates cdk5 in neurons, and is associated with the actin cytoskeleton. Journal of cell science,2000.113(6):p. 975-983.
41. Koyama, H., et al., Fibrillar collagen inhibits arterial smooth muscle proliferation through regulation of Cdk2 inhibitors. Cell,1996.87(6):p.1069-1078.
42. Diez-Juan, A. and V. Andres, Coordinate control of proliferation and migration by the p27Kipl/cyclin-dependent kinase/retinoblastoma pathway in vascular smooth muscle cells and fibroblasts. Circulation research,2003.92(4):p.402-410.
43. Zhan, Y, et al., Role of JNK, p38, and ERK in platelet-derived growth factor-induced vascular proliferation, migration, and gene expression. Arteriosclerosis, thrombosis, and vascular biology,2003.23(5):p.795-801.
44. Wakino, S., et al., Peroxisome proliferator-activated receptor y ligands inhibit retinoblastoma phosphorylation and G1→S transition in vascular smooth muscle cells. Journal of Biological Chemistry,2000.275(29):p.22435-22441.
45. Zhang, Y., et al., PGC-la inhibits oleic acid induced proliferation and migration of rat vascular smooth muscle cells. PLoS One,2007.2(11):p. e1137.
46. Jiang, X., et al.,17β-Estradiol inhibits oleic acid-induced rat VSMC Proliferation and migration by restoring PGC-1α expression. Molecular and cellular endocrinology,2010.315(1):p.74-80.
47. Forstermann, U., Oxidative stress in vascular disease:causes, defense mechanisms and potential therapies. Nature clinical practice Cardiovascular medicine,2008.5(6): p.338-349.
48. Qu, A., et al., PGC-1α attenuates neointimal formation via inhibition of vascular smooth muscle cell migration in the injured rat carotid artery. American Journal of Physiology-Cell Physiology,2009.297(3):p. C645-C653.
49. Mitra, A. and D. Agrawal, In stent restenosis:bane of the stent era. Journal of clinical pathology,2006.59(3):p.232-239.
50. McEver, R.P., GMP-140:A receptor for neutrophils and monocytes on activated platelets and endothelium. Journal of cellular biochemistry,1991.45(2):p.156-161.
51. Hayashi, S.-i., et al., Roles of P-selectin in inflammation, neointimal formation, and vascular remodeling in balloon-injured rat carotid arteries. Circulation,2000. 102(14):p.1710-1717.
52. Spertini, O., et al., P-selectin glycoprotein ligand 1 is a ligand for L-selectin on neutrophils, monocytes, and CD34+hematopoietic progenitor cells. The Journal of cell biology,1996.135(2):p.523-531.
53. Walcheck, B., et al., Neutrophil-neutrophil interactions under hydrodynamic shear stress involve L-selectin and PSGL-1. A mechanism that amplifies initial leukocyte accumulation of P-selectin in vitro. Journal of Clinical Investigation,1996.98(5):p. 1081.
54. Manka, D.R., et al., Arterial Injury Increases Expression of Inflammatory Adhesion Molecules in the Carotid Arteries of Apolipoprotein-E-Deficient Micel. Journal of vascular research,1999.36(5):p.372-378.
55. Collins, T. and M.I. Cybulsky, NF-κB:pivotal mediator or innocent bystander in atherogenesis? Journal of Clinical Investigation,2001.107(3):p.255-264.
56. Welt, F.G, et al., Neutrophil, not macrophage, infiltration precedes neointimal thickening in balloon-injured arteries. Arteriosclerosis, thrombosis, and vascular biology,2000.20(12):p.2553-2558.
57. Kim, H.-J., et al., Effects of PGC-1α on TNF-α-induced MCP-1 and VCAM-1 expression and NF-κB activation in human aortic smooth muscle and endothelial cells. Antioxidants & redox signaling,2007.9(3):p.301-307.
58. Stein, S., et al., ApoE-/- PGC-1α-/- mice display reduced IL-18 levels and do not develop enhanced atherosclerosis. PloS one,2010.5(10):p. e13539.
59. Qi, X., et al., Effect of PGC-1α on Proliferation, Migration, and Transdifferentiation of Rat Vascular Smooth Muscle Cells Induced by High Glucose. BioMed Research International,2012.2012.
60. Cade, J.F., Lithium salts in the treatment of psychotic excitement. BULLETIN-WORLD HEALTH ORGANIZATION,2000.78(4):p.518-520.
61. Morgan, T.H., The relation between normal and abnormal development of the embryo of the frog, as determined by injury to the yolk-portion of the egg. Archiv fur Entwicklungsmechanik der Organismen,1902.15(2):p.238-313.
62. Jamison, K., Manic-depressive illness and accomplishment:Creativity, leadership, and social class. Manic-depressive illness,1990:p.332-367.
63. MAEDA, Y., Influence of ionic conditions on cell differentiation and morphogenesis of the cellular slime molds. Development, growth & differentiation,1970.12(3):p. 217-227.
64. Van Lookeren Campagne, M.M., et al., Lithium respecifiescyclic-AMP-Induced cell-type specific gene expression in Dictyostelium. Developmental genetics,1988. 9(4-5):p.589-596.
65. Davies, J.A. and D.R. Garrod, Induction of early stages of kidney tubule differentiation by lithium ions. Developmental biology,1995.167(1):p.50-60.
66. Ptashne, K., F.E. Stockdale, and S. Conlon, Initiation of DNA synthesis in mammary epithelium and mammary tumors by lithium ions. Journal of cellular physiology, 1980.103(1):p.41-46.
67. Nestler, E.J., R.Z. Terwilliger, and R.S. Duman, Regulation of Endogenous ADP Ribosylation by Acute and Chronic Lithium in Rat Brain. Journal of neurochemistry, 1995.64(5):p.2319-2324.
68. Jope, R.S. and M.B. Williams, Lithium and brain signal transduction systems. Biochemical pharmacology,1994.47(3):p.429-441.
69. Avissar, S., et al., Lithium inhibits adrenergic and cholinergic increases in GTP binding in rat cortex.1988.
70. Phiel, C.J. and P.S. Klein, Molecular targets of lithium action. Annual review of pharmacology and toxicology,2001.41(1):p.789-813.
71. Berridge, M.J., C.P. Downes, and M.R. Hanley, Neural and developmental actions of lithium:a unifying hypothesis. Cell,1989.59(3):p.411-419.
72. York, J.D., J.W. Ponder, and P.W. Majerus, Definition of a metal-dependent/Li (+)-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core structure. Proceedings of the National Academy of Sciences, 1995.92(11):p.5149-5153.
73. Klein, P.S. and D.A. Melton, A molecular mechanism for the effect of lithium on development. Proceedings of the National Academy of Sciences,1996.93(16):p. 8455-8459.
74. COHEN, P., et al., Separation and characterisation of glycogen synthase kinase 3, glycogen synthase kinase 4 and glycogen synthase kinase 5 from rabbit skeletal muscle. European Journal of Biochemistry,1982.124(1):p.21-35.
75. Plyte, S.E., et al., Glycogen synthase kinase-3:functions in oncogenesis and development. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer,1992. 1114(2):p.147-162.
76. Woodgett, J.R., Molecular cloning and expression of glycogen synthase kinase-Vfactor A. The EMBO journal,1990.9(8):p.2431.
77. Stambolic, V., L. Ruel, and J.R. Woodgett, Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Current Biology, 1996.6(12):p.1664-1669.
78. Harwood, A., et al., Glycogen synthase kinase 3 regulates cell fate in Dictyostelium. Cell,1995.80(1):p.139-148.
79. Nusse, R., et al., Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15.1984.
80. Peifer, M. and P. Polakis, Wnt signaling in oncogenesis and embryogenesis--α look outside the nucleus. Science,2000.287(5458):p.1606-1609.
81. Polakis, P., Wnt signaling and cancer. Genes & development,2000.14(15):p. 1837-1851.
82. Hall, A.C., F.R. Lucas, and P.C. Salinas, Axonal remodeling and synoptic differentiation in the cerebellum is regulated by WNT-7a signaling. Cell,2000. 100(5):p.525-535.
83. Kikuchi, A., Modulation of Wnt signaling by Axin and Axil. Cytokine& growth factor reviews,1999.10(3):p.255-265.
84. Riggleman, B., P. Schedl, and E. Wieschaus, Spatial expression of the Drosophila segment polarity gene< i> armadillo is posttranscriptionally regulated by< i> wingless. Cell,1990.63(3):p.549-560.
85. Nelson, R.W. and B.M. Gumbiner, A cell-free assay system for β-catenin signaling that recapitulates direct inductive events in the early Xenopus laevis embryo. The Journal of cell biology,1999.147(2):p.367-374.
86. Rogers, I. and S. Varmuza, LiCl disrupts axial development in mouse but does not act through the β-catenin/Lef-1 pathway. Molecular reproduction and development,2000.55(4):p.387-392.
87. Singh, L.P. and E.D. Crook, The effects of glucose and the hexosamine biosynthesis pathway on glycogen synthase kinase-3 and other protein kinases that regulate glycogen synthase activity. Journal of investigative medicine:the official publication of the American Federation for Clinical Research,2000.48(4):p.251-258.
88. Hoeflich, K.P., et al., Requirement for glycogen synthase kinase-3β in cell survival and NF-κB activation. Nature,2000.406(6791):p.86-90.
89. Kim, Y.R., et al., Functional MRI of delayed chronic lithium treatment in rat focal cerebral ischemia. Stroke,2008.39(2):p.439-447.
90. Chuang, D.M., et al., Neuroprotective effects of lithium in cultured cells and animal models of diseases. Bipolar disorders,2002.4(2):p.129-136.
91. Kaga, S., et al., Glycogen synthase kinase-3β/β-catenin promotes angiogenic and anti-apoptotic signaling through the induction of VEGF, Bcl-2 and survivin expression in rat ischemic preconditioned myocardium. Journal of molecular and cellular cardiology,2006.40(1):p.138-147.
92. Guo, S., et al., Lithium upregulates vascular endothelial growth factor in brain endothelial cells and astrocytes. Stroke,2009.40(2):p.652-655.
93. Pardo, R., et al., Opposed effects of lithium on the MEK-ERK pathway in neural cells:inhibition in astrocytes and stimulation in neurons by GSK3 independent mechanisms. Journal of neurochemistry,2003.87(2):p.417-426.
94. Silva, R., et al., Lithium prevents stress-induced reduction of vascular endothelium growth factor levels. Neuroscience letters,2007.429(1):p.33-38.
95. Hashimoto, R., et al., Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons:an essential step for neuroprotection against glutamate excitotoxicity. Neuropharmacology,2002.43(7):p.1173-1179.
96. Zahler, S., et al., Anti-angiogenic potential of small molecular inhibitors of cyclin dependent kinases in vitro. Angiogenesis,2010.13(3):p.239-249.
97. Rossig, L., et al., Glycogen synthase kinase-3 couples AKT-dependent signaling to the regulation of p21Cip1. degradation. Journal of Biological Chemistry,2002. 277(12):p.9684-9689.
98. Cheng, C.-w., S.K. Smith, and D.S. Charnock-Jones, Wnt-1 signaling inhibits human umbilical vein endothelial cell proliferation and alters cell morphology. Experimental cell research,2003.291(2):p.415-425.
99. Choi, S.-E., et al., Atherosclerosis induced by a high-fat diet is alleviated by lithium chloride via reduction of VCAM expression in ApoE-deficient mice. Vascular pharmacology,2010.53(5):p.264-272.
100. Bowes, A.J., et al., Valproate attenuates accelerated atherosclerosis in hyperglycemic apoE-deficient mice:evidence in support of a role for endoplasmic reticulum stress and glycogen synthase kinase-3 in lesion development and hepatic steatosis. The American journal of pathology,2009.174(1):p.330-342.
101. Raghavendra, P.B., E. Lee, and N. Parameswaran, Regulation of Macrophage Biology by Lithium:A New Look at an Old Drug. Journal of Neuroimmune Pharmacology,2013:p.1-8.
102. Whittle, B.J., et al., Reduction of experimental colitis in the rat by inhibitors of glycogen synthase kinase-3/3. British journal of pharmacology,2006.147(5):p. 575-582.
103. Zhang, P., J. Katz, and S.M. Michalek, Glycogen synthase kinase-3β (GSK3β) inhibition suppresses the inflammatory response to< i> Francisella infection and protects against tularemia in mice. Molecular immunology,2009.46(4):p. 677-687.
104. De Meyer, I., et al., Inhibition of inositol monophosphatase by lithium chloride induces selective macrophage apoptosis in atherosclerotic plaques. British journal of pharmacology,2011.162(6):p.1410-1423.
105. Hodgson, P.S., et al., The neurotoxicity of drugs given intrathecally (spinal). Anesthesia & Analgesia,1999.88(4):p.797-809.
106. Phillips, O.C., et al., Neurologic Complications Following Spinal Anesthesia with Lidocaine:A Prospective Revieiv of 10,440 Cases. Anesthesiology,1969.30(3):p. 284-289.
107. Vandam, L.D.and R.D. Dripps, Long-term follow-up of patients who received 10,098 spinal anesthetics:syndrome of decreased intracranial pressure (headache and ocular and auditory difficulties). Journal of the American medical association, 1956.161(7):p:586-591.
108. Horlocker, T.T., et al., A retrospective review of 4767 consecutive spinal anesthetics: central nervous system complications. Anesthesia & Analgesia,1997.84(3):p. 578-584.
109. Polaner, D.M., et al., Pediatric Regional Anesthesia Network (PRAN):a multi-institutional study of the use and incidence of complications of pediatric regional anesthesia. Anesthesia & Analgesia,2012.115(6):p.1353-1364.
110. Pollock, J.E., Transient Neurologic. Complications in Regional Anesthesia and Pain Medicine,2012:p.144.
111. Wong, C.A., Nerve injuries after neuraxial anaesthesia and their medicolegal implications. Best Practice & Research Clinical Obstetrics & Gynaecology,2010. 24(3):p.367-381.
112. Werdehausen, R., et al., Lipophilicity but not stereospecijicity is a major determinant of local anaesthetic-induced cytotoxicily in human T-lymphoma cells. European Journal of Anaesthesiology (EJA),2012.29(1):p.35-41.
113. Cherng, C.-H., et al., Glutamate release and neurologic impairment after intrathecal administration of lidocaine and bupivacaine in the rat. Regional anesthesia and pain medicine,2011.36(5):p.452-456.
114. Brastianos, P.K., et al., The toxicity of intrathecal bevacizumab in a rabbit model of leptomeningeal carcinomatosis. Journal of neuro-oncofogy,2012.106(1):p.81-88.
115. Lundy, J.S., H.E. ESSEX, and J.W. KERNOHAN, Experiments with Anesthetics:Ⅳ. Lesions Produced in the Spinal Cord of Dogs by a Dose of Procaine Hydrochloride Sufficient to Cause Permanent and Fatal Paralysis. Journal of the American Medical Association,1933.101(20):p.1546-1550.
116. Lambert, L.A., D.H. Lambert, and G.R. Strichartz, Irreversible conduction block in isolated nerve by high concentrations of local anesthetics. Anesthesiology,1994. 80(5):p.1082-1093.
117. Bainton, C.R. and G.R. Strichartz, Concentration dependence of lidocaine-induced irreversible conduction loss in frog nerve. Anesthesiology,1994.81(3):p.657-667.
118. Kanai, Y., H. Katsuki, and M. Takasaki, Graded, irreversible changes in crayfish giant axon as manifestations of lidocaine neurotoxicity in vitro. Anesthesia & Analgesia,1998.86(3):p.569-573.
119. Johnson, M.E. and C.B. Uhl, Toxic elevation of cytoplasmic calcium by high dose lidocaine in a neuronal cell line. Regional Anesthesia and Pain Medicine,1997. 22(2):p.68.
120. Radwan, I.A., S. Saito, and F. Goto, The neurotoxicity of local anesthetics on growing neurons:a comparative study of lidocaine, bupivacaine, mepivacaine, and ropivacaine. Anesthesia & Analgesia,2002.94(2):p.319-324.
121. Hillerup, S., R.H. Jensen, and B.K. Ersboll, Trigeminal nerve injury associated with injection of local anesthetics Needle lesion or neurotoxicity? The Journal of the American Dental Association,2011.142(5):p.531-539.
122. Chabal, C., L. Jacobson, and J. Little, Effects of intrathecal fentanyl and lidocaine on somatosensory-evoked potentials, the H-reflex, and clinical responses. Anesthesia & Analgesia,1988.67(6):p.509-513.
123. Liu, S., D.J. Kopacz, and R.L. Carpenter, Quantitative assessment of differential sensory nerve block after lidocaine spinal anesthesia. Anesthesiology,1995.82(1):p. 60-63.