大鼠脑小胶质细胞对次声的反应
摘要
次声(infrasound)是由物体(物质)的机械性振动所产生,频率为0.0001～20Hz的声波。次声广泛存在于我们的环境中,凡有噪声的地方,都可能存在次声。这些低频噪声除污染环境并危害着人们的健康外,次声武器作为一种新技术武器已经开始研究并装备到部队。此外次声对人类也有许多益处:可以利用次声观测火山、海啸、地震等自然灾难进行提前报警,还可以用次声诊断和治疗疾病。小胶质细胞(microglia MI)作为中枢神经系统常驻的免疫细胞一方面保护中枢神经系统免受外来微生物的侵入,清除不需要的碎片,另一方面产生细胞因子以及与免疫系统联系。活化的MI可以参与中枢神经系统急性损伤、卒中、炎性以及神经变性性疾病的发病过程。
一定强度的次声噪音和次声武器作用于人体后可产生多种危害,可以引起机体行为学、形态学、蛋白结构、基因分子等多方面的改变。一些研究表明次声声级水平愈高,损伤愈严重。而小胶质细胞在神经组织的损伤以及炎性反应的发生、发展过程中发挥着重要的作用。以往文献报道次声作用后可以引起神经元损伤、星形胶质细胞的活化,但有关脑内小胶质细胞是否对次声刺激起反应,小胶质细胞形态上有何改变以及时间过程如何,目前均未见到报道。因此,研究次声作用后小胶质细胞的变化对了解次声性脑损害机制和脑保护的研究具有十分重要的理论和实用价值。
本实验进行了2个实验:
实验一:
将成年SD雄性大鼠反复暴露于声压级16Hz 130dB的次声环境中。在次声作用后不同时间点处死大鼠,对脑组织进行免疫组织化学染色,扫描电镜和透射电镜观察。观察在体:次声作用后即刻,12h,1d, 7d,14d大鼠海马、下丘脑室旁核小胶质细胞的变化情况及其与中枢神经系统中其他细胞间关系变化;次声作用后即刻,1d, 7d,扫描电镜和透射电镜下脑组织超微结构的变化。
结果表明:
(1)光镜下:正常大鼠小胶质细胞数量较少,一般为静息状态(静息型),与其他细胞无特别联系。次声作用后即刻大鼠小胶质细胞开始被活化、增殖,表现为光镜下:0X42阳性细胞深染,胞体变大变圆,突起变短、变粗长、变少,呈肥大型或阿米巴型小胶质细胞,并且还可以看出小胶质细胞数量显著增多(P〈0.01),这种变化在7d以后逐渐减弱。次声作用后第7d起星形胶质细胞变多,胞体变大,突起变粗,染色深,第14d达到高潮;小胶质细胞和星形胶质细胞之间的关系密切:次声作用后第7d可见到小胶质细胞与星形胶质细胞间有双标记橙黄色突起,这些突起数量在第14d达到高潮。此外还可见正常对照组小胶质细胞分布无特定规律,而活化的小胶质细胞主要分布与神经元周围。
(2)电镜下:可见正常大鼠小胶质细胞数量较小,较少,次声作用后1d小胶质细胞细胞核变大,突起增多,细胞内结构变丰富可见其内有吞噬小泡和溶酶体颗粒。活化的小胶质细胞主要分布于神经元、毛细血管周围,有的包绕神经元。在次声连续作用7d以后小胶质细胞数量较次声作用1d减少,但仍表现为活化状态。此外次声作用后还可发现从毛细血管内游走出的小胶质细胞。
实验二:
将体外培养小胶质细胞暴露于次声环境中30min,1h,而后采用免疫细胞化学法和Luminex液相芯片法观察不同时间点(0h,4h,12h,24h)小胶质细胞的变化以及其细胞因子分泌的变化情况。
结果表明:
(1)细胞形态的改变:可见正常对照组与保温箱对照组小胶质细胞表现为细胞胞体较小,为圆形或扁平细胞,拥有短的突起或是没有突起,细胞胞膜光滑,细胞内无吞噬小泡的阿米巴样小胶质细胞或是其前体细胞。荧光染色可见均匀一致的小而圆的红色细胞。次声作用30min后即刻小胶质细胞就开始发生改变,相差显微镜下可见细胞胞体肿胀、折光不均。在次声作用后12h,可见细胞肿胀更明显,细胞形态不规则,细胞膜上出现囊泡状物质,细胞边缘可见毛刺状突起;荧光显微镜下可见细胞荧光强度加大,CD11b主要表达于细胞膜;此外还可发现双核细胞比率显著增多(45%±5%),并且可见许多小的OX42阳性细胞,提示小胶质细胞存在细胞增殖、分裂。而到次声作用后24h,小胶质细胞内空泡增多,细胞内也可见一些吞噬小泡,细胞形态更加不规则考虑为过渡活化所致。此时仍可见许多双核细胞,同时可发现小的阳性细胞比率增加。在次声作用1h与30min相比变化规律相同,不同的是细胞活化更强烈,但在1h组双核细胞较30min组少(20%±8%)。在次声作用1h后24h,细胞状态变差,大体积的阿米巴样MI变少,有部分细胞坏死;可见部分分枝状小胶质细胞,拥有两个或是多个自胞体发出的长突起,成分枝状,且突起长与细胞胞体直径。
(2)细胞因子的变化:我们用液相芯片技术检测了小胶质细胞培养上清液中4种细胞因子的含量,发现次声可以引起小胶质细胞细胞培养液中细胞因子TNF-α, IL-1β, IL-10and IL-18的增加。在次声作用30min后即刻IL-10就开始升高,到12h达到高峰. TNF-α和IL-1β的表达则是在次声作用后12h升高至峰值,然后降低。细胞因子IL18则除次声作用后即刻含量有所减低外,随后含量呈持续性升高在24h达到高峰。INF-γ可以抑制小胶质细胞分泌这些因子,各组小胶质细胞上清液中均没有检测出INF-γ的分泌。在次声作用1h后,小胶质细胞细胞培养液中炎性因子TNF-α与IL1-β含量虽呈持续性升高;IL-18在次声作用后即刻增高之后逐渐下降;而保护性因子IL-10在4h和24h出现双峰值,并且各观察点数值与对照组相比增高。此外,免疫细胞染色发现,细胞内TGF-β的表达在30min次声作用后呈持续增高趋势而在1h次声作用后呈持续降低趋势。
本实验结论如下:
(1)大鼠暴露于16Hz 130dB次声后,脑内小胶质细胞活化,并且这种反应较星形胶质细胞的反应早。
(2)次声引起的活化的小胶质细胞一方面主要分布于神经元、毛细血管周围,另一方面可与星形胶质细胞发生密切联系。
(3)次声同样可以引起体外培养的小细胞活化。次声暴露30min后,小胶质细胞主要分泌保护性细胞因子,而暴露1h后小胶质细胞主要分泌炎性细胞因子。
Infrasound (IS) is the sound below 20 Hz . It is acoustic energy with physical characters of strong penetration and less attenuation in long distance propagating. A large variety of natural and man-made phenomena produce infrasound, including avalanches, meteors, ocean waves, tornadoes, auroras, earthquakes, atmospheric nuclear tests, rockets, supersonic aircraft and so on.It is usually inaudible,but humans can perceive infrasound if the level is sufficiently high. Experimental studies reported that humans or various species of animals such as rats and mice exposed to infrasound at 90 dB or higher for short or long terms up to several months exhibited significant toxicological effects.Involvement of the limbicoreticular complex, hypothalamus, and other subcortical structures into responses to higher factor levels on human beings stipulates a sharply prominent pathological discomfort as a manifestation of the infrasonic diencephalic hypothalamic syndrome with sensorisomatic and autonomic visceral symptoms. Microglia are the resident immune cells of the central nervous system (CNS) .
Microglial activation and migration play an important role in neuroinflammation propagation. It is actively involved in pathogenesis of a number of neurodegenerative diseases including multiple sclerosis (MS), Alzheimer’sdisease (AD), Parkinson’s disease (PD)et al. Microglia responded to brain injury by migrating to sites of tissue damage, undergoing marked changes in morphology, proliferating and engulfing tissue debris. In addition, microglia can release potent neurotoxins, which may cause neuronal damage. Microglia are potentially also promotors of the migration, axonal growth, and terminal differentiation of different neuronal subsets, through the release of extracellular matrix components, soluble factors and direct cell–cell contact.
With the development of modern industry and transportation, infrasound plays a more and more important role in noise pollution. Although there have been some studies on infrasonic toxicology, relative little is known about the adverse effects of infrasound on inflammation of CNS.Since microglia as an important cell in the inflammation of CNS is becoming topical in society, the need for further research in this field is clearly indicated.In the present study, we sought to determine whether infrasound could induce microglial activation in the brain.
Experiments were carried out in rats both in vitro and in vivo.
Experiment 1:
Rats were exposed to infrasound for 2 hours daily during 1days, 7days and 14days. Exposure to infrasound with a main frequency of 16 Hz and a sound pressure level of 130 dB. The changes of microglia were investigated utilizing the immunohistochemical and electron microscope methods.
The results were showed as the following:
(1) Light microscopic observation:the OX42-positive cells and GFAP-positive cells were rare in normal group.The amplitude of the OX42-positive cells significantly increased at once when rats were exposed to infrasound after exposure to 16 Hz, 130 dB. and then decreased after 7 days,while GFAP-positive cells were increased on the 7st day,and peaked on the 14st day , the double labeling between two cells significant increased on the 14st day.
(2) Electron microscopic observation: Microglia was rare in normal group. On the 1st day of infrasound exposing, the number of Microglia significantly increased and the cytoplasm of microglia cell formed a thin rim around nucleus, but extended out in quite broad processes. When cells was in perineuronal positions these process seem partially to encompass the neuron.The activated microglia had nuclei with an irregular outline in which the chromatin was clumped beneath the nuclear envelope.The cytoplasm was rather pale and the process extending from the lower pole of the cell shows the long cisternae of the granular endoplasmic reticulum , which were the characteristic of these cells.The upper pole of the cell was largely occupied by inclusion bodies,some of which had granular contents,and others of which had membranous inclusion.These were swollen processes and contain a variety of vesicles and tubules.
Experiment 2:
Microglia were exposed to infrasound for 30min or 1h ,and then observe changes of microglia and cytokine through cytochemistry and Luminex liquid phase chip.
The results were showed as the following:
(1) The changes of cell morphology: Twenty-four hours after isolation, microglia showed a vacuolated cytoplasm and circular shape. Microglia enlarged at once after IS exposed. 4h after IS exposed, ameboid cells thrived and binucleated ameboid cells were often observed with occasional telophase pairs and mitotic figures present general. We can see microglia were densely packed with vesicles 12 hr after IS exposed and meoid microglia had multiple short spinous processes which remained on cell surfaces well. In contrast, there is no significant changes in control cells. 24h after IS expose, we can see some cells began to develop thin cytoplasmic projections. These“process-bearing”cells showed a complex multipolar pattern or, more commonly, a uni- or bipolar morphology.
(2) The changes of cytokine: 30min exposure of microglia to IS has increased the concentrations of TNF-α, IL-1β, IL-10 and IL-18 in the supernatant. We observed the expected strong induction of TNF-α, IL-1β, IL-10 and IL-18 in response. IL-10 was released as early as 0h after exposing, and the level of its concentration reached the higlhest at 12 hours after exposing. While the significant upregulation in release of TNF-αor IL-1βwas detected at 12 hours and then degraded. The concentration of IL-18 was detected at a lower level at 0h but showed a gradually increasing process until 24h after exposing. We also found the inhibiting effect of INF-γon the 4 Cytokines introduced above by adding it in supernatant 2h before esposing and detecting at 12h after exposing, but in the supernatant of each groups INF-γhad not been found. After 1h exposing to IS, the level of TNF-αand IL1-βelevated gradually until the end point of observation. IL-18 reached its peak level right after exposing and showed a descending tendency in the following 24h. IL-10, previously known as a protective factor, showed two peak levels at 4h and 24h and the level was higher in all observing points compared to control. In addition, by immunocytochemistry,we found that the expression of TGF-βupragulate continuously after 30min exposing and downragulated after 1h exposing.
The following is the conclusion of experiments:
(1) In vivo, microglia could be activated by exposing to infrasound of 16 Hz, 130 dB. The microglial reactions were ahead of the activation of astrocyte.
(2) The activated microglia distributed around neuron and vessels and formed synapse with astrocyte.
(3) In vitro, Infrasound could also induce activation of microglia. After 30min exposing, microglia secreted protective cytokines mainly but the level of inflammatory cytokines increased after 1h exposing.
一定强度的次声噪音和次声武器作用于人体后可产生多种危害,可以引起机体行为学、形态学、蛋白结构、基因分子等多方面的改变。一些研究表明次声声级水平愈高,损伤愈严重。而小胶质细胞在神经组织的损伤以及炎性反应的发生、发展过程中发挥着重要的作用。以往文献报道次声作用后可以引起神经元损伤、星形胶质细胞的活化,但有关脑内小胶质细胞是否对次声刺激起反应,小胶质细胞形态上有何改变以及时间过程如何,目前均未见到报道。因此,研究次声作用后小胶质细胞的变化对了解次声性脑损害机制和脑保护的研究具有十分重要的理论和实用价值。
本实验进行了2个实验:
实验一:
将成年SD雄性大鼠反复暴露于声压级16Hz 130dB的次声环境中。在次声作用后不同时间点处死大鼠,对脑组织进行免疫组织化学染色,扫描电镜和透射电镜观察。观察在体:次声作用后即刻,12h,1d, 7d,14d大鼠海马、下丘脑室旁核小胶质细胞的变化情况及其与中枢神经系统中其他细胞间关系变化;次声作用后即刻,1d, 7d,扫描电镜和透射电镜下脑组织超微结构的变化。
结果表明:
(1)光镜下:正常大鼠小胶质细胞数量较少,一般为静息状态(静息型),与其他细胞无特别联系。次声作用后即刻大鼠小胶质细胞开始被活化、增殖,表现为光镜下:0X42阳性细胞深染,胞体变大变圆,突起变短、变粗长、变少,呈肥大型或阿米巴型小胶质细胞,并且还可以看出小胶质细胞数量显著增多(P〈0.01),这种变化在7d以后逐渐减弱。次声作用后第7d起星形胶质细胞变多,胞体变大,突起变粗,染色深,第14d达到高潮;小胶质细胞和星形胶质细胞之间的关系密切:次声作用后第7d可见到小胶质细胞与星形胶质细胞间有双标记橙黄色突起,这些突起数量在第14d达到高潮。此外还可见正常对照组小胶质细胞分布无特定规律,而活化的小胶质细胞主要分布与神经元周围。
(2)电镜下:可见正常大鼠小胶质细胞数量较小,较少,次声作用后1d小胶质细胞细胞核变大,突起增多,细胞内结构变丰富可见其内有吞噬小泡和溶酶体颗粒。活化的小胶质细胞主要分布于神经元、毛细血管周围,有的包绕神经元。在次声连续作用7d以后小胶质细胞数量较次声作用1d减少,但仍表现为活化状态。此外次声作用后还可发现从毛细血管内游走出的小胶质细胞。
实验二:
将体外培养小胶质细胞暴露于次声环境中30min,1h,而后采用免疫细胞化学法和Luminex液相芯片法观察不同时间点(0h,4h,12h,24h)小胶质细胞的变化以及其细胞因子分泌的变化情况。
结果表明:
(1)细胞形态的改变:可见正常对照组与保温箱对照组小胶质细胞表现为细胞胞体较小,为圆形或扁平细胞,拥有短的突起或是没有突起,细胞胞膜光滑,细胞内无吞噬小泡的阿米巴样小胶质细胞或是其前体细胞。荧光染色可见均匀一致的小而圆的红色细胞。次声作用30min后即刻小胶质细胞就开始发生改变,相差显微镜下可见细胞胞体肿胀、折光不均。在次声作用后12h,可见细胞肿胀更明显,细胞形态不规则,细胞膜上出现囊泡状物质,细胞边缘可见毛刺状突起;荧光显微镜下可见细胞荧光强度加大,CD11b主要表达于细胞膜;此外还可发现双核细胞比率显著增多(45%±5%),并且可见许多小的OX42阳性细胞,提示小胶质细胞存在细胞增殖、分裂。而到次声作用后24h,小胶质细胞内空泡增多,细胞内也可见一些吞噬小泡,细胞形态更加不规则考虑为过渡活化所致。此时仍可见许多双核细胞,同时可发现小的阳性细胞比率增加。在次声作用1h与30min相比变化规律相同,不同的是细胞活化更强烈,但在1h组双核细胞较30min组少(20%±8%)。在次声作用1h后24h,细胞状态变差,大体积的阿米巴样MI变少,有部分细胞坏死;可见部分分枝状小胶质细胞,拥有两个或是多个自胞体发出的长突起,成分枝状,且突起长与细胞胞体直径。
(2)细胞因子的变化:我们用液相芯片技术检测了小胶质细胞培养上清液中4种细胞因子的含量,发现次声可以引起小胶质细胞细胞培养液中细胞因子TNF-α, IL-1β, IL-10and IL-18的增加。在次声作用30min后即刻IL-10就开始升高,到12h达到高峰. TNF-α和IL-1β的表达则是在次声作用后12h升高至峰值,然后降低。细胞因子IL18则除次声作用后即刻含量有所减低外,随后含量呈持续性升高在24h达到高峰。INF-γ可以抑制小胶质细胞分泌这些因子,各组小胶质细胞上清液中均没有检测出INF-γ的分泌。在次声作用1h后,小胶质细胞细胞培养液中炎性因子TNF-α与IL1-β含量虽呈持续性升高;IL-18在次声作用后即刻增高之后逐渐下降;而保护性因子IL-10在4h和24h出现双峰值,并且各观察点数值与对照组相比增高。此外,免疫细胞染色发现,细胞内TGF-β的表达在30min次声作用后呈持续增高趋势而在1h次声作用后呈持续降低趋势。
本实验结论如下:
(1)大鼠暴露于16Hz 130dB次声后,脑内小胶质细胞活化,并且这种反应较星形胶质细胞的反应早。
(2)次声引起的活化的小胶质细胞一方面主要分布于神经元、毛细血管周围,另一方面可与星形胶质细胞发生密切联系。
(3)次声同样可以引起体外培养的小细胞活化。次声暴露30min后,小胶质细胞主要分泌保护性细胞因子,而暴露1h后小胶质细胞主要分泌炎性细胞因子。
Infrasound (IS) is the sound below 20 Hz . It is acoustic energy with physical characters of strong penetration and less attenuation in long distance propagating. A large variety of natural and man-made phenomena produce infrasound, including avalanches, meteors, ocean waves, tornadoes, auroras, earthquakes, atmospheric nuclear tests, rockets, supersonic aircraft and so on.It is usually inaudible,but humans can perceive infrasound if the level is sufficiently high. Experimental studies reported that humans or various species of animals such as rats and mice exposed to infrasound at 90 dB or higher for short or long terms up to several months exhibited significant toxicological effects.Involvement of the limbicoreticular complex, hypothalamus, and other subcortical structures into responses to higher factor levels on human beings stipulates a sharply prominent pathological discomfort as a manifestation of the infrasonic diencephalic hypothalamic syndrome with sensorisomatic and autonomic visceral symptoms. Microglia are the resident immune cells of the central nervous system (CNS) .
Microglial activation and migration play an important role in neuroinflammation propagation. It is actively involved in pathogenesis of a number of neurodegenerative diseases including multiple sclerosis (MS), Alzheimer’sdisease (AD), Parkinson’s disease (PD)et al. Microglia responded to brain injury by migrating to sites of tissue damage, undergoing marked changes in morphology, proliferating and engulfing tissue debris. In addition, microglia can release potent neurotoxins, which may cause neuronal damage. Microglia are potentially also promotors of the migration, axonal growth, and terminal differentiation of different neuronal subsets, through the release of extracellular matrix components, soluble factors and direct cell–cell contact.
With the development of modern industry and transportation, infrasound plays a more and more important role in noise pollution. Although there have been some studies on infrasonic toxicology, relative little is known about the adverse effects of infrasound on inflammation of CNS.Since microglia as an important cell in the inflammation of CNS is becoming topical in society, the need for further research in this field is clearly indicated.In the present study, we sought to determine whether infrasound could induce microglial activation in the brain.
Experiments were carried out in rats both in vitro and in vivo.
Experiment 1:
Rats were exposed to infrasound for 2 hours daily during 1days, 7days and 14days. Exposure to infrasound with a main frequency of 16 Hz and a sound pressure level of 130 dB. The changes of microglia were investigated utilizing the immunohistochemical and electron microscope methods.
The results were showed as the following:
(1) Light microscopic observation:the OX42-positive cells and GFAP-positive cells were rare in normal group.The amplitude of the OX42-positive cells significantly increased at once when rats were exposed to infrasound after exposure to 16 Hz, 130 dB. and then decreased after 7 days,while GFAP-positive cells were increased on the 7st day,and peaked on the 14st day , the double labeling between two cells significant increased on the 14st day.
(2) Electron microscopic observation: Microglia was rare in normal group. On the 1st day of infrasound exposing, the number of Microglia significantly increased and the cytoplasm of microglia cell formed a thin rim around nucleus, but extended out in quite broad processes. When cells was in perineuronal positions these process seem partially to encompass the neuron.The activated microglia had nuclei with an irregular outline in which the chromatin was clumped beneath the nuclear envelope.The cytoplasm was rather pale and the process extending from the lower pole of the cell shows the long cisternae of the granular endoplasmic reticulum , which were the characteristic of these cells.The upper pole of the cell was largely occupied by inclusion bodies,some of which had granular contents,and others of which had membranous inclusion.These were swollen processes and contain a variety of vesicles and tubules.
Experiment 2:
Microglia were exposed to infrasound for 30min or 1h ,and then observe changes of microglia and cytokine through cytochemistry and Luminex liquid phase chip.
The results were showed as the following:
(1) The changes of cell morphology: Twenty-four hours after isolation, microglia showed a vacuolated cytoplasm and circular shape. Microglia enlarged at once after IS exposed. 4h after IS exposed, ameboid cells thrived and binucleated ameboid cells were often observed with occasional telophase pairs and mitotic figures present general. We can see microglia were densely packed with vesicles 12 hr after IS exposed and meoid microglia had multiple short spinous processes which remained on cell surfaces well. In contrast, there is no significant changes in control cells. 24h after IS expose, we can see some cells began to develop thin cytoplasmic projections. These“process-bearing”cells showed a complex multipolar pattern or, more commonly, a uni- or bipolar morphology.
(2) The changes of cytokine: 30min exposure of microglia to IS has increased the concentrations of TNF-α, IL-1β, IL-10 and IL-18 in the supernatant. We observed the expected strong induction of TNF-α, IL-1β, IL-10 and IL-18 in response. IL-10 was released as early as 0h after exposing, and the level of its concentration reached the higlhest at 12 hours after exposing. While the significant upregulation in release of TNF-αor IL-1βwas detected at 12 hours and then degraded. The concentration of IL-18 was detected at a lower level at 0h but showed a gradually increasing process until 24h after exposing. We also found the inhibiting effect of INF-γon the 4 Cytokines introduced above by adding it in supernatant 2h before esposing and detecting at 12h after exposing, but in the supernatant of each groups INF-γhad not been found. After 1h exposing to IS, the level of TNF-αand IL1-βelevated gradually until the end point of observation. IL-18 reached its peak level right after exposing and showed a descending tendency in the following 24h. IL-10, previously known as a protective factor, showed two peak levels at 4h and 24h and the level was higher in all observing points compared to control. In addition, by immunocytochemistry,we found that the expression of TGF-βupragulate continuously after 30min exposing and downragulated after 1h exposing.
The following is the conclusion of experiments:
(1) In vivo, microglia could be activated by exposing to infrasound of 16 Hz, 130 dB. The microglial reactions were ahead of the activation of astrocyte.
(2) The activated microglia distributed around neuron and vessels and formed synapse with astrocyte.
(3) In vitro, Infrasound could also induce activation of microglia. After 30min exposing, microglia secreted protective cytokines mainly but the level of inflammatory cytokines increased after 1h exposing.
引文
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3. Rice CG. British Medceal Journa1. 1994; 308(5)-355
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5.牛兰杰李京华.次声在军事上的应用.探测与控制学报-2007:29 (B08) -1-4
6.郭毅军蔡绍皙赵志强.次声波与次声武器.《生物学通报》-2007年42卷7期-3-5页
7. Harris CS , Sommer HC , Johoson DL. Review of the effects of infrasound on man. Aviation Space and Environment Medicine , 1978 ,49 : 582-586.
8. Backteman o,Sjoberg l.Infrasound tutorial and Review:Part 4[J].J Low Freq Noise Vib(S0263—0923),1984 ,3 :28—67.
9.裴兆辉,陈景藻,朱妙章,裴建明.次声对人类的影响.中国自然医学杂志2004年6月第6卷第2期125-127
10. Landstrom ULF. Laboratory and field studies on infrasound and its effects on humans.J Low Freq Noise Vib,1987.6:29-33.
11.刘朝晖[1]陈景藻[2]谭永霞[2]邱建勇[2]陈丹[3]刘静[2] 8Hz 90dB次声对大鼠海马细胞内钙离子及内质网钙通道蛋白RyRs表达的影响第四军医大学学报-2005:26(2)-185-188
12.裴兆辉[1]陈景藻[2]朱妙章[1]裴建明[1]刘朝晖[2]谭永霞[3]次声作用后血浆NO、ET-1、SOD、MDA水平的变化中国病理生理杂志-2005:21(1)-188-190
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14.鲁荣,王贵学,赵志强次声在生物医学中的研究及应用中华医学研究杂志2007年第7卷第2期134-136
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2.陈景藻.次声的存在及其基本生物效应和研究意义.中华物理医学与康复杂志,1999,21:131-133.
3. Rice CG. British Medceal Journa1. 1994; 308(5)-355
4. Barbara Starr. Non - lethal weapon puzzle for US Arm. Internation defense review , 1993 , 4 : 319-320.
5.牛兰杰李京华.次声在军事上的应用.探测与控制学报-2007:29 (B08) -1-4
6.郭毅军蔡绍皙赵志强.次声波与次声武器.《生物学通报》-2007年42卷7期-3-5页
7. Harris CS , Sommer HC , Johoson DL. Review of the effects of infrasound on man. Aviation Space and Environment Medicine , 1978 ,49 : 582-586.
8. Backteman o,Sjoberg l.Infrasound tutorial and Review:Part 4[J].J Low Freq Noise Vib(S0263—0923),1984 ,3 :28—67.
9.裴兆辉,陈景藻,朱妙章,裴建明.次声对人类的影响.中国自然医学杂志2004年6月第6卷第2期125-127
10. Landstrom ULF. Laboratory and field studies on infrasound and its effects on humans.J Low Freq Noise Vib,1987.6:29-33.
11.刘朝晖[1]陈景藻[2]谭永霞[2]邱建勇[2]陈丹[3]刘静[2] 8Hz 90dB次声对大鼠海马细胞内钙离子及内质网钙通道蛋白RyRs表达的影响第四军医大学学报-2005:26(2)-185-188
12.裴兆辉[1]陈景藻[2]朱妙章[1]裴建明[1]刘朝晖[2]谭永霞[3]次声作用后血浆NO、ET-1、SOD、MDA水平的变化中国病理生理杂志-2005:21(1)-188-190
13. Filatov VV. Experimental study of infrasonic phonophoresis Vestn Oftalmol. 2001 Nov-Dec;117(6):35-7
14.鲁荣,王贵学,赵志强次声在生物医学中的研究及应用中华医学研究杂志2007年第7卷第2期134-136
15. Li ZH, Lu J, Tay SS, Wu YJ, Mice with targeted disruption of neurofilament light subunit display formation of protein aggregation in motoneurons and downregulation of complement receptor type 3 alpha subunit in microglia in the spinal cord at their earlier age: a possible feature in pre-clinical development of neurodegenerative diseases. Brain Res 2006 1113 (1): 200–209.
16. S. Sugama, Fujita,Hashimoto and Conti. Stress induced morphological microglial activation in the rodent brain: involvement of interleukin-18 Neuroscience 146 (2007) 1388–1399
17. Giulian and Baker, D. Giulian and T.J. Baker, Characterization of ameboid microglia isolated from developing mammalian brain, J Neurosci 6 1986, 2163–2178.
18. Oehmichen, M. Inflammatory cells in the central nervous system. Prog. Neuropathol. 1983 5: 277-325.
19. S. Fedoroff and L. Hertz, eds, Ling, E. A. The origin and nature of microglia. Cellular Neurobiology, 1981Vol. 2 33-82.
20. Frederik Vilhardt Microglia: phagocyte and glia cell The International Journal of Biochemistry & Cell Biology 37 (2005) 17–21
21. Uwe-Karsten Hanisch & Helmut Kettenmann. Microglia: active sensor and versatile effector cells in the normal and pathologic brain Nature neuroscience volume 10 number 11 november 2007 1387-1394.
22. Aloisi, F., 2001. Immune function of Microglia. Glia 36, 165–179.
23. Town, T., Nikolic, V., Tan, The Microglial“activation”continuum: from innate to adaptive responses. J. Neuroinflamm. 2005 2 24.
24. Seong Kimand Tong H. Joh Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson’s disease Yoon Experimental and molecular medicine, Vol. 38, No. 4, 333-347, August 2006
25. Lv Li, Jia Lu, Samuel Sam Wah Tay.The function of microglia, either neuroprotection or neurotoxicity, is determined by the equilibrium among factors released from activated microglia in vitro Brain Research 2007.04.066 29-39
26. Oleg Butovsky, Steffen Jungand Michal Schwartza. Microglia can be induced by IFN-γor IL-4 to express neural or dendritic-like markers Cell. Neurosci. 2007
27. Kazuyuki Takataa, Yoshihisa Kitamuraa, Daijiro Yanagisawaa, Microglial transplantation increases amyloid-b clearance in Alzheimer model rats. FEBS Letters 581 (2007) 475–478。
28. Butovsky O,Koronyo-Hamaoui M, Kunis G. Glatiramer acetate fights against Alzheimer's disease by inducing dendritic-like Microglia expressing insulin-like growth factor 1 .Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11784-9
29. XiaoMin Sua , Kathleen A. Maguire-Zeiss ,Rita Giuliano a,Synuclein activates Microglia in a model of Parkinson’s disease Neurobiology of Aging 2007 May 28
30. Butovsky O, Landa G, Kunis G, Ziv Y, . J Clin Invest.Induction and blockage of oligodendrogenesis by differently activated Microglia in an animal model of multiple sclerosis Apr;116(4):905-15. Epub 2006 Mar
31. Janus faces of Microglia in multiple sclerosis Patricia Sanders, Jacques De Keyser Brain researchreviews 54(2007) 274–285
32. D.R. Borchelt, Amyotrophic Lateral Sclerosis—are Microglia killing motor neurons? N Engl J Med 12 (2006), pp. 1611–1613.
33. Krishna Puttaparthi, Luc Van Kaer and Jeffrey L. Elliott Assessing the role of immuno-proteasomes in a mouse model of faMilial ALS Experimental Neurology, Volume 206, Issue 1, July 2007, Pages 53-58
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