Study for reactive gliosis induced in distant regions following central nervous system injury

横断背柱引起延髓背柱核强烈的小胶质和星形胶质反应。为了验证这些反应是由背柱神经元的神经分化引起的假设，我们检查了消除背柱纤维终止的神经元的影响。通过诱导右丘脑后外侧腹侧核（VPL）的电解损伤，使左侧股薄核的这类神经元通过逆行变性而消失。病变后4周，在脊髓T8水平两侧横切背柱。免疫组化分析显示，神经元变性的右侧股薄核小胶质细胞活化和星形胶质细胞增殖明显减弱。为了阐明这种神经胶质反应与脱神经背柱神经元活性之间的关系，我们观察了细胞色素氧化酶（CYO）的活性。结果表明，在背柱横断后6小时，CYO活性显著增加。同时，检测到小胶质细胞活化，然后积累了含有神经营养物质碱性成纤维细胞生长因子（bFGF）的反应性星形胶质细胞。这些发现表明，在背柱核中观察到的小胶质/星形胶质反应与背柱神经元的脱传入有关，并受到来自脱传入神经元的某些因素的促进。此外，损伤后丘脑VPL核的电刺激可诱导类似的神经胶质反应和bFGF的表达。本研究的观察结果表明，中枢神经系统损伤后远区诱导的神经胶质反应与胚胎期突触发生相关的神经胶质反应相似，表明损伤神经回路的再生/重组潜力与成年哺乳动物中枢神经系统的神经胶质反应密切相关

Transection of the dorsal column causes strong microglial and astroglial responses in the dorsal column nucleus in medulla oblongata. In order to test the hypothesis that these responses are caused by deafferentation of dorsal column neurons, we examined the effect of elimination of neurons at which dorsal column fibers terminate. Such neurons of the left nucleus gracilis were eliminated through retrograde degeneration by inducing electrolytic lesions made in the nucleus ventralis posterolateralis (VPL) of the right thalamus. At 4 weeks post-lesion, the dorsal columns were transected bilaterally at the T8 level of the spinal cord. Immunohistochemical analysis revealed that microglial activation and astroglial proliferation were far less pronouncedin the right nucleus gracilis which neurons had been degenerated.In order to clarify that the relation between such glial reaction and activity of deafferented dorsal column neurons, cytochrome oxidase (CYO) activity was observed. The results … More indicated that CYO activity significantly increased at 6 hours following dorsal column transection. Concurrently, the microglial activation appeared to be detected, then reactive astrocytes containing a neurotrophic substance, basic fibroblast growth factor (bFGF) were accumulated. These findings suggest that the microglial/astroglial responses observed in the dorsal column nucelus are related to deafferentation of dorsal column neurons and promoted by certain factors derived from deafferented neurons.In addition, similar glial reactions and bFGF expression can be induced in the somatosensory cortex following the electrical stimulation of VPL nucleus of thalamus following the injury. The observations of the present studies indicates that these glial reactions induced in distant regions following CNS injury mimics those related to synaptogenesis at embryonal stage, suggesting a potential for regeneration/reorganaization of injured neural circuits appeared closely related to such glial reactions at even adult mammalian CNS Less