Astrocyte and microglial activation in the lateral geniculate nucleus and visual cortex of glaucomatous and optic nerve transected primates
Astrocyte and microglial activation in the lateral geniculate nucleus and visual cortex of glaucomatous and optic nerve transected primates
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发表时间：
2009-10
期刊：
影响因子：
2.2
通讯作者：
D. Lam;J. Jim;E. To;C. Rasmussen;P. Kaufman;J. Matsubara
中科院分区：
文献类型：
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作者：
D. Lam;J. Jim;E. To;C. Rasmussen;P. Kaufman;J. Matsubara
目的观察猴单侧视神经切断（ONT）或高眼压（OHT）后中枢神经系统（CNS）早期细胞变化，包括星形胶质细胞反应性和小胶质细胞活化。方法采用猴单侧ONT或OHT模型，持续2周至2个月。心内灌注后，通过免疫组织化学方法检测外侧膝状体核（LGN）和视皮层（V1）的胶质细胞酸性蛋白（GFAP）和CD 11b（补体3受体亚基和巨噬细胞和小胶质细胞的标记物（MAC-1））。通过细胞色素氧化酶（CO）组织化学评价交替连续切片，以评估代谢活性。结果ONT和OHT均可引起LGN和V1眼层代谢活性降低。在ONT动物中，GFAP和MAC-1免疫反应性在与LGN和V1的治疗眼层的空间配准中升高。在OHT动物，GFAP，但不是MAC-1，免疫反应性升高的空间寄存器与治疗的眼睛层的LGN和V1。因此，在OHT或ONT后的前几周内，ONT组的代谢活性丧失伴随着星形胶质细胞和小胶质细胞活化，OHT动物中的星形胶质细胞活化。结论单侧OHT或ONT激活了不同的信号通路，促进了CNS胶质细胞群的差异活化。星形胶质细胞反应性存在于所有研究的大脑中，并证明代谢活性的丧失伴随着GFAP免疫反应性的增加。仅在ONT脑中观察到小胶质细胞活化。迟至OHT后两个月缺乏小胶质细胞活化可能代表了早期治疗的时间窗，以防止OHT后CNS中的长期神经元损失。
Purpose To examine early cellular changes, including astrocyte reactivity and microglial activation, in the central nervous system (CNS) after unilateral optic nerve transection (ONT) or ocular hypertension (OHT) in monkeys. Methods Unilateral ONT or OHT was achieved in monkeys for periods ranging from two weeks to two months in duration. After intracardial perfusion, sections of the lateral geniculate nucleus (LGN) and visual cortex (V1) were examined by immunohistochemistry for glial fibrillary acidic protein (GFAP) and CD11b, a subunit of the complement 3 receptor and marker of macrophage and microglia cells (MAC-1). Alternate serial sections were evaluated by cytochrome oxidase (CO) histochemistry to assess metabolic activity. Results Both ONT and OHT caused a reduction in metabolic activity in the treated eye layers of the LGN and V1. GFAP and MAC-1 immunoreactivities were elevated in spatial register with the treated eye layers of the LGN and V1 in ONT animals. In the OHT animals, GFAP, but not MAC-1, immunoreactivity was elevated in spatial register with the treated eye layers of LGN and V1. Thus, during the first weeks after OHT or ONT, loss of metabolic activity was accompanied by astrocyte and microglial activation in the ONT group and astrocyte activation in the OHT animals. Conclusions These results suggest that unilateral OHT or ONT triggers separate signaling pathways that promote differential activation of CNS glial populations. Astrocyte reactivity was present in all brains studied and demonstrates the loss of metabolic activity is accompanied by increased GFAP immunoreactivity. Microglial activation was only observed in ONT brains. The lack of microglial activation as late as two months following OHT may represent a time window for early treatment to prevent long-term neuronal loss in the CNS after OHT.