Early Events of Secondary Degeneration after Partial Optic Nerve Transection: An Immunohistochemical Study
Early Events of Secondary Degeneration after Partial Optic Nerve Transection: An Immunohistochemical Study
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DOI：
10.1089/neu.2009.1112
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发表时间：
2010-02-01
影响因子：
4.2
通讯作者：
Dunlop, Sarah A.
中科院分区：
文献类型：
--
作者：
Fitzgerald, Melinda;Bartlett, Carole A.;Dunlop, Sarah A.
中枢神经系统中的继发性变性涉及对远离初始损伤的神经元和神经胶质的间接损伤。背侧视神经（ON）的部分横断导致在腹侧放置的轴突和母体胞体中原发性创伤与迟发性退行性事件的精确空间分离。在这里，我们进行了一个限制性的，背侧ON横切后的第一个3天，在轴突和周围的次生细胞变化和他们的父母视网膜神经节细胞（RGC）胞体的免疫组织化学调查。这是在通过未损伤的ON腹侧部分投射的RGCs和轴突的继发性损失之前。（MnSOD;氧化应激的标志物）共定位于星形胶质细胞网络中的整个ON分布。免疫荧光标记的继发性星形胶质细胞肥大从3小时开始明显，到24小时，整个神经的髓鞘碱性蛋白免疫反应性持续增加。NG-2阳性少突胶质细胞前体细胞、艾德-1阳性活化小胶质细胞/巨噬细胞和Iba 1阳性反应性驻留小胶质细胞/巨噬细胞数量的增加仅见于3天后易继发变性的ON。在24小时内检测到RGC胞体内的变化，专门易受继发性变性，证明了锰超氧化物歧化酶免疫反应性的增加，随后在3天的c-jun免疫反应性的增加。电压门控钙通道阻滞剂洛美利嗪治疗没有改变任何测量结果。我们的结论是，通过星形胶质细胞网络和从受伤的轴突父母RGC胞体的氧化应激传播是一个早期事件在继发性变性，和遏制可能是必要的，以防止进一步损害神经。
Secondary degeneration in the central nervous system involves indirect damage to neurons and glia away from the initial injury. Partial transection of the dorsal optic nerve (ON) results in precise spatial separation of the primary trauma from delayed degenerative events in ventrally placed axons and parent somata. Here we conduct an immunohistochemical survey of secondary cellular changes in and around axons and their parent retinal ganglion cell (RGC) somata during the first 3 days after a restricted, dorsal ON transection. This is before the secondary loss of RGCs and axons projecting through the uninjured, ventral portion of the ON. Within 5 min, manganese superoxide dismutase (MnSOD; a marker of oxidative stress) co-localizes within the astrocytic network across the entire profile of the ON. Secondary astrocyte hypertrophy of immunofluorescent labeling was evident from 3 h, with sustained increases in myelin basic protein immunoreactivity across the nerve by 24 h. Increases in NG-2-positive oligodendrocyte precursor cells, ED-1-positive activated microglia/macrophages, and Iba1-positive reactive resident microglia/macrophage numbers were only seen in ON vulnerable to secondary degeneration by 3 days. Changes within RGC somata exclusively vulnerable to secondary degeneration were detected at 24 h, as evidenced by increases in MnSOD immunoreactivity, followed by increases in c-jun immunoreactivity at 3 days. Treatment with the voltage-gated calcium channel blocker lomerizine did not alter any measured outcome. We conclude that oxidative stress spreading via the astrocytic network and from injured axons to parent RGC somata is an early event during secondary degeneration, and containment is likely to be required in order to prevent further damage to the nerve.