Carbon monoxide treatment reduces microglial activation in the ischemic rat retina
Carbon monoxide treatment reduces microglial activation in the ischemic rat retina
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DOI：
10.1007/s00417-016-3435-6
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发表时间：
2016-07
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通讯作者：
Felix Ulbrich;U. Goebel;D. Böhringer;P. Charalambous;W. Lagrèze;J. Biermann
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文献类型：
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作者：
Felix Ulbrich;U. Goebel;D. Böhringer;P. Charalambous;W. Lagrèze;J. Biermann
目的缺血再灌注（I/R）损伤视网膜神经元。视网膜损伤伴随着小胶质细胞的激活，其使死亡或垂死的神经元复活，但是现在越来越多的证据表明，缺血后在脑中激活的变形虫状小胶质细胞本身具有神经毒性和损伤性质。先前的研究表明，一氧化碳（CO）后处理通过抗凋亡和抗炎机制保护I/R后的视网膜神经节细胞（RGCs）。本研究的目的是调查和量化的激活后，I/R与CO postconditioning.MethodsAdult Sprague-Dawley大鼠视网膜缺血增加眼压到120毫米汞柱1小时，通过针插入前房后，视网膜小胶质细胞。通过移除针头诱导再灌注。I/R后，将一组动物保持在CO（250 ppm）气氛中1小时;另一组保持在室内空气（空气）中。在I/R后1、2、3和7天，摘出眼睛并固定。分析心内血液中CO或I/R的全身效应。从眼睛的中间三分之一处取出视网膜横截面，并用抗Iba-1染色。根据形态学标准，将小胶质细胞分为变形样或分枝表型。视网膜厚度determined.ResultsEvaluation的视网膜组织发现一个显着减少变形小胶质细胞后I/R + CO相比，I/R +空气组。变形样小胶质细胞数量在I/R + Air后第2天达到高峰。CO后处理减弱了这种升高（I/R +空气与I/R + CO分别为815与572个细胞/mm 2;p= 0.005）。CO减少并进一步推迟了缺血眼中变形样和分支小胶质细胞数量的峰值，并阻止了对侧眼中小胶质细胞的激活。吸入CO可抑制I/R诱导的白细胞增多。I/R后的视网膜厚度的减少是更严重的空气吸入后相比，CO group. ConclusionsMany激活的小胶质细胞出现在I/R后的视网膜内层，CO治疗显着减弱这种胶质反应。拮抗小胶质细胞活化可能是CO的进一步神经保护作用，除了其直接的抗凋亡能力。
PurposeIschemia and reperfusion (I/R) injury damages retinal neurons. Retinal injury is accompanied by activation of microglia, which scavenge the dead or dying neurons, but increasing evidence now indicates that amoeboid-shaped microglia cells activated in the brain after ischemia have neurotoxic and damaging properties in their own right. A previous study showed that postconditioning with carbon monoxide (CO) protects retinal ganglion cells (RGCs) after I/R through anti-apoptotic and anti-inflammatory mechanisms. The present study was designed to investigate and quantify the activation of retinal microglia after I/R with and without CO postconditioning.MethodsAdult Sprague–Dawley rats underwent retinal ischemia by increasing the ocular pressure to 120 mmHg for 1 h through a needle inserted into the anterior chamber. Reperfusion was induced by removing the needle. After I/R, one group of animals was kept in a CO (250 ppm) atmosphere for 1 h; the other group was kept in room air (Air). At 1, 2, 3, and 7 days after I/R, the eyes were enucleated and fixed. Intracardiac blood was analyzed for systemic effects of CO or I/R. Retinal cross sections were taken from the middle third of the eye and were stained with anti-Iba-1. Microglia cells were graded as amoeboid or ramified phenotypes according to morphologic criteria. Retinal thicknesses were determined.ResultsEvaluation of retinal tissue revealed a significant reduction of amoeboid microglia cells after I/R + CO when compared to the I/R + Air group. The peak number of amoeboid microglia was observed at day 2 post-I/R + Air. This rise was attenuated by CO postconditioning (815 versus 572 cells/mm2for I/R + Air versus I/R + CO, respectively;p= 0.005). CO reduced and further postponed the peak in the numbers of amoeboid and ramified microglia cells in ischemic eyes and prevented microglial activation in the contralateral eyes. I/R-induced leucocytosis was inhibited by CO inhalation. The reduction of retinal thickness after I/R was more serious after Air inhalation when compared to the CO group.ConclusionsNumerous activated microglia cells appear in the inner retina after I/R, and CO-treatment significantly attenuates this glial response. Antagonism of microglial activation may be a further neuroprotective effect of CO, apart from its direct anti-apoptotic capacity.