Emergency Medicine, Emory University, Atlanta, GA 30322, USA; Ophthalmology, Emory University, Atlanta, GA 30322, USA.
Emergency Medicine, Emory University, Atlanta, GA 30322, USA.
Exp Neurol. 2014 Apr;254:206-15. doi: 10.1016/j.expneurol.2014.02.005. Epub 2014 Feb 8.
Middle cerebral artery occlusion (MCAO) using the intraluminal suture technique is a common model used to study cerebral ischemia in rodents. Due to the proximity of the ophthalmic artery to the middle cerebral artery, MCAO blocks both arteries, causing both cerebral ischemia and retinal ischemia. While previous studies have shown retinal dysfunction at 48h post-MCAO, we investigated whether these retinal function deficits persist until 9days and whether they correlate with central neurological deficits. Rats received 90min of transient MCAO followed by electroretinography at 2 and 9days to assess retinal function. Retinal damage was assessed with cresyl violet staining, immunohistochemistry for glial fibrillary acidic protein (GFAP) and glutamine synthetase, and TUNEL staining. Rats showed behavioral deficits as assessed with neuroscore that correlated with cerebral infarct size and retinal function at 2days. Two days after surgery, rats with moderate MCAO (neuroscore <5) exhibited delays in electroretinogram implicit time, while rats with severe MCAO (neuroscore ≥5) exhibited reductions in amplitude. Glutamine synthetase was upregulated in Müller cells 3days after MCAO in both severe and moderate animals; however, retinal ganglion cell death was only observed in MCAO retinas from severe animals. By 9days after MCAO, both glutamine synthetase labeling and electroretinograms had returned to normal levels in moderate animals. Early retinal function deficits correlated with behavioral deficits. However, retinal function decreases were transient, and selective retinal cell loss was observed only with severe ischemia, suggesting that the retina is less susceptible to MCAO than the brain. Temporary retinal deficits caused by MCAO are likely due to ischemia-induced increases in extracellular glutamate that impair signal conduction, but resolve by 9days after MCAO.
大脑中动脉阻塞（MCAO）采用管腔内缝线技术是一种常用的研究啮齿动物脑缺血的模型。由于眼动脉与大脑中动脉接近，MCAO 阻塞了这两条动脉，导致脑和视网膜缺血。虽然以前的研究表明，MCAO 后 48 小时会出现视网膜功能障碍，但我们研究了这些视网膜功能缺陷是否持续到 9 天，以及它们是否与中枢神经功能缺陷相关。大鼠接受 90 分钟的短暂 MCAO 后，在 2 天和 9 天进行视网膜电图检查以评估视网膜功能。用 cresyl 紫染色、胶质纤维酸性蛋白（GFAP）和谷氨酰胺合成酶免疫组化以及 TUNEL 染色评估视网膜损伤。大鼠的行为缺陷通过神经评分进行评估，该评分与大脑梗死面积和 2 天的视网膜功能相关。手术后 2 天，中度 MCAO 大鼠（神经评分<5）的视网膜电图隐时延迟，而重度 MCAO 大鼠（神经评分≥5）的振幅降低。在严重和中度动物中，MCAO 后 3 天，Müller 细胞中谷氨酰胺合成酶上调；然而，只有在严重 MCAO 视网膜中才观察到视网膜神经节细胞死亡。MCAO 后 9 天，中度动物的谷氨酰胺合成酶标记和视网膜电图均恢复正常水平。早期视网膜功能缺陷与行为缺陷相关。然而，视网膜功能下降是短暂的，仅在严重缺血时观察到选择性视网膜细胞丢失，这表明视网膜比大脑对 MCAO 的敏感性较低。MCAO 引起的暂时视网膜缺陷可能是由于缺血诱导的细胞外谷氨酸增加，从而损害信号传导，但在 MCAO 后 9 天会恢复正常。
