Severity of middle cerebral artery occlusion determines retinal deficits in rats

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• 作者：Rachael S. Allen^a ; ^b ; ^{restewa@emory.edu" class="auth_mail} ; Iqbal Sayeed^a ; ^{isayeed@emory.edu" class="auth_mail} ; Heather A. Cale^a ; ^{hcale@u.washington.edu" class="auth_mail} ; Katherine C. Morrison^a ; ^{cillakat@gmail.com" class="auth_mail} ; Jeffrey H. Boatright^b ; ^{jboatri@emory.edu" class="auth_mail} ; Machelle T. Pardue^b ; ^c ; ^{mpardue@emory.edu" class="auth_mail} ; Donald G. Stein^a ; ^{donald.stein@emory.edu" class="auth_mail}
• 关键词：MCAO ; middle cerebral artery occlusion ; GFAP ; glial fibrillary acidic protein ; LDF ; laser-Doppler flowmetry ; ERG ; electroretinogram ; GS ; glutamine synthetase ; GLAST ; glutamate aspartate transporter
• 刊名：Experimental Neurology
• 出版年：April, 2014
• 年：2014
• 卷：254
• 期：Complete
• 页码：206-215
• 全文大小：1980 K

文摘

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 48 h post-MCAO, we investigated whether these retinal function deficits persist until 9 days and whether they correlate with central neurological deficits.

Rats received 90 min of transient MCAO followed by electroretinography at 2 and 9 days 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 2 days. Two days after surgery, rats with moderate MCAO (neuroscore < 5) exhibited delays in electroretinogram implicit time, while rats with severe MCAO (neuroscore 鈮?#xA0;5) exhibited reductions in amplitude. Glutamine synthetase was upregulated in M眉ller cells 3 days after MCAO in both severe and moderate animals; however, retinal ganglion cell death was only observed in MCAO retinas from severe animals. By 9 days 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 9 days after MCAO.