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Author Notes:

Corresponding Author: Donald G. Stein, Ph.D., Emory University Department of Emergency Medicine, 1365B Clifton Road NE, Suite 5100, Atlanta, GA 30322, Telephone: (404) 712 - 2540, Fax: (404) 727 - 2388, donald.stein@emory.edu

We thank Paul Choi for his help with sectioning and ERGs and Leslie McCann for her help with editing this manuscript.

Subjects:

Research Funding:

H. Allen and Company, Atlanta VA Rehab R&D Center of Excellence, The Abraham J. and Phyllis Katz Foundation, Foundation Fighting Blindness, Research to Prevent Blindness, NIH National Eye Institute R01EY014026, R01EY016470, R24EY017045, P30EY006360, and T32EY007092-24.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • Middle cerebral artery occlusion
  • Focal ischemia
  • Rat
  • Retina
  • Electroretinogram
  • Retinal ischemia
  • GLUTAMATE TRANSPORTER
  • ISCHEMIC TOLERANCE
  • OXIDATIVE STRESS
  • BRAIN
  • TRANSIENT
  • SYNTHETASE
  • INJURY
  • MICE
  • ISCHEMIA/REPERFUSION
  • ELECTRORETINOGRAM

Severity of middle cerebral artery occlusion determines retinal deficits in rats

Tools:

Journal Title:

Experimental Neurology

Volume:

Volume 254

Publisher:

, Pages 206-215

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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 ≥. 5) exhibited reductions in amplitude. Glutamine synthetase was upregulated in Müller 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.

Copyright information:

© 2014 Elsevier Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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