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Rachael Allen, Iqbal Sayeed, Heather Cale, Katherine Morrison, Paul Choi, Jeffrey Boatright, Machelle Pardue, Donald Stein; Comparison of retinal and cerebral inflammatory responses after middle cerebral artery occlusion. Invest. Ophthalmol. Vis. Sci. 2013;54(15):104.
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Ocular ischemia is often observed in cases of cerebral stroke and atherosclerosis of the ophthalmic or carotid arteries. In both diseases, visual function deficits are often a first symptom. Examining both retina and cerebral responses to disease provides an opportunity to expand our knowledge of mechanisms of disease, to translate treatments from one tissue to the other, and to optimize treatments effective for both tissues. Thus, we are investigating the common mechanism of inflammation in the middle cerebral artery occlusion (MCAO) model, a stroke model that affects both the brain and eye.
MCAO surgery was performed on male Sprague-Dawley rats. Under isoflurane anesthesia, a filament was inserted through an incision in the external carotid artery and slid into the internal carotid artery so that it blocked the right middle cerebral and ophthalmic arteries. The filament was removed after 120 minutes to allow reperfusion. For biomarker assays, MCAO rats were sacrificed at 6, 24, and 48 hours (n = 5/group). Western blots were performed and densitometry was used to quantify levels of inflammatory proteins (phosphorylated NF-kB, which indicates NF-kB pathway activity, and IL-6, a downstream inflammatory cytokine) in the brain and retina in MCAO and sham animals.
A significant increase (41%) in levels of phosphorylated NF-kB was observed in MCAO brains (2008.83 ± 241.89 a.u.) compared with shams (1427.15 ± 148.76 a.u., p < 0.05). Significant increases (69%) were observed in MCAO retinas (4940.58 a.u. ± 438.81) compared with shams as well (2924.06 ± 378.88 a.u., p < 0.05), however, we did not find a significant correlation between brain and retina levels. We also observed a trend towards increased levels of IL-6 in MCAO retinas (58%) and brains (45%, p = 0.051).
MCAO surgery increases inflammation in the retina as it does in the brain. However, the fact that retina and brain increases are not correlated may indicate a difference in the timing of the response or the responsiveness of the tissue. The retina represents an additional avenue that can be explored when using the MCAO model to investigate stroke and its potential treatments.
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