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Rachael S Allen, Iqbal Sayeed, Yuliya Oumarbaeva, Katherine Morrison, Irina Lucaciu, Heather Cale, Paul H Choi, Jeffrey H Boatright, Machelle T Pardue, Donald G Stein; Progesterone treatment shows greater protection in brain vs. retina in a rat model of middle cerebral artery occlusion. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1892.
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To determine whether progesterone, which has been shown to reduce inflammation and infarct size in the brain and improve behavioral outcomes after middle cerebral artery occlusion (MCAO), reduces inflammation and improves electroretinogram (ERG) responses in the retina after MCAO.
MCAO surgery was performed on male Sprague-Dawley rats. Progesterone or vehicle was given systemically at 1, 6, 24, and 48 h post-MCAO. Grip-strength and sticky tape task were performed at 1-day post-MCAO and ERGs assessed at 2 days post-MCAO. Brains and retinas were taken for histology at 3 days post-MCAO. In another set of rats, protein levels of cytosolic NF-κB, nuclear NF-κB, phosphorylated NF-κB, IL-6, TNF-α, CD11b, progesterone receptor A and B, and pregnane X receptor were assessed in retinas and brains at 24 and 48 h post-MCAO (n = 5/group).
Following MCAO, vehicle-treated rats showed significant deficits in behavioral tests, while progesterone-treated rats showed significant improvements (71-84% recovery). Vehicle-treated rats also showed significant reductions in ERG amplitude in ipsilateral eyes post-MCAO, while progesterone-treated rats showed a trend for increased ERG amplitudes (23% recovery). Contralateral eyes from vehicle-treated rats also showed significant reductions in ERG amplitude post-MCAO, while contralateral eyes from progesterone-treated rats showed significant increases (64% recovery). After MCAO, vehicle-treated rats exhibited increased levels of pNF-κB, nuclear NF-κB, IL-6, TNF-α, and CD11b and decreased levels of cytosolic NF-κB in both brain and retina. Progesterone treatment in MCAO rats significantly attenuated levels of nuclear NF-κB and IL-6 in both brain and retina, while levels of cytosolic NF-κB showed significant increases. Progesterone treatment significantly attenuated levels of pNF-κB, TNF-α, and CD11b after MCAO in brain, with smaller reductions in retina. After MCAO, progesterone receptor A and B were upregulated in brain and downregulated in retina.
While progesterone treatment reduced inflammation in both brain and retina, protective effects were more dramatic in brain. Progesterone treatment also resulted in greater improvements in brain function-based behavioral tasks than in the retina-based ERG. This differential effect may be due to differences in expression of progesterone receptors in brain and retina after injury.
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