Progesterone treatment shows greater protection in brain vs. retina in a rat model of middle cerebral artery occlusion: Progesterone receptor levels may play an important role

Article type: Research Article

Authors: Allen, Rachael S.^{a; b; c; *} | Sayeed, Iqbal^a | Oumarbaeva, Yuliya^a | Morrison, Katherine C.^a | Choi, Paul H.^a | Pardue, Machelle T.^{b; c} | Stein, Donald G.^a

Affiliations: [a] Department of Emergency Medicine, Emory University, Atlanta, GA, USA | [b] Department of Ophthalmology, Emory University, Atlanta, GA, USA | [c] Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, USA

Correspondence: [*] Corresponding author: Rachael S. Allen, Ph.D., Atlanta VA Center for Visual and Neurocognitive Rehabilitation, Research Service (151 Oph), 1670 Clairmont Rd., Decatur, GA 30033, USA. Tel.: +1 404 321 6111 /Ext. 17524; Fax: +1 404 778 2630; E-mail: [email protected].

Abstract: Background/Objective: To determine whether inflammation increases in retina as it does in brain following middle cerebral artery occlusion (MCAO), and whether the neurosteroid progesterone, shown to have protective effects in both retina and brain after MCAO, reduces inflammation in retina as well as brain. Methods: MCAO rats treated systemically with progesterone or vehicle were compared with shams. 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 using western blots. Results: Following MCAO, significant increases were observed in the following inflammatory markers: pNF-κB and CD11b at 24 h in both brain and retina, nuclear NF-κB at 24 h in brain and 48 h in retina, and TNF-α at 24 h in brain. Progesterone treatment in MCAO animals significantly attenuated levels of the following markers in brain: pNF-κB, nuclear NF-κB, IL-6, TNF-α, and CD11b, with significantly increased levels of cytosolic NF-κB. Retinas from progesterone-treated animals showed significantly reduced levels of nuclear NF-κB and IL-6 and increased levels of cytosolic NF-κB, with a trend for reduction in other markers. Post-MCAO, progesterone receptors A and B were upregulated in brain and downregulated in retina. Conclusion: Inflammatory markers increased in both brain and retina after MCAO, with greater increases observed in brain. Progesterone treatment reduced inflammation, with more dramatic reductions observed in brain than retina. This differential effect may be due to differences in the response of progesterone receptors in brain and retina after injury.

Keywords: Focal ischemia, inflammation, middle cerebral artery occlusion, NF-kB, progesterone, progesterone receptor, rat, retina, retinal ischemia

DOI: 10.3233/RNN-160672

Journal: Restorative Neurology and Neuroscience, vol. 34, no. 6, pp. 947-963, 2016