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

• Type of Material: Article
• Authors: Rachael S. Allen, Emory University; Iqbal Sayeed, Emory University; Yuliya Oumarbaeva, Emory University; Katherine C. Morrison, Emory University; Paul H. Choi, Emory University; Machelle Pardue, Emory University; Donald G Stein, Emory University
• Language: English
• Date: 2016-01-01
• Publisher: IOS Press
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 IOS Press and the authors. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.3233/RNN-160672
• Title of Journal or Parent Work: Restorative Neurology and Neuroscience
• ISSN: 0922-6028
• Volume: 34
• Issue: 6
• Start Page: 947
• End Page: 963
• Grant/Funding Information: H. Allen and Company, Atlanta VA Rehab R&D Center of Excellence, Laney Graduate School of Emory University, Foundation Fighting Blindness, unrestricted departmental grant from Research to Prevent Blindness, NIH National Eye Institute, P30EY006360, and T32EY007092-24.
• Keywords: Neurosciences & Neurology; GLUCOCORTICOID-RECEPTOR; retinal ischemia; GLIAL-CELLS; inflammation; DEVELOPING PURKINJE-CELL; GENE-EXPRESSION; Science & Technology; SPINAL-CORD; middle cerebral artery occlusion; FACTOR-KAPPA-B; Neurosciences; NF-kappa B; PREGNANE-X-RECEPTOR; SEX STEROIDS; Life Sciences & Biomedicine; rat; ACTIVATED PROTEIN-KINASE; Focal ischemia; progesterone receptor; progesterone; retina; UP-REGULATION
• Research Categories: Health Sciences, Rehabilitation and Therapy; Health Sciences, Opthamology; Health Sciences, Medicine and Surgery

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 48h using western blots. Results: Following MCAO, significant increases were observed in the following inflammatory markers: pNF-κB and CD11b at 24h in both brain and retina, nuclear NF-κB at 24h in brain and 48h in retina, and TNF-α at 24h 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.