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

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 × 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.

Progesterone in the Brain: Hormone, Neurosteroid and Neuroprotectant

“…After a transient cerebral ischemia, no significant changes in PR mRNA were noticed in the cortical penumbra obtained from cerebral cortex of male rats at 24h after ischemia [83]. However, another study showed an up-regulation of PR protein in the cytosol fraction prepared from the cortical penumbra at 24 and 48h post-ischemia [84]. After a permanent cerebral ischemia in rats, Stanojlovic et al showed that levels of PR were decreased in both the cytosolic and nuclear fractions from the prefrontal cortex at 7 days post-injury and that progesterone treatment restored the PR levels to those observed in rats subjected to sham-operation [85].…”

“…Different studies provided important information. For example, progesterone treatment decreased BBB disruption [150,155], hemorrhagic transformation [156], inflammatory response [84,[157][158][159][160], mitochondrial dysfunction and oxidative damage [161][162][163][164][165], and apoptosis [166]. Moreover, progesterone has been reported to increase neurogenesis [167] and the survival of newborn neurons [168].…”

Long-Term Functional and Structural Consequences of Primary Blast Overpressure to the Eye

“…Because retinal neurons are accessible for imaging and functional testing in a way that other neural tissue is not, the retina can be used to provide information about risk, onset, and progression of pathogenesis in a variety of diseases, including stroke, diabetes, Alzheimer's, Parkinson's, multiple sclerosis, schizophrenia, autism, and seasonal affective disorder. 52,[70][71][72][73][74][75][76] Historically, getting a diagnosis of blast injury has been difficult, especially because PTSD and blast injury can have many overlapping symptoms. 3 Blast injury, like chronic traumatic encephalopathy, 77 has characteristic pathological hallmarks that can be confirmed in postmortem tissue.…”

Stem/progenitor cell-based transplantation for retinal degeneration: a review of clinical trials

“…However, adverse reactions of the eyes (such as endophthalmitis, uveitis, retina split holes and vitreous haemorrhage) and systemic adverse reactions (such as hypertension, myocardial infarction and stroke) caused by frequent intravitreal injections and the high cost of treatment lead to poor patient compliance and compromised effectiveness 31 . Neuroprotective interventions are generally divided into two categories 19 -drugs including steroids 32 , dopamine-related therapies 33 and neurotrophic factors 34 , and rehabilitative methods including physical exercise and electrical stimulation 35,36 ; they have been widely used in numerous fundamental studies to slow degenerative progress in the retina by protecting neuronal structure and function 19 , yet their exact clinical efficacy requires further observation and confirmation. Laser therapy is capable of clearing drusen in AMD patients, but may cause inflammatory-related damage and is unable to prevent progression to advanced AMD 37,38 .…”