J Neuroinflamm
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Sodium butyrate (NaB) is a histone deacetylase (HDAC) inhibitor exhibiting anti-inflammatory and neuroprotective effects in a rat ischemic model of stroke as well as a myocardial ischemia model. Although clinical evidence shows that older women are at higher risk for stroke occurrence and greater stroke severity, no studies have evaluated the effectiveness of NaB either in females or in older animals. ⋯ These data provide the first evidence that delayed (>6 h) NaB treatment post-stroke is neuroprotective in older female rats. Additionally, these data also show that in addition to its well-known anti-inflammatory actions, NaB may exert a biphasic effect after stroke, operating initially to reduce BBB permeability and oxidative stress in the brain, and later, elevating IGF-1 expression in peripheral tissues.
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Traumatic brain injury (TBI) patients in military settings can be exposed to prolonged periods of hypobaria (HB) during aeromedical evacuation. Hypobaric exposure, even with supplemental oxygen to prevent hypoxia, worsens outcome after experimental TBI, in part by increasing neuroinflammation. Cell cycle activation (CCA) after TBI has been implicated as a mechanism contributing to both post-traumatic cell death and neuroinflammation. Here, we examined whether hypobaric exposure in rats subjected to TBI increases CCA and microglial activation in the brain, as compared to TBI alone, and to evaluate the ability of a cyclin-dependent kinase (CDK) inhibitor (CR8) to reduce such changes and improve behavioral outcomes. ⋯ HB exposure following TBI increases CCA, neuroinflammation, and associated neuronal cell loss. These changes and post-traumatic cognitive deficits are reduced by CDK inhibition; such drugs may therefore serve to protect TBI patients requiring aeromedical evacuation.