Microglia: Rheostats of space radiation effects in the CNS microenvironment.

Microglia are innate immune cells within the brain that arise from a distinct myeloid lineage. Like other tissue resident macrophages, microglia respond to injury or immune challenges and participate in reparative processes such as phagocytosis to preserve normal function. Importantly, they also participate in normal homeostatic processes including maintenance of neurogenic niches and synaptic plasticity associated with development. This review highlights aspects of microglial biology and how repeated insults that occur with age, neurodegenerative disease and possibly radiation exposure may heighten microglial responses and contribute to their dysfunction, creating a situation where their normal reparative mechanisms are no longer sufficient to maintain brain health. These ideas are discussed in the context of an evolving literature focused on microglial responses as possible targets for mitigation of late CNS radiation effects that represent potential risks for future exploration of deep space environments.

Matters of size: Roles of hyaluronan in CNS aging and disease.

Involvement of extracellular matrix (ECM) components in aging and age-related neurodegeneration is not well understood. The role of hyaluronan (HA), a major extracellular matrix glycosaminoglycan, in malignancy and inflammation is gaining new understanding. In particular, the differential biological effects of high molecular weight (HMW-HA) and low molecular weight hyaluronan (LMW-HA), and the mechanism behind such differences are being uncovered. Tightly regulated in the brain, HA can have diverse effects on cellular development, growth and degeneration. In this review, we summarize the homeostasis and signaling of HA in healthy tissue, discuss its distribution and ontogeny in the central nervous system (CNS), summarize evidence for its involvement in age-related neurodegeneration and Alzheimer Disease (AD), and assess the potential of HA as a therapeutic target in the CNS.

Prehospital supplemental oxygen for acute stroke - A retrospective analysis.

OBJECTIVE: Brief early administration of supplemental oxygen (sO2) to create hyperoxia may increase oxygenation to penumbral tissue and improve stroke outcomes. Hyperoxia may also result in respiratory compromise and vasoconstriction leading to worse outcomes. This study examines the effects of prehospital sO2 in stroke. METHODS: This is a retrospective analysis of adult acute stroke patients (aged ≥18 years) presenting via EMS to an academic Comprehensive Stroke Center between January 1, 2013 and December 31, 2017. Demographic and clinical characteristics obtained from Get with the Guidelines-Stroke registry and subjects' medical records were compared across three groups based on prehospital oxygen saturation and sO2 administration. Chi-square, ANOVA, and multivariate logistic regression were used to determine if sO2 status was associated with neurological outcomes or respiratory complications. RESULTS: 1352 eligible patients were identified. 62.7% (n = 848) did not receive sO2 ("controls"), 10.7% (n = 144) received sO2 due to hypoxia ("hypoxia"), and 26.6% (n = 360) received sO2 despite normoxia ("hyperoxia"). The groups represented a continuum from more severe deficits (hypoxia) to less severe deficits (controls): mean prehospital GCS (hypoxia -12, hyperoxia - 2, controls - 14 p ≤ 0.001), mean initial NIHSS (hypoxia - 15, hyperoxia - 13, controls - 8 p < 0.001). After controlling for potential confounders, all groups had similar rates of respiratory complications and favorable neurological outcomes. CONCLUSIONS: Hyperoxic subjects had no significant increase in respiratory complications, nor did they differ in neurologic outcomes at discharge when controlling for confounders. While limited by the retrospective nature, this suggests brief, early sO2 for stroke may be safe to evaluate prospectively.

Cyclooxygenase-2 modulates brain inflammation-related gene expression in central nervous system radiation injury.

Although the contribution of cyclooxygenase-2 (COX-2) to peripheral inflammation is well documented, little is known about its role in brain inflammation. For this purpose we studied COX-2 expression in the mouse brain following ionizing radiation in vivo, as well as in murine glial cell cultures in vitro. The possible role of COX-2 in modulating brain inflammation was examined utilizing NS-398, a COX-2 selective inhibitor. Our results indicate that COX-2 is significantly induced in astrocyte and microglial cultures by radiation injury as well as in brain. Increased levels of prostaglandin E(2) in irradiated brain were reduced by NS-398. Moreover, NS-398 administration significantly attenuated levels of induction for the majority of inflammatory mediators examined, including TNFalpha, IL-1beta, IL-6, iNOS, ICAM-1, and MMP-9. In contrast, the chemokines MIP-2 and MCP-1 showed enhanced levels of induction following NS-398 administration. These results indicate that COX-2 modulates the inflammatory response in brain following radiation injury, and suggest the use of COX-2 selective inhibitors for the management of CNS inflammation.