Translational stroke research
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Traumatic brain injuries and their associated treatments carry high cost in both financial impact and morbidity to human life. Recent studies and trials present promising results in reducing secondary injury in the days and weeks following the primary insult. A number of studies, both pre-clinical and clinical, have found that different populations of stem/progenitor cells result in a reduction of inflammation, maintenance of the blood brain barrier, and an overall improved prognosis. ⋯ The spleen has become an area of intense interest as an arena where therapeutic cells interact with reactive macrophages to cause system-level changes in immune activity. Additionally, the spleen enacts anti-inflammatory responses originating in the CNS, delivered through vagal activity with a recently described mechanism culminating in acetylcholine release. This review provides a summary of recent findings as to the mechanisms of action observed in current cellular therapies.
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Although inflammatory immune cells clearly contribute to the development of middle cerebral artery occlusion (MCAO) in mice, the failure to block neutrophil-associated injury in clinical stroke trials has discouraged further development of immunotherapeutic approaches. However, there is renewed interest in a possible protective role for regulatory T- and B-cells that can suppress inflammation and limit central nervous system damage induced by infiltrating pro-inflammatory cells. ⋯ These MCAO-induced changes were completely prevented in B-cell-restored mice after transfer of highly purified WT B-cells but not IL-10-deficient B-cells. Our novel observations are the first to implicate IL-10-secreting B-cells as a major regulatory cell type in stroke and suggest that enhancement of regulatory B-cells might have application as a novel therapy for this devastating neurologic condition.
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Despite more than 30 years of clinical use, questions remain about the safety of xenon gas in Xenon-CT cerebral blood flow (XeCTCBF) studies. In particular, xenon's effect on brain oxygen (PbtO2) in comatose patients is not well defined. Our objective was to assess the effect of a 4.5-min inhalation of 28 % stable xenon on several physiologic variables, including intracranial pressure (ICP), cerebral perfusion pressure (CPP), and PbtO2 in comatose patients (Glasgow Coma Scale [GCS] ≤ 8). ⋯ There was a varied response to xenon in most measured variables. Clinically significant changes in each were infrequent, and readily reversed with the cessation of the gas. We conclude that xenon does not appear to have a clinically significant effect on ICP, CPP, and PbtO2 and so appears safe to evaluate cerebral blood flow in comatose patients.