Lymphocyte recruitment and activation have been implicated in the progression of cerebral ischemia-reperfusion (I/R) injury, but the roles of specific lymphocyte subpopulations and cytokines during stroke remain to be clarified. Here we demonstrate that the infiltration of T cells into the brain, as well as the cytokines interleukin-23 (IL-23) and IL-17, have pivotal roles in the evolution of brain infarction and accompanying neurological deficits. Blockade of T cell infiltration into the brain by the immunosuppressant FTY720 reduced I/R-induced brain damage. The expression of IL-23, which was derived mostly from infiltrated macrophages, increased on day 1 after I/R, whereas IL-17 levels were elevated after day 3, and this induction of IL-17 was dependent on IL-23. These data, together with analysis of mice genetically disrupted for IL-17 and IL-23, suggest that IL-23 functions in the immediate stage of I/R brain injury, whereas IL-17 has an important role in the delayed phase of I/R injury during which apoptotic neuronal death occurs in the penumbra. Intracellular cytokine staining revealed that gammadeltaT lymphocytes, but not CD4(+) helper T cells, were a major source of IL-17. Moreover, depletion of gammadeltaT lymphocytes ameliorated the I/R injury. We propose that T lymphocytes, including gammadeltaT lymphocytes, could be a therapeutic target for mitigating the inflammatory events that amplify the initial damage in cerebral ischemia.

CKD is an important predictor of poor clinical outcomes after acute ischemic stroke. Proteinuria independently contributes to the increased risks of neurologic deterioration, mortality, and poor functional outcome, but the eGFR may not be relevant to these outcomes.

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MD; for the FSR InvestigatorsBackground and Purpose-Diabetes mellitus is an established risk factor for stroke. However, it is uncertain whether prestroke glycemic control (PSGC) status affects clinical outcomes of acute ischemic stroke. The aim of this study was to elucidate the association between PSGC status and neurological or functional outcomes in patients with acute ischemic stroke. Methods-From the Fukuoka Stroke Registry (FSR), a multicenter stroke registry in Japan, 3627 patients with first-ever ischemic stroke within 24 hours after onset were included in the present analysis. The patients were categorized into 4 groups based on their PSGC status: excellent (hemoglobin [Hb] A1c on admission Ͻ6.2%), good (6.2-6.8%), fair (6.9 -8.3%) and poor (Ն8.4%). Study outcomes were neurological improvement (Ն4 points decrease in the National Institutes of Health Stroke Scale [NIHSS] score during hospitalization or 0 points on NIHSS score at discharge), neurological deterioration (Ն1 point increase in NIHSS score) and poor functional outcome (death or dependency at discharge, modified Rankin Scale 2-6). Results-The age-and sex-adjusted ORs for neurological improvement were lower, and those for neurological deterioration and a poor functional outcome were higher in patients with poorer PSGC status. After adjusting for multiple confounding factors, these trends were unchanged (all probability values for trends were Ͻ0.002). These findings were comparable in patients with noncardioembolic and cardioembolic infarctions. Conclusions-In ischemic stroke patients, HbA1c on admission was an independent significant predictor for neurological and functional outcomes. (Stroke. 2011;42:2788-2794.)

Platelet derived growth factor (PDGF)-B plays a neuroprotective role in brain damages, including ischemic stroke. It has been suggested recently that PDGF receptor β (PDGFRβ) expressed in brain pericytes as well as in neurons and astrocytes may mediate the neuroprotective role of PDGF-B. The aims of this study were to elucidate the roles of PDGFRβ signaling in brain pericytes after ischemic stroke. In a rat middle cerebral artery occlusion (MCAO) model, PDGFRβ expression was induced specifically in the pericytes in peri-infarct areas and its level was gradually increased. PDGF-B induced marked phosphorylation of Akt in cultured brain pericytes. Consistently, PDGF-B was upregulated in endothelial cells in per-infarct areas and Akt was strongly phosphorylated in the PDGFRβ-expressing pericytes in periinfarct areas after MCAO. In the cultured pericytes, PDGF-B induced cell growth and anti-apoptotic responses through Akt. Furthermore, PDGF-B significantly increased the expression of nerve growth factor (NGF) and neurotrophin-3 (NT-3) through Akt in the pericytes. Thus, the PDGFRβ-Akt signaling in brain pericytes may play various important roles leading to neuroprotection after ischemic stroke.