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Abstract: Background and purpose: To evaluate the strength of the in vivo evidence of relationships between flavonoids and risk of stroke. Methods: We reviewed the literature more broadly for flavonoids and stroke and conducted an evidence-based review of original publication experiments on tea or tea components on induced coronary occlusion in animal models and on the observational epidemiology on stroke and either tea or flavonoids in man. Each of the studies was evaluated by two independent reviewers. The evidence in total was compared with the Bradford Hill and Stroke Therapy Academic Industry Roundtable (STAIR) [1] Abbreviations Used: STAIR, Stroke Therapy Academic Industry Roundtable; EGCG, epigallocatechin gallate; MCAO, middle cerebral artery occlusion; SHRSP rats, Sprague–Dawley or Wistar rats, Mongolian gerbil, ddY mice, or spontaneously hypertensive stroke-prone rats 1 quality-assessment criteria . Results: The search of epidemiologic publications revealed 7 cohort studies on flavonoid intake and stroke and 7 cohort studies and 3 case control studies on tea and stroke. In studies of tea there was a consistent protective effect. However, the epidemiologic research on flavonoids and stroke was much less consistent. Eleven animal experiments were identified that examined tea or tea components and stroke relevant sequelae, eight of which reported on infarct volume. All studies demonstrated reduced infarct volumes in animals exposed either to tea extracts, theanine or tea catechins prior to or shortly after reperfusion. Conclusions: Hill’s criteria of causality are largely met in the case of tea and stroke. A high level of consistency across preclinical studies, of the effect of tea components as single agents effective in reducing stroke volume after middle cerebral artery occlusion, is noted in all rodent models (rat, mouse, and gerbil). Reductions in infarct volume are seen with both tea extracts consumed orally and tea components introduced intra-peritoneally. Observational epidemiology supports this finding in man for tea – the studies are consistent across countries and type of tea and the relative risks are moderately strong. That is not the case for the body of evidence on flavonoid intakes and stroke. [Copyright &y& Elsevier]

MiR-126, a microRNA implicated in blood vessel integrity, angiogenesis and vascular inflammation, is markedly decreased in the sera of patients with intracerebral hemorrhage (ICH). The current study aims to evaluate the potential therapeutic effect of miR-126-3p on brain injuries in a rat model of collagenase-induced ICH. Intracerebroventricular administration of a miR-126-3p mimic significantly alleviated behavioral defects 24 h after ICH, as examined by paw placement and corner tests. ICH led to increased blood-brain barrier (BBB) permeability and cerebral edema, both of which were attenuated by miR-126-3p mimic. Treatment with miR-126-3p mimic reduced the numbers of myeloperoxidase (MPO)-positive, OX42-positive, Fluoro Jade B (FJB)-positive and NEUN/TUNEL double-positive cells around the hematoma, implying that miR-126-3p inhibited neutrophil infiltration, microglial activation and neuronal apoptosis following hemorrhage. In addition, miR-126-3p mimic suppressed the upregulation of phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) in the perihematomal area and maintained the activation of Akt. Furthermore, in vitro assays confirmed upregulation of PIK3R2 upon knockdown of miR-126-3p in rat brain microvascular endothelial cells (BMECs), and silencing of miR-126-3p resulted in impaired BMEC barrier permeability and reversed vascular endothelial growth factor (VEGF)- and angiopoietin-1 (Ang-1)-induced activation of Akt and inhibition of BMEC apoptosis. In summary, our results suggest that exogenous miR-126-3p may alleviate BBB disruption, cerebral edema and neuronal injury following ICH by targeting PIK3R2 and the Akt signaling pathway in brain vascular endothelium. [ABSTRACT FROM AUTHOR]