Stroke remains a significant unmet clinical need with limited therapeutic options. The peculiar feature of ischemic stroke is the interruption in brain circulation, resulting in a cascade of detrimental cerebrovasculature alterations. Treatment strategies designed to maintain potency of the cerebrovasculature may protect against stroke. The present study assessed the effects of short bouts of exercise prior to stroke induction and characterized cerebral blood flow and motor functions in vivo. Adult Sprague-Dawley rats were exposed to a single short bout of exercise (30-min or 60-min forced running wheel) then subjected to transient middle cerebral artery occlusion (MCAO). Non-exercise stroke rats served as controls while nonstroke rats represented shams. Cerebral blood flow (CBF) was evaluated by laser Doppler at baseline (prior to MCAO), during MCAO, and during reperfusion. Behavioral tests using the elevated body swing test was conducted at baseline, day 0 (day of stroke), and at days 1 and 3 after stroke. Animals that received exercise displayed typical alterations in CBF after stroke, but exhibited improved motor performance compared to non-exercise rats. Exercised stroke rats showed a reduction in infarct size and an increased number of surviving cells in the peri-infarct area, with a trend towards prolonged duration of the exercise. Immunofluorescence staining and Western blot analysis of the peri-infarct area revealed increased levels of endothelial markers/angiogenesis markers, VEGF, VEGFR-2, and Ang-2, and endothelial progenitor cell marker CD34+ in exercise groups compared with the controls. These results demonstrated that prophylactic exercise affords neuroprotection possibly by improving cerebrovascular potency.

Myocardial infarction (MI) is the leading cause of morbidity and mortality in the world. The infarcted heart displays typical cell death cascades characterized by a loss of cells and fibrotic scarring in the myocardium. Cardiac hypertrophy and fibrosis largely contribute to ventricular wall thickening and stiffening, altogether defining an adverse cardiac remodeling that ultimately leads to impaired cardiac function and subsequent heart failure. Finding a strategy to promote therapeutic, instead of detrimental, cardiac remodeling may pose as a potent MI treatment. Accumulating evidence shows that microRNAs (miRNAs) may play an essential role in cardiovascular diseases. In particular, microRNA-133a (miR-133a) is one of the most abundant miRNAs in the heart. Multiple studies have demonstrated that miR-133a participates in the early pathology of MI, as well as in subsequent cardiac remodeling. In this review, we summarize recent research progress highlighting the regulatory effects of miR-133a in ischemic myocardial diseases, such as inhibiting angiogenesis, apoptosis, fibrosis, hypertrophy, and inflammation, while promoting therapeutic cardiac remodeling. The goal is to elicit a critical discussion on the translational direction of miRNA-mediated treatments towards a safe and effective MI therapy.

Soluble epoxide hydrolase (sEH) degrades epoxides of fatty acids including epoxyeicosatrienoic acid isomers (EETs), which are produced as metabolites of the cytochrome P450 branch of the arachidonic acid pathway. EETs exert a variety of largely beneficial effects in the context of inflammation and vascular regulation. sEH inhibition is shown to be therapeutic in several cardiovascular and renal disorders, as well as in peripheral analgesia, via the increased availability of anti-inflammatory EETs. The success of sEH inhibitors in peripheral systems suggests their potential in targeting inflammation in the central nervous system (CNS) disorders. Here, we describe the current roles of sEH in the pathology and treatment of CNS disorders such as stroke, traumatic brain injury, Parkinson's disease, epilepsy, cognitive impairment, dementia and depression. In view of the robust anti-inflammatory effects of stem cells, we also outlined the potency of stem cell treatment and sEH inhibitors as a combination therapy for these CNS disorders. This review highlights the gaps in current knowledge about the pathologic and therapeutic roles of sEH in CNS disorders, which should guide future basic science research towards translational and clinical applications of sEH inhibitors for treatment of neurological diseases.