Neuroscience
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The intense and prolonged inflammatory response after ischemic stroke significantly contributes to the secondary neural injury. PI3Kγ, which is involved in the regulation of vascular permeability, chemotactic leukocyte migration and microglia activation, is a key target for intervention in the inflammatory response. In this study, we identified the protective effect of the PI3Kγ inhibitor AS605240 against stroke-related injury in the mouse model of transient intraluminal middle cerebral artery occlusion (tMCAO). ⋯ AS605240 treatment significantly reduced the astrocyte activation markers and the morphological changes of cells. We also identified 13 inflammatory factors whose expression was significantly upregulated by IL-6/sIL-6R and significantly inhibited by AS605240 at the protein level, and seven of those factors were verified at the mRNA level. These results indicated that specific inhibition of PI3Kγ could reduce astrocyte activation induced by inflammation, which might aid the repair and remodeling of neurons in the later stage after ischemic stroke.
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Stroke is a major life-threatening and disabling disease with a restricted therapeutic approach. Bone marrow stromal cells (BMSCs) possess proliferative ability and a multi-directional differentiation potential, and secrete a range of trophic/growth factors that can protect neurons after cerebral ischemia/reperfusion. Transient receptor potential canonical (TRPC) is a family of non-selective channels permeable to Ca2+, with several functions including neuronal survival. ⋯ In the present study, we report that over-expression of TRPC6 via a CRISPR-based synergistic activation mediator in BMSCs provided a greater reduction of brain injury in a rat model of ischemia/reperfusion. Further, the improved neurofunctional outcomes were associated with increased TRPC6 and brain derived neurotrophic factor expression levels. Overall, these data suggest that TRPC6 over-expressing BMSCs may be a promising therapeutic agent for ischemic stroke.