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Leptin Induces Neuroprotection Neurogenesis and Angiogenesis after Stroke

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Leptin is a potent AMP kinase (AMPK) inhibitor that is central to cell survival. Hence, we explored the effects of leptin on neurogenesis and angiogenesis after stroke. Neural stem cells (NSC) were grown as neurospheres in culture and treated with vehicle or leptin and neurosphere size and terminal differentiation were then determined. We then explored the effects of leptin on endogenous repair mechanisms in vivo. Sabra mice underwent photothrombotic stroke, were given vehicle or leptin and newborn cells were labeled with Bromo-deoxy-Uridine. Functional outcome was studied with the neurological severity score for 90 days post stroke and the brains were then evaluated with immunohistochemistry. In a subset of animals the brains were also evaluated for changes in the expression of leptin receptor and AMPK. In vitro, leptin led to a 2-fold increase in neurosphere size but did not change the differentiation of newborn cells. Following stroke, exogenous leptin led to a 4-fold increase in the number of NSC in the cortex abutting the lesion. There was a 1.5-fold increase in the number of newborn neurons and glia in leptin treated animals. Leptin also significantly increased the number of blood vessels in the peri-lesioned cortex. Leptin treated mice had increased expression of leptin receptor and increased phosphorylated AMPK concentration. Animals treated with leptin also had significantly better functional states. In conclusion, leptin induces neurogenesis and angiogenesis after stroke and leads to increased leptin receptor and pAMPK concentrations. This may explain at least in part the better functional outcome observed in leptin treated animals after stroke.

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Keywords: Angiogenesis; Gliogenesis; Growth of Mouse Neurospheres; Immunohistochemistry; Protein Expression; Trypsin-EDTA; cardiovascular diseases; cerebral vessels; cerebrovascular disease; hemispheric volume; leptin; myocardial infarction; neurogenesis; neuroprotection; stroke

Document Type: Research Article

Publication date: November 1, 2011

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  • Current Neurovascular Research (CNR) provides a cross platform for the publication of scientifically rigorous research that addresses disease mechanisms of both neuronal and vascular origins in neuroscience. The journal serves as an international forum for the publication of novel and pioneering original work as well as timely neuroscience research reviews in the disciplines of cell developmental disorders, plasticity, and degeneration that bridge the gap between basic science research and clinical discovery. CNR emphasizes the elucidation of disease mechanisms, both cellular and molecular, which can impact the development of unique therapeutic strategies for neuronal and vascular disorders.
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