Platelet Microparticles Induce Angiogenesis and Neurogenesis after Cerebral Ischemia

Yael      Hayon; Olga      Dashevsky; Ela      Shai; Alex      Brill; David      Varon; Ronen      R. Leker

Abstract

Activated platelets shed microparticles, which contain a variety of growth factors central to angiogenesis and neurogenesis. The aim of this study was to explore whether platelet derived microparticles (PMP) can boost endogenous neural stem cells dependent repair mechanisms following stroke in a rat model.

To examine the effects of PMP therapy in-vivo, we delivered PMP or vehicle via a biodegradable polymer to the brain surface after permanent middle cerebral artery occlusion (PMCAO) in rats.

Rats were tested with the neurological severity score and infarct volumes were measured at 90 days post-ischemia. Immunohistochemistry was used to determine the fate of newborn cells and to count blood vessels in the ischemic brain.

The results show that PMP led to a dose dependent increase in cell proliferation, neurogenesis and angiogenesis at the infarct boundary zone and significantly improved behavioral deficits.

Keywords: Angiogenesis, Cerebral ischemia, Microparticles, Neurogenesis, Platelets, Stroke, endogenous, fibroblastic, platelet microparticles, neural stem cell, brain-derived neurotrophic factor (BDNF), subcellualr fragments, endothelial, PMP, PLX-5A