Cell-Driven Angiogenesis and Neurogenesis after Stroke Is Regulated by Platelet's Microparticles.

Abstract

Repair mechanisms based on the proliferation of endogenous cells have been identified in ischemic brain regions suggesting that precursors at the ventricular surface proliferate, migrate to sites of injury and differentiate into neurons. However, this response is significantly limited by short survival times and poor differentiation capacity of these cells. External factors can boost endogenous neural stem cells (eNSC)-dependent repair mechanisms in the cerebral cortex. Upon activation, platelets shed platelet derived microparticles (PMP) which contain a variety of growth factors central to angiogenesis and neurogenesis. We have previously reported a pro angiogenic effect of PMPs, both in vitro and in vivo. We thus hypothesized that the functional benefits obtained from the presence of newborn cells can be further enhanced by increasing the survival rates, migration and differentiation potential of these cells, as well as by promoting angiogenic response, applying PMPs at the site of a stroke. Spontaneously hypertensive rats underwent permanent middle cerebral artery occlusion (PMCAO) and were given BrdU to label newborn cells. Animals were treated with vehicle or PMP delivered via a biodegradable polymer applied to the brain surface. Rats were tested with a neurological severity score and infarct volumes were measured at 90 days post –PMCAO. We used immunohistochemistry to determine the fate of newborn cells and to count blood vessels in the ischemic brain. The results show that PMP treatment led to a dose dependent increase in neurogenesis and angiogenesis at the infarct boundary zone. PMP also significantly improved behavioral deficits without affecting infarct volumes.