Abstract T P76: Human Neural Stem Cells Rapidly Ameliorate Symptomatic Inflammation In Ischemic-Reperfusion Cerebral Injury

Abstract

Ischemic stroke injury results not only from ischemia but also from reperfusion. Stroke causes a loss of cerebral parenchyma and its associated cells, disruption of neuronal connections, compromise of the blood-brain barrier, and inflammation. We tested whether exogenously engrafted human neural stem cells (hNSCs) could migrate rapidly and extensively to damaged regions following intracranial transplantation and counteract a number of these pathological processes. We used a stroke mouse model with middle cerebral artery occlusion (MCAO) to induce focal ischemia followed by reperfusion. We transplanted hNSCs 24 hours after MCAO to correspond to the upregulation of endogenous proinflammatory cytokines, which can act as stem cell-recruiting factors. We found that 24 hrs post-transplantation, engrafted hNSCs had migrated extensively to the lesion, brain infarct volume was reduced, and behavioral function was significantly improved compared to MCAO controls. Because the time course of this repair was too short for cell replacement, we hypothesized that the mechanisms of therapeutic action are anti-inflammatory. Microglial activation and proinflammatory gene expression (TNF-α, IL-6, and IL-1β) were reduced, and blood-brain barrier damage was ameliorated in hNSC-transplanted mice. Our findings demonstrate clear benefits of transplanting hNSCs during the early stages of ischemic stroke.