Mechanism of Post-stroke Axonal Outgrowth and Functional Recovery

Abstract

Axonal outgrowth after stroke plays an important role in tissue repair and is critical for functional recovery. In the peri-infarct area of a rat middle cerebral artery occlusion model, we found that the axons and dendrites that had fallen off in the acute phase of stroke (7 days) were regenerated in the chronic phase of stroke (56 days). In vitro, we showed that phosphatase tensin homolog deleted on chromosome 10/Akt/Glycogen synthase kinase 3β signaling is implicated in postischemic axonal regeneration. In a rat model of chronic cerebral hypoperfusion, oral administration of L-carnitine induced axonal and oligodendrocyte regeneration in the cerebral white matter, resulting in myelin thickening, and it improved cognitive impairment in rats with chronic cerebral ischemia. Recently, it has been shown that exosomes enhanced functional recovery after stroke. Exosome treatment has less tumorigenicity, does not occlude the microvascular system, has low immunogenicity, and does not require a host immune response compared to conventional cell therapy. Several studies demonstrated specific microRNA in exosomes, which regulated signaling pathways related to neurogenesis after stroke. Collectively, there are various mechanisms of axonal regeneration and functional recovery after stroke, and it is expected that new therapeutic agents for stroke with the aim of axonal regeneration will be developed and used in real-world clinical practice in the future.