Coupling of neurogenesis and angiogenesis after ischemic stroke

Abstract

Stroke is a leading cause of mortality and severe long-term disability worldwide. Development of effective treatment or new therapeutic strategies for ischemic stroke patients is therefore crucial. Ischemic stroke promotes neurogenesis by several growth factors including FGF-2, IGF-1, BDNF, VEGF and chemokines including SDF-1, MCP-1. Stroke-induced angiogenesis is similarly regulated by many factors most notably, eNOS and CSE, VEGF/VEGFR2, and Ang-1/Tie2. Important findings in the last decade have revealed that neurogenesis is not the stand-alone consideration in the fight for full functional recovery from stroke. Angiogenesis has been also shown to be critical in improving post-stroke neurological functional recovery. More than that, recent evidence has shown a highly possible interplay or dependence between stroke-induced neurogenesis and angiogenesis. Moving forward, elucidating the underlying mechanisms of this coupling between stroke-induced neurogenesis and angiogenesis will be of great importance, which will provide the basis for neurorestorative therapy.

Stroke Repair via Biomimicry of the Subventricular Zone

“…The only current therapy for ischemic stroke being administration of recombinant tissue plasminogen activator (rtPA). While the treatment of rtPA therapy can be beneficial, it is currently constrained to just 2-5% of stroke patients, as rtPA is only effective if administered 4.5 h following symptom onset (Ruan et al, 2015). For patients who are unable to meet the criteria for rtPA therapy, intracranial hemorrhage often causes permanent neurological functional deficits (Ruan et al, 2015).…”

“…While the treatment of rtPA therapy can be beneficial, it is currently constrained to just 2-5% of stroke patients, as rtPA is only effective if administered 4.5 h following symptom onset (Ruan et al, 2015). For patients who are unable to meet the criteria for rtPA therapy, intracranial hemorrhage often causes permanent neurological functional deficits (Ruan et al, 2015). A need for therapies that can be administered beyond a short therapeutic window remains, in addition to those that have the potential to restore the damaged tissue cavity that is formed by hypoxic conditions following stroke.…”

“…In addition to neurogenesis, the process of angiogenesis, or development of new blood vessels, is necessary to achieve functional neurological recovery following stroke (Ruan et al, 2015). The peri-infarct area is hypoxic, triggering angiogenesis through upregulation of EC-secreted vascular endothelial growth factor (VEGF) within 6-24 h following occlusion.…”

“…Many factors beyond VEGF, such as fibroblast growth factor (FGF) and brainderived neurotrophic factor (BDNF) regulate angiogenesis. These function to promote vasodilation and increase circulation and tissue oxygenation as initial steps for repair following ischemic damage (Ruan et al, 2015).…”

“…Following NSC proliferation, neuroblasts (cells differentiated from NSCs that are committed to neuronal fate) migrate to the ischemic region and boundary of the infract region. This migration is characterized by cellular interactions between immature neuroblasts and blood vessels, suggesting that angiogenesis and neurogenesis are time-dependent and codependent upon one another (Ruan et al, 2015).…”