Ectopic expression of human angiopoietin-1 promotes functional recovery and neurogenesis after focal cerebral ischemia

Neuropathologic processes such as cerebral ischemia can enhance neurogenesis. Angiopoietin-1 (Ang1) emerges as a critical regulator of physiological and pathological angiogenesis during embryonic and postnatal life. Although Ang1 could protect peripheral vasculature from vascular leakage following ischemic injury, the role of Ang1 in long-term neurological recovery after ischemic stroke remains elusive. This study aims to examine whether Ang1 overexpression via lentivirus-mediated gene transfer enhances neurovascular remodeling and improves functional outcome in a rat model of focal cerebral ischemia. Our results demonstrated that lentivirus-mediated Ang1 gene transfer led to improved neurological behavior and reduced infarction volume, and protected against blood-brain barrier (BBB) leakage in the ischemic rats. In addition, we revealed that these effects of Ang1 are related to the ability of Ang1 to increase vascular density and accelerate endogenous neuronal differentiation. These findings suggest that Ang1 is a promising agent for the treatment of cerebral ischemia.