Agonistic analog of growth hormone–releasing hormone promotes neurofunctional recovery and neural regeneration in ischemic stroke

Significance Stroke is a leading cause of mortality and permanent disability in adults worldwide. Although most pharmacological neuroprotectants have beneficial effects in experimental studies, they fail in clinical trials. Here, we report that MR-409, a synthetic analog of growth hormone–releasing hormone, can reduce mortality and improve neurological functional recovery in mice operated on for tMCAO. Mechanistically, MR-409 stimulates endogenous neurogenesis and improves tMCAO-induced loss of neuroplasticity by activation of AKT/CREB and BDNF/TrkB pathways. Our preclinical studies support the notion that MR-409 has remarkable neuroprotective effects through enhancing endogenous neurogenesis and may represent a potential new therapy for cerebral ischemic stroke.