Melanocortins Defend their Territory: Multifaceted Neuroprotection in Cerebral Ischemia

Stroke is the leading cause of adult disability and the third leading cause of death (1). Its dramatic, often catastrophic attack unleashes an extremely challenging therapeutic target. Typically, an intravascular blood clot occludes a vessel such as the middle cerebral artery, causing focal ischemia deep in its perfusion territory, and triggering a rapidly closing window of opportunity for treatment before neurological damage becomes irreversible. The sole approved therapy is to attempt reperfusion using thrombolytic agents within 3 h of symptom onset, but most patients are excluded by this requirement or by other eligibility criteria, and the treatment exposes patients to significant risk of intracerebral hemorrhage. Only a fraction of treated patients experience some benefit (2, 3). Consequently, a major goal of stroke research is to develop interventions that are effective and safe after longer treatment delays. Against this backdrop, in this issue Giuliani et al. (4) report promising findings of pharmacological neuroprotection in cerebral ischemia by a synthetic melanocortin (ACTH/MSH-related peptide).