Cortistatin deficiency worsens neuroinflammation and vascular dysfunction in ischemic stroke, while administration improves outcomes.

Ischemic stroke is a leading cause of death and disability, with current therapies often falling short in addressing its complex pathophysiology. Key contributors to both acute injury and chronic decline include neuroinflammation, blood-brain barrier disruption, and immune dysregulation. Understanding endogenous factors that regulate these processes is crucial for developing effective treatments. Cortistatin, a neuropeptide found in the nervous and immune systems, possesses potent immunomodulatory actions, yet its specific role in neuroinflammatory conditions like stroke has remained largely undefined.

Researchers combined human and murine transcriptomic analyses with a preclinical stroke model in cortistatin-deficient mice. The study investigated cortistatin's endogenous and therapeutic roles during acute (48 hours) and subacute (7 days) phases of ischemic stroke. They compared outcomes in cortistatin-deficient mice to wild-type controls following ischemia. Therapeutic cortistatin administration was also assessed for its effects on neuronal survival, immune function, and vascular integrity. Primary endpoints included transcriptional programs, neuroinflammation markers, glial/neurovascular function, and neurological outcomes.