Lack of cortistatin drives neuroimmune and vascular dysfunction in brain ischemia

We demonstrate for the first time that cortistatin deficiency amplified ischemia-induced transcriptional programs, heightening neuroinflammation and glial/neurovascular dysfunction, and worsening neurological outcomes. Interestingly, cortistatin deficiency accelerated aging-associated pathological features, underscoring its essential role in neuroimmune and cerebrovascular homeostasis. Conversely, cortistatin administration improved neuronal survival, mitigated immune dysfunction, and preserved myelin and vascular integrity during both the acute and subacute stages.

These findings provide the first evidence identifying cortistatin as an endogenous neuroimmune regulator in ischemic stroke and a promising multimodal therapeutic agent for improving acute and long-term outcomes.