Potential neuroprotective role of dexmedetomidine in preventing postoperative cerebral hyperperfusion syndrome: from mechanisms to clinical applications.

Cerebral hyperperfusion syndrome (CHS) is an uncommon but serious problem that can occur following carotid endarterectomy, carotid artery stenting, and revascularization procedures for moyamoya disease (MMD). Clinically, CHS can lead to cerebral edema, intracerebral hemorrhage, or status epilepticus, all of which are linked to poor neurological outcomes. The syndrome is believed to be triggered by impaired autonomic regulation, endothelial dysfunction, and disruption of the blood-brain barrier (BBB), leading to oxidative stress, inflammation, ischemia-reperfusion injury, and neuronal impairment. The 24-72 hours postoperatively is a critical "amplification phase" during which BBB disruption and oxidative-inflammatory feedforward damage can gradually worsen, ultimately resulting in neurological deficits. Despite careful perioperative hemodynamic management, some patients still develop CHS; this persistent susceptibility suggests the need for specific approaches to stabilize neurovascular function. Importantly, the underlying pathophysiological mechanisms of CHS vary across surgical populations, including impaired autonomic regulation in patients with carotid stenosis and chronic vascular fragility in patients with MMD. Dexmedetomidine (DEX) is a highly selective α2-adrenergic receptor agonist that has shown neuroprotective effects in experimental models and clinical practice. Its protective mechanisms include inhibiting sympathetic activity, reducing cerebral blood flow and metabolic demands, mitigating inflammation and oxidative responses, maintaining BBB integrity, and reducing ischemia-reperfusion injury by stabilizing mitochondria. Importantly, DEX acts as a hemodynamic buffer during the acute reperfusion phase and as a molecular stabilizer during the 24-72 hour delayed phase, while simultaneously promoting cellular recovery and reducing white matter damage. However, despite promising preclinical data, clinical data on DEX specifically for the prevention of CHS remain limited. This review summarizes current experimental and clinical evidence to highlight the time-dependent and population-specific therapeutic benefits of DEX. Based on this, we propose a personalized pharmacological framework that provides targeted neurovascular protection for high-risk patients on top of systemic blood pressure control.