Dexmedetomidine in ischemic and hemorrhagic brain injury: Neuroprotection from mechanisms to therapy

Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist extensively used for sedation in clinical anesthesia, has recently attracted significant attention for its neuroprotective properties. These effects are mediated through multiple mechanisms, including anti-inflammatory and antioxidative stress responses, inhibition of apoptosis and autophagy, preservation of mitochondrial function, and maintenance of blood-brain barrier integrity. Brain injury, encompassing neonatal hypoxic-ischemic encephalopathy, ischemic stroke, traumatic brain injury, and other related cerebral pathologies, remains a leading cause of global neurological disability. Despite advances in critical care, effective interventions to prevent secondary neuronal damage and long-term neurological dysfunction remain limited. The neuroprotective actions of DEX suggest its potential as a therapeutic candidate for mitigating neurological deficits following brain injury. This review synthesizes preclinical and clinical evidence on DEX across various forms of brain injury, spanning molecular mechanisms, animal models, and clinical applications, thereby providing a foundation for exploring its therapeutic strategies in neurocritical care.