Anesthetic Neuroprotection Based on Ion-Channel-Modulating Drugs in Acute Traumatic Brain Injury

Traumatic brain injury (TBI) remains a major cause of disability and mortality. Secondary brain injury, driven by ionic imbalance, excitotoxicity, mitochondrial dysfunction, and inflammation, plays a critical role in neurological deterioration. Ion-channel dysregulation, particularly calcium overload and sustained membrane depolarization, represents a key therapeutic target. This narrative review synthesizes recent evidence (2020-2025) on anesthetic agents that modulate ion channels in acute TBI. Dexmedetomidine, ketamine, propofol, volatile anesthetics, nimodipine, magnesium, lidocaine, and xenon exert neuroprotective effects through N-methyl-D-aspartate (NMDA) antagonism, sodium- and calcium-channel modulation, enhancement of inhibitory signaling, and stabilization of neuronal excitability. Preclinical studies demonstrate reduced apoptosis, preserved mitochondrial function, and attenuation of excitotoxic injury. Clinical translation remains limited by heterogeneity in injury patterns and study design. Nonetheless, a mechanism-guided approach to anesthetic selection, aligned with predominant secondary injury pathways and hemodynamic priorities, may enhance neuroprotective strategies in both neuro-intensive care unit (ICU) and intraoperative settings. Further high-quality clinical trials are required to define the optimal role of ion-channel-modulating anesthetics in TBI management.