Hydrogen inhalation and intrathecal magnesium sulfate ameliorate ischemia by suppressing cortical spreading depolarization in a rat subarachnoid hemorrhage model

Abstract

This study investigated whether inhaled hydrogen and intrathecal magnesium could mitigate cortical spreading depolarization and delayed cerebral ischemia in a rat model of subarachnoid hemorrhage. Adult male rats underwent subarachnoid hemorrhage induction with nitric oxide synthase inhibition and high-potassium application to elicit cortical spreading depolarization. Animals were assigned to sham, control, H₂, Mg, or combined H₂ and Mg treatment groups. We measured direct current potentials, cerebral blood flow, brain water content, bodyweight changes, and neurological outcomes. Compared with controls, the H₂ and Mg groups had significantly reduced total depolarization and hypoperfusion times. The combined treatment produced similar benefits. H₂ alone rapidly shortened depolarization duration, suggesting that it may offer neuroprotection until Mg effects fully manifest. Neither treatment altered physiological parameters, brain water content, bodyweight, or neurological deficits. These findings indicate that H₂ and Mg reduce key pathophysiological processes related to early brain injury and delayed cerebral ischemia following subarachnoid hemorrhage, potentially improving outcomes by minimizing depolarization events and associated ischemia. H₂ therapy may provide early protective effects before Mg exertion.