Combination of HBO and Memantine in Focal Cerebral Ischemia: Is There a Synergistic Effect?

Hyperbaric oxygen (HBO) therapy and memantine, a non-competitive NMDA antagonist, are both promising treatment strategies for improving stroke prognosis. However, HBO's narrow therapeutic time window (< 6 h post-stroke) and the adverse effect of high-dose MEM administration limits the use of these therapeutic interventions. In this study, we investigated whether or not MEM could prolong the narrow therapeutic window of HBO treatment. Transient focal cerebral ischemia was induced in male Sprague-Dawley rats by middle cerebral artery occlusion (MCAO) for 120 min. MCAO produced neurobehavioral deficits, increased infarction volume, increased Evans blue (EB) content and levels of pro-inflammatory factors, as well as depleted glutathione (GSH), and reduced catalase (CAT) and superoxide dismutase (SOD) activity in the ischemic ipsilateral hemisphere. The combination of 5 mg/kg MEM treatment 15 min after the onset of ischemic event and HBO therapy 12 h post-reperfusion significantly restored neurologic scores, EB concentration and IL-10 levels, as well as significantly decreased infarct volume and increased antioxidant activity. These results imply that the combination of MEM and HBO therapy not only prolongs the therapeutic window of HBO treatment, but also lowers the dosage requirement of MEM. The mechanism underlying the neuroprotective effects of the combined treatment may lie in alleviated blood-brain barrier (BBB) permeability, inhibited inflammatory response, and up-regulation of the antioxidant enzyme activity.