Sex-Dependent Long-Term Neurobehavioral Recovery in Experimental Neonatal Hypoxic-Ischemic Encephalopathy

This study investigates the sex-dependent effects of therapeutic hypothermia and a neuroprotectant (CHF6467) on long-term neurobehavioral recovery in neonatal rats subjected to hypoxic-ischemic encephalopathy. Using the Rice-Vannucci model, rats were divided into five groups: sham lesion, hypoxic-ischemic insult, hypoxic-ischemic insult with CHF6467, hypoxic-ischemic insult with hypothermia, and hypoxic-ischemic insult with CHF6467 combined with hypothermia. Behavioral tests at postnatal day 30 (P30) and 60 (P60) revealed significant improvements in motor coordination and spatial memory in treated groups compared to the vehicle-treated group, associated with reductions in infarct size at P60. Notably, female rats exhibited superior motor coordination recovery compared to males, despite similar neuroprotection levels. This suggests that motor coordination recovery is not solely dependent on the extent of neuronal damage. Conversely, spatial memory impairment was sex-independent and closely associated with the degree of neuroprotection. These findings highlight the importance of considering sex differences in neuroprotective treatment efficacy and suggest potential variations in responses between males and females in clinical settings.