Early hypoxia-ischemia causes hemisphere and sex-dependent cognitive impairment and histological damage

Neonatal cerebral hypoxia-ischemia (HI) is an important cause of neurological disorders. In the preterm children, HI causes preferentially white matter damage and late cognitive impairments. Rodent HI performed at postnatal day 3 (HIP3) provides valuable information on the brain response to injury in immature animals as related to sensory, motor and cognitive impairments observed in humans born prematurely. The present study aimed to observe the effects of brain lateralization and sexual dimorphism following HIP3 on behavior and histological damage assessed in adulthood. Male and female Wistar rats had their right or left common carotid artery occluded and exposed to 8% oxygen for 1.5 h; control rats received sham surgery and exposure to 1.5 h of room air in isolation of their dams. Sensory and cognitive parameters were assessed by the use of elevated plus maze, cylinder test and Morris water maze. After behavioral testing, hemisphere and hippocampus volumes were used to define brain damage extension; white matter damage was estimated through corpus callosum area ratio. No motor impairments were shown in HIP3 rats and anxiety-related changes were observed only in right injured animals. Females having left occlusion were more vulnerable to HIP3 injury since they presented spatial memory impairment and greater histological damage. These results show the modulation exerted by sex and brain lateralization following early HI at postnatal day 3.

► Hypoxia-ischemia (HI) is a major cause of neurological damage. ► Performed at postnatal day 3 (HIP3) mimics HI occurring in preterm infants. ► Anxiety-related, cognitive and histological parameters were altered by HIP3. ► HIP3 damage is dependent on the animals' sex and hemisphere injured. ► The left hemisphere of female rats was more vulnerable to HIP3.