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Updated: May 14, 2026

Sex Differences in Mouse Hippocampal Astrocytes after In-Vitro Ischemia
Published on: October 25, 2016
Early hypoxia-ischemia causes hemisphere and sex-dependent cognitive impairment and histological damage
E F Sanches1, N S Arteni, F Nicola
1Post-Graduation Program of Neuroscience, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Brazil. ef.sanches@yahoo.com
Insights
Neonatal hypoxia-ischemia (HI) in rats at postnatal day 3 caused brain damage and cognitive issues. Female rats with left-sided injury showed greater vulnerability, indicating sex and brain lateralization impact outcomes.
Area of Science:
- Neuroscience
- Developmental Biology
- Neurology
Background:
- Neonatal cerebral hypoxia-ischemia (HI) is a leading cause of neurological disorders.
- In preterm infants, HI primarily affects white matter, leading to long-term cognitive deficits.
- Rodent models, like hypoxia-ischemia at postnatal day 3 (HIP3), mimic preterm brain injury and its consequences.
Purpose of the Study:
- To investigate the influence of brain lateralization and sexual dimorphism on behavioral and histological outcomes after HIP3.
- To assess long-term sensory, motor, and cognitive impairments in adult rats subjected to HIP3.
Main Methods:
- Wistar rats underwent unilateral carotid artery occlusion and systemic hypoxia (HIP3) or sham surgery.
- Behavioral tests (elevated plus maze, cylinder test, Morris water maze) assessed sensory and cognitive functions.
- Histological analysis evaluated hemisphere/hippocampus volumes and white matter damage (corpus callosum area).
Main Results:
- HIP3 rats did not exhibit motor impairments, but right-sided injury induced anxiety-like behaviors.
- Female rats with left-sided HIP3 injury displayed significant spatial memory deficits.
- Left-sided HIP3 injury in females correlated with more extensive histological damage compared to other groups.
Conclusions:
- Sex and the lateralization of brain injury significantly modulate the effects of early-life hypoxia-ischemia.
- Female rats are more susceptible to HIP3-induced neurodevelopmental and cognitive impairments when the left hemisphere is affected.
- Findings highlight the importance of considering sex and injury location in understanding and treating neonatal brain injury.
Abstract:
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 1.5h; control rats received sham surgery and exposure to 1.5h 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.
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