Sex differences in brain MRI abnormalities and neurodevelopmental outcomes in a rat model of neonatal hypoxia-ischemia

Abstract

Purpose/aim of the study: Hypoxic-ischemic brain injury (HIBI) is associated with high mortality and neurodevelopmental deficits. We explored gender influence in a HIBI rat model. Materials and methods: Sprague–Dawley rats underwent HIBI on postnatal day (P) 7. Nervous reflexes, footprints, Morris water maze performances and magnetic resonance imaging (MRI) were analyzed. Results: Mortality rate was higher in HIBI males (20%) than in females (12.5%). Growth rate was slower in the HIBI group (p < 0.05), but was similar between HIBI males and females. HIBI rats showed impaired performances in the cliff aversion reflex, negative geotaxis reflex and gait tests at P14 (p < 0.05), but not at P9 or P11. There were no significant differences for the cliff aversion reflex and gait tests between genders. Negative geotaxis reflex impairment at P14 was more severe in HIBI males (p < 0.05). Step length and toe distance contralateral (but not ipsilateral) to the cerebral damage were shorter in HIBI rats, and were shorter in HIBI males than females (p < 0.05). Morris water maze latency time and swimming distance were longer in the HI group than in controls, and prolonged in HIBI males compared with females (p < 0.05). In the HIBI group, MRI showed more severe injury at P10 and P67 in males than in females (p < 0.05). Conclusions: Male rats are more vulnerable to the detrimental consequences of HIBI, with more severe nervous reflex deficits, brain injury, memory impairment and hemiplegic paralysis than female rats. Serial neurobehavioral follow-up is still executed on the HIBI infants who is absent of detectable abnormalities in early children.

KEYWORDS:

• hypoxic-ischemic brain injury
• long-term neural development
• sex differences
• MRI
• SD rat
• neurodevelopmental outcomes

Acknowledgments

We thank all the people who helped in this study. We are grateful for the kind help given by Dr Weihua Ren.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This work was supported by grants from the Anhui Province Natural Science Fund [grant number KJ2011Z171].