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- Title
Sex Differences in Mechanisms and Outcome of Neonatal Hypoxia-Ischemia in Rodent Models: Implications for Sex-Specific Neuroprotection in Clinical Neonatal Practice.
- Authors
Hill, Courtney A.; Fitch, R. Holly
- Abstract
Clinical findings show that male infants with hypoxic-ischemic injury (HI) fare more poorly than matched females on cognitive outcomes. Rodentmodels of neonatal hypoxia-ischemia support this difference, with data showing that perinatal brain injury leads to long-term behavioral deficits primarily in male rodents and in female rodents treated with early androgens. Results support the idea that sex-specific gonadal hormonesmay modulate developmental response to injury and dovetail with overwhelming evidence of developmental androgen effects on typical brain morphology and behavior. However, mechanisms underlying sex differences in response to early brain injury may be more complicated. Specifically, activation of cell death pathways in response to HI may also differ by sex. In females, the preferential activation of the caspase-dependent apoptotic pathway may actually afford greater protection, potentially due to the actions of X-linked inhibitor of apoptosis (XIAP) within this pathway. This contrasts the pattern of preferential activation of the caspase-independent pathway in males. While an integrated model of sex-specific hormonal and geneticmodulation of response to early injury remains to be fully elucidated, these findings suggest that infants might benefit from sex-specific neuroprotection following HI injury.
- Subjects
GENDER specific care; HEALTH outcome assessment; NEWBORN infants' injuries; HYPOXEMIA; ANIMAL models of ischemia; COGNITIVE analysis; PHYSICIAN practice patterns; CASPASES regulation; X-linked inhibitor of apoptosis protein
- Publication
Neurology Research International, 2012, p1
- ISSN
2090-1852
- Publication type
Article
- DOI
10.1155/2012/867531