Sex differences in mechanisms and outcome of neonatal hypoxia-ischemia in rodent models: implications for sex-specific neuroprotection in clinical neonatal practice.
Sex differences in mechanisms and outcome of neonatal hypoxia-ischemia in rodent models: implications for sex-specific neuroprotection in clinical neonatal practice.
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DOI：
10.1155/2012/867531
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发表时间：
2012
影响因子：
1.5
通讯作者：
Fitch RH
中科院分区：
文献类型：
--
作者：
Hill CA;Fitch RH
临床研究结果表明，男婴缺氧缺血性损伤（HI）的认知结果比匹配的女性更差。啮齿动物的新生儿缺氧缺血模型支持这种差异，数据显示围产期脑损伤主要导致雄性啮齿动物和早期雄激素治疗的雌性啮齿动物的长期行为缺陷。结果支持了性别特异性性腺激素可能调节对损伤的发育反应的观点，并与雄激素对典型脑形态和行为的发育作用的压倒性证据相吻合。然而，性别差异对早期脑损伤的反应机制可能更为复杂。具体来说，HI对细胞死亡通路的激活也可能因性别而异。在雌性中，caspase依赖性凋亡通路的优先激活实际上可能提供更大的保护，这可能是由于X-linked inhibitor of apoptosis （XIAP）在该通路中的作用。这对比了优先激活模式的caspase独立途径在男性。虽然性别特异性激素和基因调节对早期损伤反应的综合模型仍有待完全阐明，但这些发现表明，婴儿可能受益于HI损伤后的性别特异性神经保护。
Clinical findings show that male infants with hypoxic-ischemic injury (HI) fare more poorly than matched females on cognitive outcomes. Rodent models 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 hormones may 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 genetic modulation of response to early injury remains to be fully elucidated, these findings suggest that infants might benefit from sex-specific neuroprotection following HI injury.