Protective effect of sex steroid hormones on morphological and cellular outcomes after neonatal hypoxia-ischemia: A meta-analysis of preclinical studies

Abstract

Sex steroid hormones play an important role in fetal development, brain functioning and neuronal protection. Growing evidence highlights positive effects of these hormones against brain damages induced by neonatal hypoxia-ischemia (HI). This systematic review and meta-analysis aim to verify the efficacy of sex steroid hormones to prevent HI-induced brain damage in rodent models. The protocol was registered at PROSPERO and a total of 22 articles were included. Moderate to large effects were observed in HI animals treated with sex steroid hormones in reducing cerebral infarction size and cell death, increasing neuronal survival and mitigating neuroinflammatory responses and astrocyte reactivity. A small effect was evidenced for cognitive function, and there was no significant effect for motor function. In summary, published rodent data suggest that sex steroid hormones such as progesterone and 17β estradiol improve morphological and cellular outcomes following neonatal HI. Additional research is paramount to examine neurological function during neonatal HI recovery.