Male and Female Mice Exhibit Divergent Responses of the Cortical Vasculature to Traumatic Brain Injury

雄性和雌性小鼠的皮质血管对创伤性脑损伤表现出不同的反应

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作者:Amandine Jullienne, Arjang Salehi, Bethann Affeldt, Mohsen Baghchechi, Elizabeth Haddad, Angela Avitua, Mark Walsworth, Isabelle Enjalric, Mary Hamer, Sonali Bhakta, Jiping Tang, John H Zhang, William J Pearce, André Obenaus

Abstract

We previously reported that traumatic brain injuries (TBI) alter the cerebrovasculature near the injury site in rats, followed by revascularization over a 2-week period. Here, we tested our hypothesis that male and female adult mice have differential cerebrovascular responses following a moderate controlled cortical impact (CCI). Using in vivo magnetic resonance imaging (MRI), a new technique called vessel painting, and immunohistochemistry, we found no differences between males and females in lesion volume, neurodegeneration, blood-brain barrier (BBB) alteration, and microglia activation. However, females exhibited more astrocytic hypertrophy and heme-oxygenase-1 (HO-1) induction at 1 day post-injury (dpi), whereas males presented with increased endothelial activation and expression of β-catenin, shown to be involved in angiogenesis. At 7 dpi, we observed an increase in the number of vessels and an enhancement in vessel complexity in the injured cortex of males compared with females. Cerebrovasculature recovers differently after CCI, suggesting biological sex should be considered when designing new therapeutic agents.

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