Sex hormones modulate pathogenic processes in experimental traumatic brain injury

Journal of Neurochemistry
Christina GölzMichael K E Schäfer

Abstract

Clinical and animal studies have revealed sex-specific differences in histopathological and neurological outcome after traumatic brain injury (TBI). The impact of perioperative administration of sex steroid inhibitors on TBI is still elusive. Here, we subjected male and female C57Bl/6N mice to the controlled cortical impact (CCI) model of TBI and applied pharmacological inhibitors of steroid hormone synthesis, that is, letrozole (LET, inhibiting estradiol synthesis by aromatase) and finasteride (FIN, inhibiting dihydrotestosterone synthesis by 5α-reductase), respectively, starting 72 h prior CCI, and continuing for a further 48 h after CCI. Initial gene expression analyses showed that androgen (Ar) and estrogen receptors (Esr1) were sex-specifically altered 72 h after CCI. When examining brain lesion size, we found larger lesions in male than in female mice, but did not observe effects of FIN or LET treatment. However, LET treatment exacerbated neurological deficits 24 and 72 h after CCI. On the molecular level, FIN administration reduced calpain-dependent spectrin breakdown products, a proxy of excitotoxicity and disturbed Ca2+ homeostasis, specifically in males, whereas LET increased the reactive astrocyte marker glial fibril...Continue Reading

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Citations

Jul 14, 2020·Frontiers in Neurology·Colin J Saldanha
Sep 24, 2020·British Journal of Pharmacology·Regina HummelMichael K E Schäfer
Feb 9, 2021·Frontiers in Immunology·Geoffrey P DobsonJodie L Morris
Oct 27, 2020·Frontiers in Neurology·Joseph T McCabe, Laura B Tucker
Feb 4, 2021·Mediators of Inflammation·Katharina RitterMichael K E Schäfer
Mar 27, 2021·Mechanisms of Ageing and Development·Julie A Chowen, Luis M Garcia-Segura
Apr 4, 2021·International Journal of Molecular Sciences·David GustafssonElham Rostami
Sep 28, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Ricardo Mario Arida

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