Effects of sex steroid hormones on neuromedin S and neuromedin U۲ receptor expression following experimental traumatic brain injury

Objective(s): Neuroprotective effects of female gonadal steroids are mediated through several pathways involving multiple peptides and receptors after traumatic brain injury (TBI). Two of these peptides are including the regulatory peptides neuromedin U (NMU) and neuromedin S (NMS), and their common receptor neuromedin U۲ receptor (NMUR۲). This study investigates the effects of physiological doses of estradiol and progesterone on brain edema, NMS and NMU as well as NMUR۲ expression following TBI. Materials and Methods: Ovariectomized female rats were given high-and low-dose of female sex steroid hormones through implantation of capsules for a week before trauma. The brain NMUR۲ expression, prepro-NMS expression, NMU content, and water content (brain edema) were evaluated ۲۴ hr after TBI induced by Marmarou’s method. Results: Percentage of brain water content in high- and low-dose estradiol, and in high- and low- dose progesterone was less than vehicle (P<۰.۰۱).  Results show high expression of prepro-NMS in high dose progesterone (TBI-HP) rats compared to the high dose estrogen (TBI-HE), as well as vehicle (P<۰.۰۱). NMU content in low-dose progesterone (TBI-LP) group was more than that of vehicle group (P<۰.۰۰۱). Furthermore a difference in NMU content observed between TBI-HP compared to TBI-HE, and vehicle (P<۰.۰۵). The NMUR۲ mRNA expression revealed an upregulation in TBI-HP rats compared to the TBI-HE group (P<۰.۰۰۱). Conclusion: Findings indicate that progesterone attenuates brain edema and induces an increase in NMS and its receptor which may mediate the anti-edematous effect of progesterone after TBI.

Keywords:

Estradiol , Neuromedin U , NMS , NMUR۲ , Progesterone , Traumatic brain injury