Changes in neuromedin S and its receptor after traumatic brain injury in cycling rats

Animal studies indicate that gonadal steroids have prominent neuroprotective effects in several models of experimental traumatic brain injury (TBI). Neuromedin U (NMU) and neuromedin S (NMS) are regulatory peptides involved in inflammatory and stress responses, and modulation of the gonadotropic axis. Since steroid hormone levels change during the estrous cycle, we sought to determine whether variations in ovarian hormones would affect blood-brain barrier (BBB) permeability and brain levels of NMS, NMU, and neuromedin S receptor 2 in experimental TBI. Two groups (proestrus and non-proestrus) of female rats underwent diffuse TBI. At 24 hrs after TBI, results showed a significantly decrease in BBB permeability in traumatic-proestrus animals (TBI-P) in comparison to traumatic non-proestrus (TBI-NP) rats. Western blot analyzes demonstrated an enhanced expression of prepro-NMS in TBI-P compared with that in the TBI-NP group. Likewise, TBI-P rats exhibited significantly higher NMUR2 gene expression compared with those of TBI-NP, whereas no significant difference in brain NMU content was seen between sham and traumatic animals. Our findings indicate that diffuse TBI induces an increase in prepro-NMS and neuromedin S receptor 2 expression in traumatic-proestrus rats which may mediate the anti-edematous effects of gonadal hormones in proestrus rats following trauma.