Effects of Estrogen Receptor Antagonist ICI182.780 on a Rat Model of Traumatic Brain Injury.

Understanding the roles of estrogen receptors (ERs) in the pathogenesis of traumatic brain injury (TBI) is an important topic of putative value for therapeutic approaches. The present study aimed to investigate the effects of a non-selective ER-α/β antagonist ICI182.780 (ICI) on a rat model of TBI. The TBI model was induced by the weight-drop injury and assessed by the Morris water maze (MWM). ICI was dissolved by DMSO and intracerebroventricularly administered before TBI. Adult male rats were randomly divided into three groups: sham + veh, TBI + veh, and TBI + ICI. The level of central estrogen in the cerebral spinal fluid (CSF) was assessed by ELISA. The expressions of aromatase cytochrome P-450 (AROM) and synaptophysin (SYN) as well as glial fibrillary acidic protein (GFAP) were evaluated by Western blotting and immunofluorescence analyses, respectively. Compared with the sham + veh group, the TBI + veh one showed longer escape latency and less number of platform crossings in the MWM test, an elevated level of endogenous estrogen in the CSF, and increased expressions of AROM and SYN as well as GFAP in the injured hippocampus. The TBI + ICI group displayed longer escape latency and less number of platform crossings in the MWM test and more expressions of GFAP in the hippocampus than that of the TBI + veh one. In conclusion, single-dose intracerebroventricular administration of ICI may increase the cognitive deficits and hippocampal astrocytic activation after TBI, but not for the central aromatization and hippocampal synaptogenesis. [ABSTRACT FROM AUTHOR]