Improved spatial memory, neurobehavioral outcomes, and neuroprotective effect after progesterone administration in ovariectomized rats with traumatic brain injury: Role of RU۴۸۶ progesterone receptor antagonist

Objective(s): The contribution of classic progesterone receptors (PR) in interceding the neuroprotective efficacy of progesterone (P۴) on the prevention of brain edema and long-time behavioral disturbances was assessed in traumatic brain injury (TBI). Materials and Methods: Female Wistar rats were ovariectomized and apportioned into ۶ groups: sham, TBI, oil, P۴, vehicle, and RU۴۸۶. P۴ or oil was injected following TBI. The antagonist of PR (RU۴۸۶) or DMSO was administered before TBI. The brain edema and destruction of the blood-brain barrier (BBB) were determined. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and beam walk (BW) task were evaluated previously and at various times post-trauma. Long-time locomotor and cognitive consequences were measured one day before and on days ۳, ۷, ۱۴, and ۲۱ after the trauma. Results: RU۴۸۶ eliminated the inhibitory effects of P۴ on brain edema and BBB leakage (p <۰.۰۵, p <۰.۰۰۱, respectively). RU۴۸۶ inhibited the decremental effect of P۴ on ICP as well as the increasing effect of P۴ on CPP (p <۰.۰۰۱) after TBI. Also, RU۴۸۶ inhibited the effect of P۴ on the increase in traversal time and reduction in vestibulomotor score in the BW task (p <۰.۰۰۱). TBI induced motor, cognitive, and anxiety-like disorders, which lasted for ۳ weeks after TBI; but, P۴ prevented these cognitive and behavioral abnormalities (p <۰.۰۵), and RU۴۸۶ opposed this P۴ effect (p <۰.۰۰۱). Conclusion: The classic progesterone receptors have neuroprotective effects and prevent long-time behavioral and memory deficiency after brain trauma.

Keywords:

Behavioral disorders , Mifepristone , Neuroprotection , Progesterone , Spatial Memory , TBI