The effect of angiotensin receptor type 2 inhibition and estrogen on experimental traumatic brain injury

Estrogen interferes with renin-angiotensin system (RAS). Increasing evidence suggests that estrogen interferes with the RAS such as decreasing angiotensin receptor in the brain. This study aimed at investigating the mutual interaction between estrogen and candesartan (an angiotensin receptor blocker) to inhibit or amplify each other's neuroprotective effects after traumatic brain injury (TBI). Female rats were divided into 11 groups and the ovaries were removed in nine groups. Study groups included sham, TBI, oil, vehicle (Veh), a low dose (LC) and a high dose (HC) of candesartan, estrogen (E2), Veh + Veh, and a combination of estrogen with a low dose (E2 + LC) and a high dose (E2 + HC) of candesartan. TBI was induced by the Marmarou's method. Brain edema and integrity of blood–brain barrier (BBB) were assayed by calculating brain water content (BWC) and Evans blue content, respectively. The neurological outcome was evaluated using the veterinary coma scale (VCS). The results showed that the BWC in the E2 group was less than that of the oil group (P < 0.01) and in the HC group was also less than that of the Veh group (P < 0.05). Posttraumatic Evans blue content in the TBI, oil, and Veh groups was higher than that in the E2 (P < 0.001) and HC (P < 0.001) groups. Although there was no significant difference in the above indicators between the LC and Veh groups, both the BWC and Evans blue content in the E2 + LC group were lower compared to the oil + Veh group (P < 0.001). In addition, the VCS increased in the E2, HC, and combined groups after TBI (P < 0.01). Prescribing estrogen alone and a high dose of candesartan and a low dose of candesartan with estrogen has a neuroprotective effect on brain edema, permeability of BBB, and neurological scores. This may suggest that estrogen and candesartan (especially in a low dose) act via similar paths.