The Effect of Angiotensin Receptor Type 2 Inhibition and Estrogen on Experimental Traumatic Brain Injury

Document Type: Original Article

Authors

1 Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences

2 Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences

3 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

Abstract

Background: Estrogen interferes with renin‑angiotensin system (RAS). Increasing evidence suggests that estrogen interferes with the RAS
such as decreasing angiotensin receptor in the brain. Objectives: 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).
Materials and Methods: 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). Results: 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). Conclusion: 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.

Keywords


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