Roles of Astrocytic Endothelin ET_B Receptor in Traumatic Brain Injury

Traumatic brain injury (TBI) is an intracranial injury caused by accidents, falls, or sports. The production of endothelins (ETs) is increased in the injured brain. ET receptors are classified into distinct types, including ET_A receptor (ET_A-R) and ET_B receptor (ET_B-R). ET_B-R is highly expressed in reactive astrocytes and upregulated by TBI. Activation of astrocytic ET_B-R promotes conversion to reactive astrocytes and the production of astrocyte-derived bioactive factors, including vascular permeability regulators and cytokines, which cause blood-brain barrier (BBB) disruption, brain edema, and neuroinflammation in the acute phase of TBI. ET_B-R antagonists alleviate BBB disruption and brain edema in animal models of TBI. The activation of astrocytic ET_B receptors also enhances the production of various neurotrophic factors. These astrocyte-derived neurotrophic factors promote the repair of the damaged nervous system in the recovery phase of patients with TBI. Thus, astrocytic ET_B-R is expected to be a promising drug target for TBI in both the acute and recovery phases. This article reviews recent observations on the role of astrocytic ET_B receptors in TBI.