Neurochemistry international
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Traumatic brain injury (TBI) is the leading cause of mortality and morbidity worldwide and is characterized by immediate brain damage and secondary injuries, such as brain edema and ischemia. However, the exact pathological mechanisms that comprise these associated secondary injuries have not been fully elucidated. This study aimed to investigate the role of the Na(+)-K(+)-2Cl(-) cotransporter-1 (NKCC1) in the disruption of ion homeostasis and neuronal apoptosis in TBI. ⋯ Furthermore, NKCC1 inhibition also significantly inhibited TBI-induced extracellular signal-regulated kinase (Erk) activation. Erk inhibition significantly protected neurons from TBI injury; however, Erk inhibition had no effect on NKCC1 expression or the neuroprotective effect of NKCC1 inhibition against TBI. This study demonstrates the role of NKCC1 in TBI-induced brain cortex injury, establishing that NKCC1 may play a neurotoxic role in TBI and that the inhibition of NKCC1 may protect neurons from TBI via the regulation of Erk signaling.