Inhibition of the Na +–K +–2Cl −-cotransporter in choroid plexus attenuates traumatic brain injury-induced brain edema and neuronal damage

Abstract

The present study was aimed to elucidate the possible role of Na +–K +–2Cl −-cotransporter (NKCC1) on traumatic brain injury-induced brain edema, cerebral contusion and neuronal death by using traumatic brain injury animal model. Contusion volume was verified by 2,3,5,-triphenyltetrazolium chloride monohydrate staining. NKCC1 mRNA expression was detected by RT-PCR and the protein expression of NKCC1 was measured by Western blot. We found that the expression of NKCC1 RNA and protein were up-regulated in choroid plexus apical membrane from 2 h after traumatic brain injury, peaked at 8 h, and lasted for 24 h. Rats in the experimental group displayed severe brain edema (water content: 81.45 ±0.32% compared with 78.38 ± 0.62% of sham group) and contusion volume significantly increased 8 h after traumatic brain injury (864.14 ±28.07 mm 3). Administration of the NKCC1 inhibitor bumetanide (15 mg/kg, I.V.) significantly attenuated the contusion volume (464.03 ±23.62 mm 3) and brain edema (water content: 79.12 ± 0.28%) after traumatic brain injury. Our study demonstrates that NKCC1 contributes to traumatic brain injury-induced brain edema and neuronal damage.