Spinal cord injury (SCI) affects more than 2.5 million people worldwide. Spinal cord
edema plays critical roles in the pathological progression of SCI. This study aimed to delineate the roles of
aquaporin 4 (AQP4) and
Na+-K+-Cl- cotransporter 1 (NKCC1) in acute phase
edema and tissue destruction after SCI and to explore whether inhibiting both AQP4 and NKCC1 could improve SCI-induced spinal
edema and damage. Rat SCI model was established by modified Allen's method. Spinal cord water content, cerebrospinal fluid
lactose dehydrogenase (LDH) activity, AQP4 and NKCC1 expression, and spinal cord pathology from 30 min to 7 days after SCI were monitored. Additionally, aforementioned parameters in rats treated with AQP4 and/or NKCC1 inhibitors were assessed 2 days after SCI. Spinal cord water content was significantly increased 1 h after SCI while AQP4 and NKCC1 expression and spinal fluid LDH activity elevated 6 h after SCI. Spinal cord
edema and spinal cord destruction peaked around 24 h after SCI and maintained at high levels thereafter. Treating rats with AQP4 inhibitor
TGN-020 and NKCC1 antagonist
bumetanide significantly reduced spinal cord
edema, tissue destruction, and AQP4 and NKCC1 expression after SCI in an additive manner. These results demonstrated the benefits of simultaneously inhibiting both AQP4 and NKCC1 after SCI.