Cheng, Shiqi, Mao, Xiang, Lin, Xiangjiang, Wehn, Antonia, Hu, Senbin, Mamrak, Uta, Khalin, Igor, Wostrack, Maria, Ringel, Florian, Plesnila, Nikolaus, and Terpolilli, Nicole A.
Traumatic brain injury (TBI) causes long-lasting neurodegeneration and cognitive impairments; however, the underlying mechanisms of these processes are not fully understood. Acid-sensing ion channels 1a (ASIC1a) are voltage-gated Na+- and Ca2+-channels shown to be involved in neuronal cell death; however, their role for chronic post-traumatic brain damage is largely unknown. To address this issue, we used ASIC1a-deficient mice and investigated their outcome up to 6 months after TBI. ASIC1a-deficient mice and their wild-type (WT) littermates were subjected to controlled cortical impact (CCI) or sham surgery. Brain water content was analyzed 24 h and behavioral outcome up to 6 months after CCI. Lesion volume was assessed longitudinally by magnetic resonance imaging and 6 months after injury by histology. Brain water content was significantly reduced in ASIC1a–/– animals compared to WT controls. Over time, ASIC1a–/– mice showed significantly reduced lesion volume and reduced hippocampal damage. This translated into improved cognitive function and reduced depression-like behavior. Microglial activation was significantly reduced in ASIC1a–/– mice. In conclusion, ASIC1a deficiency resulted in reduced edema formation acutely after TBI and less brain damage, functional impairments, and neuroinflammation up to 6 months after injury. Hence, ASIC1a seems to be involved in chronic neurodegeneration after TBI. [ABSTRACT FROM AUTHOR]