Acid-Ion Sensing Channel 1a Deletion Reduces Chronic Brain Damage and Neurological Deficits after Experimental Traumatic Brain Injury

Cheng, Shiqi; Mao, Xiang; Lin, Xiangjiang; Wehn, Antonia; Hu, Senbin; Mamrak, Uta; Khalin, Igor; Wostrack, Maria; Ringel, Florian; Plesnila, Nikolaus und Terpolilli, Nicole A. (2021): Acid-Ion Sensing Channel 1a Deletion Reduces Chronic Brain Damage and Neurological Deficits after Experimental Traumatic Brain Injury. In: Journal of Neurotrauma, Bd. 38, Nr. 11: S. 1572-1584

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0897-7151
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198