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

Shiqi Cheng, Xiang Mao, Xiangjiang Lin, Antonia Wehn, Senbin Hu, Uta Mamrak, Igor Khalin, Maria Wostrack, Florian Ringel, Nikolaus Plesnila, Nicole A. Terpolilli

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

4 Zitate (Scopus)

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+- A nd 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.

OriginalspracheEnglisch
Seiten (von - bis)1572-1584
Seitenumfang13
FachzeitschriftJournal of Neurotrauma
Jahrgang38
Ausgabenummer11
DOIs
PublikationsstatusVeröffentlicht - 1 Juni 2021

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