TY - JOUR
T1 - Acid-Ion Sensing Channel 1a Deletion Reduces Chronic Brain Damage and Neurological Deficits after Experimental Traumatic Brain Injury
AU - Cheng, Shiqi
AU - Mao, Xiang
AU - Lin, Xiangjiang
AU - Wehn, Antonia
AU - Hu, Senbin
AU - Mamrak, Uta
AU - Khalin, Igor
AU - Wostrack, Maria
AU - Ringel, Florian
AU - Plesnila, Nikolaus
AU - Terpolilli, Nicole A.
N1 - Publisher Copyright:
© 2021 Mary Ann Liebert Inc.. All rights reserved.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
KW - animal studies
KW - brain edema
KW - cognitive function
KW - controlled cortical impact
KW - traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=85107501020&partnerID=8YFLogxK
U2 - 10.1089/neu.2020.7568
DO - 10.1089/neu.2020.7568
M3 - Article
C2 - 33779289
AN - SCOPUS:85107501020
SN - 0897-7151
VL - 38
SP - 1572
EP - 1584
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
IS - 11
ER -