Targeting ASIC1a Promotes Neural Progenitor Cells Migration and Neurogenesis in Ischemic Stroke

Potentiating is NOT GOOD ENOUGH! Will you deliver results instead of 'potential'? My god, I'd fire the lot of you for not solving stroke, just twiddling your thumbs.

 Targeting ASIC1a Promotes Neural Progenitor Cells Migration and Neurogenesis in Ischemic Stroke

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Targeting ASIC1a Promotes Neural Progenitor Cells Migration and Neurogenesis
in Ischemic Stroke
Hongfei Ge,1,3,# Tengyuan Zhou,1,3,# Chao Zhang,1,3,# Yupeng Cun,2 Weixiang Chen,1
Yang Yang,1 Qian Zhang,3 Huanhuan Li,1 Jun Zhong,1 Xuyang Zhang,1 Hua Feng,1,*
Rong Hu,1,3,*
1 Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest
Hospital, Third Military Medical University (Army Medical University), 400038
Chongqing, China.
2 Pediatric Research Institute, Ministry of Education Key Laboratory of Child
Development and Disorders, National Clinical Research Center for Child Health and
Disorders, Children’s Hospital of Chongqing Medical University, 400014 Chongqing,
China
3 Medical Research Center, Southwest Hospital, Third Military Medical University
(Army Medical University), 400038 Chongqing, China.
# These authors contributed equally to this work.
* Correspondence should be addressed to Rong Hu; huchrong@tmmu.edu.cn and Hua
Feng; fenghua8888@163.vip.com
Short Title：ASIC1a inhibition promotes NPCs migration and neurogenesisDownloaded from https://spj.science.org on March 25, 2023

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Abstract

Cell replacement therapy using neural progenitor cells (NPCs) has been shown to
be an effective treatment for ischemic stroke(Really? Where is the protocol for that?). However, the therapeutic effect is
unsatisfactory due to the imbalanced homeostasis of the local microenvironment after
ischemia. Microenvironmental acidosis is a common imbalanced homeostasis in the
penumbra and could activate acid-sensing ion channels 1a (ASIC1a), a subunit of
proton-gated cation channels following ischemic stroke. However, the role of ASIC1a
in NPCs post-ischemia remains elusive. Here, our results indicated that ASIC1a was
expressed in NPCs with channel functionality, which could be activated by extracellular
acidification. Further evidence revealed that ASIC1a activation inhibited NPCs
migration and neurogenesis through RhoA signaling-mediated reorganization of
filopodia formation, which could be primarily reversed by pharmacological or genetic
disruption of ASIC1a. In vivo data showed that the knockout of the ASIC1a gene
facilitated NPCs migration and neurogenesis in the penumbra to improve behavioral
recovery after stroke. Subsequently, ASIC1a gain-of-function partially abrogated this
effect. Moreover, the administration of ASIC1a antagonists (Amiloride or Psalmotoxin
1) promoted functional recovery by enhancing NPCs migration and neurogenesis.
Together, these results demonstrate targeting ASIC1a is a novel strategy potentiating
NPCs migration toward penumbra to repair lesions following ischemic stroke, and even
for other neurological diseases with the presence of niche acidosis.Downloaded