Protective Role of Low Ethanol Administration Following Ischemic Stroke via Recovery of KCC2 and p75NTR Expression

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Khirug , S , Soni , S , Saez Garcia , M , Tessier , M , Zhou , L , Kulesskaya , N , Rauvala , H , Lindholm , D , Ludwig , A , Molinari , F & Rivera , C 2021 , ' Protective Role of Low Ethanol Administration Following Ischemic Stroke via Recovery of KCC2 and p75NTR Expression ' , Molecular Neurobiology , vol. 58 , pp. 1145-1161 . https://doi.org/10.1007/s12035-020-02176-x

Title: Protective Role of Low Ethanol Administration Following Ischemic Stroke via Recovery of KCC2 and p75NTR Expression
Author: Khirug, Stanislav; Soni, Shetal; Saez Garcia, Marta; Tessier, Marine; Zhou, Liang; Kulesskaya, Natalia; Rauvala, Heikki; Lindholm, Dan; Ludwig, Anastasia; Molinari, Florence; Rivera, Claudio
Contributor organization: Neuroscience Center
Helsinki Institute of Life Science HiLIFE
University of Helsinki
Biosciences
Medicum
Department of Biochemistry and Developmental Biology
Faculty of Medicine
Helsinki In Vivo Animal Imaging Platform (HAIP)
Date: 2021-03
Language: eng
Number of pages: 17
Belongs to series: Molecular Neurobiology
ISSN: 1559-1182
DOI: https://doi.org/10.1007/s12035-020-02176-x
URI: http://hdl.handle.net/10138/333001
Abstract: A striking result from epidemiological studies show a correlation between low alcohol intake and lower incidence for ischemic stroke and severity of derived brain injury. Although reduced apoptosis and inflammation has been suggested to be involved, little is known about the mechanism mediating this effect in vivo. Increase in intracellular chloride concentration and derived depolarizing GABAAR-mediated transmission are common consequences following various brain injuries and are caused by the abnormal expression levels of the chloride cotransporters NKCC1 and KCC2. Downstream pro-apoptotic signaling through p75NTR may link GABAA depolarization with post-injury neuronal apoptosis. Here, we show that changes in GABAergic signaling, Cl− homeostasis, and expression of chloride cotransporters in the post-traumatic mouse brain can be significantly reduced by administration of 3% ethanol to the drinking water. Ethanol-induced upregulation of KCC2 has a positive impact on neuronal survival, preserving a large part of the cortical peri-infarct zone, as well as preventing the massive post-ischemic upregulation of the pro-apoptotic protein p75NTR. Importantly, intracortical multisite in vivo recordings showed that ethanol treatment could significantly ameliorate stroke-induced reduction in cortical activity. This surprising finding discloses a pathway triggered by low concentration of ethanol as a novel therapeutically relevant target.
Subject: 3112 Neurosciences
Apoptosis
Trauma
Chloride homeostasis
GABA(A) transmission
Neurotrophines
COTRANSPORTER KCC2
HIPPOCAMPAL-NEURONS
ALCOHOL-CONSUMPTION
DOWN-REGULATION
UP-REGULATION
BDNF
ACTIVATION
NEOCORTEX
MORTALITY
INJURY
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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