Loss of Acid sensing ion channel-1a and bicarbonate administration attenuate the severity of traumatic brain injury

Terry Yin; Timothy E Lindley; Gregory W Albert; Raheel Ahmed; Peter B Schmeiser; M Sean Grady; Matthew A Howard; Michael J Welsh

doi:10.1371/journal.pone.0072379

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Loss of Acid sensing ion channel-1a and bicarbonate administration attenuate the severity of traumatic brain injury

Journal article

Open access

Peer reviewed

Loss of Acid sensing ion channel-1a and bicarbonate administration attenuate the severity of traumatic brain injury

Terry Yin, Timothy E Lindley, Gregory W Albert, Raheel Ahmed, Peter B Schmeiser, M Sean Grady, Matthew A Howard and Michael J Welsh

PloS one, Vol.8(8), pp.e72379-e72379

2013

DOI: 10.1371/journal.pone.0072379

PMCID: PMC3753246

PMID: 23991103

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Abstract

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in people of all ages. Following the acute mechanical insult, TBI evolves over the ensuing minutes and days. Understanding the secondary factors that contribute to TBI might suggest therapeutic strategies to reduce the long-term consequences of brain trauma. To assess secondary factors that contribute to TBI, we studied a lateral fluid percussion injury (FPI) model in mice. Following FPI, the brain cortex became acidic, consistent with data from humans following brain trauma. Administering HCO3 (-) after FPI prevented the acidosis and reduced the extent of neurodegeneration. Because acidosis can activate acid sensing ion channels (ASICs), we also studied ASIC1a(-/-) mice and found reduced neurodegeneration after FPI. Both HCO3 (-) administration and loss of ASIC1a also reduced functional deficits caused by FPI. These results suggest that FPI induces cerebral acidosis that activates ASIC channels and contributes to secondary injury in TBI. They also suggest a therapeutic strategy to attenuate the adverse consequences of TBI.

Severity of Illness Index

Fear

Bicarbonates - administration & dosage

Bicarbonates - therapeutic use

Brain Injuries - drug therapy

Humans

Memory

Acid Sensing Ion Channels - genetics

Brain Injuries - genetics

Brain Injuries - psychology

Details

Title: Subtitle: Loss of Acid sensing ion channel-1a and bicarbonate administration attenuate the severity of traumatic brain injury
Creators: Terry Yin - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Timothy E Lindley
Gregory W Albert
Raheel Ahmed
Peter B Schmeiser
M Sean Grady
Matthew A Howard
Michael J Welsh
Resource Type: Journal article
Publication Details: PloS one, Vol.8(8), pp.e72379-e72379
DOI: 10.1371/journal.pone.0072379
PMID: 23991103
PMCID: PMC3753246
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: Howard Hughes Medical Institute
Language: English
Date published: 2013
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Iowa Neuroscience Institute; Neurosurgery; Otolaryngology; Internal Medicine
Record Identifier: 9984020766302771

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