The Neuroprotective Effect of Ethanol Intoxication in Traumatic Brain Injury Is Associated with the Suppression of ErbB Signaling in Parvalbumin-Positive Interneurons

Journal of Neurotrauma
Akila ChandrasekarFrancesco Roselli

Abstract

Ethanol intoxication (EI) is a frequent comorbidity of traumatic brain injury (TBI), but the impact of EI on TBI pathogenic cascades and prognosis is unclear. Although clinical evidence suggests that EI may have neuroprotective effects, experimental support is, to date, inconclusive. We aimed at elucidating the impact of EI on TBI-associated neurological deficits, signaling pathways, and pathogenic cascades in order to identify new modifiers of TBI pathophysiology. We have shown that ethanol administration (5 g/kg) before trauma enhances behavioral recovery in a weight-drop TBI model. Neuronal survival in the injured somatosensory cortex was also enhanced by EI. We have used phospho-receptor tyrosine kinase (RTK) arrays to screen the impact of ethanol on TBI-induced activation of RTK in somatosensory cortex, identifying ErbB2/ErbB3 among the RTKs activated by TBI and suppressed by ethanol. Phosphorylation of ErbB2/3/4 RTKs were upregulated in vGlut2+ excitatory synapses in the injured cortex, including excitatory synapses located on parvalbumin (PV)-positive interneurons. Administration of selective ErbB inhibitors was able to recapitulate, to a significant extent, the neuroprotective effects of ethanol both in sensorimotor per...Continue Reading

References

Jul 1, 1992·Brain Injury : [BI]·C P Kaplan, J D Corrigan
May 1, 1997·Journal of Neurosurgery·D F KellyD A Hovda
Oct 24, 1998·Clinical Pharmacokinetics·B A Boucher, S D Hanes
Sep 27, 2003·Epilepsia·John Bruns, W Allen Hauser
May 5, 2005·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·Olli SavolaMatti Hillbom
Feb 7, 2007·Brain Research·Mia ThompsonCynthia Shannon Weickert
May 25, 2007·Neuron·Ran-Sook WooLin Mei
May 15, 2008·Nature Reviews. Neuroscience·Lin Mei, Wen-Cheng Xiong
Sep 5, 2008·Archives of Clinical Neuropsychology : the Official Journal of the National Academy of Neuropsychologists·Rael T LangeMichael D Franzen
Oct 28, 2008·Nature Neuroscience·Marc FlajoletPaul Greengard
Nov 27, 2008·The Journal of Head Trauma Rehabilitation·Eduard ZaloshnjaAnbesaw W Selassie
May 22, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dmitriy KedrinJeffrey E Segall
Aug 29, 2009·Nature Protocols·Michael A FlierlEsther Shohami
Sep 29, 2009·Bioorganic & Medicinal Chemistry Letters·Lixin QiaoGregory D Cuny
Oct 13, 2009·The Journal of Trauma·Ali SalimDaniel R Margulies
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Lei WenLin Mei
Apr 16, 2010·Journal of Neurotrauma·Sherman C SteinSeema S Sonnad
Apr 8, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mark J NoltMatthew B Dalva
May 18, 2011·The Journal of Biological Chemistry·Martin KriebelHansjürgen Volkmer
Sep 3, 2011·Science·Christopher J MagnusScott M Sternson
Nov 5, 2011·The American Journal of Pathology·Ryuichi KatadaHiroshi Matsumoto
Apr 21, 2012·Trends in Neurosciences·Sean I Sheffler-Collins, Matthew B Dalva
Sep 14, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hideki TamuraSadao Shiosaka
Oct 19, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jennifer WuchterHansjürgen Volkmer
Jan 4, 2013·PloS One·Dasuni S AlwisRamesh Rajan
Jan 12, 2013·PloS One·John ThundyilThiruma V Arumugam
Jan 15, 2013·Journal of Pharmacokinetics and Pharmacodynamics·Susan F Hudachek, Daniel L Gustafson
Mar 13, 2013·Experimental Biology and Medicine·Tina M SchwarzkopfJochen Klein
May 15, 2013·International Journal of Molecular Sciences·Vivek K GuptaStuart L Graham
Jun 1, 2013·The Journal of Surgical Research·Michael D GoodmanTimothy A Pritts
Aug 15, 2013·Nature Reviews. Neuroscience·Hilmar Bading

❮ Previous
Next ❯

Citations

May 8, 2020·European Journal of Trauma and Emergency Surgery : Official Publication of the European Trauma Society·Henry Alexander LeijdesdorffInger Birgitta Schipper

❮ Previous
Next ❯

Methods Mentioned

BETA
protein assay
sandwich immunoassay
enzyme-linked immunosorbent assay
antibody array

Software Mentioned

ImageJ
GraphPad
GraphPad Prism

Related Concepts

Related Feeds

Barrel cortex

Here is the latest research on barrel cortex, a region of somatosensory and motor corticies in the brain, which are used by animals that rely on whiskers for world exploration.

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.