Neuroinflammatory pathways in binge alcohol-induced neuronal degeneration: oxidative stress cascade involving aquaporin, brain edema, and phospholipase A2 activation Journal Article


Authors: Collins, M. A.; Neafsey, E. J.
Article Title: Neuroinflammatory pathways in binge alcohol-induced neuronal degeneration: oxidative stress cascade involving aquaporin, brain edema, and phospholipase A2 activation
Abstract: Chronic binge alcohol exposure in adult rat models causes neuronal degeneration in the cortex and hippocampus that is not reduced by excitotoxic receptor antagonists, but is prevented by antioxidants. Neuroinflammatory (glial-neuronal) signaling pathways are believed to underlie the oxidative stress and brain damage. Based on our experimental results as well as increased knowledge about the pro-neuroinflammatory potential of glial water channels, we propose that induction of aquaporin-4 can be a critical initiating factor in alcohol's neurotoxic effects, through the instigation of cellular edema-based neuroinflammatory cascades involving increased phospholipase A2 activities, polyunsaturated fatty acid release/membrane depletion, decreased prosurvival signaling, and oxidative stress. A testable scheme for this pathway is presented that incorporates recent findings in the alcohol-brain literature indicating a role for neuroimmune activation (upregulation of NF-kappaB, proinflammatory cytokines, and toll-like receptors). We present the argument that such neuroimmune activation could be associated with or even dependent on increased aquaporin-4 and glial swelling as well.
Journal Title: Neurotoxicity Research
Volume: 21
Issue: 1
ISSN: 1476-3524
Publisher: Unknown  
Journal Place: United States
Date Published: 2012
Start Page: 70
End Page: 78
Language: English
DOI/URL:
Notes: ID: 12209; Record Owner: From MEDLINE, a database of the U.S. National Library of Medicine.; Status: MEDLINE; [Review]; Publishing Model: Journal available in: Print-Electronic Citation processed from: Internet; NLM Journal Code: 100929017; CAS Registry/EC Number/Name of Substance: 0 (Aquaporin 4). 64-17-5 (Ethanol). EC 3-1-1-4 (Phospholipases A2).; Grant Number: AA011543 (United States NIAAA NIH HHS), AA014436 (United States NIAAA NIH HHS), AA018279 (United States NIAAA NIH HHS), T32AA013527 (United States NIAAA NIH HHS); Electronic Date of Publication: 20110917; Entry Date: 20120416