PMID- 11083227
OWN - NLM
STAT- MEDLINE
DCOM- 20001130
LR  - 20220223
IS  - 0271-678X (Print)
IS  - 0271-678X (Linking)
VI  - 20
IP  - 11
DP  - 2000 Nov
TI  - The lipid peroxidation by-product 4-hydroxynonenal is toxic to axons and 
      oligodendrocytes.
PG  - 1529-36
AB  - Lipid peroxidation and the cytotoxic by-product 4-hydroxynonenal (4-HNE) have 
      been implicated in neuronal perikaryal damage. This study sought to determine 
      whether 4-HNE was involved in white matter damage in vivo and in vitro. 
      Immunohistochemical studies detected an increase in cellular and axonal 4-HNE 
      within the ischemic region in the rat after a 24-hour period of permanent middle 
      cerebral artery occlusion. Exogenous 4-HNE (3.2 nmol) was stereotaxically 
      injected into the subcortical white matter of rats that were killed 24 hours 
      later. Damaged axons detected by accumulation of beta-amyloid precursor protein 
      (beta-APP) were observed transversing medially and laterally away from the 
      injection site after intracerebral injection of 4-HNE. In contrast, in the 
      vehicle-treated animals, axonal damage was restricted to an area immediately 
      surrounding the injection site. Exogenous 4-HNE produced oligodendrocyte cell 
      death in culture in a time-dependent and a concentration-dependent manner. After 
      4 hours, the highest concentration of 4-HNE (50 micromol/L) produced 100% 
      oligodendrocyte cell death. Data indicate that lipid peroxidation and production 
      of 4-HNE occurs in white matter after cerebral ischemia and the lipid 
      peroxidation by-product 4-HNE is toxic to axons and oligodendrocytes.
FAU - McCracken, E
AU  - McCracken E
AD  - Wellcome Surgical Institute and Hugh Fraser Laboratories. University of Glasgow, 
      Scotland.
FAU - Valeriani, V
AU  - Valeriani V
FAU - Simpson, C
AU  - Simpson C
FAU - Jover, T
AU  - Jover T
FAU - McCulloch, J
AU  - McCulloch J
FAU - Dewar, D
AU  - Dewar D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cereb Blood Flow Metab
JT  - Journal of cerebral blood flow and metabolism : official journal of the 
      International Society of Cerebral Blood Flow and Metabolism
JID - 8112566
RN  - 0 (Aldehydes)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Free Radicals)
RN  - 0 (Neurotoxins)
RN  - K1CVM13F96 (4-hydroxy-2-nonenal)
SB  - IM
MH  - Aldehydes/analysis/*metabolism
MH  - Amyloid beta-Protein Precursor/analysis
MH  - Animals
MH  - Axons/chemistry/metabolism/*pathology
MH  - Brain Ischemia/metabolism/pathology
MH  - Free Radicals/metabolism
MH  - In Vitro Techniques
MH  - Infarction, Middle Cerebral Artery/*metabolism/pathology
MH  - *Lipid Peroxidation
MH  - Male
MH  - Neurotoxins/*metabolism
MH  - Oligodendroglia/chemistry/metabolism/*pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2000/11/18 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/18 11:00
PHST- 2000/11/18 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/18 11:00 [entrez]
AID - 10.1097/00004647-200011000-00002 [doi]
PST - ppublish
SO  - J Cereb Blood Flow Metab. 2000 Nov;20(11):1529-36. doi: 
      10.1097/00004647-200011000-00002.