PMID- 10929238
OWN - NLM
STAT- MEDLINE
DCOM- 20001207
LR  - 20191025
IS  - 0937-9827 (Print)
IS  - 0937-9827 (Linking)
VI  - 113
IP  - 4
DP  - 2000
TI  - The role of tumor necrosis factor-alpha in diffuse axonal injury following 
      fluid-percussive brain injury in rats.
PG  - 221-8
AB  - The immunolocalization of tumor necrosis factor-alpha (TNF alpha) after diffuse 
      axonal injury (DAI) is demonstrated using a midline fluid percussion rat model 
      (moderate brain injury of 1000 mm Hg was generated) and the effects of TNF alpha 
      on the axolemmal permeability using horseradish peroxidase as a tracer. In 
      addition, the accumulation of beta-amyloid precursor protein (beta-APP) was 
      investigated, which has recently been shown to be a reliable marker for the 
      diagnosis of DAI in cases with fatal head injury. TNF alpha levels in brain 
      tissues from the impact site and the cortex including the corpus callosum, 
      gradually increased during the first 1 h, rose to a maximal elevation at 3 h, 
      gradually decreased at 6 h and decreased further at 24 h. Horseradish peroxidase 
      (HRP) tracer experiments revealed that primary axonal damage appeared as early as 
      15 min after impact but rapidly recovered and that 1 h after impact, secondary 
      axonal damage occurred in the corpus callosum and the brain stem. By 
      immunoelectron microscopy it was seen that beta-APP accumulated in the axon from 
      1 h after impact demonstrating that there was functional axonal damage. TNF alpha 
      reactions were detected in the lysosomes of microglia 30 min after impact and 1 h 
      after impact these reactions were mainly detected in the glial cells (such as 
      microglia, astrocytes and oligodendrocytes) in the corpus callosum and the brain 
      stem. It is generally accepted that TNF alpha directly induces primary 
      demyelination and oligodendrocyte apoptosis. Therefore, TNF alpha conveyed from 
      the microglial cells is one cofactor contributing to the formation of the delayed 
      axonal damage observed at these sites. The present study suggests that TNF alpha 
      conveyed from the glial cells may contribute to the pathogenic mechanism of DAI 
      formation following fluid percussive brain injury.
FAU - Kita, T
AU  - Kita T
AD  - Department of Forensic Medicine, School of Medicine, University of Occupational 
      and Environmental Health, Kitakyushu, Japan. kita@med.uoeh-u.ac.jp
FAU - Tanaka, T
AU  - Tanaka T
FAU - Tanaka, N
AU  - Tanaka N
FAU - Kinoshita, Y
AU  - Kinoshita Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Int J Legal Med
JT  - International journal of legal medicine
JID - 9101456
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Axons/*ultrastructure
MH  - Brain Injuries/metabolism/*physiopathology
MH  - Disease Models, Animal
MH  - Forensic Medicine
MH  - Immunohistochemistry
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Microscopy, Immunoelectron
MH  - Rats
MH  - Rats, Wistar
MH  - Tumor Necrosis Factor-alpha/*physiology
EDAT- 2000/08/10 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/08/10 11:00
PHST- 2000/08/10 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/08/10 11:00 [entrez]
AID - 10.1007/s004149900095 [doi]
PST - ppublish
SO  - Int J Legal Med. 2000;113(4):221-8. doi: 10.1007/s004149900095.