PMID- 9332715
OWN - NLM
STAT- MEDLINE
DCOM- 19980217
LR  - 20190826
IS  - 0169-328X (Print)
IS  - 0169-328X (Linking)
VI  - 48
IP  - 2
DP  - 1997 Sep
TI  - Global cerebral ischemia activates nuclear factor-kappa B prior to evidence of 
      DNA fragmentation.
PG  - 187-96
AB  - The oxidative stress responsive transcription factor nuclear factor-kappa B 
      (NF-kappa B) consists of a p50 (50 kDa) and p65/RelA (65 kDa) component and can 
      be activated in vitro by TNF alpha, IL1 beta, hydrogen peroxide and oxygen 
      radicals. All of the above factors are also known to be elevated at certain times 
      after transient global ischemia. The present study was performed to determine if 
      NF-kappa B was activated in vivo by transient global forebrain ischemia. Adult 
      male rats were subjected to 30 min of 4-vessel occlusion (4-VO) and sacrificed at 
      selected post-ischemic time points. Levels of NF-kappa B p50 and p65 subunits 
      were determined by immunocytochemistry, Western blot and electrophoretic 
      mobility-shift analysis. The enhancer complex was also confirmed by 
      immuno-gel-shift analysis. Specific labeling of DNA strand breaks and DNA 
      fragmentation was examined in situ by means of the terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) method. Western blot analysis 
      of hippocampus showed induction of p50 and p65. A time course of NF-kappa B 
      induction in hippocampus showed a p50-specific band at 6 h that increased in 
      intensity over 12, 48 h and then decreased by 96 h post-ischemia. 
      Immunocytochemistry revealed at 24 h post-ischemia that p65 and p50 
      immunoreactivity was present in neuronal nuclei of hippocampal CA1 neurons as 
      well as all other hippocampal regions and several other forebrain regions which 
      were not vulnerable to transient forebrain ischemia. At 72 h post-ischemia, 
      nuclear NF-kappa B immunoreactivity had disappeared in all brain areas except in 
      hippocampal CA1 neurons which were degenerating. No evidence for DNA 
      fragmentation as revealed by TUNEL staining could be observed at 24 h. However, 
      at 72 h, hippocampal CA1 neurons were heavily labeled. The results of this study 
      demonstrate that global forebrain ischemia causes a transient activation of 
      NF-kappa B in many forebrain regions. NF-kappa B remains persistently activated 
      in the vulnerable hippocampal CA1 sector. Because of the persistent activation of 
      NF-kappa B in these neurons, the possibility exists that NF-kappa B has a role in 
      programmed cell death in hippocampal CA1 neurons.
FAU - Clemens, J A
AU  - Clemens JA
AD  - Lilly Research Laboratories, Eli Lilly and Co., CNS Division, Indianapolis, IN 
      46285, USA.
FAU - Stephenson, D T
AU  - Stephenson DT
FAU - Dixon, E P
AU  - Dixon EP
FAU - Smalstig, E B
AU  - Smalstig EB
FAU - Mincy, R E
AU  - Mincy RE
FAU - Rash, K S
AU  - Rash KS
FAU - Little, S P
AU  - Little SP
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Brain Res Mol Brain Res
JT  - Brain research. Molecular brain research
JID - 8908640
RN  - 0 (NF-kappa B)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Blotting, Western
MH  - Brain Ischemia/*metabolism
MH  - *DNA Fragmentation
MH  - Electrophoresis/methods
MH  - Hippocampus/cytology
MH  - Immunohistochemistry
MH  - Male
MH  - NF-kappa B/*metabolism
MH  - Neurons/physiology
MH  - Rats
MH  - Rats, Wistar
EDAT- 1997/10/23 00:00
MHDA- 1997/10/23 00:01
CRDT- 1997/10/23 00:00
PHST- 1997/10/23 00:00 [pubmed]
PHST- 1997/10/23 00:01 [medline]
PHST- 1997/10/23 00:00 [entrez]
AID - S0169328X97000922 [pii]
AID - 10.1016/s0169-328x(97)00092-2 [doi]
PST - ppublish
SO  - Brain Res Mol Brain Res. 1997 Sep;48(2):187-96. doi: 
      10.1016/s0169-328x(97)00092-2.