PMID- 15353213
OWN - NLM
STAT- MEDLINE
DCOM- 20060323
LR  - 20151119
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1022
IP  - 1-2
DP  - 2004 Oct 1
TI  - Necrosis, apoptosis and hybrid death in the cortex and thalamus after barrel 
      cortex ischemia in rats.
PG  - 54-61
AB  - Focal ischemia in the cerebral cortex results in acute and delayed cell death in 
      the ischemic cortex and non-ischemic thalamus. We examined the hypothesis that 
      neurons in ischemic and non-ischemic regions died from different mechanisms; 
      specifically, we tested whether a mixed form of cell death containing both 
      necrotic and apoptotic changes could be identified in individual cells. Focal 
      barrel cortex ischemia in rats was induced by occlusion of small branches of the 
      middle cerebral artery (MCA) corresponding to the barrel cortex, local blood flow 
      was measured by quantitative autoradiography. Cell death was visualized by 
      2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&E) 
      staining, the terminal deoxyribonucleotidyl transferase-mediated dUTP nick end 
      labeling (TUNEL), and caspase-3 staining 1 to 10 days after the ischemia. 
      Electron microscopy was used for ultrastructural examination. Cell death occurred 
      in the ipsilateral cortex 24 h after ischemia, followed by selective neuronal 
      death in the ventrobasal (VB) thalamus 3 days later. TUNEL positive neurons were 
      found in these two regions, but with striking morphological differences, 
      designated as type I and type II TUNEL positive cells. The type I TUNEL positive 
      cells in the ischemic cortex underwent necrotic changes. The type II TUNEL 
      positive cells in the thalamus and the cortex penumbra region represented a 
      hybrid death, featured by concurrent apoptotic and necrotic alterations in 
      individual cells, including marked caspase-3 activation, nuclear 
      condensation/fragmentation, but with swollen cytoplasm, damaged organelles and 
      deteriorated membranes. Cell death in the thalamus and the cortex penumbra were 
      attenuated by delayed administration of the caspase inhibitor 
      benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (Z-VAD-FMK). Our data suggest 
      that TUNEL staining should be evaluated with morphological changes, the hybrid 
      death but not typical apoptosis occurs in the penumbra region and non-ischemic 
      thalamus after cerebral ischemia.
FAU - Wei, Ling
AU  - Wei L
AD  - Department of Neurology, School of Medicine, Washington University, St. Louis, 
      MO, USA.
FAU - Ying, Da-Jun
AU  - Ying DJ
FAU - Cui, Lin
AU  - Cui L
FAU - Langsdorf, Jennifer
AU  - Langsdorf J
FAU - Yu, Shan Ping
AU  - Yu SP
LA  - eng
GR  - NS 37372/NS/NINDS NIH HHS/United States
GR  - NS 42236/NS/NINDS NIH HHS/United States
GR  - NS 45155/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
RN  - 7OL20RET2I (triphenyltetrazolium)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Amino Acid Chloromethyl Ketones/administration & dosage
MH  - Analysis of Variance
MH  - Animals
MH  - Apoptosis/drug effects/*physiology
MH  - Autoradiography/methods
MH  - Brain Ischemia/etiology/*pathology/prevention & control
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cell Count/methods
MH  - Cerebral Cortex/*pathology/ultrastructure
MH  - Functional Laterality
MH  - Infarction, Middle Cerebral Artery/complications/pathology
MH  - Injections, Intraventricular/methods
MH  - Microscopy, Electron/methods
MH  - Necrosis/metabolism/pathology/prevention & control
MH  - Neurons/drug effects/metabolism/*pathology/ultrastructure
MH  - Neuroprotective Agents/administration & dosage
MH  - Rats
MH  - Rats, Wistar
MH  - Regional Blood Flow/physiology
MH  - Staining and Labeling/methods
MH  - Tetrazolium Salts
MH  - Thalamus/*pathology/ultrastructure
MH  - Time Factors
EDAT- 2004/09/09 05:00
MHDA- 2006/03/24 09:00
CRDT- 2004/09/09 05:00
PHST- 2004/06/07 00:00 [accepted]
PHST- 2004/09/09 05:00 [pubmed]
PHST- 2006/03/24 09:00 [medline]
PHST- 2004/09/09 05:00 [entrez]
AID - S0006-8993(04)01072-8 [pii]
AID - 10.1016/j.brainres.2004.06.080 [doi]
PST - ppublish
SO  - Brain Res. 2004 Oct 1;1022(1-2):54-61. doi: 10.1016/j.brainres.2004.06.080.