PMID- 15082229
OWN - NLM
STAT- MEDLINE
DCOM- 20040622
LR  - 20141120
IS  - 0197-0186 (Print)
IS  - 0197-0186 (Linking)
VI  - 45
IP  - 1
DP  - 2004 Jul
TI  - Spatiotemporal evidence of apoptosis-mediated ischemic injury in organotypic 
      hippocampal slice cultures.
PG  - 117-27
AB  - Oxygen-glucose deprivation (OGD) induced neuron-specific cell death in 
      organotypic hippocampal slice cultures. Neuronal death was first evident in the 
      CA1 region 24 h after the injury as assessed by propidium iodide (PI) labeling, 
      and continued to extend to the CA3/4 region up to 72 h. At 6 days post-OGD, PI 
      labeling was weak and diffuse with no clear demarcation of pyknotic nuclei. To 
      characterize biochemical changes produced by OGD, cellular efflux of three key 
      amino acid neurotransmitters was evaluated. OGD elicited large increases in the 
      release of GABA and aspartate (55- and 4.5-fold increase over basal, 
      respectively), while there were no detectable changes in extracellular glutamate 
      levels. In order to ascertain the existence of the synaptic pool of glutamate, 
      sister cultures were treated with sodium azide. This evoked a strong increase in 
      glutamate release, suggesting the intactness of the glutamate system. Further 
      studies revealed a time-dependent activation of caspase 3 following OGD, shown by 
      immunoblot analysis as well as by confocal laser scanning microscopy. While we 
      did not observe the activation of caspases 1, 2, or 8 in our model, the 
      activation of caspase 9 was evident, peaking at 12 h post-OGD. Despite no 
      apparent increase in glutamate release by ischemic slices, treatment with a 
      N-methyl-D-aspartate (NMDA) antagonist or an 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist 
      significantly reduced neuronal death. Furthermore, a pan-caspase inhibitor 
      (zVAD-fmk), but not the caspase 3 inhibitor (DEVD-fmk), provided partial 
      neuroprotection. Inhibition of a Ca(2+)-dependent cysteine protease, calpain, by 
      MDL28170 also elicited partial neuroprotective effects.
FAU - Cho, Seongeun
AU  - Cho S
AD  - Neuroscience, Wyeth Research, CN 8000, Princeton, NJ 08543, USA. chos1@wyeth.com
FAU - Liu, Danni
AU  - Liu D
FAU - Fairman, Denise
AU  - Fairman D
FAU - Li, Ping
AU  - Li P
FAU - Jenkins, Lorayne
AU  - Jenkins L
FAU - McGonigle, Paul
AU  - McGonigle P
FAU - Wood, Andrew
AU  - Wood A
LA  - eng
PT  - Journal Article
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Neuroprotective Agents)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/*physiology
MH  - Caspases/metabolism
MH  - Cell Death/drug effects/physiology
MH  - Cell Hypoxia/drug effects/physiology
MH  - Hippocampus/drug effects/*metabolism/pathology
MH  - Neuroprotective Agents/pharmacology
MH  - Organ Culture Techniques
MH  - Rats
MH  - Time Factors
EDAT- 2004/04/15 05:00
MHDA- 2004/06/24 05:00
CRDT- 2004/04/15 05:00
PHST- 2003/05/21 00:00 [received]
PHST- 2003/10/20 00:00 [revised]
PHST- 2003/11/19 00:00 [accepted]
PHST- 2004/04/15 05:00 [pubmed]
PHST- 2004/06/24 05:00 [medline]
PHST- 2004/04/15 05:00 [entrez]
AID - S0197018603002729 [pii]
AID - 10.1016/j.neuint.2003.11.012 [doi]
PST - ppublish
SO  - Neurochem Int. 2004 Jul;45(1):117-27. doi: 10.1016/j.neuint.2003.11.012.