PMID- 12322783
OWN - NLM
STAT- MEDLINE
DCOM- 20030310
LR  - 20191106
IS  - 0885-7490 (Print)
IS  - 0885-7490 (Linking)
VI  - 17
IP  - 3
DP  - 2002 Sep
TI  - Similar time-course of interleukin-1 beta production and 
      extracellular-signal-regulated kinase (ERK) activation in permanent focal brain 
      ischemic injury.
PG  - 131-8
AB  - The present study investigated the activation of extracellular-signal-regulated 
      kinase (ERK) and the potential role of interleukin-1 beta (IL-1beta) in the 
      brain's response to focal brain ischemia in the permanent middle cerebral artery 
      occlusion (pMCAO) model. Phosphorylated ERK p44 and p42 were increased 
      time-dependently and significantly 18- and 28-fold, respectively, at 24-h 
      post-pMCAO. Similarly, IL-1beta protein levels were significantly increased with 
      the peak at 24 h in the lesioned core of the ischemic hemisphere compared to the 
      contralateral side. Previous studies using various stimuli have shown 
      ERK-dependent IL-1 induction. The results from our study suggest that this 
      relation may also exist in vivo in ischemic brain tissue. Based on the 
      progressive nature of IL-1 induction, we hypothetized that inhibition of 
      interleukin-converting enzyme (ICE) could provide an extended time-window for 
      neuroprotection. Therefore, we applied 
      N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD x fmk), an ICE blocker 3 
      or 6 h after pMCAO. Reductions of infarct volume, however, were not observed. 
      Taken together with previous results, where we showed protective activity of zVAD 
      x fmk when given immediately after pMCAO, we conclude that the time window for 
      zVAD x fmk is less than 3 h.
FAU - Skifter, Donald A
AU  - Skifter DA
AD  - Department of Pharmacology, Nebraska Medical Center, Omaha, USA.
FAU - Allegrini, Peter R
AU  - Allegrini PR
FAU - Wiessner, Christoph
AU  - Wiessner C
FAU - Mir, Anis K
AU  - Mir AK
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Metab Brain Dis
JT  - Metabolic brain disease
JID - 8610370
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Interleukin-1)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - Animals
MH  - Brain Ischemia/enzymology/*metabolism
MH  - Caspase 1/metabolism
MH  - Caspase Inhibitors
MH  - Enzyme Activation/physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Immunoblotting
MH  - Infarction, Middle Cerebral Artery/metabolism/pathology
MH  - Interleukin-1/*antagonists & inhibitors/*biosynthesis
MH  - *JNK Mitogen-Activated Protein Kinases
MH  - Kinetics
MH  - Ligation
MH  - MAP Kinase Kinase 4
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Cerebral Artery/physiology
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Rats
MH  - Rats, Inbred F344
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2002/09/27 06:00
MHDA- 2003/03/11 04:00
CRDT- 2002/09/27 06:00
PHST- 2002/09/27 06:00 [pubmed]
PHST- 2003/03/11 04:00 [medline]
PHST- 2002/09/27 06:00 [entrez]
AID - 10.1023/a:1019917803470 [doi]
PST - ppublish
SO  - Metab Brain Dis. 2002 Sep;17(3):131-8. doi: 10.1023/a:1019917803470.