PMID- 19111539
OWN - NLM
STAT- MEDLINE
DCOM- 20090320
LR  - 20211020
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 216
IP  - 1
DP  - 2009 Mar
TI  - TIMP-3 and MMP-3 contribute to delayed inflammation and hippocampal neuronal 
      death following global ischemia.
PG  - 122-31
LID - 10.1016/j.expneurol.2008.11.022 [doi]
AB  - Hippocampal neuronal death following transient global ischemia in the mouse takes 
      days to occur, providing a potential timeframe for therapeutic intervention. 
      Since matrix metalloproteinase-3 (MMP-3) enhances inflammation and tissue 
      inhibitor of metalloproteinases-3 (TIMP-3) promotes apoptosis in ischemia, we 
      hypothesized that they are involved in neuronal death secondary to transient 
      global ischemia. Timp-3 knockout (T3KO) and wild type (T3WT) mice underwent 30 
      min bilateral carotid artery occlusion (BCAO), which causes hippocampal neuronal 
      death 7 days after reperfusion. Mice lacking the Timp-3 gene have significantly 
      less astrocytosis, microglial reactivity, MMP-3 activity and neuronal cell death. 
      In addition, T3KO mice had decreased tumor necrosis factor (TNF) receptor-1 
      (TNFR1) expression and increased TNF-alpha converting enzyme (TACE) activity. 
      Mmp-3 KO mice with a similar BCAO showed significantly fewer microglial cells, 
      reduced TNF-alpha expression, and less neuronal death than the Mmp-3 WT. To see 
      if TIMP-3 and MMP-3 cell death pathways were independent, we blocked MMPs with 
      the broad-spectrum MMP inhibitor, BB-94, on days 3 through 6 of reperfusion in 
      T3WT and T3KO mice. BB-94 rescued hippocampal neurons at 7 days in both T3WT and 
      T3KO mice, but significantly fewer neurons died in T3KO mice treated with BB-94. 
      Our results indicate a novel additive role for TIMP-3 and MMP-3 in delayed 
      neuronal death, and show that delayed treatment with MMP inhibitors can be used 
      to reduce hippocampal death.
FAU - Walker, Espen J
AU  - Walker EJ
AD  - Department of Neurology, University of New Mexico Health Sciences Center, 
      Albuquerque, NM 87131, USA.
FAU - Rosenberg, Gary A
AU  - Rosenberg GA
LA  - eng
GR  - R01 NS045847/NS/NINDS NIH HHS/United States
GR  - R01 NS045847-04/NS/NINDS NIH HHS/United States
GR  - R01 NS052305/NS/NINDS NIH HHS/United States
GR  - 5R01 NS04547/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20081210
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Thiophenes)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-3)
RN  - 0 (Tnfrsf1a protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 47E5O17Y3R (Phenylalanine)
RN  - BK349F52C9 (batimastat)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (Adam17 protein, mouse)
SB  - IM
MH  - ADAM Proteins/metabolism
MH  - ADAM17 Protein
MH  - Animals
MH  - Apoptosis/drug effects/physiology
MH  - Brain Ischemia/complications/*enzymology/physiopathology
MH  - Disease Models, Animal
MH  - Encephalitis/*enzymology/etiology/physiopathology
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation, Enzymologic/drug effects/genetics
MH  - Gliosis/enzymology/genetics/physiopathology
MH  - Hippocampus/*enzymology/pathology/physiopathology
MH  - Matrix Metalloproteinase 3/*genetics/metabolism
MH  - Matrix Metalloproteinase Inhibitors
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nerve Degeneration/*enzymology/etiology/physiopathology
MH  - Neuroprotective Agents/pharmacology
MH  - Phenylalanine/analogs & derivatives/pharmacology
MH  - Receptors, Tumor Necrosis Factor, Type I/metabolism
MH  - Reperfusion Injury/enzymology/genetics/physiopathology
MH  - Thiophenes/pharmacology
MH  - Tissue Inhibitor of Metalloproteinase-3/*genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC2709713
MID - NIHMS84087
EDAT- 2008/12/30 09:00
MHDA- 2009/03/21 09:00
PMCR- 2010/03/01
CRDT- 2008/12/30 09:00
PHST- 2008/09/03 00:00 [received]
PHST- 2008/11/07 00:00 [revised]
PHST- 2008/11/19 00:00 [accepted]
PHST- 2008/12/30 09:00 [entrez]
PHST- 2008/12/30 09:00 [pubmed]
PHST- 2009/03/21 09:00 [medline]
PHST- 2010/03/01 00:00 [pmc-release]
AID - S0014-4886(08)00444-5 [pii]
AID - 10.1016/j.expneurol.2008.11.022 [doi]
PST - ppublish
SO  - Exp Neurol. 2009 Mar;216(1):122-31. doi: 10.1016/j.expneurol.2008.11.022. Epub 
      2008 Dec 10.