PMID- 14511330
OWN - NLM
STAT- MEDLINE
DCOM- 20031205
LR  - 20220317
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 18
IP  - 6
DP  - 2003 Sep
TI  - Neuronal activity-dependent increase of net matrix metalloproteinase activity is 
      associated with MMP-9 neurotoxicity after kainate.
PG  - 1507-17
AB  - Matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs) are 
      emerging as important modulators of brain physiopathology. Dramatic changes in 
      the expression of MMPs and TIMPs occur during excitotoxic/neuroinflammatory 
      processes. However, only the measurement of net protease activity is relevant 
      physiologically, and the functional consequences of MMP/TIMP ratio modifications 
      in the brain remain elusive. In order to assess MMP activity and effects in brain 
      tissue, we combined in vivo and organotypic culture models of kainate 
      (KA)-induced excitotoxicity to provoke selective neuronal death and 
      neuroinflammation in the hippocampus. Using in situ zymography, we show that 
      KA-induced excitotoxic seizures in rats increase net MMP activity in hippocampal 
      neurons 8 h after seizures, before their death, and that this increase is 
      neuronal activity-dependent. Three days after KA, proteolytic activity increases 
      in blood vessels and reactive glial cells of vulnerable areas, in relation with 
      neuroinflammation. At 7 and 15 days, proteolysis remains high in blood vessels 
      whereas it is reduced in glia. In organotypic hippocampal cultures, which lack 
      blood cell-mediated inflammation and extrinsic connections, a broad-spectrum 
      inhibitor of MMPs (MMPI), but also a selective MMP-9 inhibitor, protect 
      hippocampal neurons against KA-induced excitotoxicity. Moreover, recombinant 
      MMP-9, but not MMP-2, induces selective pyramidal cell death in these cultures 
      and KA-induced neuronal activity exacerbates the neuronal death promoting effects 
      of MMP-9. These data strongly implicate MMPs, and MMP-9 in particular, in both 
      excitotoxic neuronal damage and subsequent neuroinflammatory processes, and 
      suggest that selective MMPIs could be therapeutically relevant in related 
      neurological disorders.
FAU - Jourquin, Jerome
AU  - Jourquin J
AD  - Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, CNRS FRE 
      2533. IFR Jean Roche. Universite de la Mediterranee. Faculte de Medecine de 
      Marseille, 27 Bd. Jean Moulin 13385, Marseille cedex 05, France.
FAU - Tremblay, Evelyne
AU  - Tremblay E
FAU - Decanis, Nadege
AU  - Decanis N
FAU - Charton, Gerard
AU  - Charton G
FAU - Hanessian, Stephen
AU  - Hanessian S
FAU - Chollet, Anne-Marie
AU  - Chollet AM
FAU - Le Diguardher, Thierry
AU  - Le Diguardher T
FAU - Khrestchatisky, Michel
AU  - Khrestchatisky M
FAU - Rivera, Santiago
AU  - Rivera S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antigens, Surface)
RN  - 0 (Avian Proteins)
RN  - 0 (Blood Proteins)
RN  - 0 (Bsg protein, Gallus gallus)
RN  - 0 (Bsg protein, rat)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (GABA Modulators)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Phenanthrolines)
RN  - 0 (Phenylmercury Compounds)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 136894-56-9 (Basigin)
RN  - 3550-44-5 (4-aminophenylmercury chloride)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - Q3JTX2Q7TU (Diazepam)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Animals
MH  - *Antigens, CD
MH  - *Antigens, Neoplasm
MH  - *Antigens, Surface
MH  - *Avian Proteins
MH  - Basigin
MH  - *Blood Proteins
MH  - Blood Vessels/metabolism
MH  - Cell Count
MH  - Cell Death/drug effects
MH  - Diazepam/pharmacology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Encephalitis/*enzymology
MH  - Excitatory Amino Acid Agonists/*toxicity
MH  - GABA Modulators/pharmacology
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Hippocampus/drug effects/metabolism/pathology
MH  - Immunohistochemistry
MH  - Kainic Acid/*toxicity
MH  - Male
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Matrix Metalloproteinases/*metabolism
MH  - Membrane Glycoproteins/metabolism
MH  - Neuroglia/drug effects/metabolism
MH  - Neurons/*drug effects/enzymology
MH  - Organ Culture Techniques
MH  - Phenanthrolines/pharmacology
MH  - Phenylmercury Compounds/pharmacology
MH  - Protease Inhibitors/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Seizures/chemically induced/enzymology/*metabolism
MH  - Time Factors
MH  - Tissue Inhibitor of Metalloproteinase-1/pharmacology
EDAT- 2003/09/27 05:00
MHDA- 2003/12/06 05:00
CRDT- 2003/09/27 05:00
PHST- 2003/09/27 05:00 [pubmed]
PHST- 2003/12/06 05:00 [medline]
PHST- 2003/09/27 05:00 [entrez]
AID - 2876 [pii]
AID - 10.1046/j.1460-9568.2003.02876.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2003 Sep;18(6):1507-17. doi: 10.1046/j.1460-9568.2003.02876.x.