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Gelatinase B and TIMP‐1 are regulated in a cell‐ and time‐dependent manner in association with neuronal death and glial reactivity after global forebrain ischemia
Author(s) -
Rivera Santiago,
Ogier Crystel,
Jourquin Jérôme,
Timsit Serge,
Szklarczyk Arkadius W.,
Miller Karen,
Gearing Andrew J. H.,
Kaczmarek Leszek,
Khrestchatisky Michel
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2001.01838.x
Subject(s) - gelatinase a , matrix metalloproteinase , microbiology and biotechnology , neuroinflammation , biology , gelatinase , astrocyte , extracellular matrix , neuroscience , central nervous system , immunology , inflammation , biochemistry
Matrix metalloproteinases (MMPs) belong to a large family of endopeptidases that regulate the pericellular environment through the cleavage of protein components of the extracellular matrix, membrane receptors and cytokines. MMP activity is controlled by the multifunctional tissue inhibitors of metalloproteinases (TIMPs). Proteases and their inhibitors are critically involved in developmental and pathological processes in numerous organs, including the brain. Global transient cerebral ischemia induces selective delayed neuronal death and neuroinflammation. We compared, in discrete vulnerable and resistant areas of the ischemic rat hippocampus, the kinetics and cellular distribution of gelatinase B and its principal inhibitor TIMP‐1 and we assessed by in situ zymography, the net gelatinolytic activity at the cellular level. We show that gelatinases are expressed and active in neurons, suggesting that MMPs play a role in maintaining neural homeostasis. In the ischemic rat brain, expression and activity of gelatinase B, and expression of TIMP‐1 are altered in a time‐, region‐ and cell‐dependent manner. Gelatinase B is induced first in reactive microglia and subsequently in reactive astrocytes. In situ , increases in gelatinase activity accompanied the progression of neuronal death and glial reactivity. Our results suggest that MMPs and TIMPs are involved in cell viability and tissue remodelling in the ischemic brain, and reinforces the idea that the MMP/TIMP system contributes both to neuronal demise and tissue repair in the context of glial reactivity.