Regional expression of gelatinases in the central nervous system of excitotoxin-treated rats

Evidence suggest that extracellular matrix (ECM)-ECM receptor interaction is critical for cell survival. Degradation of ECM and interruption of the interaction in the CNS make neurons vulnerable to injurous insults. The purpose of these studies was to assess the expression of two ECM-degrading enzymes, the matrix metalloproteinase 2 (MMP-2) and MMP-9, in a animal model of neuronal degeneration where kainate was administered to induced a well-characterized lesion in limbic brain areas. A Triton X-100 extraction and affinity-support purification method was developed to measure MMP-2 and MMP-9 activity from regional brain tissue. MMP-2 and MMP-9 were found to be differentially distributed in untreated rat brain regions with the highest activity in the hippocampus and the lowest in cerebellum, although basal MMP-2 activity was expressed at 10-fold greater levels compared with MMP-9.; After kainate treatment in Sprague-Dawley rats, MMP-9 and MMP-2 were differentially induced in kainate-sensitive brain regions, with an early elevation of MMP-9 activity (6-24 h) and a late elevation of MMP-2 activity (72 h). In addition, induction of latent, proenzymes of the MMPs was followed by appearance of corresponding, low molecular weight forms, indicating that potentially active enzymes were generated. Treatment with bicuculline, a GABA{dollar}rmsb{lcub}A{rcub}{dollar} receptor antagonist that induces seizure but does not result in neuronal degeneration, only transiently stimulated MMP-9 activity in hippocampus. Content of glial fibrillary acidic protein was elevated in brain regions where MMP-2 was induced.; Because certain inflammatory markers are overexpressed in the brain of aged rats, and MMPs are classical markers of inflammation, it was of interest to characterize MMP-2 and MMP-9 expression in young and old F344/BN rats after administration of kainate. Old rats were significantly more vulnerable to the neurotoxin, although animals in both age group displayed similar limbic seizure behavior. The extent of the hippocampal lesion was not different between young and old rats. The induction profiles for both MMPs followed the patterns seen in Sprague-Dawley rats. With the exception of increased MMP-9 production in the amygdal/intorhinal cortex of old rats, the magnitude of MMP induction did not differ between young and rats. Staining of laminin-1 disappeared 3 day after kainate in brain regions with neuronal degeneration. However, laminin immunoreactivity was markedly overexpressed in cells in the temporal lobe of young rats 16 days after kainate treatment.; These data demonstrate that MMP-9 and MMP-2 are differentially expressed with respect to time after kainate injection and suggest that they are regulated by convulsion and/or neurodegenerative-associated mechanisms, respectively. Although similar in catalytic activity, MMP-9 and MMP-2 may play different roles in response to kainate-induced seizure and neuronal degeneration.