{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T20:49:37Z","timestamp":1794257377741,"version":"4.9.0"},"reference-count":57,"publisher":"Society for Neuroscience","issue":"36","license":[{"start":{"date-parts":[[2012,3,7]],"date-time":"2012-03-07T00:00:00Z","timestamp":1331078400000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2011,9,7]]},"abstract":"<jats:p>Recurrent seizure activity has been shown to induce a variety of permanent structural changes in the brain. Matrix metalloproteinases (MMPs) function to promote neuronal plasticity, primarily through cleavage of extracellular matrix proteins. Here, we investigated the role of MMP-9 in the development of pentylenetetrazole (PTZ)-induced kindled seizure in mice. Repeated treatment with PTZ (40 mg\/kg) produced kindled seizure, which was accompanied by enhanced MMP-9 activity and expression in the hippocampus. No change in MMP-9 activity was observed in the hippocampi of mice with generalized tonic seizure following single administration of PTZ (60 mg\/kg). MMP-9 colocalized with the neuronal marker NeuN and the glial marker GFAP in the dentate gyrus of the kindled mouse hippocampus. Coadministration of diazepam or MK-801 with PTZ inhibited the development of kindling and the increased MMP-9 levels in the hippocampus. Marked suppression of kindled seizure progression in response to repeated PTZ treatment was observed in MMP-9<jats:sup>(\u2212\/\u2212)<\/jats:sup>mice compared with wild-type mice, an observation that was accompanied by decreased hippocampal levels of mature brain-derived neurotrophic factor. Microinjecting the BDNF scavenger TrkB-Fc into the right ventricle before each PTZ treatment significantly suppressed the development of kindling in wild-type mice, whereas no effect was observed in MMP-9<jats:sup>(\u2212\/\u2212)<\/jats:sup>mice. On the other hand, bilateral injections of pro-BDNF into the hippocampal dentate gyrus significantly enhanced kindling in wild-type mice but not MMP-9<jats:sup>(\u2212\/\u2212)<\/jats:sup>mice. These findings suggest that MMP-9 is involved in the progression of behavioral phenotypes in kindled mice because of conversion of pro-BDNF to mature BDNF in the hippocampus.<\/jats:p>","DOI":"10.1523\/jneurosci.3118-11.2011","type":"journal-article","created":{"date-parts":[[2011,9,7]],"date-time":"2011-09-07T18:54:38Z","timestamp":1315421678000},"page":"12963-12971","source":"Crossref","is-referenced-by-count":182,"title":["Matrix Metalloproteinase-9 Contributes to Kindled Seizure Development in Pentylenetetrazole-Treated Mice by Converting Pro-BDNF to Mature BDNF in the 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