Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Enhanced cerebrovascular expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 via the MEK/ERK pathway during cerebral ischemia in the rat

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. The significance of anti-neuronal antibodies for acute psychiatric disorders: a retrospective case-controlled study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Early events triggering delayed vasoconstrictor receptor upregulation and cerebral ischemia after subarachnoid hemorrhage

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. MAPK signaling pathway regulates cerebrovascular receptor expression in human cerebral arteries

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Transcranial magnetic stimulation with a half-sine wave pulse elicits direction-specific effects in human motor cortex

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Does inflammation have a role in migraine?

    Research output: Contribution to journalReviewResearchpeer-review

  2. The changing faces of migraine

    Research output: Contribution to journalEditorialResearchpeer-review

  3. Some aspects on the pathophysiology of migraine and a review of device therapies for migraine and cluster headache

    Research output: Contribution to journalReviewResearchpeer-review

  4. CGRP receptor antagonist MK-8825 attenuates cortical spreading depression induced pain behavior

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations
BACKGROUND: Cerebral ischemia is usually characterized by a reduction in local blood flow and metabolism and by disruption of the blood-brain barrier in the infarct region. The formation of oedema and opening of the blood-brain barrier in stroke is associated with enhanced expression of metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). RESULTS: Here, we found an infarct volume of 24.8 +/- 2% and a reduced neurological function after two hours of middle cerebral artery occlusion (MCAO), followed by 48 hours of recirculation in rat. Immunocytochemistry and confocal microscopy revealed enhanced expression of MMP-9, TIMP-1, and phosphorylated ERK1/2 in the smooth muscle cells of the ischemic MCA and associated intracerebral microvessels. The specific MEK1/2 inhibitor U0126, given intraperitoneal zero or 6 hours after the ischemic event, reduced the infarct volume significantly (11.8 +/- 2% and 14.6 +/- 3%, respectively; P <0.05), improved neurological function, normalized expression of phosphorylated ERK1/2, and reduced expression of MMP-9 and TIMP-1 in the vessel walls. Administration of U0126 12 hours after MCAO did not alter the expression of MMP-9. Immunocytochemistry showed no overlap in expression between MMP-9/TIMP-1 and the astrocyte/glial cell marker GFAP in the vessel walls. CONCLUSION: These data are the first to show that the elevated vascular expression of MMP-9 and TIMP-1, associated with breakdown of the blood-brain barrier following focal ischemia, are transcriptionally regulated via the MEK/ERK pathway.
Original languageEnglish
JournalB M C Neuroscience
Volume10
Pages (from-to)56
ISSN1471-2202
DOIs
Publication statusPublished - 1 Jan 2009

    Research areas

  • Actins, Animals, Astrocytes, Brain Infarction, Butadienes, Disease Models, Animal, Extracellular Signal-Regulated MAP Kinases, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Infarction, Middle Cerebral Artery, MAP Kinase Kinase Kinases, Male, Matrix Metalloproteinase 1, Matrix Metalloproteinase 9, Microvessels, Muscle, Smooth, Neurologic Examination, Nitriles, Rats, Rats, Wistar, Signal Transduction, Tetrazolium Salts, Tissue Inhibitor of Metalloproteinase-1

ID: 30970095