Brain regional and cellular localization of gelatinase activity in rat that have undergone transient middle cerebral artery occlusion

D. Amantea, M. T. Corasaniti, N. B. Mercuri, G. Bernardi, G. Bagetta

Research output: Contribution to journalArticle

Abstract

Matrix metalloproteinases (MMPs) have been implicated in the pathophysiology of ischemic stroke. In particular, the gelatinases MMP-2 and MMP-9 contribute to disruption of the blood-brain barrier and hemorrhagic transformation following ischemic injury. In addition to extracellular matrix degradation, MMPs may directly regulate neuronal cell death through mechanisms that are not completely understood. Here we describe the spatio-temporal distribution of activated MMP-2 and MMP-9 in the brain of rats subjected to 2 h middle cerebral artery occlusion (MCAo) followed by different periods of reperfusion (15 min, 2 h, 6 h and 22 h). By in situ zymography we have observed that gelatinases become activated 15 min and 2 h after the beginning of reperfusion in the ischemic core and penumbra, respectively. In situ zymography signal broadly co-localized with NeuN-positive cells, thus suggesting that proteolysis mainly occurs in neurons. Gelatinolytic activity was mainly detected in cell nuclei, marginally appearing in the cytosol only at later stages following the insult; we did not detect variations in gelatinolysis in the extracellular matrix. Finally, we report that pharmacological inhibition of MMPs by N-[(2R)-2-(hydroxamidocarbonylmethyl)-4-methylpenthanoyl]-l-tryptophan methylamide (GM6001) significantly reduces brain infarct volume induced by transient MCAo. Taken together our data underscore the crucial role of gelatinases during the early stages of reperfusion and further extend previous observations documenting the detrimental role of these enzymes in the pathophysiology of brain ischemia.

Original languageEnglish
Pages (from-to)8-17
Number of pages10
JournalNeuroscience
Volume152
Issue number1
DOIs
Publication statusPublished - Mar 3 2008

Fingerprint

Gelatinases
Middle Cerebral Artery Infarction
Matrix Metalloproteinases
Reperfusion
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Extracellular Matrix
Brain
Brain Ischemia
Blood-Brain Barrier
Cell Nucleus
Tryptophan
Cytosol
Proteolysis
Cell Death
Stroke
Pharmacology
Neurons
Wounds and Injuries
Enzymes

Keywords

  • GM6001
  • in situ zymography
  • matrix metalloproteinases
  • neuroinflammation
  • reperfusion injury
  • stroke

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Brain regional and cellular localization of gelatinase activity in rat that have undergone transient middle cerebral artery occlusion. / Amantea, D.; Corasaniti, M. T.; Mercuri, N. B.; Bernardi, G.; Bagetta, G.

In: Neuroscience, Vol. 152, No. 1, 03.03.2008, p. 8-17.

Research output: Contribution to journalArticle

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