Endogenous proteolytic activity in a rat model of spontaneous cerebral stroke

Luigi Sironi, Anna Maria Calvio, Stefano Bellosta, Barbara Lodetti, Uliano Guerrini, Mara Monetti, Elena Tremoli, Luciana Mussoni

Research output: Contribution to journalArticlepeer-review


We evaluated the expression of two extra-cellular protease systems in a model of spontaneous cerebrovascular pathology: spontaneously hypertensive stroke-prone rats (SHRSP). The appearance of brain damage in individual animals was imaged and followed by means of magnetic resonance imaging (MRI). In situ zymography of brain slices obtained 3 days after the appearance of brain damage showed an increase in plasminogen activator (PA)/plasmin activity that co-localised with the cerebral damage detected by MRI; there was also concomitant accumulation/activation of inflammatory cells in the damaged area. Proteolytic activity was inhibited by the urokinase-specific inhibitor amiloride but not by an antibody against tissue-type plasminogen activator (t-PA). SDS-PAGE zymography of brain extracts revealed the presence of 58 kDa plasminogen-dependent lysis areas in the ischemic and non-ischemic tissues, and a 33 kDa lysis area in ischemic tissue only. An antibody against t-PA inhibited the former, whereas the latter was inhibited by amiloride. The specific induction of urokinase-type plasminogen activator (u-PA) in the damaged tissue was further confirmed by the fact that both u-PA protein mass and mRNA were markedly increased in the damaged cerebral areas. Concomitant metalloproteinase-2 (MMP-2) activation was only observed in the damaged area. These data suggest that u-PA is expressed and selectively catalyses proteolysis in the injured area of spontaneous brain damage in SHRSP.

Original languageEnglish
Pages (from-to)184-192
Number of pages9
JournalBrain Research
Issue number1-2
Publication statusPublished - Jun 6 2003


  • Cerebral ischemia
  • Magnetic resonance imaging
  • Matrix metalloproteinase
  • Plasminogen activator
  • Stroke-prone rat
  • Urokinase

ASJC Scopus subject areas

  • Neuroscience(all)


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