Association of plasminogen activators and matrix metalloproteinase-9 proteolytic cascade with blood-CNS barrier damage of angiostrongyliasis

Int J Exp Pathol. 2006 Apr;87(2):113-9. doi: 10.1111/j.0959-9673.2006.00459.x.

Abstract

Blood-central nervous system (blood-CNS) barrier breakdown, an important pathophysiological event in meningitis, results in extravasation of leucocytes into subarachnoid space. The blood-CNS barrier disruption is mediated by primarily two enzyme systems, the plasminogen activators (PAs) and matrix metalloproteinases (MMPs). The present study showed that the activities of tissue-type PA (tPA), urokinase-type activator (uPA) and MMP-9 in cerebrospinal-like fluid (CSF-like fluid) were significantly increased in mice with eosinophilic meningitis compared with uninfected mice. Eosinophilia significantly correlated with tPA, uPA and MMP-9 activities, and albumin concentration. In addition, when GM6001, a specific matrix metalloproteinase blocker, was injected into infected mice, MMP-9 activity and total protein concentrations declined from their preinjection highs. These results suggest that the PAs and MMP-9 proteolytic cascade may be associated with blood-CNS barrier disruption in eosinophilic meningitis caused by Angiostrongylus cantonensis.

MeSH terms

  • Albumins / cerebrospinal fluid
  • Angiostrongylus cantonensis
  • Animals
  • Blood Proteins / cerebrospinal fluid
  • Blood-Brain Barrier / injuries*
  • Blood-Brain Barrier / microbiology
  • Dipeptides / pharmacology
  • Eosinophilia / blood
  • Eosinophilia / cerebrospinal fluid
  • Eosinophilia / microbiology
  • Eosinophils
  • Leukocyte Count
  • Male
  • Matrix Metalloproteinase 9 / cerebrospinal fluid*
  • Meningitis / blood
  • Meningitis / cerebrospinal fluid*
  • Meningitis / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Plasminogen Activators / cerebrospinal fluid*
  • Protease Inhibitors / pharmacology
  • Strongylida Infections / blood
  • Strongylida Infections / cerebrospinal fluid*
  • Tissue Plasminogen Activator / cerebrospinal fluid
  • Urokinase-Type Plasminogen Activator / cerebrospinal fluid

Substances

  • Albumins
  • Blood Proteins
  • Dipeptides
  • N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
  • Protease Inhibitors
  • Plasminogen Activators
  • Tissue Plasminogen Activator
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinase 9