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

Summary 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 .