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

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.

Encephalitis Caused by Angiostrongylus cantonensis after Eating Raw Frogs Mixed with Wine as a Health Supplement

“…The brain pathological findings in patients infected with A. cantonensis includes meningitis with a predominance of eosinophils and plasma cells, tortuous tracks of various sizes in the brain and spinal cord surrounded by an inflammatory reaction and degenerating neurons, granulomatous response to the dead parasites, and nonspecific vascular reactions including thrombosis, rupture of vessels, arteritis, and aneurysm formation (19). Animal studies in mice have shown that plasminogen activators and matrix metalloproteinase -9 proteolytic cascade may be associated with blood-CNS barrier disruption in eosinophilic meningitis caused by A. cantonensis (20). Albendazole and dexamethasone co-therapy was reported to significantly decrease plasminogen activators after treatment on day 5 post-inoculation (21).…”

Matrix metalloproteinase-9 leads to blood–brain barrier leakage in mice with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis

“…Matrix metalloproteinase (MMP)-9 activity is associated with blood-CNS barrier disruption in mice with eosinophilic meningitis caused by A. cantonensis (Chen et al, 2006). In cerebral malaria, human endothelium is exposed to Plasmodium falciparum, which leads to blood-brain barrier (BBB) damage by MMP-9 (Prato et al, 2011).…”

Matrix Metalloproteinase-9 Leads to Claudin-5 Degradation via the NF-κB Pathway in BALB/c Mice with Eosinophilic Meningoencephalitis Caused by Angiostrongylus cantonensis

“…Matrix metalloproteinase (MMP)-9 activity is closely associated with angiostrongyliasis meningitis caused by infection with A. cantonensis [4], [5]. This enzyme is associated with disruption of the blood-CNS barrier in mice with angiostrongyliasis meningitis and triggers increased cellular infiltration of the subarachnoid space [6].…”