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2.
Am J Trop Med Hyg ; 78(1): 20-7, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18187780

ABSTRACT

To evaluate possible blood-brain barrier (BBB) dysfunction caused by matrix metalloproteinase-9 (MMP-9) and its regulation by tissue inhibitors of metalloproteinase (TIMPs) in patients with eosinophilic meningitis caused by infection with Angiostrongylus cantonensis, 40 patients and 28 controls were included in this study. Concentrations of MMP-2, MMP-9, TIMP-1, and cerebrospinal fluid (CSF):serum albumin ratios (Q(Alb) values) were significantly increased in patients compared with controls. However, concentrations of TIMP-4 were significantly lower in patients. In contrast to MMP-2, proteolytic activity of MMP-9 detected by gelatin zymography was only observed in patients with eosinophilic meningitis. We detected higher levels of antibodies specific for A. cantonensis and higher Q(Alb) values and MMP-9 concentrations in CSF of patients with eosinophilic meningitis, Furthermore, the increase in the Q(Alb) value was significantly correlated with the increase in MMP-9 in patients. In parallel with CSF MMP-9, patients also showed an increase in CSF leukocyte counts. Gradual decreases in levels of Q(Alb), MMP-9, and TIMP-1 and increases in levels of TIMP-4 were observed in six patients during recovery from eosinophilic meningitis. These results suggest that the source of MMP-9 in CSF of patients with eosinophilic meningitis was probably associated with leukocytes migrating from peripheral blood to CSF. Activity of MMP-9 in CSF of patients could not be completely inhibited because of the decrease of TIMP-4, which may cause BBB dysfunction, as shown by higher Q(Alb) values in patients.


Subject(s)
Angiostrongylus cantonensis , Central Nervous System Helminthiasis/cerebrospinal fluid , Matrix Metalloproteinase 9/cerebrospinal fluid , Strongylida Infections/cerebrospinal fluid , Tissue Inhibitor of Metalloproteinases/cerebrospinal fluid , Animals , Antibodies/blood , Blood-Brain Barrier/physiopathology , Case-Control Studies , Central Nervous System Helminthiasis/blood , Central Nervous System Helminthiasis/physiopathology , Enzyme-Linked Immunosorbent Assay , Eosinophilia/cerebrospinal fluid , Eosinophilia/parasitology , Eosinophilia/pathology , Humans , Serum Albumin , Strongylida Infections/blood , Strongylida Infections/physiopathology , Tissue Inhibitor of Metalloproteinase-4
3.
Int J Exp Pathol ; 86(2): 81-9, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15810979

ABSTRACT

Proteolysis depends on the balance between the proteases and their inhibitors. Matrix metalloproteinase-9 (MMP-9) and its specific inhibitors, tissue inhibitors of metalloproteinases (TIMP), contribute to eosinophilic inflammatory reaction in the subarachnoid space of the Angiostrongylus cantonensis-infected mice. The expression of MMP-9 in cerebrospinal fluid (CSF) was significantly increased in mice with eosinophilic meningitis, compared to that in uninfected ones. However, the TIMP-1 levels were unchanged and remained at basal levels at all time points, even in uninfected mice. Elevated MMP-9 mRNA expression coincided with protein levels and proteolytic activity, as demonstrated by means of positive immunoreactivity and gelatin zymography. CSF protein contents correlated significantly with MMP-9 intensity and CSF eosinophilia. In addition, immunohistochemistry demonstrated MMP-9 and TIMP-1 localization in eosinophils and macrophages. When the specific MMP inhibitor, GM6001, was added, MMP-9 enzyme activity was reduced by 45.4%. The percentage of eosinophil increased significantly upon the establishment of infection, but subsided upon inhibition. These results show that MMP-9/TIMP-1 imbalance in angiostrongyliasis may be associated with eosinophilic meningitis.


Subject(s)
Angiostrongylus cantonensis , Central Nervous System Helminthiasis/cerebrospinal fluid , Matrix Metalloproteinase 9/cerebrospinal fluid , Meningitis/cerebrospinal fluid , Strongylida Infections/cerebrospinal fluid , Animals , Blotting, Western , Central Nervous System Helminthiasis/pathology , Eosinophilia/cerebrospinal fluid , Eosinophilia/parasitology , Eosinophilia/pathology , Male , Matrix Metalloproteinase 9/genetics , Meningitis/parasitology , Meningitis/pathology , Mice , Mice, Inbred BALB C , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Strongylida Infections/pathology , Subarachnoid Space/pathology , Tissue Inhibitor of Metalloproteinase-1/cerebrospinal fluid , Tissue Inhibitor of Metalloproteinase-1/genetics , Up-Regulation
4.
Int J Parasitol ; 34(12): 1355-64, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15542096

ABSTRACT

A hallmark of parasitic meningitis is the infiltration of eosinophils into the subarachnoid space. Infection with Angiostrongylus cantonensis in mice induced proteinase activity in parallel with the pathological changes of eosinophilic meningitis. Zymogram analysis demonstrated that 70 and 55 kDa proteinases from cerebrospinal fluid (CSF) were active against the casein/plasminogen substrate. The proteinase activities were clearly inhibited by phenylmethanesulphonyl fluoride but not by ethylenediamine tetraacetic acid, 1,10-phenanthroline or leupeptin. Western blotting confirmed these enzymes to be tissue-type plasminogen activator and urokinase-type plasminogen activator, respectively. High activities of tissue-type plasminogen activator and urokinase-type plasminogen activator were detected in the CSF of mice with eosinophilic meningitis, and correlated positively with CSF eosinophil numbers and total protein, respectively. Immunohistochemistry demonstrated that tissue-type plasminogen activator and urokinase-type plasminogen activator localised in the endothelial cells of blood vessels, in blood clots and in infiltrated leukocytes. These results suggest that tissue-type plasminogen activator and urokinase-type plasminogen activator may be play a role in the pathogenesis of eosinophilic meningitis of angiostrongyliasis.


Subject(s)
Angiostrongylus cantonensis , Central Nervous System Helminthiasis/cerebrospinal fluid , Meningitis/cerebrospinal fluid , Meningitis/pathology , Plasminogen Activators/cerebrospinal fluid , Strongylida Infections/cerebrospinal fluid , Animals , Blood-Brain Barrier , Blotting, Western/methods , Central Nervous System Helminthiasis/parasitology , Eosinophilia , Immunohistochemistry/methods , Larva , Male , Mice , Mice, Inbred BALB C , Microscopy, Electron , Microscopy, Electron, Scanning , Plasminogen Activator Inhibitor 1/cerebrospinal fluid , Plasminogen Activator Inhibitor 1/genetics , Plasminogen Activators/genetics , Random Allocation , Reverse Transcriptase Polymerase Chain Reaction , Strongylida Infections/pathology , Tissue Plasminogen Activator/cerebrospinal fluid , Tissue Plasminogen Activator/genetics , Urokinase-Type Plasminogen Activator/cerebrospinal fluid , Urokinase-Type Plasminogen Activator/genetics
5.
Ceylon Med J ; 44(4): 173-4, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10895269

ABSTRACT

A case of eosinophilic meningitis is reported, a condition not previously reported from Sri Lanka. We propose Angiostrongylus cantonesis to be the most likely causative agent in this patient.


Subject(s)
Angiostrongylus cantonensis , Central Nervous System Helminthiasis/diagnosis , Central Nervous System Helminthiasis/parasitology , Eosinophilia , Meningitis/diagnosis , Meningitis/parasitology , Adult , Animals , Central Nervous System Helminthiasis/cerebrospinal fluid , Diagnosis, Differential , Eosinophilia/blood , Eosinophilia/cerebrospinal fluid , Humans , Male , Meningitis/cerebrospinal fluid , Spinal Puncture
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