Association of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-4 in cerebrospinal fluid with blood-brain barrier dysfunction in patients with eosinophilic meningitis caused by Angiostrongylus cantonensis

Hung Chin Tsai, Li Yu Chung, Eng Rin Chen, Yung Ching Liu, Susan Shin Jung Lee, Yao Shen Chen, Cheng Len Sy, Shue Ren Wann, Chuan Min Yen

Research output: Contribution to journalArticle

36 Citations (Scopus)

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 (QAlb 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 QAlb values and MMP-9 concentrations in CSF of patients with eosinophilic meningitis, Furthermore, the increase in the QAlb 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 QAlb, 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 QAlb values in patients.

Original languageEnglish
Pages (from-to)20-27
Number of pages8
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume78
Issue number1
Publication statusPublished - Jan 2008
Externally publishedYes

Fingerprint

Angiostrongylus cantonensis
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 9
Blood-Brain Barrier
Meningitis
Cerebrospinal Fluid
Tissue Inhibitor of Metalloproteinase-1
tissue inhibitor of metalloproteinase-4
Tissue Inhibitor of Metalloproteinases
Matrix Metalloproteinase 2
Gelatin
Matrix Metalloproteinases
Leukocyte Count
Serum Albumin

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

Association of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-4 in cerebrospinal fluid with blood-brain barrier dysfunction in patients with eosinophilic meningitis caused by Angiostrongylus cantonensis. / Tsai, Hung Chin; Chung, Li Yu; Chen, Eng Rin; Liu, Yung Ching; Lee, Susan Shin Jung; Chen, Yao Shen; Sy, Cheng Len; Wann, Shue Ren; Yen, Chuan Min.

In: American Journal of Tropical Medicine and Hygiene, Vol. 78, No. 1, 01.2008, p. 20-27.

Research output: Contribution to journalArticle

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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 (QAlb 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 QAlb values and MMP-9 concentrations in CSF of patients with eosinophilic meningitis, Furthermore, the increase in the QAlb 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 QAlb, 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 QAlb values in patients.",
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