title: 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.
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.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital 386, Kaohsiung City, Taiwan, Republic of China.
authors.forename: Hung-Chin
authors.initials: HC
authors.lastname: Tsai
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Chung
authors.forename: Eng-Rin
authors.initials: ER
authors.lastname: Chen
authors.forename: Yung-Ching
authors.initials: YC
authors.lastname: Liu
authors.forename: Susan Shin-Jung
authors.initials: SS
authors.lastname: Lee
authors.forename: Yao-Shen
authors.initials: YS
authors.lastname: Chen
authors.forename: Cheng-Len
authors.initials: CL
authors.lastname: Sy
authors.forename: Shue-Ren
authors.initials: SR
authors.lastname: Wann
authors.forename: Chuan-Min
authors.initials: CM
authors.lastname: Yen
mesh_terms: D017185:Angiostrongylus cantonensis; D000818:Animals; D000906:Antibodies / Q000097:blood; D001812:Blood-Brain Barrier / Q000503:physiopathology; D016022:Case-Control Studies; D020809:Central Nervous System Helminthiasis / Q000097:blood / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D004802:Eosinophilia / Q000134:cerebrospinal fluid / Q000469:parasitology / Q000473:pathology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid*; D012709:Serum Albumin; D017206:Strongylida Infections / Q000097:blood / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D019714:Tissue Inhibitor of Metalloproteinases / Q000134:cerebrospinal fluid*; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D000906:Antibodies; D020780:Matrix Metalloproteinase 9; D012709:Serum Albumin; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4