The level of MMP-9 increases in CSF of infant rats with pneumococcal meningitis, and treatment with GM6001 leads to significant reduction in mortality (Leib 2001)

The level of MMP-9 increases in CSF of infant rats with pneumococcal meningitis, and treatment with GM6001 leads to significant reduction in mortality (Leib 2001). results suggest that the PAs and MMP-9 proteolytic cascade may be associated with bloodCCNS barrier disruption in eosinophilic meningitis caused by 2004). The bloodCCNS barrier breakdown assessment using cerebrospinal fluid (CSF) is based on direct or indirect determination of protein permeability across the barrier. The appearance of plasma proteins in CSF is a hallmark of numerous CNS disorders associated with presumed or overt disruption of bloodCCNS barrier (Marchi 2003). Enzymes involved in the degeneration and remodelling of connective tissues include serine proteases, matrix metalloproteinases (MMPs) and cysteine proteases (Murphy & Reynolds 1993). The plasminogen/plasmin system is composed of an inactive proenzyme, plasminogen, that can be converted to plasmin by either of two plasminogen activators (PAs): tissue-type PA (tPA) or urokinase-type PA (uPA) (Vassalii 1991). Plasmin acts as an antithrombotic agent by degrading fibrin but also is able to degrade the extracellular matrix proteins directly or via activation of MMPs (Cuzner & Opdenakker 1999). In experimental models, the participation of PAs in the pathogenesis of inflammatory demyelination in CNS has received scant attention. Nonetheless, there is considerable literature on tPA-induced increases in BBB permeability and deposition of fibrin (Koh 1992). The ability of the uPA to recruit leucocyte and to promote bloodCCNS barrier breakdown may play an important pathophysiological role in bacterial meningitis (Winkler 2002). Additionally, MMPs are up-regulated in bacterial meningitis (Kieseier 1999) and contribute to BBB breakdown (Paul 1998). The CSF eosinophilia can be induced in angiostrongyliasis when the Acetaminophen young adult worms of parasitize the brain of nonpermissive hosts (humans and mice) (Sugaya & Yoshimura 1988; Yoshimura 1988; Sasaki 1993; Yoshimura 1994). The CSF protein levels are elevated in patients with angiostrongyliasis (Yii 1976; Wan & Weng 2004). PAs and MMP-9 contribute to eosinophilic inflammatory reaction observed in the subarachnoid space of the 2004; Lai 2004; Lee 2004). However, whether the expressions of PAs and MMP-9 cause bloodCCNS barrier disruption in parasitic meningitis remains unclear. The purpose of this study was to investigate the correlation between levels of CSF albumin and levels of PAs and MMP-9 in mice with eosinophilic meningitis. Materials and methods Experimental animals The 5-week-old male mice, BALB/c strain, were purchased from the National Laboratory Animal Center, Taipei, Taiwan. Mice were maintained Acetaminophen at a 12:12 h L/D photoperiod, provided with Purina Laboratory Chow and water and kept in our laboratory for more than 1 week before the experimental infection. Larval preparation Third-stage (infective) larvae of were obtained from naturally infected giant African snails, for 10 min. The larvae in the sediment were observed under the microscope. The morphological criteria for identification of the third-stage larvae of have been provided by Ash (1970). The third-stage larvae ranged from 425 to 524 m in length and from hSNFS 23 to 34 m in width. The posterior end of the tail always terminates as a fine point. To confirm that the larvae found were 2002). Animal infection The total 90 mice were randomly allocated to six groups: D0, D5, D10, D15, D20 and D25. Mice were prohibited food and water for 12 h before infection. The Acetaminophen mice of experimental groups (D5, D10, D15, D20 and D25) were infected with 60 larvae by oral inoculation and killed on days 5, 10, 15, 20 and 25 postinoculation (p.i.), respectively. The negative-control mice received only distilled water and killed on day 25 p.i. Collection of CSF-like fluid The mice were killed and their brains removed into a 35-mm dish. The cranial cavity and cerebral ventricles (lateral, third and fourth ventricles) were rinsed with 1 ml of 0.15 m phosphate-buffered saline (PBS) and CSF was thus harvested with PBS, the washing solution so-called CSF-like fluid. The measurement of the total protein and albumin contents The CSF-like fluid was centrifuged at 12,000 at 4 C for 10 min, and the protein contents of the supernatants were determined using protein assay kits (Bio-Rad, Hercules, CA, USA) with Acetaminophen bovine serum albumin serving as the standard. Total.