| Summary: | 博士 === 國立陽明大學 === 熱帶醫學研究所 === 96 === Infection by Toxocara canis in humans may cause cerebral toxocariasis (CT). Appreciable numbers of T. canis larvae cross the blood-brain barrier (BBB) to invade the brain causing injury thus resulting in CT. In the present studies, we evaluated the BBB permeability and BBB injury as assessed by the cerebral Evans blue (EB) concentration, pathological changes, and glial fibrillary acidic protein (GFAP) expression as well as brain injury associated biomarkers (BIAB) including TGF-β1, S100B, GFAP, NF-L, tTG, AβPP, and tau and whether presence of ubiquitin-proteosome system (UPS) impairment as assessed by Western blotting and reverse-transcriptase polymerase chain reaction in the brain of T. canis-infected mice monitored from 3 days (dpi) to 8 weeks post-infection (wpi). The vasodilation neuropeptides, the expressions of substance P (SP) and its preferred binding neurokinin-1 receptor (NK-1R) as well as claudin-5 of tight-junction proteins associated with BBB impairment were also assessed. Results revealed that BBB permeability increased as evidenced by a significantly elevated EB concentration in brains of infected mice. BBB injury appeared due to enhanced GFAP protein and mRNA expressions from 4 to 8 wpi. Leukocytes might have been unrelated to BBB impairment because there was no inflammatory cell infiltration despite T. canis larvae having invaded areas around choroid plexus of the brain; whereas markedly elevated SP protein and NK-1R mRNA expressions concomitant with enhanced claudin-5 expression seemed to be associated with persistent BBB impairment in this experimental CT model. Meanwhile, markedly increased levels of other BIAB protein including TGF-β1, S100B, NF-L, tTG, AβPP, and tau, with increases ranging from 2.0-fold to 12.0-fold were found, though their corresponding mRNA expressions were not found to be present at 8 wpi. Concomitantly, UPS impaired as evidenced by over-expression of conjugated ubiquitin and ubiquitin in the brain. Our present results suggest the possibility that cerebral infection by T. canis can have deleterious consequences and may increase the risk that CT will develop into neurodegenerative-like disease such as Alzheimer’s disease cannot be completely excluded due to that neurodegeneration associated AβPP and phosphorylated tau emerged in the brain of experimental CT.
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