TY - JOUR PY - 1997// TI - Spatio-temporal pattern of dysfunction of the blood-brain barrier in the striatum after systemic intoxication with 3-nitropropionic acid (a mitochondrial toxin) JO - Journal of Brain Science A1 - Shimano, Y. A1 - Kumazaki, M. A1 - Fukuda, A. A1 - Nishino, H. SP - 167 EP - 180 VL - 23 IS - 2-3 N2 - Systemically administered 3-nitropropionic acid (3-NPA), a suicide inhibitor that irreversibly inhibited complex II of mitochondrial electron transport chain, induced striatum specific lesions accompanied by the dysfunction of the blood-brain barrier (BBB) in the rat. In the present study, we made a spatio-temporal analysis of dysfunction of the BBB using immunohistochemistry and protein analysis (western blotting) focusing on glial fibrillary acidic protein (GFAP, a marker protein of astrocytes) and factor VIII (a marker protein of endothelial cells). The first administration (20 mg/kg, s.c.) of 3-NPA induced no motor or histological damage. Within 1 to 2 hr after the second administration on the subsequent day, a half of intoxicated rats exhibited motor symptoms (ataxic gait, rolling, paddling, etc.) without detectable histological damages yet. Around 3 hr, extravasations of IgG first appeared at two sites: the core of the striatum (STR) and around the branches of the lateral striatal (ISTR) artery, and these were extended thereafter. The former was attenuated by prior decortication and the latter often localized in areas where rectangular or acute angled bifurcation of the ISTR artery was observed. Striatal GFAP and factor VIII immunoreactions decreased and increased, respectively, at this moment, but western blot analysis did not indicate disturbance of both proteins yet. At 5 hr, GFAP positive astrocytes could not be detected in the parenchyma of the STR but sperm-like-shaped GFAP positive ones remained among the fiber bundles of the STR. Western blot analysis showed the split of GFAP positive bands but no changes in factor VIII positive ones. All these histological and protein-level disturbances were never detected outside the STR. Data may suggest that the striatal BBB is most vulnerable to 3-NPA intoxication, and the disturbance might be driven by two different mechanisms.

Language: en

LA - en SN - 1341-5301 UR - http://dx.doi.org/ ID - ref1 ER -