Chronically administered 3-nitropropionic acid induces striatal lesions attributed to dysfunction of the blood-brain barrier.
3-Nitropropionic acid (3-NPA), an irreversible inhibitor of succinate dehydrogenase, was administered to rats and the characteristics of the neuronal damage were investigated. Injections of 3-NPA (15 mg/kg s.c.) every 2 or 3 days for 1-2 weeks induced a mild neuronal loss and neutrophil invasions in the striatum (STR). The same administration for 4 weeks induced specific symmetric lesions in the lateral STR although the size was variable in each animal. Inside the lesions, strong neutrophil invasions and a strong immunoreaction for IgG, C3 as well as complement factor C3b/C4b receptor (C3b/C4br) were detected. Lesioned sites lost the immunoreaction for GFAP while the marginal areas contained abundant GFAP-labeled astrocytes around the vessels. In intoxicated animals, there was a weak but stout immunoreaction for IgG and C3b/C4br localizing around vessels in the STR even when there were no lesions or neuronal loss. The data suggest that the blood-brain barrier dysfunction is responsible for the specific vulnerability of the STR for the toxin.
Nishino
H
H
Department of Physiology, Nagoya City University Medical School, Japan.
Shimano
Y
Y
Kumazaki
M
M
Sakurai
T
T
D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001927:Brain Diseases / Q000139:chemically induced / Q000473:pathology*; D003179:Complement C3b / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007074:Immunoglobulin G; D007150:Immunohistochemistry; D008297:Male; D017072:Neostriatum / Q000473:pathology*; D009410:Nerve Degeneration / Q000187:drug effects; D009574:Nitro Compounds; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D009574:Nitro Compounds; D011422:Propionates; D003179:Complement C3b; D015935:Complement C4b; C015392:3-nitropropionic acid