Blood-brain barrier disruption in the striatum of rats treated with 3-nitropropionic acid.
3-nitropropionic acid (3-NPA) is a natural toxin that is used to induce models of Huntington's disease (HD) in experimental animals. Here we injected 3-NPA into Sprague-Dawley rats in order to evaluate its effects on the blood-brain barrier (BBB). Evans blue (EB) extravasation was used to identify injured areas in the brains of the treated animals and immunostainings of endothelial brain barrier antigen (EBA), zona occludens-1 (ZO-1) and laminin were used as markers to characterize the effects of the neurotoxin on the BBB. Treated rats had a significant loss of body weight compared to controls, and a correlation between motor affectation and body weight loss was observed in the former. The lateral part of the striatum was specifically injured in treated animals and the BBB almost disappeared in the core of the injured areas, as evidenced by a high EB extravasation and severe alterations of the immunostainings of the three BBB integrity markers compared to those of control animals. We conclude that the BBB is severely affected in the 3-NPA rat model of HD and that disruption of this barrier is a crucial event during the development of this disease.
Duran-Vilaregut
Joaquim
J
Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
del Valle
Jaume
J
Camins
Antoni
A
Pallàs
Mercè
M
Pelegrí
Carme
C
Vilaplana
Jordi
J
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001485:Basement Membrane / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects*; D003342:Corpus Striatum / Q000098:blood supply / Q000473:pathology*; D004730:Endothelium, Vascular / Q000187:drug effects; D006816:Huntington Disease / Q000139:chemically induced; D007797:Laminin / Q000032:analysis; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D009574:Nitro Compounds / Q000633:toxicity*; D010750:Phosphoproteins / Q000032:analysis; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019108:Tight Junctions / Q000187:drug effects; D062826:Zonula Occludens-1 Protein
D000954:Antigens, Surface; D007797:Laminin; D008565:Membrane Proteins; D009574:Nitro Compounds; D010750:Phosphoproteins; D011422:Propionates; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C114781:endothelial barrier antigen, rat; C015392:3-nitropropionic acid