Continuous inhibition of 20-HETE synthesis by TS-011 improves neurological and functional outcomes after transient focal cerebral ischemia in rats.
Neurosci Res
; 59(4): 475-80, 2007 Dec.
Article
em En
| MEDLINE
| ID: mdl-17933409
ABSTRACT
TS-011, a potent and selective inhibitor of 20-HETE synthesis, has been described as providing significant benefits in animal stroke models. However, no studies have investigated changes in brain 20-HETE levels after cerebral ischemia. Also lacking are studies of TS-011 pharmacodynamics with respect to brain 20-HETE levels that may explain the benefits of TS-011 in animal models of ischemic stroke. The present study sought to explore changes in 20-HETE levels in brain tissue, as well as in plasma, after a 90-min episode of transient focal cerebral ischemia. Pharmacodynamics of TS-011 were also examined. Then, we evaluated the long-term effects of TS-011 when administered as in this pharmacodynamics study. The major findings of the present study are as follows (1) brain 20-HETE levels increased significantly within 7.5h after MCAO; (2) TS-011 at doses of 0.1 and 0.3mg/kg administered at regular 6-h intervals appeared to reduce brain 20-HETE levels continuously; (3) TS-011 when administered as in this pharmacodynamics study improved long-term neurological and functional outcomes. These findings strongly suggest that 20-HETE plays an important role in the development of neurological and functional deficits after focal cerebral ischemia and that TS-011 may provide benefits in patients suffering ischemic stroke.
Buscar no Google
Bases de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Isquemia Encefálica
/
Ácidos Hidroxieicosatetraenoicos
/
Morfolinas
/
Formamidas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neurosci Res
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Japão