Monoacylglycerol Lipase Inhibitor is Safe when Combined with Delayed r-tPA Administration in Treatment of Stroke.
Inflammation
; 41(6): 2052-2059, 2018 Dec.
Article
en En
| MEDLINE
| ID: mdl-30047001
ABSTRACT
Administration of tissue plasminogen activator (tPA) during first 3-4.5 h after ischemic stroke is the main therapeutic strategy; however, its using after that, leads to reperfusion injury and neurotoxic effects. Additionally, inflammation has a critical role in secondary injury after late reperfusion therapy. Thus, this project was designed to explore the effects of JZL-184 (JZL), an agonist of type 1 cannabinoid receptor (CB1), on the side effects of recombinant tPA (r-tPA), which is administrated after 5 h of stroke onset in the mice middle cerebral artery occlusion (MCAO) model. After established the model of MCAO mouse, they were put to six groups, including intact, control, vehicle, JZL (4 mg/kg), r-tPA (9 mg/kg), and JZL plus r-tPA. Thereafter, brain levels of IL-10, TNF-α, and matrix metalloproteinase - 9 (MMP9), brain edema and infarction, and behavioral functions have been determined in the groups. JZL alone or in combination with r-tPA, but not r-tPA, reduced brain edema, infarct volume, brain levels of TNF-α, MMP9, and also improved behavioral tests. JZL and JZL plus r-tPA also increased brain levels of IL-10. According to the results, JZL can improve the effects of r-tPA to overcome stroke SSE, when used after 5 h of stroke onset. Based on the fact that there is limitation regarding using r-tPA after 3 h of stroke onset, using a combination of r-tPA/JZL can be considered for a future therapeutic strategy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piperidinas
/
Activador de Tejido Plasminógeno
/
Accidente Cerebrovascular
/
Quimioterapia Combinada
/
Benzodioxoles
/
Monoacilglicerol Lipasas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Inflammation
Año:
2018
Tipo del documento:
Article
País de afiliación:
Irán