当前位置： SCI文献检索 > BRAIN RESEARCH期刊下所有文献 > Cerebroprotective effects of TAK-937, a novel cannabinoid receptor agonist, in permanent and thrombotic focal cerebral ischemia in rats: therapeutic time window, combination with t-PA and efficacy in aged rats.

Cerebroprotective effects of TAK-937, a novel cannabinoid receptor agonist, in permanent and thrombotic focal cerebral ischemia in rats: therapeutic time window, combination with t-PA and efficacy in aged rats.

Abstract：

:Some occluded arteries of acute ischemic stroke (AIS) patients are not recanalized, even if thrombolytic therapy is performed. Considering such clinical settings, we examined the potential cerebroprotective efficacy of TAK-937, a novel cannabinoid receptor agonist, in young adult and aged rats with a permanent middle cerebral artery occlusion (MCAO) model and conducted a combination study with TAK-937 and tissue type plasminogen activator (t-PA) in a rat thrombotic MCAO model. TAK-937 significantly reduced infarct volume when it was administered 3 and 5h after permanent MCAO in young adult rats. A thrombotic MCAO was induced by photo-irradiation of the middle cerebral artery with Rose Bengal administration and a permanent MCAO was produced by thermoelectric coagulation of occluded arteries. TAK-937 (10, 30 and 100μg/kg/h) was intravenously infused 1, 3, 5, or 8-24h after MCAO. t-PA (3 or 10mg/kg) was intravenously administered 1, 1.5 or 2h after MCAO. Infarct volume was determined using a 2,3,5-triphenyltetrazolium chloride staining method 24 or 48h after MCAO. The combined treatment of TAK-937 with t-PA significantly reduced the cerebral infarction compared with t-PA treatment alone in a rat thrombotic MCAO model. TAK-937 reduced infarct volume of aged rats as well, when it was administered 1h after permanent MCAO. These results suggest that TAK-937 exerts protective effects regardless of age and has a wide therapeutic time window in permanent occlusion. Furthermore, combined treatment of TAK-937 with t-PA would provide more therapeutic efficacy compared to t-PA treatment alone.

journal_name

Brain Res

journal_title

Brain research

authors

Murakami K,Suzuki M,Suzuki N,Hamajo K,Tsukamoto T,Shimojo M

doi

10.1016/j.brainres.2013.06.014

keywords:

["(2-Hydroxypropyl)-β-cyclodextrin","2,3,5-triphenyltetrazolium chloride","AIS","Age","BDNF","BT","CB","CNS","Cannabinoid receptor agonist","Combination therapy","HPBCD","HR","MABP","MCA","MCAO","Middle cerebral artery occlusion","PaCO(2)","PaO(2)","SD","Sprague–Dawley","TTC","Tissue-type plasminogen activator","acute ischemic stroke","body temperature","brain derived neurotrophic factor","cannabinoid","central nerve system","heart rate","mean arterial blood pressure","middle cerebral artery","middle cerebral artery occlusion","oxygen saturation","partial arterial carbon dioxide","partial arterial oxygen","sO(2)","t-PA","tissue-type plasminogen activator"]

subject

Has Abstract

pub_date

2013-08-14 00:00:00

pages

84-93

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(13)00865-2

journal_volume

1526

pub_type

杂志文章

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Cerebroprotective effects of TAK-937, a novel cannabinoid receptor agonist, in permanent and thrombotic focal cerebral ischemia in rats: therapeutic time window, combination with t-PA and efficacy in aged rats.