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01-12-2015 | Original Article

A Cannabinoid Receptor 2 Agonist Prevents Thrombin-Induced Blood–Brain Barrier Damage via the Inhibition of Microglial Activation and Matrix Metalloproteinase Expression in Rats

Authors: Lin Li, Yihao Tao, Jun Tang, Qianwei Chen, Yang Yang, Zhou Feng, Yujie Chen, Liming Yang, Yunfeng Yang, Gang Zhu, Hua Feng, Zhi Chen

Published in: Translational Stroke Research | Issue 6/2015

Abstract

Thrombin mediates the life-threatening cerebral edema and blood–brain barrier (BBB) damage that occurs after intracerebral hemorrhage (ICH). We previously found that the selective cannabinoid receptor 2 (CB2R) agonist JWH-133 reduced brain edema and neurological deficits following germinal matrix hemorrhage (GMH). We explored whether CB2R stimulation ameliorated thrombin-induced brain edema and BBB permeability as well as the possible molecular mechanism involved. A total of 144 Sprague–Dawley (S-D) rats received a thrombin (20 U) injection in the right basal ganglia. JWH-133 (1.5 mg/kg) or SR-144528 (3.0 mg/kg) and vehicle were intraperitoneally (i.p.) injected 1 h after surgery. Brain water content measurement, Evans blue (EB) extravasation, Western blot, and immunofluorescence were used to study the effects of a CB2R agonist 24 h after surgery. The results demonstrated that JWH-133 administration significantly decreased thrombin-induced brain edema and reduced the number of Iba-1-positive microglia. JWH-133 also decreased the number of P44/P42(+)/Iba-1(+) microglia, lowered Evans blue extravasation, and inhibited the elevated matrix metallopeptidase (MMP)-9 and matrix metallopeptidase (MMP)-12 activities. However, a selective CB2R antagonist (SR-144528) reversed these effects. We demonstrated that CB2R stimulation reduced thrombin-induced brain edema and alleviated BBB damage. We also found that matrix metalloproteinase suppression may be partially involved in these processes.

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Title: A Cannabinoid Receptor 2 Agonist Prevents Thrombin-Induced Blood–Brain Barrier Damage via the Inhibition of Microglial Activation and Matrix Metalloproteinase Expression in Rats
Authors: Lin Li
Yihao Tao
Jun Tang
Qianwei Chen
Yang Yang
Zhou Feng
Yujie Chen
Liming Yang
Yunfeng Yang
Gang Zhu
Hua Feng
Zhi Chen
Publication date: 01-12-2015
Publisher: Springer US
Published in: Translational Stroke Research / Issue 6/2015
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-015-0425-7

2024 ASCO Annual Meeting

Springer Medicine

A Cannabinoid Receptor 2 Agonist Prevents Thrombin-Induced Blood–Brain Barrier Damage via the Inhibition of Microglial Activation and Matrix Metalloproteinase Expression in Rats

Abstract

2024 ASCO Annual Meeting

Springer Medicine

Abstract

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