Canna~Fangled Abstracts

Cannabinoid type 2 receptor stimulation attenuates brain edema by reducing cerebral leukocyte infiltration following subarachnoid hemorrhage in rats.

By April 30, 2014 No Comments
 2014 Apr 30. pii: S0022-510X(14)00270-6. doi: 10.1016/j.jns.2014.04.034. [Epub ahead of print]

pm8Cannabinoid type 2 receptor stimulation attenuates brain edema by reducing cerebral leukocyte infiltration following subarachnoid hemorrhage in rats.

Abstract

Early brain injury (EBI), following subarachnoid hemorrhage (SAH), comprises blood-brain barrier (BBB) disruption and consequent edema formation. Peripheral leukocytes can infiltrate the injured brain, thereby aggravating BBB leakage and neuroinflammation. Thus, anti-inflammatory pharmacotherapies may ameliorate EBI and provide neuroprotection after SAH. Cannabinoid type 2 receptor (CB2R) agonism has been shown to reduce neuroinflammation; however, the precise protective mechanisms remain to be elucidated. This study aimed to evaluate whether the selective CB2R agonist, JWH133 can ameliorate EBI by reducing brain-infiltrated leukocytes after SAH. Adult male Sprague-Dawley rats were randomly assigned to the following groups: sham-operated, SAH with vehicle, SAH with JWH133 (1.0mg/kg), or SAH with a co-administration of JWH133 and selective CB2R antagonist SR144528 (3.0mg/kg). SAH was induced by endovascular perforation, and all reagents were administered 1h after surgery. Neurological deficits, brain water content, Evans blue dye extravasation, and Western blot assays were evaluated at 24h after surgery. JWH133 improved neurological scores and reduced brain water content; however, SR144528 reversed these treatment effects. JWH133 reduced Evans blue dye extravasation after SAH. Furthermore, JWH133 treatment significantly increased TGF-β1 expression and prevented an SAH-induced increase in E-selectin and myeloperoxidase. Lastly, SAH resulted in a decreased expression of the tight junction protein zonula occludens-1 (ZO-1); however, JWH133 treatment increased the ZO-1 expression. We suggest that CB2R stimulation attenuates neurological outcome and brain edema, by suppressing leukocyte infiltration into the brain through TGF-β1 up-regulation and E-selectin reduction, resulting in protection of the BBB after SAH.
Copyright © 2014 Elsevier B.V. All rights reserved.

KEYWORDS:

Brain edema, Cannabinoid type 2 receptor, Early brain injury, JWH133, Subarachnoid hemorrhage

PMID:

 24819918
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Highlights

 

•This study targets anti-inflammation strategy for early brain injury after SAH.
•The mechanisms of cannabinoid type 2 receptor activation to reduce neuroinflammation studied.
•Both selective agonist and antagonist of cannabinoid type 2 receptor are used.
•Neurological deficits, brain edema, and blood–brain barrier evaluated.
•Activation of cannabinoid receptor increased TGF-β1 and reduced E-selectin, ZO-1.

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