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 (1.0 mg/kg), or SAH with a co-administration of JWH133 and selective CB2R antagonist SR144528 (3.0 mg/kg). SAH was induced by endovascular perforation, and JWH133 was administered 1 h after surgery. Neurological deficits, brain water content, Evans blue dye extravasation, and Western blot assays were evaluated at 24 h 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. © 2014 Elsevier B.V. All rigths reserved.
Original language | English |
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Pages (from-to) | 101-106 |
Number of pages | 6 |
Journal | Journal of the Neurological Sciences |
Volume | 342 |
Issue number | 1-2 |
DOIs | |
State | Published - Jul 15 2014 |
ASJC Scopus Subject Areas
- Neurology
- Clinical Neurology
Keywords
- Brain edema
- Cannabinoid type 2 receptor
- Early brain injury
- JWH133
- Subarachnoid hemorrhage
- Chemotaxis, Leukocyte/drug effects
- Brain Edema/complications
- Anti-Inflammatory Agents, Non-Steroidal/pharmacology
- Male
- Camphanes/pharmacology
- Leukocytes/cytology
- Receptor, Cannabinoid, CB2/agonists
- Brain/drug effects
- Subarachnoid Hemorrhage/complications
- Gene Expression Regulation/drug effects
- Cannabinoids/pharmacology
- Zonula Occludens-1 Protein/biosynthesis
- Rats
- Cannabinoid Receptor Agonists/pharmacology
- E-Selectin/biosynthesis
- Animals
- Peroxidase/biosynthesis
- Cannabinoid Receptor Antagonists/pharmacology
- Pyrazoles/pharmacology
- Transforming Growth Factor beta1/biosynthesis