am-630 and Cerebral-Hemorrhage

Blood‑brain barrier (BBB) disruption and consequent edema formation are the most common brain injuries following intracerebral hemorrhage (ICH). Endocannabinoid receptors can alter the permeability of various epithelial barriers and have potential neuroprotective effects. The present study aimed to explore whether the selective cannabinoid receptor 2 (CNR2) agonist, JWH133, can ameliorate BBB integrity and behavioral outcome by activating Ras‑related C3 botulinum toxin substrate 1 (Rac1) following ICH. Autologous arterial blood was injected into the basal ganglia of rats to induce ICH. Animals were randomly divided into the following groups: Sham‑operated, ICH+vehicle, ICH+JWH133, ICH+JWH13+vehicle, ICH+JWH133+AM630 (a selective CNR2 antagonist), ICH+AM630, ICH+JWH133 +NSC23766 (a Rac1 antagonist) and ICH+NSC23766. JWH133 and AM630 were independently intraperitoneally administrated at 1 h prior to ICH. NSC23766 was intracerebroventricularly (ICV) administered 30 min prior to ICH. A modified Garcia test, corner test, Evans blue extravasation and brain water content analysis were performed at 24 and 72 h following ICH. Western blotting and pull‑down assays were performed at 24 h following ICH. The results demonstrated that JWH133 treatment improved neurofunctional deficits, reduced perihematomal brain edema and alleviated BBB damage at 24 and 72 h following ICH. In addition, JWH133 treatment increased the protein expression levels of guanosine‑5'‑triphosphate‑Rac1 and of the adherens junction proteins occludin, zonula occludens‑1 and claudin‑5. However, these effects were reversed by AM630 and NSC23766 treatment. In conclusion, the present findings revealed that JWH133 treatment attenuated brain injury in a rat model of ICH via activation of the Rac1 signaling pathway, thus preserving BBB integrity.

Topics: Animals; Blood-Brain Barrier; Blotting, Western; Cannabinoids; Cerebral Hemorrhage; Indoles; Male; rac1 GTP-Binding Protein; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB2