Cannabinoid CB2 receptor stimulation attenuates brain edema and neurological deficits in a germinal matrix hemorrhage rat model

•This is the first report of the effect of cannabinoid CB2 receptor in GMH rat model.•We found that cannabinoid CB2 receptor stimulation presented neuroprotection in GMH.•JWH133 provided a potentially translatable therapeutic strategy for GMH infants.

Germinal matrix hemorrhage (GMH) is one of the most common and devastating cerebrovascular events that affect premature infants, resulting in a significant socioeconomic burden. However, GMH has been largely unpreventable, and clinical treatments are mostly inadequate. In the present study, we tested the hypothesis that JWH133, a selective CB2 receptor agonist, could attenuate brain injury and neurological deficits in a clostridial collagenase VII induced GMH model in seven-day-old (P7) S-D rat pups. Up to 1 h post-injury, the administration of JWH133 (1 mg/kg, intraperitoneal injection) significantly attenuated brain edema at 24 h post-GMH, which was reversed by a selective CB2R antagonist, SR144528 (3 mg/kg, intraperitoneal injection). Long-term brain morphology and neurofunctional outcomes were also improved. In contrast, JWH133 did not have a noticeable effect on the hematoma volume during the acute phase. These data also showed that microglia activation and inflammatory cytokine (TNF-α) release were significantly inhibited by JWH133 after GMH. This current study suggests a potential clinical utility for CB2R agonists as a potential therapy to reduce neurological injury and improve patient outcomes after GMH.