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.