Journal
BRAIN RESEARCH
Volume 1602, Issue -, Pages 127-135Publisher
ELSEVIER
DOI: 10.1016/j.brainres.2015.01.025
Keywords
Germinal matrix hemorrhage; Cannabinoid receptor; Brain edema; Inflammation
Categories
Funding
- National Natural Science Foundation of China [81070929, 81271281]
- National Key Basic Research Development Program (973 Program) of China [2014CB541606]
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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-alpha) 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. (C) 2015 Elsevier B.V. All rights reserved.
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