title: Cannabinoid CB2 receptor stimulation attenuates brain edema and neurological deficits in a germinal matrix hemorrhage rat model.
abstract: 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 1h post-injury, the administration of JWH133 (1mg/kg, intraperitoneal injection) significantly attenuated brain edema at 24h post-GMH, which was reversed by a selective CB2R antagonist, SR144528 (3mg/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.
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yihao
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Qianwei
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: zhichen@tmmu.edu.cn.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001892:Camphanes / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D020300:Intracranial Hemorrhages / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009068:Movement / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001892:Camphanes; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; D018696:Neuroprotective Agents; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; D014409:Tumor Necrosis Factor-alpha; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC
keywords: Brain edema; Cannabinoid receptor; Germinal matrix hemorrhage; Inflammation