title: Minocycline Attenuates Neonatal Germinal-Matrix-Hemorrhage-Induced Neuroinflammation and Brain Edema by Activating Cannabinoid Receptor 2.
abstract: Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns leading to detrimental neurological sequelae. Minocycline has been reported to play a key role in neurological inflammatory diseases by controlling some mechanisms that involve cannabinoid receptor 2 (CB2R). The current study investigated whether minocycline reduces neuroinflammation and protects the brain from injury in a rat model of collagenase-induced GMH by regulating CB2R activity. To test this hypothesis, the effects of minocycline and a CB2R antagonist (AM630) were evaluated in male rat pups that were post-natal day 7 (P7) after GMH. We found that minocycline can lead to increased CB2R mRNA expression and protein expression in microglia. Minocycline significantly reduced GMH-induced brain edema, microglial activation, and lateral ventricular volume. Additionally, minocycline enhanced cortical thickness after injury. All of these neuroprotective effects of minocycline were prevented by AM630. A cannabinoid CB2 agonist (JWH133) was used to strengthen the hypothesis, which showed the identical neuroprotective effects of minocycline. Our study demonstrates, for the first time, that minocycline attenuates neuroinflammation and brain injury in a rat model of GMH, and activation of CBR2 was partially involved in these processes.
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No.30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No.30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
authors.forename: Qianwei
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No.30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No.30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
authors.forename: Liming
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No.30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
authors.forename: Yihao
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No.30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No.30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
authors.forename: Hongping
authors.initials: H
authors.lastname: Miao
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No.30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No.30, Gaotanyan Street, Chongqing, 400038, People's Republic of China. zhichen@tmmu.edu.cn.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No.30, Gaotanyan Street, Chongqing, 400038, People's Republic of China. gangzhu6666@sina.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002186:Cannabinoids / Q000494:pharmacology / Q000627:therapeutic use; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020300:Intracranial Hemorrhages / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D002186:Cannabinoids; D016207:Cytokines; D007211:Indoles; D008840:Microfilament Proteins; D043885:Receptor, Cannabinoid, CB2; D014409:Tumor Necrosis Factor-alpha; D008911:Minocycline; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC; C094023:iodopravadoline
keywords: Cannabinoid receptor 2; Germinal matrix hemorrhage; Microglia; Minocycline; Neuroinflammation
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