Tang Jun, Chen Qianwei, Guo Jing, Yang Liming, Tao Yihao, Li Lin, Miao Hongping, Feng Hua, Chen Zhi, Zhu Gang
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No.30, Gaotanyan Street, Chongqing, 400038, People's Republic of China.
Mol Neurobiol. 2016 Apr;53(3):1935-1948. doi: 10.1007/s12035-015-9154-x. Epub 2015 Apr 2.
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.
生发基质出血（GMH）是导致有害神经后遗症的早产儿最常见的神经系统疾病。据报道，米诺环素通过控制一些涉及大麻素受体2（CB2R）的机制，在神经炎症性疾病中发挥关键作用。本研究调查了米诺环素是否通过调节CB2R活性来减轻胶原酶诱导的GMH大鼠模型中的神经炎症并保护大脑免受损伤。为了验证这一假设，在GMH后出生7天（P7）的雄性幼鼠中评估了米诺环素和CB2R拮抗剂（AM630）的作用。我们发现米诺环素可导致小胶质细胞中CB2R mRNA表达和蛋白表达增加。米诺环素显著减轻了GMH诱导的脑水肿、小胶质细胞活化和侧脑室体积。此外，米诺环素增加了损伤后的皮质厚度。米诺环素的所有这些神经保护作用均被AM630阻断。使用大麻素CB2激动剂（JWH133）来强化这一假设，其显示出与米诺环素相同的神经保护作用。我们的研究首次证明，米诺环素可减轻GMH大鼠模型中的神经炎症和脑损伤，并且CBR2的激活部分参与了这些过程。
