Lopez-Rodriguez Ana Belen, Siopi Eleni, Finn David P, Marchand-Leroux Catherine, Garcia-Segura Luis M, Jafarian-Tehrani Mehrnaz, Viveros Maria-Paz
Faculty of Biology, Department of Animal Physiology (Animal Physiology II), Complutense University of Madrid-Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain Instituto Cajal, Consejo Superior de Investigaciones Cientificas (CSIC), Madrid, Spain.
Faculté des Sciences Pharmaceutiques et Biologiques, Laboratoire de Pharmacologie de la Circulation Cérébrale (EA4475).
Cereb Cortex. 2015 Jan;25(1):35-45. doi: 10.1093/cercor/bht202. Epub 2013 Aug 19.
Traumatic brain injury (TBI) and its consequences represent one of the leading causes of death in young adults. This lesion mediates glial activation and the release of harmful molecules and causes brain edema, axonal injury, and functional impairment. Since glial activation plays a key role in the development of this damage, it seems that controlling it could be beneficial and could lead to neuroprotective effects. Recent studies show that minocycline suppresses microglial activation, reduces the lesion volume, and decreases TBI-induced locomotor hyperactivity up to 3 months. The endocannabinoid system (ECS) plays an important role in reparative mechanisms and inflammation under pathological situations by controlling some mechanisms that are shared with minocycline pathways. We hypothesized that the ECS could be involved in the neuroprotective effects of minocycline. To address this hypothesis, we used a murine TBI model in combination with selective CB1 and CB2 receptor antagonists (AM251 and AM630, respectively). The results provided the first evidence for the involvement of ECS in the neuroprotective action of minocycline on brain edema, neurological impairment, diffuse axonal injury, and microglial activation, since all these effects were prevented by the CB1 and CB2 receptor antagonists.
创伤性脑损伤（TBI）及其后果是年轻成年人主要的死亡原因之一。这种损伤介导胶质细胞活化和有害分子的释放，并导致脑水肿、轴突损伤和功能障碍。由于胶质细胞活化在这种损伤的发展中起关键作用，因此控制它似乎有益，并可能产生神经保护作用。最近的研究表明，米诺环素可抑制小胶质细胞活化，减少损伤体积，并在长达3个月的时间内降低TBI诱导的运动亢进。内源性大麻素系统（ECS）在病理情况下的修复机制和炎症中发挥重要作用，它通过控制一些与米诺环素途径共有的机制来实现。我们假设ECS可能参与米诺环素的神经保护作用。为了验证这一假设，我们使用了小鼠TBI模型，并结合选择性CB1和CB2受体拮抗剂（分别为AM251和AM630）。结果首次证明了ECS参与米诺环素对脑水肿、神经功能障碍、弥漫性轴突损伤和小胶质细胞活化的神经保护作用，因为所有这些作用都被CB1和CB2受体拮抗剂所阻断。
