CB1 and CB2 Cannabinoid Receptor Antagonists Prevent Minocycline-Induced Neuroprotection Following Traumatic Brain Injury in Mice

It should not be called neuroprotection, it is stopping the neuronal cascade of death. Bet this never gets approved for stroke survivors in the USA. It is better to let survivors stay disabled rather than allow 'Reefer Madness' to take place in our elderly population.
http://cercor.oxfordjournals.org/content/early/2013/08/19/cercor.bht202.abstract

1. Ana Belen Lopez-Rodriguez1,5,
2. Eleni Siopi2,
3. David P. Finn4,
4. Catherine Marchand-Leroux2,
5. Luis M. Garcia-Segura5,
6. Mehrnaz Jafarian-Tehrani2,3 and
7. Maria-Paz Viveros1⇑

+ Author Affiliations

1. ¹Faculty 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,
2. ²Faculté des Sciences Pharmaceutiques et Biologiques, Laboratoire de Pharmacologie de la Circulation Cérébrale (EA4475),
3. ³CNRS UMR 8194, UFR Biomédicale des Saints-Pères, Université Paris Descartes, Sorbonne Paris Cité, Paris, France,
4. ⁴Pharmacology and Therapeutics, School of Medicine, NCBES Neuroscience Cluster and Centre for Pain Research, National University of Ireland Galway, Galway, Ireland
5. ⁵Instituto Cajal, Consejo Superior de Investigaciones Cientificas (CSIC), Madrid, Spain

1. Address correspondence to Maria-Paz Viveros, Department of Animal Physiology (Animal Physiology II), Faculty of Biology, Complutense University of Madrid, Calle Jose Antonio Novais 2, Madrid 28040, Spain. Email: pazviver@bio.ucm.es

Abstract

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.