The endocannabinoid 2-arachidonoylglycerol reduces lesion expansion and white matter damage after spinal cord injury.
A series of pathological events secondary to spinal cord injury (SCI) contribute to the spread of the damage, which aggravates neurological deficits. Here we report that a single dose of the neuroprotective endocannabinoid 2-arachidonoyl glycerol (2-AG) administered early after SCI reduces lesion expansion, which was prevented by simultaneous blockade of both CB1 and CB2 receptors but not by blockade of either receptor alone. Treatment with 2-AG also preserves the white matter around the epicenter of the injury. Moreover, in the preserved white matter, 2-AG protects myelin from damage and reduces oligodendrocyte loss. In addition to these protective actions at the epicenter region, 2-AG also inhibits the myelin damage and delayed oligodendrocyte loss induced at 10mm from the epicenter. Interestingly, the early protective action of 2-AG is maintained 28 days after injury, when the lesion size is still smaller and the preservation of white matter is better in 2-AG-treated animals. Therefore, our results show that 2-AG protects from the expansion of the lesion and white matter damage, which suggest that this endogenous cannabinoid may be useful as a protective treatment for acute SCI.
Unidad de Neurologia Experimental, Hospital Nacional de Paraplejicos (SESCAM), Toledo, Spain. aarevalom@sescam.jccm.es
Angel
A
Arevalo-Martin
Daniel
D
Garcia-Ovejero
Eduardo
E
Molina-Holgado
D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology; D002452:Cell Count; D063388:Endocannabinoids; D005989:Glycerides / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013904:Thoracic Vertebrae
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D018696:Neuroprotective Agents; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C094503:glyceryl 2-arachidonate