Cannabidiol-treated Rats Exhibited Higher Motor Score After Cryogenic Spinal Cord Injury
- 341 Downloads
Cannabidiol (CBD), a non-psychoactive constituent of cannabis, has been reported to induce neuroprotective effects in several experimental models of brain injury. We aimed at investigating whether this drug could also improve locomotor recovery of rats submitted to spinal cord cryoinjury. Rats were distributed into five experimental groups. Animals were submitted to laminectomy in vertebral segment T10 followed or not by application of liquid nitrogen for 5 s into the spinal cord at the same level to cause cryoinjury. The animals received injections of vehicle or CBD (20 mg/kg) immediately before, 3 h after and daily for 6 days after surgery. The Basso, Beattie, and Bresnahan motor evaluation test was used to assess motor function post-lesion one day before surgery and on the first, third, and seventh postoperative days. The extent of injury was evaluated by hematoxylin-eosin histology and FosB expression. Cryogenic lesion of the spinal cord resulted in a significant motor deficit. Cannabidiol-treated rats exhibited a higher Basso, Beattie, and Bresnahan locomotor score at the end of the first week after spinal cord injury: lesion + vehicle, day 1: zero, day 7: four, and lesion + Cannabidiol 20 mg/kg, day 1: zero, day 7: seven. Moreover, at this moment there was a significant reduction in the extent of tissue injury and FosB expression in the ventral horn of the spinal cord. The present study confirmed that application of liquid nitrogen to the spinal cord induces reproducible and quantifiable spinal cord injury associated with locomotor function impairments. Cannabidiol improved locomotor functional recovery and reduced injury extent, suggesting that it could be useful in the treatment of spinal cord lesions.
KeywordsRaquimedular trauma Experimental model BBB scale
Authors are indebted to C. A da-Silva and V. F. Garcez for their skillful assistance during performance of this study. This article was a part of the Master in Sciences Thesis of Marcelo Kwiatkoski, FMRP, Physiology—USP. Financial support: CAPES, FAPESP, and CNPQ.
- El-Remessy B, Khalil E, Matragoon S, Abou-Mohamed G, Tsai J, Roon P, Caldwell B, Caldwell W, Green K, Liou I (2003) Neuroprotective effect of (-)Delta9-tetrahydrocannabinol and cannabidiol in N-methyl-d-aspartate-induced retinal neurotoxicity: involvement of peroxynitrite. Am J Pathol 163:1997–2008PubMedCrossRefGoogle Scholar
- García-Arencibia M, González S, De Lago E, Ramos Á, Mechoulam R, Fernández-Ruiz J (2007) Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson’s disease: importance of antioxidant and cannabinoid receptor-independent properties. Brain Res 1134:162–170PubMedCrossRefGoogle Scholar
- Hayakawa K, Mishima K, Nozako M, Ogata A, Hazekawa M, Liu X, Fujioka M, Abe K, Hasebe N, Egashira N, Iwasaki K, Fujiwara M (2007a) Repeated treatment with cannabidiol but not Delta9-tetrahydrocannabinol has a neuroprotective effect without the development of tolerance. Neuropharmacology 52:1079–1087PubMedCrossRefGoogle Scholar
- Hayakawa K, Mishima K, Nozako M, Hazekawa M, Irie K, Fujioka M, Orito K, Abe K, Hasebe N, Egashira N, Iwasaki K, Fujiwara M et al (2007b) Delayed treatment with cannabidiol has a cerebroprotective action via a cannabinoid receptor-independent myeloperoxidase-inhibiting mechanism. J Neurochem 102(5):1488–1496PubMedCrossRefGoogle Scholar
- Wada S, Yone K, Ishidou Y, Nagamine T, Nakahara S, Niiyama T, Sakou T (1999) Apoptosis following spinal cord injury in rats and preventative effect of N-methyl-d-aspartate receptor antagonist. J Neurosurg 91:S98–S104Google Scholar
- Watson C, Paxinos G, Kayalioglu G (2009) The spinal cord. A Christopher and Dana Reeve Foundantion text and atlas. Academic Press, San DiegoGoogle Scholar
- Xu J, Kim M, Ahmed H, Xu J, Yan P, Xu M, Hsu Y (2001) Glucocorticoid receptor-mediated suppression of activator protein-1 activation and matrix metalloproteinase expression after spinal cord injury. J Neurosci 1:92–97Google Scholar