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The Journal of Neuroscience, April 1, 2003, 23(7):2511

BRIEF COMMUNICATION
Therapeutic Action of Cannabinoids in a Murine Model of Multiple Sclerosis

Ángel Arévalo-Martín¹, José Miguel Vela², Eduardo Molina-Holgado¹, José Borrell¹, and Carmen Guaza¹

¹ Neuroimmunology Group, Neural Plasticity Department, Cajal Institute, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain, and ² Unit of Histology, School of Medicine, Department of Cell Biology, Physiology, and Immunology, Universidad Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain

Theiler's virus infection of the CNS induces an immune-mediated demyelinating disease in susceptible mouse strains and serves as a relevant infection model for human multiple sclerosis (MS). Cannabinoids may act as immunosuppressive compounds that have shown therapeutic potential in chronic inflammatory disorders. Using the Theiler's murine encephalomyelitis virus model, we report here that treatment with the synthetic cannabinoids WIN 55,212-2, ACEA, and JWH-015 during established disease significantly improved the neurological deficits in a long-lasting way. At a histological level, cannabinoids reduced microglial activation, abrogated major histocompatibility complex class II antigen expression, and decreased the number of CD4+ infiltrating T cells in the spinal cord. Both recovery of motor function and diminution of inflammation paralleled extensive remyelination. Overall, the data presented may have potential therapeutic implications in demyelinating pathologies such as MS; in particular, the possible involvement of cannabinoid receptor CB2 would enable nonpsychoactive therapy suitable for long-term use.

Key words: Theiler's virus; CB1 agonists; CB2 agonists; demyelination; neuroinflammation; remyelination; spinal cord; rotarod

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2372511-06$05.00/0

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