Does glatiramer acetate induce neurogenesis in experimental autoimmune encephalomyelitis?

摘要

Experimental autoimmune encephalomyelitis (EAE) is an animal model of autoimmune demyelinating disease which has been widely used to study the pathology of human multiple sclerosis. The model has also proved extremely useful in exploring the mechanism of action of glatiramer acetate, which abrogates disease expression, demyelination and neuronal damage in the EAE model. Treatment with GA gives rise to a specific population of GA-specific T cells in the periphery. These cells penetrate the CNS, where they exert their beneficial activity by at least three different mechanisms. Firstly, they secrete anti-inflammatory cytokines, which suppress inflammatory responses to other antigens in their vicinity and induce bystander-suppression. Secondly, they secrete the neurotrophic factor BDNF and upregulate expression of BDNF in resident cells. BDNF released will protect axons and neuronal cell bodies from damage due to inflammation of demyelination. Thirdly, by a mechanism that is not yet elucidated, they promote the proliferation of neural progenitor cells and their migration into sites of damage where they develop into mature neurones, release BDNF and stimulate reinnervation of the lesion. This multifaceted activity of GA has important consequences for the therapy of human multiple sclerosis, where GA treatment may effectively combat both the inflammatory and the neurodegenerative components of pathology.