Glatiramer Acetate Attenuates Pro-Inflammatory T Cell Responses but Does Not Directly Protect Neurons from Inflammatory Cell Death

Glatiramer acetate (GA) is a synthetic random basic copolymer capable of modulating adaptive T cell responses In animal models of various inflammatory and degenerative central nervous system disorders GA induced T cells cross the blood-brain barrier secrete high levels of anti inflammatory cytokines and neurotrophins and thus both reduce neuronal damage and promote neurogenesis Recently it has been suggested that GA itself may permeate the (impaired) blood-brain barrier and directly protect neurons under conditions of inflammation mediated neurodegeneration To test this hypothesis we examined the direct effects of GA on neuronal functionality and T cell mediated neuronal apoptosis in culture acute brain slices and focal experimental autoimmune encephalomyelitis GA caused a depolarization of the resting membrane potential and led to an immediate impairment of action potential generation in neurons Moreover GA incubated neurons underwent dose dependent apoptosis Apoptosis of ovalbumin peptide loaded major histocompatibility complex class I expressing neurons induced by ovalbumin specific effector T cells could be reduced by pre incubation of T cells but not neurons with GA Similar results could be found using acute brain slices In focal experimental autoimmune encephalomyelitis lesion size and neuronal apoptosis could be limited by pretreating rats with GA whereas intracerebral GA application into the inflammatory lesion had no effect on neuronal survival Our data suggest that GA attenuates adaptive pro inflammatory T cell responses but does not exert direct neuroprotective effects (Am J Pathol 2010 177 3051-3060; DOI 10 2353/ajpath 2010 100442)