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J. Neurochem. (2008) 104, 1565–1576.

Chondroitin sulfate (CS) is a major microenvironmental molecule in the CNS, and there have been few reports about its neuroprotective activity. As neuronal cell death by excitotoxicity is a crucial phase in many neuronal diseases, we examined the effect of various CS preparations on neuronal cell death induced by the excitotoxicity of glutamate analogs. CS preparations were added to cultured neurons before and after the administration of glutamate analogs. Then, the extents of both neuronal cell death and survival were estimated. Pre‐administration of a highly sulfated CS preparation, CS‐E, significantly reduced neuronal cell death induced by not only NMDA but also (S)‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid or kainate. Neither CS preparations other than CS‐E nor other highly sulfated polysaccharides such as heparin and dextran sulfate …