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The literature search supports the conclusion that metformin is neuroprotective against DM-induced neuronal cell degeneration in both peripheral and central nervous systems, and this effect is likely mediated via modulation of oxidative stress, inflammation, and cell death pathways.

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however, only methylcobalamin can be utilized in the central nervous system.

The hypoxia alleviation via O2 production, the redox balance disruption via glutathione consumption and the reactive oxygen species generation, together would down-regulate the expression of O6-methylguanine-DNA methyltransferase under TMZ medication, which is considered as the key to drug resistance