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Neuroprotection with Glycine-2-Methylproline-Glutamate (G-2MePE) after hypoxic-ischemic brain injury in adult rats

Sam Mathai, Paul W. Harris, Margaret A. Brimble, Alistair J. Gunn and Jian Guan

Background and Purpose: Hypoxic-ischemic brain injury, due to reduced supply of oxygen to brain, is a major cause of death and disability. There is no exclusive treatment available so far. Glycine-2-Methylproline-Glutamate (G-2MePE, NNZ 2566), an analogue of Glycine-Proline-Glutamate reduces neuronal injury after focal ischemia in adult rats. The current study investigated into the neuroprotective effects of G-2MePE after global hypoxic-ischemic brain injury in adult rats.Methods: Adult male rats received a single sub cutaneous injection of G-2MePE (1.2mg/kg) 3h post hypoxic-ischemic brain injury or the same volume of normal saline. Brains were extracted 5 days after the treatment. Tissue damage in the cortex, hippocampus and striatum was assessed. Neuronal survival, glial reactions, caspase-3 activity and TNF-α cytokine activity were also assessed.Results: The treatment with G-2MePE was associated with a significant reduction of tissue damage, improvement in neuronal survival, reduction in reactive microglia, TNF-α positive cells and caspase-3 positive cells in hippocampus and cortex but an elevation of astrocytosis.Conclusions: Neuroprotection with G-2MePE after hypoxic-ischemic brain injury in adult rats is associated with reduced neuronal necrosis, apoptosis, modulated inflammatory responses and augmented astrocytosis.