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

Abstract

Background and Purpose: Hypoxic -ischemic brain injury, due to reduced supply of oxygen, 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 (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-a cytokine activity were also assessed. Results: The treatment with G-2Me-PE was associated with a significant reduction of tissue damage, improvement in neuronal survival, reduction in reactive microglia, TNF-a positive cells and caspase-3 positive cells in hippocampus and cortex but an elevation of astrocytosis. Conclusion: Neuroprotection with G-2MePE after hypoxic -ischemic brain injury in adult rats is associated with reduced neuronal necrosis, apoptosis, modulated inflammatory response and augmented astrocytosis.