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Effect of the new pyridoindole antioxidant SMe1EC2 on functional deficits and oedema formation in rat hippocampus exposed to ischaemia in vitro.

Gáspárová Z, Janega P, Babál P, Snirc V, Stolc S, Mach M, Ujházy E.
Journal Article 2009; 30(5): 574-581 PubMed PMID: 20035262 Citation  Keywords:  Animals, Antioxidants:pharmacology, Brain Ischemia:drug therapy, Edema:drug therapy, Electrophysiology, Female, Hippocampus:cytology, Humans, Indoles:pharmacology, Male, Neuroprotective Agents:pharmacology, Pyridines:pharmacology, Rats, Rats, Wistar,.   

OBJECTIVES: The idea of neuroprotective therapy for ischaemic stroke is based on results from studies on experimental animal models of brain ischaemia demonstrating efficacy of many natural and synthetic agents. Contrary to positive conclusions with antioxidants from animal models, clinical experience failed to find neuroprotectants so efficient in human stroke, infarction, brain trauma, tissue preservation, etc. Thus new highly effective neuroprotective agents need to be discovered.

METHODS: Effects of 10-day oral treatment with the new pyridoindole derivative, code SMe1EC2, was analysed in the model of ischaemia in vitro measured five days after oral treatment, with focus on neuronal function recovery. The responses were determined by extracellular recording from rat hippocampal slices. Further, effect of SMe1EC2, applied into the incubation medium before and during ischaemia in vitro, was studied on the oedema extent in neurons of the CA1 area.

RESULTS: Ten-day oral treatment of rats with SMe1EC2 at the doses 50 or 250 mg/kg resulted in improved resistance of hippocampal neurons to 6.5-min hypoxia/hypoglycaemia in vitro measured during reoxygenation, compared to untreated rats. Application of the drug tested into the incubation medium 30 min before and during 6-min hypoxia/hypoglycaemia resulted in reduction of oedema formation in the CA1 area compared to untreated slices exposed to ischaemia in vitro.

CONCLUSION: The current study confirmed the neuroprotective effect of the pyridoindole antioxidant SMe1EC2 on the level of recovery of neuronal function as well as on affection of morphological changes expressed by reduced oedema extent in the rat hippocampus under ischemic conditions in vitro....

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