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The neuroprotective effect of glutamate receptors group II agonists in an animal model of birth asphyxia is connected with inhibition of caspase independent apoptosis
8th Global Experts Meeting on Advances in Neurology and Neuropsychiatry
Ewelina Bratek, A Ziembowicz and E Salinska
Mossakowski Medical Research Centre-Polish Academy of Sciences, Poland
Posters & Accepted Abstracts: ClinNeuropsychol
Abstract
Statement of the Problem: Hypoxic-ischemic encephalopathy is one of the leading causes of neonatal mortality and permanent neurological disability worldwide. It was shown recently that mGluR2/3 activation before or after ischemic insult results in neuroprotection, but the exact mechanism of this effect is not clear. Aim: The aim of present study was to investigate whether glutamate receptors group II agonists (mGluR2/3) activation after hypoxia-ischemia reduces brain damage and inhibits apoptotic processes. Methodology: We used an animal model of Hypoxia-Ischemia (H-I) on 7-day old rat pups. Animals underwent unilateral common carotid artery ligation combined with 75 min hypoxia at 7.4% oxygen. Control pups were sham-operated (anaesthetized and left common carotid artery dissected, but not ligated). Animals were injected intraperitoneally with mGluR2 (LY 379268) and mGluR3 (NAAG) agonists, 1 hour or 6 hours after H-I (5 mg/kg of body weight). We examined the weight deficit of the ischemic brain hemisphere and the expression of caspase independent apoptosis factors (AIF, HTR/OMI and endonuclease G). The expression of trophic factors GDNF, BDNF and TGF-beta was also measured. Results: Our results show that application of each agonist decreased brain tissue weight loss in ischemic hemisphere independently on the time of application (from 40% in H-I to 15-20% in treated). Both agonists of mGluR2/3 applied 1 hour or 6 hours after H-I decreased expression of AIF, HTR/OMI and endonuclease G proteins compared to untreated H-I. The mGluR2/3 agonists application decreased expression of TGF-beta and increased BDNF and GDNF in the ischemic hemisphere compared to H-I. Conclusion: This study demonstrated the neuroprotective effect of mGluR 2/3 agonists on neonatal hypoxic-ischemic brain injury. Presented data suggest that this effect is connected with decreasing apoptosis.Biography
Ewelina Bratek is PhD student in Dept. of Neurochem at Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. Ewelina Bratek has published more than 3 papers in reputed journals.
E-mail: ebratek@imdik.pan.pl
