The metabotropic glutamate receptors group II (mGluR2/3) agonists post-conditioning reduces brain damage in the model of birth asphyxia in seven day old rats
E Bratek, A Ziembowicz and E Salinska
Neurochem at Mossakowski Medical Research Centre, Polish Academy of Sciences, Poland
: J Pharm Sci Emerg Drugs
Abstract
Hypoxic-ischemic encephalopathy (HIE) results in permanent damage of central nervous system that may result in neonatal death or developmental disorders. 20%–30% of infants with HIE die in the neonatal period, and 33%–50% of survivors demonstrate permanent neurodevelopmental abnormalities (such as cerebral palsy) and mental retardation. It was shown recently that group II metabotropic glutamate receptors (mGluR2/3) activation before or after ischemic insult results in neuro-protection but the exact mechanism of this effect is not clear. The aim of present study was to investigate whether mGluR2/3 activation after experimental hypoxia-ischemia reduces brain damage and if the reduction of the expression of proapoptotic factors is one of the mechanisms involved. We used an animal model of hipoxia-ischemia (H-I) on seven 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 C.C.A. dissected, but not ligated). Animals were injected intraperitoneally with mGluR2 (LY 379268) and mGluR3 (NAAG) agonists 1 h or 6 h after H-I (5 mg/kg of body weight). We examined the weight deficit of the ischemic brain hemisphere and the expression of SMAC/DIABLO, cytochrome C and Apaf-1. The activation of caspase 3 and 9 was also measured. 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 h or 6 h after H-I decreased expression of SMAC/DIABLO, cytochrome C and Apaf-1 proteins compared to untreated H-I. mGluR2/3 agonists application decreased expression of caspase 3 and caspase 9 in the ischemic hemisphere compared to H-I. Hypoxic-ischemic injury to the central nervous system can have devastating lifelong effects on the developing fetus and the neonate. This study is the demonstration of the neuro-protective effect of mGluR 2/3 agonist on neonatal hypoxic-ischemic brain injury. These data suggest the possibility that post-conditioning reduces irreversible ischemic injury in part by 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
