The metabotropic glutamate receptors group II (mGluR2/3) agonists postconditioning reduces brain damage in the model of birth asphyxia in 7-day-old rats

• Published in: Folia neuropathologica Vol. 56; no. 3; p. 261
• Main Authors: Bratek, E, Ziembowicz, P, Salinska, E
• Format: Journal Article
• Language: English
• Published: Warsaw Termedia sp. z o.o 01.01.2018
• Subjects: Apoptosis; Asphyxia; Brain damage; Brain injury; Carotid artery; Caspase; Caspase-3; Caspase-9; Central nervous system; Developmental disabilities; Encephalopathy; Glutamic acid receptors (metabotropic); Hippocampus; Hypoxia; Ischemia; N-Acetylaspartylglutamic acid; Neonates; Neurodevelopmental disorders; Neuroprotection; Rodents
• ISSN: 1641-4640; 1509-572X

Hypoxic-ischemic encephalopathy (HIE) results in permanent damage of central nervous system that may result in neonatal death or developmental disorders. It was shown recently that group II metabotropic glutamate receptors (mGluR2/3) activation before or after ischemic insult results in neuroprotection but the exact mechanism of this effect is not clear. The aim of present study was to investigate whether mGluR2/3 activation after hypoxia-ischemia reduces brain damage and if the reduction of the expression of pro-apoptotic factors is one of the mechanisms involved. We used an animal model of hypoxia-ischemia (H-I) on 7-day old rat pups in which the left common carotid artery was isolated and cut between the ligatures. Thereafter the pups were subjected to hypoxia (7.4% oxygen in nitrogen for 75 min). Control pups were sham-operated. Animals were injected intraperitoneally with specific mGluR2 (LY 379268) and mGluR3 (NAAG) agonists 1 h or 6 h after H-I (5 mg/kg). The weight deficit of the ischemic hemisphere was measured. The damage in the hippocampal CA1 region was examined by Cresyl violet staining. Infarct area was measured using TTC staining. The activity of caspase 3 and 9 was measured. Our results show that application of mGluR2/3 agonists after H-I results in neuroprotection. Both applied agonists decreased weight loss in ischemic hemisphere at both times of application (from 40% in H-I to 15-20% in treated). Both mGluR2/3 agonists applied 1 h or 6 h after H-I decreased the damage of neuronal cells and the disorganization of CA1 region of hippocampus and reduced the brain infarct area. mGluR2/3 agonists reduced increased by H-I activation of caspase-3 and caspase-9. The results show that activation of mGluR2 or mGluR3 in a short time after H-I insult triggered neuroprotective mechanisms and reduced apoptotic processes initiated by HI in developing brain.