Posters-Accepted Abstracts: J Neurol Neurophysiol
Hypoxic-ischemic encephalopathy is an abnormal neurobehavioral state which results fromimpaired cerebral blood flow at
the time around birth. This condition may cause neonatal death or be manifested later as cerebral palsy or mental deficiency.
Recent investigations have not provided us with promising neuroprotective compounds to reduce perinatal hypoxic-ischemic
(HI) brain injury. 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. The aim of present study was to investigate whether mGluR2/3 activation after
hypoxia-ischemia reduces brain damage and if the activation of antioxidant enzymes and decrease of oxidative stress participate
in observed effects.We used an animal model of hipoxia-ischemia (H-I) on 7-day old rat pups. Animals were anesthetized and
the left common carotid artery was isolated and double – ligated and then cut between the ligatures. After completion of the
surgical procedure the pups were subjected to hypoxia(7.2% -7.4% oxygen in nitrogen for 75 min at 35 Ã?Â?C). Control pups were
sham-operated (anaesthetized and left c.c.a. dissected, but not ligated). Animals were injected intra peritoneal with specific
mGluR2 (LY 379268) and mGluR3 (NAAG) agonists 1 h or 6 h after H-I (5 mg/kg of body weight). Weight deficit of the
ischemic brain hemisphere, radical oxygen species (ROS) content, activity of antioxidant enzymes (superoxide dismutase - SOD,
Glutatione peroxidase - GPx, catalase - CAT) and level of reduced glutathione (GSH) were measured.
Our results show a neuroprotective effect of mGluR 2/3 agonists. Both agonists applied decreased brain tissue weight
loss in ischemic hemisphere independently on the time of application (from 40% in H-I to 15 - 20% in treated). Our results
show that both mGluR2/3 antagonists reduce ROS level in the injured hemisphere. H-I resulted inincreased activity of SOD in
the injured hemisphere, which was reduced by mGluR2/3 agonists application 1h or 6 h after H-I. The activity of glutathione
peroxidase (GPX) was also increased by H-I and its activity was decreased by both agonists. The decrease of GSH level
observed in ischemic hemisphere was not observed after agonists application, the effect was better expressed when agonists
were administered 1 h after H-I. Application of agonists resulted also in decrease in CATactivity.
Conclusions: The results show that activation of mGluR2 and mGluR3 in a short time after H-I insult triggered neuroprotective
mechanisms, which probably partly engage defence against oxidative stress and ROS production. The effect is more distinct
when agonists are applied in a short time after H-I