Hypoxic-ischemic injury in the neonatal rat brain: effects of pre- and post-treatment with the glutamate release inhibitor BW1003C87.
In a model of perinatal hypoxia-ischemia (HI) we examined the neuroprotective efficacy of pre- and post-treatment with the glutamate release inhibitor BW1003C87 [5-(2,3,5-trichlorophenyl)-2,4-diamino-pyrimidine). Ipsilateral brain damage developed in 99% of rat pups subjected to HI (unilateral common carotid artery ligation and 100 min of 7.7% oxygen exposure) with a 26 +/- 16% (mean +/- S.D.) weight deficit of the damaged hemisphere 2 weeks after the insult. Pre-treatment with BW1003C87 (10 mg/kg intraperitoneally) reduced the brain damage by 46% (P < 0.05). A higher dose (20 mg/kg) of pre-treatment was not tolerated. Administration of BW1003C87 did not affect the rectal temperature of the rats. Post-treatment with BW1003C87 (10-30 mg/kg) offered no neuroprotection in this model. In conclusion, there was a neuroprotective effect from pre- but not post-treatment with BW1003C87 in this model, supporting the concept that intra-ischemic excitatory amino acid release is important for development of brain damage. The lack of post-treatment effect indicates that BW1003C87 did not attenuate deleterious EAA cycling during reflow in the neonatal brain.
Gilland
E
E
Department of Obstetrics and Gynecology, University of Göteborg, Sweden.
Puka-Sundvall
M
M
Andiné
P
P
Bona
E
E
Hagberg
H
H
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000473:pathology*; D001925:Brain Damage, Chronic / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D007839:Functional Laterality; D002534:Hypoxia, Brain / Q000473:pathology / Q000517:prevention & control*; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009929:Organ Size; D011292:Premedication; D011743:Pyrimidines / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011920:Rats, Inbred WF
D018691:Excitatory Amino Acid Antagonists; D011743:Pyrimidines; C078265:5-(2,3,5-trichlorophenyl)pyrimidine-2,4-diamine ethane sulfonate