Hypoxia-ischemia in the neonatal rat brain: histopathology after post-treatment with NMDA and non-NMDA receptor antagonists.
In a model of perinatal hypoxic-ischemic brain damage, we examined the neuroprotective efficacy of posttreatment with the NMDA receptor antagonist MK-801 and the AMPA receptor antagonist NBQX. Unilateral brain damage developed in 95% of rat pups subjected to hypoxia-ischemia with a 27.8 +/- 1.2% weight deficit of the damaged hemisphere. MK-801 in doses of 0.3 and 0.5 mg/kg i.p. reduced the brain damage by 61% (p < 0.001) and 43% (p < 0.001), respectively. A higher dose of MK-801 (0.75 mg/kg) did not offer neuroprotection. Treatment with NBQX (40 mg/kg) reduced the hemispheric lesion by 28% (p < 0.05). In conclusion, posttreatment with both NBQX and low doses of MK-801 reduced perinatal brain damage. The NMDA receptor antagonist offered stronger neuroprotection which is in agreement with a proposed NMDA receptor hyperactivity around postnatal day 7 in rats.
Hagberg
H
H
Department of Obstetrics and Gynecology, University of Göteborg, Sweden.
Gilland
E
E
Diemer
N H
NH
Andiné
P
P
D000818:Animals; D000831:Animals, Newborn; D001925:Brain Damage, Chronic / Q000473:pathology* / Q000517:prevention & control; D002545:Brain Ischemia / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D007274:Injections, Intraperitoneal; D008297:Male; D011810:Quinoxalines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D012720:Severity of Illness Index; D016896:Treatment Outcome
D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016291:Dizocilpine Maleate