Effect of AMPA receptor antagonist nbqx on neuronal survival in basal ganglia after asphymc cardiac arrest in neonatal pigs

We tested the hypothesis that basal ganglia (BG) structures show selective neuronal vulnerability and that AMPA receptor blockade protects cells within the glutamatergic corticostriatal pathways after asphyxie cardiac arrest in oneweek-old piglets. Anesthetized piglets were exposed to 30 rain of hypoxia followed by 7 min of airway occlusion. NBQX (n=10) or vehicle (n=10) was administered before airway occlusion (30 mg/kg, i.v.) and during the first 4 h of recovery (IS mg/kg/h). Four piglets in each group died in status epilepticus (usually at 24-48 h). Neuronal survival at 96 h was highly topographic in location. Number of viable neurons in caudate (C) was significantly higher than in putamen (P) (59±28 vs. 33±25; ±SD, p<0.001) or in substantia nigra pars reticulau (SNr) (<1%). Neuronal survival was not improved by NBQX in C (S7±24) or P (20±1756) compared to vehicle in C (62±33%) or P (46±32 ). Survival in P and SNr was less man in primary sensorimotor cortex with NBQX (45±28X) or vehicle (78±13%). When groups were pooled, occurrence of non-lethal seizure activity reduced neuronal survival in C (49±27 vs. 80±12%) and P (18±17 vs. 63±21%;p<0.02). We conclude that postatphyxic basal ganglia damage is highly selective in neonatal pigs and is distributed via cortical-subcortical pathways. Seizure activity worsened histopathology, possibly by excitotoxic corticostriatal activation, and AMPA receptor blockade failed to protect against neuronal damage within this pathway. (Supported by NS20020).