NBQX Blocks Acute and Late Epileptogenic Effects of Perinatal Hypoxia

Summary: Clinically, and in experimental models, perinatal hypoxic encephalopathy is commonly associated with seizures. We previously described a rat model in which hypoxia induces seizures and permanently increases in seizure susceptibility in immature rats [postnatal day (P) 10–121 but not in older rats. In the present study, we compared the effect of pretreatment with the excitatory amino acid antagonists MK‐801 and NBQX versus lorazepam in our rat model of perinatal hypoxia. Animals exposed to hypoxia at P10 without treatment have frequent seizures during hypoxia and subsequently exhibit increased seizure susceptibility to flurothyl. Treatment with 6‐nitro‐7‐sulfamoylbenzo(f)quinoxaline‐2,3‐dione(NBQX 20 mglkg) effectively suppressed hypoxia‐induced seizures in immature rats and also protected against permanent changes in flurothyl threshold in adult‐hood, whereas treatment with MK‐801 (1 mg/kg) or lorazepam (LZP 1 mg/kg) did not prevent these hypoxia‐related epileptogenic effects. These results suggest that activation of a‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazol propionic acid (AMPA) receptors may partly mediate the age‐dependent epileptogenic effect of hypoxia in the perinatal period