Neuronal ion gradient is ATP dependent and hypoxia leads to rapid brain ATP depletion, depolarization and damage. The llama (Lama glama) is an animal tolerant to hypoxia. The fetal llama (FLL) brain responds to acute hypoxaemia with a little vasodilatation and a reduction of O2 consumption without developing seizures (Llanos, 2003). These observations suggest a brain hypometabolism in the hypoxaemic FLL as a strategy to preserve neurone integrity. We studied if FLL brain responds with a co-ordinated reduction of Na,K-ATPase and voltage-gated Na (NaVg) channels as a neuroprotective strategy upon 24 h hypoxia. Eight FLL at 70±3% of gestation were chronically instrumented (with Ethics Committee approval) under general anaesthesia (i.v. 10 mg kg-1 sodium thiopentone, inhaled 50% N2O-1% halotane). Polyvinyl catheters were placed into the fetal abdominal aorta, inferior vena cava and amniotic cavity. Experiments began after 3 days of post-operative recovery. Three FLL were submitted to 1 h normoxia, followed by 24 h hypoxia (HF). Fetal hypoxia was obtained by reducing maternal FiO2 with a N2/CO2/air mixture. Five FLL were studied in normoxia (CF). pH and blood gases were monitored. Caesarean delivery and killing of the FLL was done immediately after the end of recording. Brain cortex was used for Na,K-ATPase activity as paranitrophenol formation and ouabain binding. Immunoblot and RT-PCR measurements for poly-ADP-ribose-polymerase (PARP) and NaVg channels were performed, respectively. Fetal PO2 (13.2±0.1mmHg vs 18.2±0.3mmHg), Hb saturation (25.0±0.2% vs 42.7±1.0%) and O2 content (3.4±0.2 ml dl-1 vs 7.0±0.2 ml dl-1) obtained from descending aorta were significantly lower in the HF than the CF (P<0.05, Student′s unpaired t test). We also measured lower Na,K-ATPase activity (0.078±0.001 μmol mg-1 min-1 vs 0.113±0.006 μmol mg-1 min-1) and ouabain BMAX (33.0±2.3 pmol mg-1 vs 48.8±4.5 pmol mg-1) in the H group than the C group (P<0.05). Hypoxia did not affect ouabain KD, NaVg channel protein and transcript level, or the ratio between intact and apoptosis-induced PARP fragment. The lack of increase of apoptosis-induced PARP fragment together with the drop of Na,K-ATPase activity and density suggest a metabolic arrest neuropreservation strategy upon 24 h hypoxia in the FLL brain cortex. The absence of changes in NaVg channels expression does not exclude hypoxia-induced postranslational changes to reduce Na conductances as a co-ordinated response to the observed decrease in Na pump.