Effects of nicotine infusion on striatal glutamate and cortical non-protein-bound iron in hypoxic newborn piglets.
BACKGROUND
Perinatal asphyxia triggers a large cascade of mechanisms leading to brain damage. Release of glutamate and increased oxidative stress play substantial roles. Non-protein-bound iron (NPBI), which contributes to the production of free radical species through the Fenton reaction, increases in hypoxic-ischemic brain damage. Results from in vitro and adult animal studies show that nicotine can decrease extracellular levels of NPBI and glutamate. Nicotine's effects have further been shown to be dose-dependent, with lower doses showing neuroprotective, and higher doses showing neurotoxic effects.


OBJECTIVE
We wished to assess nicotine's effect on levels of NPBI and glutamate in an animal model of neonatal hypoxic-ischemic brain damage.


METHODS
47 anesthetized newborn piglets were randomized to one of four infusions after hypoxia (nicotine 130 microg/kg/h, 260 microg/kg/h, adrenaline 0.05 microg/kg/min, saline 2.6 ml/kg/h). Glutamate in striatum and NPBI in cortex were analyzed in microdialysate.


RESULTS
Striatal glutamate presented a significant rise for all the animals from baseline to the end of hypoxia (p < 0.001). There was a significant difference for nicotine 130 microg/kg/h versus saline (p = 0.002) 2 h after hypoxia. Cortical NPBI presented a significant rise from baseline to the end of hypoxia for all the animals (p < 0.001), and a significant difference between nicotine 130 microg/kg/h versus saline 2 h after hypoxia (p = 0.013).


CONCLUSIONS
Our findings support the hypothesis that nicotine can decrease extracellular levels of glutamate and NPBI in a neonatal model of hypoxic-ischemic brain damage. This suggests possible neuroprotective effects of a low dose of nicotine in neonates, as it has already been shown in adult models.
Andresen
Jannicke Hanne
JH
Department of Pediatric Research, Medical Faculty, Institute for Surgical Research, Rikshospitalet University Hospital, University of Oslo, Oslo, Norway. jannicke.andresen@rr-research.no
Saugstad
Ola Didrik
OD
D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007231:Infant, Newborn; D007501:Iron / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D011897:Random Allocation; D013552:Swine
D018696:Neuroprotective Agents; D018698:Glutamic Acid; D009538:Nicotine; D007501:Iron