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Abstract

Importance: This is the first study indicating a possible correlation between perinatal asphyxia and Alzheimer�´s disease, later in life. Objective: Total tau (t-tau), phosphorylated tau (p-tau) and �²-amyloid (1â��42) (A�²42) in CSF are useful biomarkers in neurodegenerative diseases. The aim was to study the role of these and other CSF biomarkers (t-tau, p-tau, A�²42, S100B and neuron-specific enolase-NSE), during hypoxia-reoxygenation in a newborn pig model. Design: 30 newborn pigs were included. One control group (n=6) and two experimental groups (n=24) were exposed to global hypoxia (8% O2) until BE reached -15 mmol/l (moderate hypoxia) or -20 mmol/l (severe hypoxia) or mean BP fell below 20 mmHg. CSF was collected 9.5 hours after the intervention. The study was conducted between October 2012 and January 2013. Results: The level of A�²42 in CSF was significantly lower for the pigs exposed to severe hypoxia compared with the control group, 922 (SD+/-445) pg/ml vs. 1290 (SD+/-143) pg/ml, (p<0.05) and there was a non-significant tendentious reduction of A�²42 in the group exposed to moderate hypoxia. Regarding t-tau and p-tau, there were no significant differences between the intervention groups and the control group. A significantly higher level of S100B was observed in the CSF of pigs receiving hypoxia than in the control group. Further on, there was a moderate negative correlation between the levels of A�²42ï� and S100B in CSF, as well as a moderate negative correlation between lactate in blood at the end of hypoxia and A�²42ï� in CSF Conclusion & Relevance: The reduced level of A�²42 in CSF could reflect an effect on neurons after neonatal hypoxia and may indicate that perinatal hypoxia could be a risk factor for Alzheimer�´s disease later in life. These findings show that CSF A�²42 and S100B are significantly changed in neonatal pigs subjected to hypoxia compared to controls, thus they may be valuable biomarkers after perinatal asphyxia. torkilben@yahoo.no

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