Abstract
ObjectiveTotal tau (T-tau), phosphorylated tau (p-Tau) and Beta-Amyloid 1–42 (AB42) in Cerebrospinal Fluid (CSF) are useful biomarkers in neurodegenerative diseases. The aim of the study was to investigate the role of these and other CSF biomarkers (T-tau, p-Tau, AB42, S100B and NSE), during hypoxia-reoxygenation in a newborn pig model.DesignThirty newborn pigs were included in a study of moderate or severe hypoxia. The moderate hypoxia group (n = 12) was exposed to global hypoxia (8% O2) until Base excess (BE) reached -15 mmol/l. The pigs in the group exposed to severe hypoxia (n = 12) received 8% O2 until BE reached -20 mmol/l or mean Blood Pressure fell below 20 mm Hg, The control group (n = 6) was kept at room air. For all treatments, the CSF was collected at 9.5 hours after the intervention.ResultsThe level of AB42 in CSF was significantly lower in the pigs exposed to severe hypoxia compared with the control group, 922(SD +/-445)pg/ml versus. 1290(SD +/-143) pg/ml (p<0.05), respectively. Further, a non-significant reduction of AB42 was observed in the group exposed to moderate hypoxia T-tau and p-Tau revealed no significant differences between the intervention groups and the control group, however a significantly higher level of S100B was seen in the CSF of pigs receiving hypoxia in comparison to the level in the control group. Further on, there was a moderate negative correlation between the levels of AB42 and S100B in CSF, as well as a moderate negative correlation between Lactate in blood at end of hypoxia and AB42 in CSF.InterpretationThis is the first study to our knowledge that demonstrated a significant drop in AB42 in CSF after neonatal hypoxia. Whether or not this has an etiological basis for adult neurodegenerative disorders needs to be studied with additional experiments and epidemiological studies. AB42 and S100B are significantly changed in neonatal pigs subjected to hypoxia compared to controls and thus may be valuable biomarkers of perinatal asphyxia.
Highlights
The level of AB42 in cerebrospinal fluid (CSF) was significantly lower in the pigs exposed to severe hypoxia compared with the control group, 922(SD +/-445)pg/ml versus. 1290(SD +/-143) pg/ml (p
A non-significant reduction of AB42 was observed in the group exposed to moderate hypoxia T-tau and p-Tau revealed no significant differences between the intervention groups and the control group, a significantly higher level of S100B was seen in the CSF of pigs receiving hypoxia in comparison to the level in the control group
This study is the first to show an association between AB42 in CSF and perinatal hypoxia
Summary
Intrapartum events are among the most common causes of neonatal death with more than 800,000 annual cases worldwide [1].Even though the majority of the children exposed to severe perinatal asphyxia will survive, many of them will suffer from long-term sequelae, such as cerebral palsy and cognitive deficits.In severe cases, perinatal asphyxia may lead to Hypoxic-Ischemic Encephalopathy (HIE), which may cause permanent neurological damage.Proteins, such as S100B and Neuron specific Enolase (NSE), released into the cerebrospinal fluid (CSF) during neuronal injury, might be useful as biomarkers in reflecting disease severity and predicting the clinical outcome after perinatal asphyxia [2].We addressed the question whether total-tau (T-tau), phospho-Tau (p-Tau) and Beta-Amyloid 1–42 (AB42), biomarkers of adult neurodegenerative disorders, could serve as markers of perinatal asphyxia [3,4,5].In pediatric populations altered T-tau levels in CSF have been found in patients with brain tumors [6] and West syndrome (Infantile spasms) [7]. Perinatal asphyxia may lead to Hypoxic-Ischemic Encephalopathy (HIE), which may cause permanent neurological damage. Proteins, such as S100B and Neuron specific Enolase (NSE), released into the cerebrospinal fluid (CSF) during neuronal injury, might be useful as biomarkers in reflecting disease severity and predicting the clinical outcome after perinatal asphyxia [2]. Magnoni et al(2012) found that T-tau in the brain extracellular space was increased and negatively correlated with Beta-Amyloid levels in the extracellular space after traumatic brain injury and that T-tau may be helpful when predicting the clinical outcome [8]
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