Benterud Torkil, Pankratov Leonid, Solberg Rønnaug, Bolstad Nils, Skinningsrud Anders, Baumbusch Lars, Sandvik Leiv, Saugstad Ola Didrik
Dept of Pediatric Research, Oslo University Hospital, Oslo, Norway.
Dept of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
PLoS One. 2015 Oct 26;10(10):e0140966. doi: 10.1371/journal.pone.0140966. eCollection 2015.
Total 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.
Thirty 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.
The 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.
This 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.
脑脊液（CSF）中的总tau蛋白（T-tau）、磷酸化tau蛋白（p-Tau）和β-淀粉样蛋白1-42（AB42）是神经退行性疾病的有用生物标志物。本研究的目的是在新生猪模型中研究这些以及其他脑脊液生物标志物（T-tau、p-Tau、AB42、S100B和NSE）在缺氧-复氧过程中的作用。
30只新生猪被纳入中度或重度缺氧研究。中度缺氧组（n = 12）暴露于全身性缺氧（8%氧气），直至碱剩余（BE）达到-15 mmol/l。重度缺氧组（n = 12）的猪接受8%氧气，直至BE达到-20 mmol/l或平均血压降至20 mmHg以下。对照组（n = 6）置于室内空气中。对于所有处理，在干预后9.5小时收集脑脊液。
与对照组相比，重度缺氧猪脑脊液中AB42水平显著降低，分别为922（标准差±445）pg/ml和1290（标准差±143）pg/ml（p<0.05）。此外，在中度缺氧组中观察到AB42有非显著降低。T-tau和p-Tau在干预组和对照组之间无显著差异，然而，与对照组相比，接受缺氧处理的猪脑脊液中S100B水平显著更高。此外，脑脊液中AB42水平与S100B水平之间存在中度负相关，缺氧末期血液中乳酸水平与脑脊液中AB42水平之间也存在中度负相关。
据我们所知，这是第一项证明新生儿缺氧后脑脊液中AB42显著下降的研究。这是否具有成人神经退行性疾病的病因学基础，需要通过额外的实验和流行病学研究来探讨。与对照组相比，缺氧新生猪的AB42和S100B有显著变化，因此可能是围产期窒息的有价值生物标志物。
