Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.
School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.
Epilepsia. 2021 Mar;62(3):817-828. doi: 10.1111/epi.16839. Epub 2021 Feb 18.
There is a major unmet need for a molecular biomarker of seizures or epilepsy that lends itself to fast, affordable detection in an easy-to-use point-of-care device. Purines such as adenosine triphosphate and adenosine are potent neuromodulators released during excessive neuronal activity that are also present in biofluids. Their biomarker potential for seizures and epilepsy in peripheral blood has, however, not yet been investigated. The aim of the present study was to determine whether blood purine nucleoside measurements can serve as a biomarker for the recent occurrence of seizures and to support the diagnosis of epilepsy.
Blood purine concentrations were measured via a point-of-care diagnostic technology based on the summated electrochemical detection of adenosine and adenosine breakdown products (inosine, hypoxanthine, and xanthine; SMARTChip). Measurements of blood purine concentrations were carried out using samples from mice subjected to intra-amygdala kainic acid-induced status epilepticus and in video-electroencephalogram (EEG)-monitored adult patients with epilepsy.
In mice, blood purine concentrations were rapidly increased approximately two- to threefold after status epilepticus (2.32 ± .40 µmol·L [control] vs. 8.93 ± 1.03 µmol·L [after status epilepticus]), and levels correlated with seizure burden and postseizure neurodegeneration in the hippocampus. Blood purine concentrations were also elevated in patients with video-EEG-diagnosed epilepsy (2.39 ± .34 µmol·L [control, n = 13] vs. 4.35 ± .38 µmol·L [epilepsy, n = 26]).
Our data provide proof of concept that the measurement of blood purine concentrations may offer a rapid, low-volume bedside test to support the diagnosis of seizures and epilepsy.
目前急需一种分子生物标志物来检测癫痫发作或癫痫，这种标志物应能在易于使用的即时检测设备中快速、经济地检测到，并且价格低廉。在神经元过度活动期间释放的嘌呤（如三磷酸腺苷和腺苷）是有效的神经调节剂，它们也存在于生物体液中。然而，嘌呤核苷作为外周血癫痫发作和癫痫的生物标志物尚未得到研究。本研究旨在确定血液嘌呤核苷测量是否可以作为近期癫痫发作的生物标志物，并支持癫痫的诊断。
采用基于腺苷和腺苷分解产物（肌苷、次黄嘌呤和黄嘌呤）的summated 电化学检测的即时诊断技术（SMARTChip）测量血液嘌呤浓度。使用内侧杏仁核海人酸诱导癫痫持续状态的小鼠样本和视频-脑电图（EEG）监测的成年癫痫患者样本进行血液嘌呤浓度测量。
在小鼠中，癫痫持续状态后血液嘌呤浓度迅速增加约 2-3 倍（对照：2.32±0.40 µmol·L；癫痫持续状态后：8.93±1.03 µmol·L），且水平与癫痫发作负荷和海马内的癫痫后神经退行性变相关。视频-脑电图诊断为癫痫的患者的血液嘌呤浓度也升高（对照：2.39±0.34 µmol·L，n=13；癫痫：4.35±0.38 µmol·L，n=26）。
我们的数据提供了概念验证，即测量血液嘌呤浓度可能提供一种快速、低体积的床边检测方法，以支持癫痫发作和癫痫的诊断。
