Department of Neonatology, Institute for Women's Health, University College London, London WC1E 6BT, UK.
Electron Microscopy Suite, Faculty of Science, Technology, Engineering and Mathematics, Open University, Milton Keynes MK7 6AA, UK.
Int J Mol Sci. 2023 Jul 16;24(14):11529. doi: 10.3390/ijms241411529.
Neonatal seizures are commonly associated with acute perinatal brain injury, while understanding regarding the downstream molecular pathways related to seizures remains unclear. Furthermore, effective treatment and reliable biomarkers are still lacking. Post-translational modifications can contribute to changes in protein function, and post-translational citrullination, which is caused by modification of arginine to citrulline via the calcium-mediated activation of the peptidylarginine deiminase (PAD) enzyme family, is being increasingly linked to neurological injury. Extracellular vesicles (EVs) are lipid-bilayer structures released from cells; they can be isolated from most body fluids and act as potential liquid biomarkers for disease conditions and response to treatment. As EVs carry a range of genetic and protein cargo that can be characteristic of pathological processes, the current study assessed modified citrullinated protein cargo in EVs isolated from plasma and CSF in a piglet neonatal seizure model, also following phenobarbitone treatment. Our findings provide novel insights into roles for PAD-mediated changes on EV signatures in neonatal seizures and highlight the potential of plasma- and CSF-EVs to monitor responses to treatment.
新生儿癫痫常与围产期急性脑损伤有关，而与癫痫相关的下游分子途径的理解仍不清楚。此外，有效的治疗方法和可靠的生物标志物仍然缺乏。翻译后修饰可以导致蛋白质功能的变化，而翻译后瓜氨酸化是由精氨酸通过钙介导的肽基精氨酸脱亚氨酶（PAD）酶家族的激活修饰为瓜氨酸引起的，与神经损伤的关系越来越密切。细胞外囊泡（EVs）是由细胞释放的脂质双层结构；它们可以从大多数体液中分离出来，并作为疾病状况和对治疗反应的潜在液体生物标志物。由于 EV 携带一系列遗传和蛋白质货物，这些货物可能是病理过程的特征，因此本研究评估了在新生猪癫痫模型中，从血浆和 CSF 中分离的 EV 中修饰的瓜氨酸化蛋白货物，以及苯巴比妥治疗后的情况。我们的研究结果为 PAD 介导的 EV 特征在新生儿癫痫中的作用提供了新的见解，并强调了血浆和 CSF-EVs 监测治疗反应的潜力。
