Avdic Una, Ahl Matilda, Öberg Maria, Ekdahl Christine T
Inflammation and Stem Cell Therapy Group, Division of Clinical Neurophysiology, Lund University, Lund, Sweden.
Department of Clinical Sciences, Epilepsy Center, Lund University, Lund, Sweden.
Front Neurol. 2019 Jul 2;10:701. doi: 10.3389/fneur.2019.00701. eCollection 2019.
Non-convulsive status epilepticus (NCSE) is a prolonged epileptic seizure with subtle symptoms that may delay clinical diagnosis. Emerging experimental evidence shows brain pathology and epilepsy development following NCSE. New diagnostic/prognostic tools are therefore needed for earlier and better stratification of treatment. Here we examined whether NCSE initiates a peripheral immune response in blood serum from rats that experienced electrically-induced NCSE. ELISA analysis showed an acute transient increase in serum protein levels including interleukin-6 6 h post-NCSE, similar to the immune reaction in the brain. At 4 weeks post-NCSE, when 75% of rats subjected to NCSE had also developed spontaneous seizures, several immune proteins were altered. In particular, markers associated with microglia, macrophages and antigen presenting cells, such as CD68, MHCII, and galectin-3, were increased and the T-cell marker CD4 was decreased in serum compared to both non-stimulated controls and NCSE rats without spontaneous seizures, without correlation to interictal epileptiform activity. Analyses of serum following intracerebral injection of lipopolysaccharide (LPS) showed an acute increase in interleukin-6, but at 4 weeks unaltered levels of MHCII and galectin-3, an increase in CD8 and CD11b and a decrease in CD68. None of the increased serum protein levels after NCSE or LPS could be confirmed in spleen tissue. Our data identifies the possibility to detect peripheral changes in serum protein levels following NCSE, which may be related to the development of subsequent spontaneous seizures.
非惊厥性癫痫持续状态（NCSE）是一种伴有细微症状的长时间癫痫发作，可能会延迟临床诊断。新出现的实验证据表明，NCSE后会出现脑部病理改变和癫痫发展。因此，需要新的诊断/预后工具，以便更早、更好地进行治疗分层。在此，我们研究了NCSE是否会在经历电诱导NCSE的大鼠血清中引发外周免疫反应。酶联免疫吸附测定（ELISA）分析显示，NCSE后6小时血清蛋白水平急性短暂升高，包括白细胞介素-6，这与大脑中的免疫反应相似。在NCSE后4周，当75%接受NCSE的大鼠也出现自发性癫痫发作时，几种免疫蛋白发生了改变。特别是，与小胶质细胞、巨噬细胞和抗原呈递细胞相关的标志物，如CD68、MHCII和半乳糖凝集素-3，在血清中增加，而T细胞标志物CD4与未受刺激的对照组和无自发性癫痫发作的NCSE大鼠相比均降低，且与发作间期癫痫样活动无关。脑内注射脂多糖（LPS）后血清分析显示白细胞介素-6急性增加，但在4周时MHCII和半乳糖凝集素-3水平未改变，CD8和CD11b增加，CD68减少。在脾脏组织中未证实NCSE或LPS后血清蛋白水平的增加。我们的数据确定了检测NCSE后血清蛋白水平外周变化的可能性，这可能与随后自发性癫痫发作的发展有关。
