丛集性头痛中的 S100B 和 NSE-胶质细胞活化的证据？
- 作者列表："Snoer AH","Vollesen ALH","Beske RP","Guo S","Hoffmann J","Jørgensen NR","Martinussen T","Ashina M","Jensen RH
OBJECTIVE:Neuronal-specific enolase (NSE) and protein S100B have gained considerable interest as the markers of CNS injury, glial cell activation, and/or blood-brain barrier (BBB) disruption. No studies have investigated NSE and S100B in cluster headache (CH), but these biomarkers could contribute to the understanding of CH. METHODS:Patients with episodic CH in bout (eCHa), in remission (eCHr), and chronic CH (cCH) were included in this randomized, double-blind, placebo-controlled, 2-way cross-over provocation study carried out at the Danish Headache Center. The primary endpoints included (1) differences of NSE and S100B in between groups (eCHa, eCHr, and cCH) at baseline; (2) differences over time in plasma concentrations of NSE and S100B between patient developing an attack and those who did not; (3) differences in plasma concentrations over time of NSE and S100B between active day and placebo day. Baseline findings were compared to the historical data on migraine patients and healthy controls and presented with means ± SD. RESULTS:Nine eCHa, 9 eCHr, and 13 cCH patients completed the study and blood samples from 11 CGRP-induced CH attacks were obtained. There were no differences in NSE levels between CH groups at baseline, but CH patients in active disease phase had higher levels compared with 32 migraine patients (9.1 ± 2.2 µg/L vs 6.0 ± 2.2 µg/L, P < .0001) and 6 healthy controls (9.1 ± 2.2 µg/L vs 7.3 ± 2.0 µg/L, P = .007). CGRP-infusion caused no NSE changes and, but a slight, non-significant, increase in NSE was seen in patients who reported a CGRP-induced CH attack (2.39 µg/L, 95% Cl [-0.26, 3.85], P = .061). At baseline S100B levels in eCHa patients were higher compared to cCH patients (0.06 ± 0.02 µg/L vs 0.04 ± 0.02 µg/L, P = .018). Infusion of CGRP and CGRP-induced attacks did not change S100B levels. Apart from induced CH-attacks no other adverse events were noted. CONCLUSIONS:At baseline eCHa patients had higher S100B plasma levels than cCH patients and there was a slight, however not significant, NSE increase in response to CGRP-induced CH attack. Our findings suggest a possible role of an ictal activation of glial cells in CH pathophysiology, but further studies are warranted.
目的: 神经元特异性烯醇化酶 (NSE) 和蛋白 S100B 作为 CNS 损伤、胶质细胞活化和/或血脑屏障 (BBB) 破坏的标志物已引起了人们的极大兴趣。没有研究调查丛集性头痛 (CH) 中的 NSE 和 S100B，但这些生物标志物可能有助于对 CH 的理解。 方法: 将发作性 CH (eCHa) 、缓解期 (eCHr) 和慢性 CH (cCH) 患者纳入本研究，随机、双盲、安慰剂对照,丹麦头痛中心开展的双向交叉激发研究。主要终点包括 (1) 基线时两组 (eCHa 、 eCHr 和 cCH) NSE 和 S100B 的差异; (2) 发生发作的患者与未发生发作的患者之间 NSE 和 S100B 血浆浓度随时间的差异; (3)活动日和安慰剂日 NSE 和 S100B 血浆浓度随时间的差异。将基线结果与偏头痛患者和健康对照的历史数据进行比较，并以平均值 ± SD 表示。 结果: 9 例 eCHa 、 9 例 eCHr 和 13 例 cCH 患者完成了研究，获得了 11 例 CGRP 诱导的 CH 发作的血液样本。基线时 CH 组之间 NSE 水平无差异,但与 32 例偏头痛患者相比，处于疾病活动期的 CH 患者水平更高 (9.1 ± 2.2 µ g/L vs 6.0 ± 2.2 µ g/L，P <.0001) 和 6 名健康对照 (9.1 ± 2.2 µ g/L vs 7.3 ± 2.0 µ g/L,P = .007)。CGRP-输注未引起 NSE 变化，在报告 CGRP 诱导的 CH 发作 (2.39 µ g/L, 95% Cl [-0.26，3.85]，P = .061)。ECHa 患者基线 S100B 水平高于 cCH 患者 (0.06 ± 0.02 µ g/L vs 0.04 ± 0.02 µ g/L，P = .018)。输注 CGRP 和 CGRP 诱导的攻击没有改变 S100B 水平。除了诱导的 CH 发作外，未观察到其他不良事件。 结论: 基线时 eCHa 患者 S100B 血浆水平高于 cCH 患者，CGRP 诱导的 CH 发作引起 NSE 轻度升高，但不显著。我们的研究结果表明胶质细胞的发作性激活在 CH 病理生理学中的可能作用，但需要进一步的研究。
METHODS::Multiple sclerosis (MS) is a chronic neurodegenerative disorder with clinical symptoms of neuroinflammation and demyelination in the central nervous system. Recently, herbal medicines are clinically effective against MS as the current disease-modifying drugs have limited effectiveness. Hence, the present study evaluated the therapeutic potential of Ocimum basilicum essential oil (OB) in ethidium bromide (EB)-induced cognitive deficits in the male rats. Further, the effect of OB (50, 100 and 200 μL/kg) was evaluated on EB-induced neuroinflammation, astrogliosis and mitochondrial dysfunction in the pre-frontal cortex (PFC) of the animals. The EB was injected through bilateral intracerebroventricular route into hippocampus to induce MS-like manifestations in the rats. OB (100 and 200 μL/kg) and Ursolic acid (UA) significantly reduced the EB-induced cognitive deficits in Morris water maze and Y-maze test paradigms. OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced neuroinflammation in terms of increase in the levels of pro-inflammatory cytokines (TNF-alpha and IL-6) in the rat PFC. Further, OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced astrogliosis in terms of increase in the levels of GFAP (Glial fibrillary acidic protein) and Iba-1 (Ionized calcium binding adaptor molecule-1) in the rat PFC. In addition, OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced decrease in the mitochondrial function, integrity, respiratory control rate and ADP/O in the PFC of the rodents. Moreover, OB (100 and 200 μL/kg) and UA significantly reduced the EB-induced mitochondria-dependent apoptosis in the PFC of the rat. Hence, it can be presumed that OB could be a potential alternative drug candidate in the pharmacotherapy of MS.
METHODS::Sleep fragmentation is an increase in sleep-wake transitions without an overall decrease in total sleep time. Sleep fragmentation is well documented during acute and chronic hospitalization and can result in delirium and memory problems in children. Sleep fragmentation is also often noted in neurodevelopmental disorders. However, it is unclear how sleep fragmentation independent of disease affects brain development and function. We hypothesized that acute sleep fragmentation during the neonatal period in otherwise healthy animals would result in neuroinflammation and would be associated with abnormalities in cognitive development. The orbital shaker method was used to fragment sleep for 72 h in postnatal day 3 New Zealand white rabbit kits (fragmentation group). To control for maternal separation, the sham group was separated from the dam and maintained in the same conditions without undergoing sleep fragmentation. A naïve control group remained with the dam. Kits underwent behavioral testing with novel object recognition and spontaneous alternation T-maze tests at 2-3 weeks post-fragmentation and were sacrificed 3-50 days after fragmentation. Sleep fragmentation resulted in acute and chronic changes in microglial morphology in the hippocampus and cortex, and regional differences in mRNA expression of pro- and anti-inflammatory cytokines at 3, 7 and 50 days post-fragmentation. Impaired novel object recognition and a longer latency in T-maze task completion were noted in the fragmented kits. This was in spite of normalization of sleep architecture noted at 2 months of age in these kits. The results indicate that transient neonatal sleep fragmentation results in short-term and long-term immune alterations in the brain, along with diminished performance in cognitive tasks long-term.
METHODS:BACKGROUND:Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a recently approved therapy for patients with drug-resistant epilepsy. To date, there is a poor understanding of the mechanism of action and lack of in vivo biomarkers. We propose a method for investigating the in vivo stimulation effects using blood-oxygen-level dependent (BOLD) MRI and present the brain activation pattern associated with ANT DBS. METHODS:Two patients undergoing ANT DBS for epilepsy underwent BOLD MRI using a block design after the DBS was programmed to alternate ON/OFF in 30 second blocks. The scanner was triggered utilizing surface electrophysiological recording to detect the DBS cycle. Nine total runs were obtained and were analyzed using a general linear model. RESULTS:Active ANT stimulation produced activation within several areas of the brain, including the thalamus, bilateral anterior cingulate and posterior cingulate cortex, precuneus, medial prefrontal cortex, amygdala, ventral tegmental area, hippocampus, striatum, and right angular gyrus. CONCLUSIONS:Utilizing block-design BOLD MRI, we were able to show widespread activation resulting from ANT DBS. Overlap with multiple areas of both the default mode and limbic networks was shown suggesting that these nodes may modulate the effect of seizure control with ANT DBS.