find
Author
"迟潇洒" 6 results
-
ObjectiveTo investigate the association between mTOR pathway and pharmacoresistance of Sprague-Dawley rat epilepsy model kindled by coriaria lactone.
MethodsA kindling model of pharmacoresistant temporal lobe epilepsy was developed by injecting Sprague-Dawley (SD) rats with coriaria lactone (CL) (1.75 mg/kg, every 84 h). Normal SD rats were injected with normal sodium (NS) served as control group. Rats with five or more consecutive stage 5 seizures were included in kindled group. Immunohistochemistry was used to detect the levels of P-S6 in both groups.
ResultsThe expressions of P-S6 in CA1 and CA3 were significantly higher compared with control group, and were mainly in astrocytes (P < 0.001). In addition, the expression of P-S6 in DG area was significantly higher than that in control group, with more granular cell and neuron (P < 0.001).
ConclusionsThe mTOR pathway may be correlated with the drug resistance of refractory lobe epilepsy kindled by coriaria lactone.
-
局灶性皮质发育不良(Focal cortical dysplasias, FCDs)是儿童难治性癫痫的常见病因,也是常需癫痫手术的原因。尽管近年来在细胞和分子生物上的进展,FCDs的病理机制仍不清楚。该研究旨在回顾FCDs的分子机制,系统地检索FCDs组织、分子和电生理方面的文献,以明确可能的治疗靶点。哺乳动物雷帕霉素靶蛋白信号通路(mammalian target of rapamycin,mTOR)是一些FCDs结构和电生理紊乱的重要机制。其他的假说包括病毒感染、早产、头部外伤和脑肿瘤。mTOR抑制剂(如:雷帕霉素)在动物和少量FCDs患者的队列癫痫控制中取得阳性结果。近期研究在发育不良组织细胞的分子和电生理机制方面取得了令人鼓舞的进展。尽管mTOR抑制剂有良好的治疗前景,但仍需大规模的随机对照研究评估其有效性和不良反应,并且需要基础研究发现新的分子水平诊断和治疗方式。
Release date：2016-11-28 01:27
Export
PDF
Favorites
Scan
-
癫痫发作可能发生在刚刚卒中发生以后或在很久以后。此外，癫痫也常发生在患有脑白质疏松的患者。尽管卒中后早期痫性发作被广泛研究，卒中后癫痫(Post-stroke epilepsy，PSE)和与脑白质疏松相关癫痫(Epilepsy associated with leukoaraiosis，EAL)研究较少。文章目的是回顾PSE和EAL相关病理生理学，预后和治疗情况。并进行了广泛的文献检索，以筛选关于PSE和EAL的动物实验和临床文章。同时，还对纳入研究中PSE和EAL发生的风险因素进行了系统的回顾分析。PSE是由于瘢痕组织内和其附近神经元兴奋性增加引起的。白质改变在EAL中的作用尚待阐明。荟萃分析显示皮质受累[ OR=3.71，95% CI (2.34, 5.90)，P < 0.001]，脑出血[ OR=2.41，95% CI (1.57, 3.70)，P < 0.001]和早期痫性发作[ OR=4.43，95% CI (2.36, 8.32)，P < 0.001]显著增加PSE发生风险。关于EAL，没有前瞻性、基于人群的研究评估不同变量对癫痫发作风险的影响。关于PSE治疗的研究相对有限。PSE药物控制效果通常良好。有关危险因素、预后和EAL治疗的资料较缺乏。PSE的病理生理学和危险因素是明确的，但在EAL中仍需进一步阐明。PSE和EAL的治疗依赖于临床医生的判断，并应在个人基础上进行调控。
Release date：2017-05-24 05:46
Export
PDF
Favorites
Scan
-
ObjectiveThe abnormal autophagy fluxis involved in the pathophysiological process of drug-resistance temporal lobe epilepsy (TLE).Hippocampal sclerosis (HS) is the main pathological type of drug-resistance TLE.Different subtypes of HS have various prognosis, etiology and pathophysiology.However, whether theabnormal block ofautophagy flux involved in this process has not been reported.This study proposed a preliminary comparison of autophagy fluxin typical and atypical HS to investigate the potential pathogenesis and drug-resistance mechanism of atypical HS.
MethodsSurgical excision of hippocampal and temporal lobe epilepsy foci were performed in 17 patients with drug-resistance TLE.Patients were grouped according to the HS classification issued by International League Against Epilepsy in 2013.The distribution and expression of LC3B, beclin-1 and P62 were detected by immunohistochemistry and Western blot in each group.
ResultsLC3B, beclin-1 and P62 are mainly expressed in neuronal cytoplasm, which is consistent with previous reports.Taking β-actin as internal reference, we found that LC3B and Beclin-1, the downstream products of autophagy flux, have increased significantly (P < 0.01) in the atypical HS group compared to typical HS group.However, the autophagy flux substrate P62 has no difference between the groups.This result suggested that compared with the typical HS group, atypical HS group had autophagy substrate accumulation and autophagy flux abnormal block.Besides, we found that glyceraldehycle-3-phosphate dehydrogenase(GAPDH) was significantly different between the two groups (P=0.003).
ConclusionThere is abnormal phenomenon of autophagy flux in atypical HS, and GAPDH elevation may be involved in its mechanism, which might provide new targets and ideas for future treatment of atypical HS.
Release date：2017-09-26 05:09
Export
PDF
Favorites
Scan
-
Lennox-Gastaut综合征(Lennox-Gastautsyndrome, LGS)是一种严重的多病因且具有特征性电生理特征的癫痫表型。前驱研究发现常见的脑网络与特征性的发作间期放电:慢棘慢复合波(Slow spike-and-wave, SSW)和阵发性快活动(Paroxysmal fast activity, PFA)。一些患者有Lennox-Gastaut样表型和皮质病灶。现旨在探讨脑网络和病灶的相互作用。选取6例具有Lennox-Gastaut表型和结构病灶的患者为研究对象, 采用3T脑电图-功能磁共振(Electroencephalography-functional magnetic resonance imaging, EEG-fMRI)进行检测。SSW和PFA时间监测用于事件相关fMRI分析, 以分析关键区域的血流动力学时间进程。结果:①PFA发生时, 额叶和顶叶的联合皮层区、丘脑和脑桥的fMRI信号增强, 且注意和静息态脑网络均同时增强, 这是一个少见的模式; ②SSW发生时, 表现为混合性的fMRI信号增强和减弱, 联合皮质区和丘脑在放电发生前信号增强, 而在放电后显著减弱, 在初级皮层区fMRI信号减弱; ③在PFA和SSW放电期间, 病灶区表现为不同的fMRI信号增强。3例患者在病灶切除术后1年无痫性发作。研究认为Lennox-Gastaut表型是一种网络癫痫, 且主要的脑网络自发不稳。Lennox-Gastaut表型和LGS的癫痫样活动, 似乎通过联合皮质区放大和表达, 这可能是由于基本的脑网络, 注意和静息态网络广泛地相互作用。接受病灶切除术后癫痫患者无癫痫发作表明皮质损伤能建立并保持这种非正常的不稳定脑网络。LGS可能是继发性脑网络癫痫, 因为其统一的癫痫临床表现, 包括PFA和SSW, 反映出脑网络功能异常而非特定的触发过程
-
哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)在皮质发育不良(Cortical dysplasia, CD)及癫痫动物模型中超活化。在神经元特异性Pten基因敲除(Neuronsubset-specific Pten knockout, NS-Pten KO)小鼠模型中, 尽管在早期癫痫发生过程中抑制mTOR信号通路能够减少癫痫样活动, 但mTOR抑制剂在癫痫建立后的作用尚不清楚。文章通过建立伴有严重慢性癫痫的NS-Pten KO成年小鼠模型, 探究mTOR抑制剂对其癫痫样活动和其他神经病理的作用。NS-Pten KO小鼠癫痫样活动、mTOR信号通路的异常调节和相关神经病理随年龄增长的变化通过视频脑电(video-electroencephalography, VEEG), 蛋白免疫印迹和免疫组化检测。NS-Pten KO小鼠出生后9周开始接受mTOR抑制剂雷帕霉素治疗(10 mg/kg i.p, 5d/周)并采用VEEG监测癫痫样活动。通过蛋白免疫印迹和免疫组化检测雷帕霉素的作用。试验发现, 随着年龄增长, NS-Pten KO小鼠的癫痫样活动恶化, 同时伴有mTOR复合物1和2(mTOR complex 1 and 2, mTORC1 and mTORC2)调节异常和进展性的星形胶质细胞和小胶质细胞增生。雷帕霉素治疗抑制癫痫样活动, 改善基线脑电活动并提高严重癫痫NS-PtenKO小鼠的预后。在分子水平, 雷帕霉素治疗降低mTORC1和mTORC2水平并减少星形胶质细胞和小胶质细胞增生。研究表明在NS-Pten KO小鼠中, 雷帕霉素成功治疗癫痫有较宽的时间窗。抑制mTOR可能是CD伴慢性癫痫及mTOR信号通路基因调节异常的潜在治疗手段。
Release date：2017-01-22 09:09
Export
PDF
Favorites
Scan
