The postictal state in epilepsy and its clinical significance / 中华神经科杂志

The postictal state refers to the abnormal condition occurring between the end of an epileptic seizure and return to baseline condition,including a variety of cognitive, motor, sensory, autonomic, mental and behavioral impairments. The symptoms which may last from seconds to days are various and the severity is different. It also may exert great impact on patients′ health and quality of life. However, the lack of relevant studies at home and abroad, along with the absence of correct understanding of this in clinical practice, may lead to frequent misdiagnosis and mistreatment. This article will review the concepts, pathophysiological mechanisms, clinical manifestations, diagnosis, differential diagnosis, clinical significance and intervention strategies, aiming at deepening the understanding of the phenomenon, as well as providing references for further clinical research.

A new polycyclic polyprenylated acylphloroglucinols from Hypericum lagarocladum N. Robson / 药学学报

Silica gel column chromatography, reversed phase C18 column chromatography, Sephadex LH-20 gel column chromatography, high performance liquid chromatography and medium performance semi preparative liquid chromatography were performed to separate and purify the chemical constituents of Hypericum lagarocladum N. Robson. Spectroscopic methods such as MS and NMR combined with physicochemical properties were applied in identifying the structures of the isolated compounds. A total of 11 compounds were isolated and identified as hyperlagarone A (1), hyperpatulone E (2), hyperbeanol G (3), uralione D (4), tomoeone F (5), pyramidatone A (6), tomoeone A (7), tomoeone B (8), hyperbeanol C (9), hyperbeanol A (10), and hypercohone G (11), respectively. Compound 1 is a new polycyclic polyprenylated acylphloroglucinol derivative, and compounds 2-11 are isolated from this plant for the first time. 11 compounds were tested for glucose uptake in L6 cells, and the results showed that compounds 7 and 8 had significant effect on glucose uptake.

Prognosis and its influencing factors of patients with seizure recurrence after anti-epileptic drug withdrawal / 中华神经科杂志

Objective:To explore the seizure recurrence and prognosis of epilepsy in relapse after anti-epileptic drugs (AEDs) withdrawal, and the influencing factors for these conditions.Methods:From December 2009 to August 2018, patients from the Affiliated Brain Hospital of Nanjing Medical University who relapsed after AEDs withdrawal were collected and followed up for at least 18 months. The seizure recurrence and prognosis of these patients were prospectively observed. The Kaplan-Meier method was used for survival analysis. The associated risk factors of the second relapse in the enrolled patients were analyzed by multivariate Cox analysis. The included patients were divided into good prognosis group and poor prognosis group according to whether they had achieved seizure freedom for at least one year after the first relapse. A multivariate Cox regression model was used to analyze the independent risk factors affecting their prognosis.Results:A total of 56 patients with epilepsy in relapse after AEDS withdrawal were collected. The average follow-up period was 46.23 months (18-120 months) from the initial time of seizure recurrence, and 21 patients (37.5%) had the second seizure recurrence. The relapsing risk in patients who continued to be observed without adding AEDs was higher than those who were treated immediately with drugs [9/16 vs 30.0% (12/40)], but without statistically significant difference (χ2=2.220, P=0.071). The results of univariate analysis showed that focal seizures, seizure frequency more than once per month before remission and poly-drug therapy before AEDs withdrawal were associated with high risk of the second relapse. Poly-drug therapy was an independent risk factor for the second relapse by multivariate Cox analysis ( HR=3.383, 95% CI 1.257-9.105). Of the 56 patients with epilepsy in relapse after AEDs withdrawal, 47 patients (83.9%) had a good prognosis without seizure for at least one year, and of 33 patients who were followed up for three years or more, 26 (78.8%) had no seizure for at least two years. Between the group retreated immediately after the first recurrence and the group without immediate treatment [87.5% (35/40) vs 12/16],there were no statistically significant differences on the proportions of good prognosis (χ2=2.333, P=0.258). Univariate analysis showed that the course of epilepsy>6 months before initial treatment, the frequency of seizures>1/month before remission, symptomatic epilepsy and poly-drug therapy were associated with the poor prognosis. However, none of independent risk factors was found for the poor prognosis through the multivariate analysis. Conclusions:The prognosis of patients with epilepsy in relapse after AEDs withdrawal is well, and about 2/3 patients with epilepsy in relapse after AEDs withdrawal have no more seizure recurrences. The poly-drug therapy before AEDs withdrawal may be an independent risk factor for the second seizure relapse.

Construction of targeted cryptotanshinone liposomes and research on its in vitro anti-glioma effect / 药学学报

Cryptotanshinone (CPT), an active ingredient with the inhibitory effect on brain glioma cells, is trapped with poor solubility and low tumor permeability. Therefore, it is urgent to design nano drug delivery systems characterized with deep penetration and accurate targeting. In the present study, tLyp-1 modified liposomes loaded with CPT (tLipo/CPT) was prepared by emulsion solvent evaporation method. Peptide tLyp-1 which targeting tumor angiogenesis and neuropilin receptors (NRP) was modified on surface of CPT liposomes, with the aim of active targeting brain glioma cells and further release CPT precisely. The size and polymer dispersity index (PDI) of tLipo/CPT were (162.2 ± 14.6) nm and 0.24 ± 0.03. The optimal molar ratio of tLyp-1 modified on CPT liposomes was 0.5% determined by intracellular fluorescence parameters. The morphology displayed a smooth sphericity structure as determined by transmission electron microscope. Efficiency of CPT encapsulated in tLipo/CPT was detected by high performance liquid chromatography. The encapsulation efficiency of CPT was (70.06 ± 7.22) %. Liposomes modified with tLyp-1 peptide (tLipo) were internalized more than liposomes not modified with tLyp-1 (Lipo) by GL261 cells. Fluorescence intensity of tLipo in GL261 cells increased 40% than that of Lipo. Furthermore, we proved that the intake of tLipo/CPT in GL261 cells was mediated by NRP-1 receptor. MTT analysis indicated that tLipo/CPT significantly inhibit the proliferation of GL261 cells. The half maximal inhibitory concentration (IC50) was 5.70 μmol·L-1. In vitro blood-brain barrier (BBB) model experiment indicated that tLipo/CPT could penetration across BBB. Moreover, in vivo fluorescence biodistribution study indicated tail vein injection of DiR labeled tLipo after 0.5 h, DiR fluorescence could be observed in the brain of mice. Even after 24 h, DiR fluorescence still was observed in the brain. Our research certified that tLipo/CPT can penetrate the BBB and show effect of anti-glioma by inhibiting the proliferation of GL261 cells. The animal experiment was carried out in accordance with protocol evaluated and approved by the Ethics Committee of Nanjing University of Chinese Medicine.

Spatial heterogeneity and physical structure basis of antibacterial activity of Ma-Xing-Shi-Gan Decoction / 药学学报

Ma-Xing-Shi-Gan Decoction is a classic prescription. However, the interaction among multiple components of the decoction and the change of phase state are not clear. Moreover, the relationship between the physical phase state aggregated by multiple components and the efficacy still needs to be studied. In this study, we monitored the particle size changes of Ma-Xing-Shi-Gan Decoction in real time. Then we isolated different phase states by centrifugation, analyzed their composition distribution and tested their antibacterial activity. We added chemical interference agents to investigate the interaction of multi-component physical phase states accompanied by the observation of particle size change and morphology. We also studied the correlation between antibacterial activity and physical structure of phase states. The results showed during boiling process the degree of hybridization of particles was decreased and the particle size distribution was narrowed and stabilized at 170 nm. The distribution of organic and inorganic components was heterogeneous among different phase states. S-13500, supernatant isolated by 13 500 ×g centrifugation, constituted by ephedrine, amygdalin, glycyrrhizic acid and inorganic components Ca, K, Mg, etc., had the strongest antibacterial activity. The molecular interaction force in the active physical phase state was mainly hydrophobic and hydrogen bond. The destruction of the interaction force will lead to the change of phase structure and the decrease of antibacterial activity in vitro and in vivo. This study confirms that, in the boiling process of the Ma-Xing-Shi-Gan Decoction, the chemical components interweave and interact to form new physical phase states, leading to heterogeneous distribution of components. The antimicrobial activity of the active phase depends on both chemical composition and physical structure, which provides a direct evidence for the physical basis of the efficacy of traditional Chinese medicine.

Quality evaluation of fried Glycyrrhizae Radix et Rhizoma pieces by HPLC fingerprint and multicomponent quantitative analysis / 中国中药杂志

To establish the HPLC fingerprint and multi-component determination method of fried Glycyrrhizae Radix et Rhizoma pieces. HPLC analysis was performed on Thermo Acclaim ~(TM)120 C_(18) column(4.6 mm×250 mm, 5 μm). Acetonitrile-0.1% phosphoric acid aqueous solution was taken as the mobile phase for gradient elution. The flow rate was 1 mL·min~(-1),the column temperature was maintained at 30 ℃, and the detection wavelength was 237 nm and 360 nm. The similarity of 15 batches of fried Glycyrrhizae Radix et Rhizoma pieces was higher than 0.849, and 17 common peaks were identified. Liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, isoliquiritigenin and glycyrrhizic acid were identified; among them, the mass fractions of Liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, glycyrrhizic acid were were 0.519%-3.058%, 0.227%-0.389%, 0.070%-0.439%, 0.038%-0.173%, 1.381%-4.252%, respectively. According to the cluster analysis, the 15 batches of decoction pieces were classified into three categories; principal component analysis screened out four principal components, with the cumulative variance contribution rate of 86.630%, indicating that the principal components contained most information of original data. Partial least squares discriminant ana-lysis marked 6 differential components in the decoction pieces. The established fingerprint and multicomponent determination are stable and reliable, and can provide a reference for the quality control of Radix Glycyrrhizae Radix et Rhizomae and fried Glycyrrhizae Radix et Rhizoma pieces.

A target lipidomics approach to investigate the acute inflammatory irritation induced by indolealkylamines from Chansu water fraction in rats / 中国天然药物

Chansu has demonstrated adverse reactions in clinical settings, which is associated with its toxicity and limits its clinical applications. But there are methodological limitations for drug safety evaluation. In the current study, ultra-high performance liquid chromatography, lipidomic profiling, and molecular docking were used to systemically assess Chansu-induced acute inflammatory irritation and further identify the underlying drug targets. Compared with the EtOAc extract, Chansu water fraction containing indolealkylamines caused acute inflammatory irritation in rats, including acute pain (spontaneous raising foot reaction), and inflammation (paw edema). At the molecular level, lipids analysis revealed significantly higher levels of pro-inflammatory mediators of the COX and LOX pathways. However, anti-inflammatory mediators from the CYP 450, ALA, and DHA pathways markedly decreased after exposure to Chansu water fraction. Moreover, four indolealkylamines from Chansu showed a high theoretical affinity to a known irritation target, 5-HT

Challenges and strategies in progress of drug delivery system for traditional Chinese medicine Salviae Miltiorrhizae Radix et Rhizoma (Danshen) / 中草药·英文版

Traditional Chinese medicines (TCMs), with a history of thousands of years, are widely used clinically with effective treatment. However, the drug delivery systems (DDSs) for TCMs remains major challenges due to the characteristics of multi-components including alkaloids, flavones, anthraquinones, glycosides, proteins, volatile oils and other types. Therefore, the novel preparations and technology of modern pharmaceutics is introduced to improve TCM therapeutic effects due to instability and low bioavailability of active ingredients. Salviae Miltiorrhizae Radix et Rhizoma, the radix and rhizomes of Salvia miltiorrhiza Bunge (Danshen in Chinese), is a well known Chinese herbal medicine for protecting the cardiovascular system, with active ingredients mainly including lipophilic tanshinones and hydrophilic salvianolic acids. In this review, this drug is taken as an example to present challenges and strategies in progress of DDSs for TCMs. This review would also summary the characteristics of active ingredients in it including physicochemical properties and pharmacological effects. The purpose of this review is to provide inspirations and ideas for the DDSs designed from TCMs by summarizing the advances on DDSs for both single- and multi-component from Danshen.

Structural Chinese medicine: new research field on pharmacodynamic substance basis of traditional Chinese medicine / 中国中药杂志

The research on the pharmacodynamic substance basis of traditional Chinese medicine(TCM) is a key scientific issue for the inheritance and development of TCM. At present, a large number of remarkable achievements have been made in the field of chemical components in Chinese medicine, however, another important aspect, namely the physical structure and mode of action of the multi-component assembly of TCM, has not been clearly understood and deeply studied. From the bottleneck of restricting material ba-sic research, we objectively analyzed the common cause of the existing problems. Based on the new discoveries and advances of active substances from TCM emerging in recent years, we extracted and summarized the concept of structural Chinese medicine, elaborated the basic ideas, main features and research modes, hoping to provide theoretical and practical references for the study on the pharmacodynamic substance basis and other research fields of TCM.

Correctly understanding the relationship between autoimmune epilepsy and autoimmune encephalitis / 中华神经科杂志

Both autoimmune epilepsy and autoimmune encephalitis are new clinical concepts proposed in recent years with the development of neuroimmunology. Is it appropriate for the patients with new-onset epileptic seizures and positive neuron antibodies diagnosed as autoimmune encephalitis or autoimmune epilepsy? There are still disputes and misunderstandings. Because there are usually some common anti-neuronal antibodies detected in the serum or cerebrospinal fluid of them both, and additionally their clinical manifestations have certain overlaps, such as drug resistant epilepsy and cognitive impairment, both concepts are often confused in clinical practice, resulting in unnecessary excessive long-term anti-epileptic treatment. This review interprets the differences and connections between the two diseases on concepts, epidemiology, pathogenesis and related risk factors, clinical manifestations, auxiliary examination, treatment and prognosis.

Reconsideration of the definition of drug resistant epilepsy / 中华神经科杂志

International League Against Epilepsy published a unified standard for drug resistant epilepsy by numbers of unsuccessful anti-epileptic drugs, criteria for seizure control and follow-up time in 2009. However, there are still some problems and even some controversies in the clinical application of this standard. To provide references for future clinical application and scientific research, we reconsider the definition of drug resistant epilepsy from its historical definitions, core elements and existing problems, and propose that some drug resistant epilepsy patients are probably more appropriately defined as chronic epilepsy.

Correctly understanding the relationship between autoimmune epilepsy and autoimmune encephalitis / 中华神经科杂志

Both autoimmune epilepsy and autoimmune encephalitis are new clinical concepts proposed in recent years with the development of neuroimmunology.Is it appropriate for the patients with new-onset epileptic seizures and positive neuron antibodies diagnosed as autoimmune encephalitis or autoimmune epilepsy? There are still disputes and misunderstandings.Because there are usually some common anti-neuronal antibodies detected in the serum or cerebrospinal fluid of them both,and additionally their clinical manifestations have certain overlaps,such as drug resistant epilepsy and cognitive impairment,both concepts are often confused in clinical practice,resulting in unnecessary excessive long-term anti-epileptic treatment.This review interprets the differences and connections between the two diseases on concepts,epidemiology,pathogenesis and related risk factors,clinical manifestations,auxiliary examination,treatment and prognosis.

Interictal epileptiform discharges in antiepileptic drug withdrawal in patients with epilepsy / 中华神经科杂志

Approximately two-thirds of patients with epilepsy become seizure-free with the adequate antiepileptic drug therapy.It is generally believed that antiepileptic treatment might be gradually withdrawn until stopped after a minimum period of two years of seizure freedom,as well as making a careful evaluation of the risk/benefit ratio.In the antiepileptic drugs discontinuance literature,the most consistent risk factors predictive of relapse are remote symptomatic causes,abnormal electroencephalogram and special epilepsy syndrome.The impacts of abnormal electroencephalogram,especially interictal epileptiform discharges on the seizure relapse after antiepileptic drugs withdrawal are not completely clear for now.In this article the literature describing the predictive value of interictal epileptiform discharges in different withdrawal periods is reviewed.

Material Basis and Action Mechanism of Wendantang in Treatment of Nervous System Diseases / 中国实验方剂学杂志

Wendantang (WDT) is a classical traditional Chinese medicine prescription composed of Pinelliae Rhizoma, Bambuseae Caulis in Taenias, Aurantii Fructus Immaturus, Citri Reticulatae Pericarpium, Zingiberis Rhizoma Recens, Glycyrrhizae Radix et Rhizoma, with the effect in regulating Qi-movement and phlegm and relieving stomach and gallbladder. The clinical studies have proved that WDT has significant therapeutic effects on depression, insomnia, schizophrenia, Alzheimer's disease and other nervous system diseases, but wihtout systematic understanding of material basis and compatibility principle because of the complex chemical composition and the scattered research results. Focusing on the neurological diseases and based on the origin of ancient recipes and modern research examples, the author sorted out and summarized the active ingredients constituting the recipe, paid attention to the effect of the compatibility on the composition and efficacy transmission, and judged the rationality of composition intention and selection. On this basis, it comprehensively identifies the potential components and effective paths that can well treat the nervous system diseases, and had the overall understanding about mutual relationship between composition and efficiency. In this article, we expect to find its scientific basis of effective materials and the key technology of quality standards, and define the direction of future research, so as to provide valuable reference for secondary development and new preparations designed of classic prescriptions.

Effect of family factors on the prognosis of patients with epilepsy / 中华神经科杂志

Objective To investigate the effect of family factors on the prognosis of patients with epilepsy and the relationship between family factors and clinical characteristics of epilepsy.Methods Data were collected from 107 patients definitely diagnosed with epilepsy who were treated by antiepileptic drugs for at least two years.All the patients were divided into good or poor prognosis group according to whether achieving at least one year free of seizures.The clinical and family data were colleeted.The questionnaire Family Adaptability and Cohesion Evaluation Scale-Ⅱ-Chinese Version containing 30 items was used for patients and the Epilepsy Knowledge Questionnaire containing 34 questions for primary caregiver.We compared the clinical and family factors between the two groups to identify the predictors of poor control of seizures with univariate and multiple Logistic regression,and observed the relationship between family factors and clinical features such as course,type of seizure,seizure frequency,etc,with Pearson correlation analysis.Results Patients with poor prognosis were more likely to have interictal epileptiform discharges (IEDs),multidrug treatment and pre-treatment seizure frequency of more than once monthly (84.6％ (44/52) vs 50.9 ％ (28/55),x2 =13.797,P =0.000;63.5 ％ (33/52) vs 34.5 ％ (19/55),x2 =8.947,P =0.003;38.5％ (20/52) vs 5.5％ (3/55),x2 =17.257,P =0.000).Family in rural area,unbalanced family type,number of family members were much more in poor prognosis group than in good prognosis group (51.9％ (27/52) vs 25.5 ％ (14/55),x2 =7.923,P =0.005;80.8 ％ (42/52) vs 49.1％ (27/55),x2 =11.712,P=0.000;4.1 ± 1.1 vs 3.6 ±0.8,t=2.631,P=0.010).And average family income,education level of father,the level of epilepsy knowledge of primary caregiver were significantly lower in poor prognosis group than in good prognosis group (19/20/13 vs 11/17/27,x2 =7.198,P =0.027;15/30/7 vs 4/34/17,x2 =10.709,P =0.005;36/11/5 vs 15/25/15,x2 =19.022,P =0.000).Multiple Logistic regression analysis demonstrated that IEDs (OR =12.332,95％ CI 2.756-55.190,P =0.001),pretreatment seizure frequency of more than once monthly (OR =8.401,95％ CI 1.573-44.884,P =0.013)were clinical risk factors of unfavorable prognosis;more family members (OR =3.021,95％ CI 1.554-5.870,P =0.001),poor epilepsy knowledge of primary caregiver (OR =3.392,95％ CI 1.304-8.821,P=0.012) and unbalanced family type (OR=4.794,95％ CI 1.217-18.894,P=0.025) were independent family risk factors of poor prognosis.The level of epilepsy knowledge of primary caregiver was inversely associated with duration (r =-0.237,P =0.014).Conclusions The prognosis of epilepsy is not only affected by clinical factors,but also by family factors.More family members,poor epilepsy knowledge of primary caregiver and unbalanced family type are independent risk factors of unfavorable prognosis.The poorer epilepsy knowledge the primary caregivers have,the longer duration the disease has.

Effects of downregulated pregnane X receptor on glutamate-induced expression and activity of P-glycoprotein in the mouse brain microvascular endothelial cells / 临床神经病学杂志

Objective To investigate the effects of downregulated pregnane X receptor (PXR)on expression and activity of P-glycoprotein(P-gp)in mouse brain microvascular endothelial cells (mBMEC)exposed to glutamate (GLU)to mimic conditions during seizures. Methods The bEnd.3 cells,were cultured in vitro and treated with culture medium containing 0 μmol,10 μmol,50 μmol,100 μmol GLU for 30 min and exposed to 100 μM GLU for different durations (0 min,15 min,30 min). With PXR knockdown using siRNA,the cells were divided into NC siRNA plus GLU group and siRNA-PXR plus GLU group. Western blotting was used to detect the protein expressions of P-gp and PXR in each group. Immunofluorescence assay was used to detect localization of PXR in cells. The expression of P-gp mRNA was detected by RT-qPCR. Rhodamine123 (Rh123)accumulation assay was used to study the activity of the P-gp in cells.Results PXR and P-gp protein expressions in the 50 μmol and 100 μmol GLU group were significantly higher than that in the blank group(P＜0.05),especially maximal expressions occurred in the 100 μmol GLU group. GLU exposures as short as 15 min and 30 min significantly increased PXR expressions(all P＜0.05);P-gp expression in the 30 min groups was higher than that in the blank group (P＜0.05 ). The data of immunofluorescence analysis suggested that the PXR nuclear accumulation increased in the 100 μM GLU group, compared with the blank group(P＜0.05). Compared with NC siRNA plus GLU group,the protein level of PXR was decreased by approximately 37%[(1.00 ± 0.00)vs(0.63 ± 0.18);t＝3.41,P＝0.02]and the levels of P-gp protein and mRNA were respectively decreased by 43%[(1.00 ± 0.00)vs (0.57 ± 0.09);t＝7.94,P＝0.00] and 52%[(1.00 ± 0.04)vs (0.48 ± 0.08);t ＝10.98,P＝0.00]in the siRNA-PXR plus GLU group. The fluorescence intensity of intracellular Rh123 in the GLU group (0.72 ± 0.01)was lower than that in the blank group [(1.00 ± 0.03);t ＝9.66,P＝0.00]. The fluorescence intensity of Rh123 in the GLU plus verapamil (P-gp inhibitor)group (1.07 ± 0.04)was higher than that in the GLU group (t＝ －11.93,P＝0.00). The fluorescence intensity of Rh123 in the siRNA-PXR plus GLU group (0.91 ± 0.03)was higher than that in the NC siRNA plus GLU group[(0.69 ± 0.05);t＝ －7.52,P＝0.00]. Conclusions Downregulation of PXR expression results in the inhibition of P-gp expression and activity in the mBMEC exposed to GLU to mimic seizures. PXR may play an important role in the regulation of seizure-induced expression and activity of P-gp in the blood-brain barrier.

Survey of precipitants of epileptic seizure / 中华神经科杂志

Objective To investigate precipitants of epileptic seizure, and to explore the correlation between various precipitants and relationship between precipitants and clinical features of epilepsy.Methods Data were collected from 154 patients attending a tertiary-care epilepsy clinic of Nanjing Brain Hospital between April 2015 and April 2016.The patients with epilepsy were older than 16 years, had a clinical history of one year or more, and one seizure at least a year and one seizure at least in the latest three months.An enclosed questionnaire was combined with open interview to identify and characterize seizure precipitants and clinical characteristics of patients.Patients were asked respectively whether there were some precipitants three months before and during last three months.Correlation between seizure precipitants and relationship between precipitants and clinical characteristics, such as age, gender, course, seizure frequency and so on, were calculated.Results A total of 125 (81.2%) participants reported at least one precipitant.Common precipitants (in descending order) were as follows: emotional stress (56.0%), sleep disorder (38.4%), fatigue (27.2%), missed medication (20.0%).There were one to six different precipitants for one patient, and 60.8% of patients had two or more precipitants.There was a correlation between emotional stress and sleep disorders as well as fatigue (χ2=4.665, 8.668;P<0.05).Patients with idiopathic epilepsy were more sensitive to sleep disorders.There was no relationship between total precipitants and clinical features such as age, gender, age of onset, duration, type of seizure, seizure frequency, number of drug taking and so on.Conclusions Seizure precipitants were found widespread.The most common precipitants were found to be emotional stress, sleep disorders, fatigue and missed medication.There existed a correlation between emotional stress and sleep disorders as well as fatigue.There was no connection between total precipitants and patient′s demographic characteristics as well as clinical features.However, the type of seizure precipitants was different in patients with different demographic and clinical characteristics.

Prognosis and its influencing factors of post-encephalitic epilepsy / 临床神经病学杂志

Objective To investigate the prognosis and its influencing factors of post-encephalitic epilepsy ( PEE) .Methods Fifty viral encephalitis patients with PEE were followed up, which prognosis was observed by whether their no seizures for at least 1 year or not.The clinical data of patients was collected, and the relate risk factors on the poor prognosis of PEE were analyzed.Results The disturbance of consciousness and the seizure presence during acute encephalitis, more than ten seizures in poor prognosis group were much higner than the good one (all P0.05 ) .Multiple logistic regression analysis demonstrated that disturbance of consciousness during acute encephalitis、seizures presence in acute encephalitis were independent risk factors of poor outcome in PEE ( OR=7.269,95%CI:1.22 -43.35,P=0.029;OR =22.893,95%CI:4.02 -130.43,P=0.000).Conclusion Disturbance of consciousness during acute encephalitis, seizure presence in acute encephalitis both are the single risk factors of poor prognosis in PEE.

Effect of activation of nuclear factor-κB/hypoxia-inducible factor-1α pathway on the hippocampal neurodegeneration caused by status epilepticus in rats / 中华神经科杂志

Objective To observe the roles of nuclear factor-κB (NF-κB) and hypoxia-inducible factor-1 o (HIF-1 α) in hippocampal neurodegeneration of status epilepticus (SE) rats, and explore whether HIF-1α activation is regulated by NF-κB.Methods A total of 110 male Sprague-Dawley rats were randomly divided into seven groups : (1) Control group treated with saline (control, n =15), (2) sham group implanted cannula into lateral ventricle and treated with saline (sham, n =15), (3) SE group treated with pilocarpine (SE, n =20), (4) NF-κB activity inhibitor pyrrolidine dithiocarbamate (PDTC) group treated only with PDTC (PDTC, n =15), (5) SE + PDTC group treated with pilocarpine plus PDTC (SE + PDTC, n =15), (6) SE + HIF-1o siRNA group implanted cannula into lateral ventricle and treated with pilocarpine plus HIF-1 α siRNA (SE + HIF-1α siRNA, n =15), (7) SE + control siRNA group implanted cannula into lateral ventricle and treated pilocarpine plus control siRNA (n =15).SE was induced by injecting lithium chloride and pilocarpine.The seizure of rats was observed.The protein expressions of NF-κB and HIF-1 α in hippocampus of rats were examined by Western blotting.The degenerating neurons in hippocampus were detected by Fluoro-Jade C (FJC) staining.Results Twenty-four hours after termination of SE, the nuclear protein expressions of NF-κB and HIF-1α in hippocampus of rats were increased in SE group (0.57 × 0.06, 0.47 ± 0.07) compared with those in control group (0.23 ± 0.03, 0.20 ± 0.03;P ＜0.05);and compared with SE group PDTC significantly decreased the nuclear protein expressions of NF-κB and HIF-1 α in SE + PDTC group (0.23 ± 0.03, 0.14 ± 0.03;P ＜ 0.05);in SE + PDTC group the numbers of FJC positive cells in CA1 area (28.33 ±5.03) were decreased compared with that in SE group (76.67 ± 13.32);HIF-1 o siRNA injected into lateral ventricle of rats significantly decreased the expression of HIF-1α in hippocampus (0.22 ±0.03) and the number of FJC positive cell in CA1 area (27.34 ±7.02) in SE + HIF-1α siRNA group compared with those in SE group (0.39 ±0.06, 76.67 ± 13.32;P ＜0.05).Conclusions These data suggest that SE can result in activation of NF-κB/HIF-1o pathway in brain.Inhibition of the pathway can attenuate hippocampal neurodegeneration caused by SE, which has the brain protective effect.

HMGB1 upregulates P-glycoprotein expression in the brain microvascular endothelial cells of the mouse / 医学研究生学报

[Abstract ] Objective High-mobility group box-1 (HMGB1) is abundantly released in the epileptogenic brain tissue , but few reports are seen about the effect of HMGB 1 on the expression of P-glycoprotein ( P-gp) in the vascular endothelial cells of the epi-leptogenic tissue .This study is to explore whether HMGB 1 can regulate P-gp expression in the brain microvascular endothelial cells of the mouse in vitro . Methods Immortalized brain microvascular endothelial bEnd .3 cells of the mouse were cultured in vitro and al-located to different concentration groups ( treated with culture medium containing 10 , 100 , 500 , and 1000 ng/mL HMGB1 for 8 hours), treatment duration groups (treated with culture medium containing 100 ng/mL HMGB1 for 4, 8, 16, 24, and 32 hours), and a control group ( treated with culture medium without HMGB 1 ) .The mRNA expression of P-gp-encoding gene-multidrug resistance gene 1a (mdr1a) was detected by real-time qPCR, and its protein expression determined by Western blot and immunocytochemistry . Results The results of qPCR manifested that the expressions of mdr 1a mRNA were 1.646 ±0.176, 1.777 ±0.135, 1.617 ±0.043, and 1.398 ±0.182 in the 10, 100, 500, and 1000 ng/mL HMGB1 groups, respectively, significantly higher than 1.030 ±0.284 in the control group (P<0.05), and so were those in the 4, 8, 16, 24 h, and 32 h groups (2.655 ±0.112, 2.168 ±0.212, 1.823 ± 0.232, 1.418 ±0.376, and 1.445 ±0.123) than in the control (1.010 ±0.164) (P <0.05).Western blot showed a significant increase in the P-gp protein expression in all the concentration groups (P<0.05) as well as in the 8 h and 16 h treatment duration groups as compared with the control group (P<0.05).Immunocytochemis-try also revealed a higher P-gp expression in the HMGB1-treated than in the control cells (P<0.01). Conclusion HMGB1 can upregu-late the expressions of mdr1a mRNA and P-gp protein in the brain microvascular endothelial cells of the mouse , which may associated with drug resistance of central nervous system diseases , especially that of epilepsy .