Genotypic and phenotypic characteristics of sodium channel-associated epilepsy in Chinese population.

Variants in voltage-gated sodium channel (VGSC) genes are implicated in seizures, epilepsy, and neurodevelopmental disorders, constituting a significant aspect of hereditary epilepsy in the Chinese population. Through retrospective analysis utilizing next-generation sequencing (NGS), we examined the genotypes and phenotypes of VGSC-related epilepsy cases from a cohort of 691 epilepsy subjects. Our findings revealed that 5.1% of subjects harbored VGSC variants, specifically 22 with SCN1A, 9 with SCN2A, 1 with SCN8A, and 3 with SCN1B variants; no SCN3A variants were detected. Among these, 14 variants were previously reported, while 21 were newly identified. SCN1A variant carriers predominantly presented with Dravet Syndrome (DS) and Genetic Epilepsy with Febrile Seizures Plus (GEFS + ), featuring a heightened sensitivity to fever-induced seizures. Statistically significant disparities emerged between the SCN1A-DS and SCN1A-GEFS+ groups concerning seizure onset and genetic diagnosis age, incidence of status epilepticus, mental retardation, anti-seizure medication (ASM) responsiveness, and familial history. Notably, subjects with SCN1A variants affecting the protein's pore region experienced more frequent cluster seizures. All SCN2A variants were of de novo origin, and 88.9% of individuals with SCN2A variations exhibited cluster seizures. This research reveals a significant association between variations in VGSC-related genes and the clinical phenotype diversity of epilepsy subjects in China, emphasizing the pivotal role of NGS screening in establishing accurate disease diagnoses and guiding the selection of ASM.

Leigh Syndrome: A Study of 209 Patients at the Beijing Children's Hospital.

OBJECTIVE: Leigh syndrome (LS) is a heterogeneous neurodegenerative disease and the most frequent pediatric manifestation of mitochondrial disease. In the largest patient collection to date, this study aimed to provide new insights into the clinical and genetic spectrum of LS, defect-specific associations, and predictors of disease course and survival. METHODS: Clinical, metabolic, neuroimaging, onset, and survival data were collected from the medical records of 209 patients referred to the Beijing Children's Hospital with symmetrical basal ganglia and/or brainstem neuroimaging changes indicative of LS by 30 centers from the Chinese network of mitochondrial disease (mitoC-NET) between January 2013 and July 2021 for exploratory analysis. RESULTS: Pathogenic variants were identified in 52 genes, most frequently MT-ATP6, SURF1, and PDHA1. Maternally inherited variants accounted for 42% (heteroplasmy level ≥90% in 64%). Phenotypes spanned 92 Human Phenotype Ontology terms. Elevated serum lactate (144/195), global developmental delay (142/209), and developmental regression (103/209) were most frequent. Discriminating neuroimaging and/or clinical features were identified for MT-ATP6 (m.9176T>C), MT-ND5, PDHA1, SUCLG1, and SURF1. Poorest survival was associated with MT-ND5, MT-ATP6 (m.8993T>C and m.9176T>C), SURF1, and ALDH5A1 (≤50% 3 year's survival), in contrast to milder defects with specific treatment (ECHS1 and SLC19A3, 100% 3 year's survival). INTERPRETATION: Our data define phenotype, onset, and survival of LS in a defect-specific manner, identifying features discriminating between genetic defects and predictive of disease outcome. These findings are essential to early diagnosis, in optimizing family counseling, and to the design and monitoring of future clinical trials, the next frontier of LS research. ANN NEUROL 2022;91:466-482.

[Clinical and genetic analysis of a patient with Gitelman syndrome misdiagnosed as hypokalemic periodic paralysis].

OBJECTIVE: To explore the genetic basis for a child suspected for hypokalemic periodic paralysis. METHODS: Clinical data of the patient was collected, and venous blood samples were taken from the patient and his parents for the extraction of genomic DNA. Next generation sequencing (NGS) with target capture was carried out to detect potential variants. Suspected variants were validated by Sanger sequencing. RESULTS: The child developed fatigue without obvious reason at the age of 15. Laboratory test revealed hypokalemia but normal serum magnesium. Genetic testing discovered that he has carried two variants in the SLC12A3 gene, namely c.179C>T and c.539C>A. The patient was diagnosed with Gitelman syndrome. CONCLUSION: For children with hypokalemia, genetic testing should be considered for the differential diagnosis of Gitelman syndrome from hypokalemia due to other causes.

[Clinical and genetic analysis of a case with Nicolaides-Baraitser syndrome].

OBJECTIVE: To explore the genetic etiology of a girl featuring epilepsy, speech delay and mild mental retardation. METHODS: Peripheral blood samples of the child and her parents were collected. Genomic DNA was extracted and subjected to next generation sequencing. Suspected variant was confirmed by Sanger sequencing. RESULTS: The child was found to carry a de novo heterozygous c.3592G>A (p.V1198M) variant of the SMARCA2 gene, which was predicted to be pathogenic by bioinformatic analysis. CONCLUSION: The child was diagnosed with Nicolaides-Baraitser syndrome due to heterozygous variant of the SMARCA2 gene.

[Analysis of DOCK6 gene mutation in a child affected with Adams-Oliver syndrome type 2].

OBJECTIVE: To detect pathogenic mutation of DOCK6 gene in a patient with convulsive seizure and refractory epilepsy. METHODS: CytoScan HD-Array and next generation sequencing were used to detect the potential mutation in the patient. RESULTS: The proband has carried compound heterozygous mutations of c.188C>T (p.Arg63Gln) and c.5374C>T (p.Glu1792Lys) of the DOCK6 gene, which were respectively inherited from his mother and father. Neither mutation was reported previously. Bioinformatic analysis indicated that the two amino acids are highly conserved. Based on the ACMG guidelines, the c.188C>T mutation was predicted to be likely pathogenic, while the c.5374C>T mutation was of uncertain significance. CONCLUSION: The compound heterozygous mutations of c.188C>T (p.Arg63Gln) and c.5374C>T (p.Glu1792Lys) of the DOCK6 gene probably underlie the disease in this patient.

[Novel mutations of GLB1 gene identified in a Chinese pedigree affected with GM1 gangliosidosis].

OBJECTIVE: To explore the genetic cause for a child with growth retardation by next generation sequencing (NGS). METHODS: Clinical data of the patient was collected. Peripheral venous blood samples were taken from the neonate and his parents. Targeted capturing and NGS were carried out to detect mutations of genes associated with inborn errors of metabolism. Suspected mutations were validated by Sanger sequencing. RESULTS: The 15-month-old female patient was admitted to hospital for growth retardation for 4 months. Hypomyelination was found upon cranium MRI. Genetic testing revealed two novel insertional mutations in the GLB1 gene in the patient, namely c.2006-2007insT and c.475-476 insGGTCC. CONCLUSION: The c.2006-2007insT and c.475-476 insGGTCC mutations of the GLB1 gene probably underlie the GM1 gangliosidosis resulting in the growth retardation in the child.

Cardiac injury progression in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection: a review.

The symptoms and signs of infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are milder in children than in adults. However, in April 2020, British pediatricians first reported that coronavirus disease 2019 (COVID-19) may present as multisystem inflammatory syndrome in children and adolescents (MIS-C), similar to that observed in Kawasaki disease. MIS-C can be associated with multiple systemic injuries and even death in children. In addition to digestive system involvement, cardiac injury is prominent. This article reviews the pathogenesis, clinical manifestations, and treatment of cardiac injury caused by MIS-C, which may help clinicians in early diagnosis and timely commencement of treatment.

Nusinersen effectiveness and safety in pediatric patients with 5q-spinal muscular atrophy: a multi-center disease registry in China.

OBJECTIVE: To evaluate the effectiveness and safety of nusinersen for the treatment of 5q-spinal muscular atrophy (SMA) among Chinese pediatric patients. METHODS: Using a longitudinal, multi-center registry, both prospective and retrospective data were collected from pediatric patients with 5q-SMA receiving nusinersen treatment across 18 centers in China. All patients fulfilling the eligibility criteria were included consecutively. Motor function outcomes were assessed post-treatment by SMA type. Safety profile was evaluated among patients starting nusinersen treatment post-enrollment. Descriptive analyses were used to report baseline characteristics, effectiveness, and safety results. RESULTS: As of March 2nd, 2023, 385 patients were included. Most patients demonstrated improvements or stability in motor function across all SMA types. Type II patients demonstrated mean changes [95% confidence interval (CI)] of 4.4 (3.4-5.4) and 4.1 (2.8-5.4) in Hammersmith Functional Motor Scale-Expanded (HFMSE), and 2.4 (1.7-3.1) and 2.3 (1.2-3.4) in Revised Upper Limb Module (RULM) scores at months 6 and 10. Type III patients exhibited mean changes (95% CI) of 3.9 (2.5-5.3) and 4.3 (2.6-6.0) in HFMSE, and 2.1 (1.2-3.0) and 1.5 (0.0-3.0) in RULM scores at months 6 and 10. Of the 132 patients, 62.9% experienced adverse events (AEs). Two patients experienced mild AEs (aseptic meningitis and myalgia) considered to be related to nusinersen by the investigator, with no sequelae. CONCLUSIONS: These data underscore the significance of nusinersen in Chinese pediatric patients with SMA regarding motor function improvement or stability, and support recommendations on nusinersen treatment by Chinese SMA guidelines and continuous coverage of nusinersen by basic medical insurance.

The impact of Water Ecological Civilization City Pilot on urban green innovation: the case of China.

As an essential part of ecological civilization, water ecological civilization has significant influence on the green and sustainable development of cities. Under the background of China's Water Ecological Civilization City Pilot (WECCP), based on data from 275 cities in China from 2007 to 2019 by using the difference-in-differences (DID) model, we empirically analyzed the influence of the WECCP establishment on urban green innovation and explored the impact mechanism in depth using a mediating effect model, which aimed to verify whether the "Porter hypothesis" holds true in China. The result indicated that the WECCP had made a remarkable contribution to enhancing urban green innovation in the pilot cities. Further research found that the input mechanism played an important mediating role. In addition, the heterogeneity test indicated that cities in the central region, at low administrative levels, and in the first batch of pilots gained more from the policy establishment. This paper has theoretical implications for understanding the derived innovation benefits of the environmental policy, practical implications for identifying new drivers of urban innovation, and provides related experience for the country to further promote and expand water ecological civilization construction and useful policy inspiration for other developing countries to formulate ecological and environmental policies.

Effectiveness and tolerability of perampanel monotherapy in children with newly diagnosed focal epilepsy.

Objective: To examine the clinical effectiveness and tolerability of perampanel (PER) as initial monotherapy in pediatric patients with newly diagnosed focal epilepsy. Methods: A retrospective analysis was conducted on 62 children with newly diagnosed focal epilepsy who were treated with PER at the Epilepsy Center of Jinan Children's Hospital from July 2021 to July 2022. The treatment status, prognosis, and adverse reactions were followed up for a minimum of 6 months after the initiation of PER monotherapy. The effectiveness of the patients was estimated by the PER effective rate at 3-, 6-, and 12-month follow-up evaluations and adverse reactions were also recorded. The effective rates of PER in different etiologies and epilepsy syndromes were also statistically analyzed. Results: The effective rates of PER treatment at the different time points of evaluation were 88.7% (3 months), 79.1% (6 months), and 80.4% (12 months). With PER treatment, seizure freedom varied over time, with 61.3%, 71.0%, and 71.7% of patients at the 3-, 6-, and 12-month follow-ups, respectively. Among the etiologies of epilepsy, the effective rates of genetic etiology, structural etiology, and unknown etiology were generally above 50% at the 3-, 6-, and 12-month follow-ups. Among the epilepsy syndromes, the categories with higher treatment efficacy were self-limiting epilepsy with centrotemporal spikes (SeLECTs), self-limited epilepsy with autonomic seizures (SeLEAS), and childhood occipital visual epilepsy (COVE), with an effective rate of above 80%. Adverse events were documented in 22 patients (35.5%), but they were mild and tolerable. The most common adverse events comprised irritability, drowsiness, dizziness, and increased appetite. Conclusion: PER has favorable effectiveness and tolerability as initial monotherapy for children with newly diagnosed focal epilepsy, which could be a potential option for long-term medication in the treatment of focal epilepsy in children. The current study provided potential evidence for PER as initial monotherapy in children with focal epilepsy in clinical practice.

Influence Mechanism of Different Environmental Regulations on Carbon Emission Efficiency.

The rational use of environmental regulation tools has become an important means by which to improve the efficiency of carbon emissions. Different types of environmental regulations and their combinations have different impacts on carbon emission efficiency. In order to determine the environmental regulation configurations that may achieve high carbon emission efficiency or lead to low carbon emission efficiency, we constructed an analytical framework of connections between environmental regulation configurations and carbon emission efficiency. Moreover, 30 Chinese provinces from the period covering 2016 to 2019 were selected as research cases. In addition, the super slacks-based measure of efficiency (SE-SBM) model was applied to evaluate carbon emission efficiency. Finally, the fuzzy-set qualitative comparative analysis (fsQCA) method was employed to analyze the impact of different environmental regulation configurations on carbon emission efficiency. The results showed that the carbon emission efficiency of various regions of China is generally low (with most regions not having reached an effective level) and that there are large regional differences. We found that there are four environmental regulation configurations that can achieve high carbon emission efficiency and two environmental regulation configurations that lead to low carbon emission efficiency. Based on these configurations, we draw three conclusions: (1) There are three paths to achieving high carbon emission efficiency: one that values command-and-control environmental regulation but disfavors market-incentive environmental regulation, another that combines command-and-control environmental regulation with market-incentive environmental regulation, and a third that couples command-and-control environmental regulation with voluntary environmental regulation. (2) Two paths that may lead to low carbon emission efficiency were established: excessive penalties and the lack of specific measures. (3) In some conditions, environmental governance investment and fiscal expenditure could be substituted for each other; environmental protection administrative penalties and pollution charges are synchronized; environmental governance investment in the promotion of carbon emission efficiency is indispensable. Policies and suggestions on how the government can use environmental regulation tools to improve carbon emission efficiency are proposed from a general coordinative perspective in the final section of this paper.

Study on the Mechanism of Jiawei Shengjiang Powder in Improving Male Asthma-Induced Asthenospermia Based on Network Pharmacology and Bioinformatics.

BACKGROUND: Jiawei Shengjiang Powder (JWSJP) is a classical Chinese medicinal formula, which has been widely applied in the treatment of asthma and complications for many years due to its curative effect. AIM: To verify the effect of JWSJP in improving abnormal sperm motility caused by asthma and to explore its potential mechanism. MATERIALS AND METHODS: The active compounds of JWSJP were obtained from high performance liquid chromatography tandem mass spectrometry and the Traditional Chinese Medicine System Pharmacology. The key active components and targets of JWSJP were predicted based on network pharmacological analysis and bioinformatics research. Rats were randomly divided into normal, model and treatment groups. The rat model of allergic asthma was induced by intraperitoneal injection of ovalbumin solution. The experiment judged improvement of semen quality by evaluating sperm motility, and detected the expression of related proteins in testicular tissue of Sprague-Dawley rats by RT-qPCR and Western blot methods. Hematoxylin and eosin (HE) staining was used to observe the changes in testicular tissue structure in rats. RESULTS: Through the analysis of network pharmacology and bioinformatics, it was found that beta-sitosterol, quercetin, gallic acid, pelargonidin and kaempferol were the key active components of Jiawei Shengjiang Powder. Tumor necrosis factor (TNF), interleukin-6 (IL-6) and insulin (INS) genes are crucial targets of JWSJP in the treatment of spermatogenic dysfunction caused by acute asthma. After 8 weeks of intervention, compared with the model group, the treatment group had significantly improved sperm motility (P < 0.05). There were significant differences in TNF, IL6, and INS proteins in the treatment group, and the HE staining of testicular tissue structure in the treatment group was significantly improved. CONCLUSION: JWSJP can improve the abnormal sperm motility induced by asthma, and its mechanism may be related to the expression of related proteins and mRNA of TNF, IL6, and INS.

Molecular Genetics Analysis of 70 Chinese Families With Muscular Dystrophy Using Multiplex Ligation-Dependent Probe Amplification and Next-Generation Sequencing.

Background: Muscular dystrophy (MD) includes multiple types, of which dystrophinopathies caused by dystrophin (DMD) mutations are the most common types in children. An accurate identification of the causative mutation at the genomic level is critical for genetic counseling of the family, and analysis of genotype-phenotype correlations, as well as a reference for the development of gene therapy. Methods: Totally, 70 Chinese families with suspected MD probands were enrolled in the study. The multiplex ligation-dependent probe amplification (MLPA) was first performed to screen large deletions/duplications of DMD exons in the patients, and then, next-generation sequencing (NGS) was carried out to detect small mutations in the MLPA-negative patients. Results: Totally, 62 mutations of DMD were found in 62 probands with DMD/BMD, and two compound heterozygous mutations in LAMA2 were identified in two probands with MDC1A (a type of congenital MD), indicating that the diagnostic yield was 91.4% by MLPA plus NGS for MD diagnosis in this cohort. Out of the mutations, 51 large mutations encompassing 47 (75.8%) deletions and four duplications (6.5%) were identified by MLPA; 11 small mutations including six (9.7%) nonsense, two (3.2%) small deletions, two splice-site mutations (3.2%), and one small insertion (1.6%) were found by NGS. Large mutations were found most frequently in the hotspot region between exons 45 and 55 (70.6%). Out of the 11 patients harboring point mutations in DMD, 8 were novel mutations. Additionally, one novel mutation in LAMA2 was identified. All the novel mutations were analyzed and predicted as pathogenic according to American College of Medical Genetics and Genomics (ACMG) guideline. Finally, 34 DMD, 4 BMD, 24 BMD/DMD, and 2 MDC1A were diagnosed in the cohort. Conclusion: Our data indicated that the MLPA plus NGS can be a comprehensive and effective tool for precision diagnosis and potential treatment of MD and is particularly necessary for the patients at very young age with only two clinical indicators (persistent hyperCKemia and typical myopathy performance on electromyogram) but no definite clinical manifestations.

Effect of Qigong on self-rating depression and anxiety scale scores of COPD patients: A meta-analysis.

OBJECTIVE: To explore the clinical efficacy and safety of Qigong in reducing the self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores of patients with chronic obstructive pulmonary disease (COPD). METHODS: We searched CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE for studies published as of Dec 31, 2018. All randomized controlled trials of Qigong in COPD patients, which met the inclusion criteria were included. The Cochrane bias risk assessment tool was used for literature evaluation. RevMan 5.3 software was used for meta-analysis. RESULTS: Six studies (combined n = 415 patients) met the inclusion criteria. Compared with conventional therapy alone, Qigong in combination with conventional therapy significantly improved the following outcome measures: SDS score [mean difference (MD) -3.99, 95% CI (-6.17, -1.82), P < .001, I = 69%]; SAS score[MD -4.57, 95% CI (-5.67, -3.48), P < .001, I = 15%]; forced expiratory volume in one second/prediction (FEV1% pred) [MD 3.77, 95% CI (0.97,6.58), P < .01, I = 0]; forced expiratory volume in one second (FEV1) [MD 0.21, 95% CI (0.13, 0.30), P < .001, I = 0%]; forced vital capacity (FVC) [MD 0.28, 95% CI (0.16, 0.40), P < .001, I = 0]; 6-minute walk test (6MWT) distance [MD 39.31, 95% CI (18.27, 60.34), P < .001, I = 32%]; and St. George's Respiratory Questionnaire (SGRQ) total score [MD -11.42, 95% CI (-21.80, -1.03), P < .05, I = 72%]. CONCLUSION: Qigong can improve the SDS and SAS scores of COPD patients, and has auxiliary effects on improving lung function, 6MWT distance, and SGRQ score.

The effect of the ketogenic diet on hippocampal GluR5 and Glu(6 mRNA expression and Q/R site editing in the kainate-induced epilepsy model.

Treatment with the ketogenic diet has been used to control refractory epilepsy for many years, although its anticonvulsant mechanism is unknown. By modulating synaptic transmission in the hippocampus, kainate receptors and their RNA editing might play a role in the antiseizure action of the treatment. To investigate the potential effect of the ketogenic diet on GluR(5) mRNA and GluR(6) mRNA expression and Q/R site editing, we used the kainate-induced epilepsy model in the present study. Reverse transcription polymerase chain reaction was performed to determine GluR(5) and GluR(6) mRNA expression, and RNA editing was analyzed with the BbvIota restriction enzyme assay. The results demonstrated that expression of GluR(6) mRNA, but not GluR(5) mRNA, was significantly increased after 8 weeks of dietary treatment. Neither the GluR(5) nor the GluR(6) RNA editing rate at the Q/R site was significantly changed by dietary treatment. These data indicate that GluR(6) may be involved in the anticonvulsant mechanism of ketogenic diet treatment.

Jinwei Tang modulates HDAC2 expression in a rat model of COPD.

The aim of the present study was to investigate the effect of a Traditional Chinese Herbal Medicine (TCHM), named Jinwei Tang on histone deacetylase 2 (HDAC2) and its role in the regulation of corticosteroid resistance in a rat model of chronic obstructive pulmonary disease (COPD). Male Wistar rats were divided into five groups (each n=10): COPD group, established by the intratracheal instillation of lipopolysaccharide and passive smoke exposure, and control, budesonide, theophylline + budesonide and Jinwei Tang + budesonide groups. Lung function was measured, lung tissue histopathology was examined and HDAC2 expression in the lung was assessed by immunohistochemistry. In addition, protein levels of interleukin-8 (IL-8), tumor necrosis factor (TNF)-α and HDAC2 in lung homogenate were quantified by ELISA. The rat COPD model exhibited alterations of the ratio of forced expiratory volume in 0.2 sec (FEV0.2) to the forced vital capacity, FEV0.2, dynamic compliance and airway resistance. HDAC2 expression was markedly reduced in the lung tissue of the COPD group compared with the control group, and treatment with Jinwei Tang + budesonide or theophylline + budesonide resulted in significant attenuation of the reduction of HDAC2 expression in the lungs (P<0.05). However, treatment with budesonide alone did not significantly alter HDAC2 expression. In the Jinwei Tang + budesonide and theophylline + budesonide groups, IL-8 and TNF-α expression was significantly decreased (P<0.05) and the HDAC2 level increased (P<0.05) compared with that in the COPD group. In conclusion, Jinwei Tang modulates airway inflammation and may enhance the anti-inflammatory effect of glucocorticoid through the upregulation of HADC2 expression in a rat model of COPD.

A prospective study on the treatment of infantile spasms with first-line topiramate followed by low-dose ACTH.

PURPOSE: A prospective study was conducted for the purpose of identifying the efficacy and safety of a protocol, first-line topiramate (TPM) followed by low-dose adrenocorticotropic hormone (ACTH) as the second drug, in the treatment of infantile spasms. METHODS: 40 children newly diagnosed with infantile spasms between 2007 and 2008 were enrolled in this study. They received an initial dose of 0.5-1mg/kg/day TPM, with 0.5-1mg/kg/day ascending every 3-7 days up to the target dose within the first 1 month. Partial/nonresponders for TPM were subsequently added low-dose and short-duration ACTH as the second treatment. Both efficiency and side effects were evaluated during the follow-up period. RESULTS: Infants became spasms-free in 27 (67.5%) of all patients comprising 10 patients treated with TPM monotherapy and 17 with the combination of TPM and ACTH. Greater than 75% reduction in the frequency of spasms was found in 4 of all patients and at least 50% reduction in 4 patents as well. Side effects occurred in 29 (72.5%) patients; apart from 6 patients who needed moderately medical intervention, side effects throughout the trial were mild and well tolerated. CONCLUSIONS: This prospective study demonstrated that, on the basis of primary TPM therapy, the combination treatment both TPM and low-dose ACTH was effective and available for the patients with infantile spasms.

[Effect of ketogenic diet on hippocampus synaptic reorganization and GluR5 expression in kainic acid induced rat model of epilepsy].

OBJECTIVE: Ketogenic diet (KD) is a high fat, low protein, low carbohydrate diet. Its antiepileptic effect is certain but the underlying mechanism is unknown. The aim of the study was to reveal the possible mechanism from the view points of synaptic reorganization and GluR(5) expression in hippocampus. METHODS: Epilepsy was induced in Sprague-Dawley rats by kainic acid at postnatal day 28, all control animals were fed with normal rodent chow, whereas experimental rats were fed with ketogenic feed for 8 weeks. Spontaneous recurrent seizures were recorded. Mossy fiber sprouting and neuron damage in hippocampus were investigated by Timm staining and Nissl staining. Western blot and RT-PCR methods were applied to detect the expression of GluR(5) and GluR(5) mRNA in hippocampus. RESULTS: KD-fed rats (1.40 +/- 1.03) had significantly fewer spontaneous recurrent seizures than control diet-fed rats (7.36 +/- 3.75). The mean A of mossy fiber sprouting in the inner molecular layer of dentate gyrus was markedly higher in KA induced animals than that in saline control animals but it was similar in different diet fed groups. No significant differences were found in the mean A of Timm staining in CA(3) area and Nissl staining of neuron in hilus, CA(3) and CA(1) area. After KA kindling, KD-fed animals [(189.38 +/- 40.03)/mg pro] had significantly higher GluR(5) expression in hippocampus than control diet-fed animals [(128.79 +/- 46.51)/mg pro] although their GluR(5) mRNA was the same. CONCLUSION: Mossy fiber sprouting may be responsible for epileptogenesis in KA induced model and KD can suppress seizures in these animals. KD may upregulate young rat GluR(5) in inhibitory interneurons of CA(1) thus lead to an increased inhibition to prevent the propagation of seizure.

[Expression of multidrug resistance gene and topiramate affect expression of multidrug resistance gene in the hippocampus of spontaneous epileptic rats].

OBJECTIVE: Refractory temporal lobe epilepsy (TCE) shows a unique type of hippocampal damage, referred to as hippocampal sclerosis. The mechanisms underlying drug-refractoriness in TCE are poorly understood, which may be connected with pharmacoresistance to antiepileptic drugs (AEDs). Some studies show that expression of the multidrug resistance gene (mdr1a and mdr1b) and p-glycoprotein encoded by mdr1a and mdr1b are high in the brain, especially in the hippocampus, and the expression may lead to reduction of AEDs concentration in the brain. But most of these studies focused on acute epileptic activity shortly after status epilepticus (SE), spontaneous seizures are seldom studied. The authors used a rat model of kainic acid induced spontaneous seizures to investigate expression of mdr1a and mdr1b mRNA, and explore whether topiramate (TPM) affects expression of mdr1a and mdr1b in the hippocampus. METHODS: Seizures were induced by intraperitoneal injection of 10 mg/kg kainic acid at postnatal day 28. Control rats were injected with sodium chloride. All rats were divided into 4 groups 1 week after spontaneous seizures developed: status epilepticus complicated with spontaneous seizures (SE, n = 8) group, status epilepticus complicated with spontaneous seizures treated with TPM (SE + TPM, n = 9) group, spontaneous seizures without status epilepticus (N-SE, n = 7) group, spontaneous seizures without status epilepticus treated with TPM (N-SE + TPM, n = 8) group, control (n = 7) group and control treated with TPM (control + TPM, n = 7) group. The treated rats were given therapeutic dose of TPM (25 mg/kg). All the rats were killed on the 42nd day of administration. The mdr1a and mdr1b mRNAs in the hippocampus were measured by RT-PCR. RESULTS: Expression of mdr1a and mdr1b mRNA in the hippocampus increased significantly in the SE + TPM group, SE group and N-SE + TPM group compared with control group (P < 0.001 or < 0.05). The mRNA in SE + TPM group increased significantly compared with the SE group, too (P < 0.01). The mdr1a and mdr1b mRNA expression in the hippocampus in control + TPM and N-SE groups did not change. CONCLUSION: Frequent seizures, especially status epilepticus resulted in overexpression of mdr1a and mdr1b mRNAs in the hippocampus. The drug-refractoriness mechanism in TCE may be related to overexpression of mdr1a and mdr1b mRNAs. TPM could enhance the expression of mdr1a and mdr1b mRNAs in the hippocampus. Seizure activity and TPM are likely to be the main determinant in enhancing mdr1a and mdr1b mRNA expression in epilepsy.