Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in viv...Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.展开更多
BACKGROUND Nikethamide,a respiratory stimulant,is used to treat hypoxemia caused by coronavirus disease 2019(COVID-19),but it carries a risk of convulsions.Magnesium sulfate(MgSO_(4)),a seizure inhibitor,might serve a...BACKGROUND Nikethamide,a respiratory stimulant,is used to treat hypoxemia caused by coronavirus disease 2019(COVID-19),but it carries a risk of convulsions.Magnesium sulfate(MgSO_(4)),a seizure inhibitor,might serve as a rescue agent against nikethamide-induced seizures.AIM To investigate the therapeutic effect of MgSO_(4)on nikethamide-induced seizures in COVID-19 patients through animal experiments,providing experimental support for the clinical application of MgSO_(4)in preventing and treating seizures caused by nikethamide.METHODS Forty mice were randomly divided into four groups:(1)Physiological saline;(2)Low-dose MgSO_(4)(50 mg/kg);(3)Medium-dose MgSO_(4)(100 mg/kg);and(4)High-dose MgSO_(4)(200 mg/kg).After 15 minutes of intraperitoneal injection of different doses of MgSO_(4)or an equal volume of physiological saline,the mice were injected with nikethamide(250 mg/kg).RESULTS Compared to the normal saline group,all doses of MgSO_(4)significantly prolonged the seizure latency and reduced the severity of convulsions.However,they also extended the duration of seizures and correspondingly increased survival time(P<0.05).The incidence of seizures and mortality rate in the MgSO_(4)-treated groups were significantly lower than those in the normal saline group(P<0.05).CONCLUSION MgSO_(4)can prevent and treat seizures caused by nikethamide in mice.This finding has implications for the application of MgSO_(4)in treating and preventing seizures caused by nikethamide in COVID-19 treatment.展开更多
Objective:The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics.We investigated the role of endothelial progenitor cells(EPCs)in a pentylenetetrazole(PTZ)-induced ra...Objective:The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics.We investigated the role of endothelial progenitor cells(EPCs)in a pentylenetetrazole(PTZ)-induced rat seizure model.A selected panel of long noncoding RNAs(lncRNAs),which maintain an elaborate balance in brain neural regulatory networks as well as the autophagy pathway,was also targeted.Methods:The impact of intravenously administered EPCs on PTZ-induced kindling in rats was evaluated by measuring the expression of neuronal damage markers,neurotrophic factors,and relevant lncRNA genes.Rat behavior was assessed using Y-maze test and open field test(OFT).Results:EPCs mitigated seizure associated neurological damage and reversed PTZ-induced working memory and locomotor activity deficits,as evidenced by improved performance in the Y-maze test and OFT.EPC treatment reversed the downregulation of the expression of the lncRNAs Evf2,Pnky,Dlx1,APF,HOTAIR,and FLJ11812.EPCs also boosted vascular endothelial growth factor(VEGF)expression.The ameliorative effect achieved by EPCs was comparable to that produced by valproate.Conclusions:These findings indicate that EPCs ameliorate kindling epileptic seizures and their associated abnormalities and that the effect of EPCs may be mediated via the upregulation of certain regulatory lncRNAs.展开更多
BACKGROUND Non-ketotic hyperglycaemic(NKH)seizures are a rare neurological complication of diabetes caused by hyperglycaemia in non-ketotic and non-hyperosmotic states.The clinical characteristics of NKH seizures are ...BACKGROUND Non-ketotic hyperglycaemic(NKH)seizures are a rare neurological complication of diabetes caused by hyperglycaemia in non-ketotic and non-hyperosmotic states.The clinical characteristics of NKH seizures are atypical and lack unified diagnostic criteria,leading to potential misdiagnoses in the early stages of the disease.CASE SUMMARY This report presents a rare case of NKH seizures in a 52-year-old male patient with a history of type 2 diabetes mellitus.We performed comprehensive magnetic resonance imaging(MRI)studies at admission,12 d post-admission,and 20 d post-discharge.The imaging techniques included contrast-enhanced head MRI,T2-weighted imaging(T2WI),fluid-attenuated inversion recovery(FLAIR),diffusion-weighted imaging,susceptibility-weighted imaging,magnetic reso-nance spectroscopy(MRS),and magnetic resonance venography.At the time of admission,T2WI and FLAIR of the cranial MRI showed that the left parieto-occipital cortex had gyrus-like swelling and high signal,and subcortical stripes had low signal.MRS showed a reduced N-acetylaspartate peak and increased creatine and choline peaks in the affected areas.A follow-up MRI 20 d later showed that the swelling and high signal of the left parieto-occipital cortex had disappeared,and the low signal of the subcortex had disappeared.CONCLUSION This case study provides valuable insights into the potential pathogenesis,diagnosis,and treatment of NKH seizures.The comprehensive MRI findings highlight the potential utility of various MRI sequences in diagnosing and characterizing NKH seizures.展开更多
BACKGROUND Seizures are one of the most common neurological complications encountered in the intensive care unit(ICU).They can occur in the background of exacerbation of a known neurological disease or secondary to no...BACKGROUND Seizures are one of the most common neurological complications encountered in the intensive care unit(ICU).They can occur in the background of exacerbation of a known neurological disease or secondary to non-neurological conditions such as sepsis and metabolic disturbances.However,there is a paucity of literature on the incidence and pattern of new-onset seizures in ICUs.AIM To study the incidence and patterns of new-onset seizures in patients admitted to the medical ICU.METHODS This was a prospective,multicenter,observational study performed in two tertiary care centers in Hyderabad,India over a period of 1 year.Patients upon ICU admission,who developed new-onset generalized tonic clonic seizures(GTCS),were enrolled.Those with a pre-existing seizure disorder,acute cerebrovascular accident,head injury,known structural brain lesions,or chronic liver disease were excluded as they have a higher likelihood of developing seizures.All enrolled patients were subjected to biochemical routines,radiological imaging of either computed tomography or magnetic resonance imaging,and other relevant laboratory tests as per clinical suspicion according to the protocol,and their data were recorded.Statistical analyses were conducted using descriptive statistics,χ^(2) tests,and linear regression.RESULTS A total of 61 of 2522 patients developed GTCS.Among all etiologies of seizures,metabolic causes were most frequent(35%)followed by infective causes(27%)and others(new-onset structural,drug withdrawal,druginduced,toxicology-related,and miscellaneous factors).Logistic regression analysis showed that increased sodium and calcium levels were associated with a lower likelihood of developing seizures.CONCLUSION This study identified the etiology of new-onset seizures developing in critically ill patients admitted to the ICU.These findings highlight the need for targeted monitoring of those at risk of developing seizures.展开更多
Introduction: Seizures are one of the most common neurological complications in the infant period. The aim of our study was to describe the epidemiological, clinical, therapeutic and prognostic features of seizures in...Introduction: Seizures are one of the most common neurological complications in the infant period. The aim of our study was to describe the epidemiological, clinical, therapeutic and prognostic features of seizures in infants at the Albert Royer Children’s Hospital (Senegal). Materials and Methods: This was a retrospective, descriptive study from 1 January 2012 to 30 September 2018 of infants aged 0 days to 2 months who presented with seizures. Results: The hospital rate was 8.5%. Almost all the mothers (99.1%) had undergone at least 3 antenatal visits. Urogenital infection, gestational arterial hypertension and funicular anomalies were the main pregnancy-related pathologies. Delivery was vaginal in the majority of cases (80.9%). Most infants (43.6%) had not cried at birth. The majority of infants (63%) were born at term. Trophicity was normal in 68% of cases. The average age of the infants was 6.7 days. The main causes of seizures were hypoxic-ischemic encephalopathy (48.7%), metabolic disturbances (48.1%) and central ոеrvοսѕ system infections (15.6%). Phenobarbital was the 1st-line anticonvulsant. The case fatality rate was 39.5%. The main sequela observed were delayed psychomotor development (20.6%). Conclusion: Optimal management of infant seizures requires early diagnosis and etiological treatment by improving the quality of perinatal care to ensure better management of risk factors, as well as increasing the availability of neuroimaging equipment.展开更多
BACKGROUND The SETD1B gene is instrumental in human intelligence and nerve development.Mutations in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders,seizures,and language delay.CASE S...BACKGROUND The SETD1B gene is instrumental in human intelligence and nerve development.Mutations in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders,seizures,and language delay.CASE SUMMARY This study aimed to analyze the clinical manifestations and treatment of three patients suffering from mental retardation,epilepsy,and language delay resulting from a new mutation in the SETD1B gene.Three individuals with these symptoms were selected,and their clinical symptoms,gene test results,and treatment were analyzed.This article discusses the impact of the SETD1B gene mutation on patients and outlines the treatment approach.Among the three patients(two females and one male,aged 8,4,and 1,respectively),all exhibited psychomotor retardation,attention deficit,and hyperactivity disorder,and two had epilepsy.Antiepileptic treatment with sodium tripolyvalproate halted the seizures in the affected child,although mental development remained somewhat delayed.Whole exome sequencing revealed new mutations in the SETD1B gene for all patients,specifically with c.5473C>T(p.Arg1825trp),c.4120C>T(p.Gln1374*,593),c.14_15insC(p.His5Hisfs*33).CONCLUSION Possessing the SETD1B gene mutation may cause mental retardation accompanied by seizures and language delay.Although the exact mechanism is not fully understood,interventions such as drug therapy,rehabilitation training,and family support can assist patients in managing their symptoms and enhancing their quality of life.Furthermore,genetic testing supplies healthcare providers with more precise diagnostic and therapeutic guidance,informs families about genetic disease risks,and contributes to understanding disease pathogenesis and drug research and development.展开更多
Objective Measuring the serum concentrations of adrenocorticotropic hormone （ACTH） and cortisol in epileptic seizures during sleep to investigate their link to the EEG changes. Methods Pre-surgical evaluation was pe...Objective Measuring the serum concentrations of adrenocorticotropic hormone （ACTH） and cortisol in epileptic seizures during sleep to investigate their link to the EEG changes. Methods Pre-surgical evaluation was performed by videoEEG monitoring using 24 channel recording. Thirty six epilepsy patients could be attributed to two groups： 28 patients had spontaneous seizures, and the other 8 patients whose seizures were induced by bemegride. Another 11 persons with confirmed psychogenic non-epileptic seizures （PNES） served as control group. Blood samples were obtained at five points： wake （08：00 a.m.）, sleep （00：00 a.m.）, and shortly before, during and after an epileptic seizure. The serum ACTH and cortisol were measured and analyzed by chemiluminescent immunoassay. Results The levels of ACTH and cortisol in serum underwent significant changes： declining below the average sleep-level shortly before seizures, increasing during seizures, and far above the average wake-level after seizures （P 〈 0.001）. Such changes did not occur in the control group （P 〉 0.05）. The ACTH and cortisol levels had no significant difference between spontaneous group and bemegride-induced group （P 〉 0.05）. Conclusion The serum concentrations of ACTH and cortisol during sleep seizures are linked with pre-ictal and ictal EEG changes in epilepsy patients.展开更多
As a leading cause for morbidity and mortality in young adults,traumatic brain injury（TBI）,along with the poorly understood TBI-related seizures inducing their predispositions,pose a major health and socioeconomic p...As a leading cause for morbidity and mortality in young adults,traumatic brain injury（TBI）,along with the poorly understood TBI-related seizures inducing their predispositions,pose a major health and socioeconomic problem in the world（Huang,2013）.展开更多
BACKGROUND Hypereosinophilic syndrome(HES)is a condition characterized by increased eosinophil proliferation in the bone marrow,as well as tissue eosinophilia,often causing organ damage.The cause of the disease is unk...BACKGROUND Hypereosinophilic syndrome(HES)is a condition characterized by increased eosinophil proliferation in the bone marrow,as well as tissue eosinophilia,often causing organ damage.The cause of the disease is unknown.Initial symptoms include fatigue,cough,shortness of breath,myalgia,angioedema,fever,and pneumonia.In addition to the respiratory symptoms,damage to the central nervous system can lead to severe seizures.Here,we report a case with pneumonia and complex partial seizures secondary to HES.CASE SUMMARY A 94-year-old woman was admitted to our hospital for heart failure and bloody stools.After admission,she also showed symptoms of pneumonia.Non-contrast computed tomography of the chest showed pleural effusion and infiltrative shadows.Lower gastrointestinal endoscopy showed multiple ulcers in the sigmoid colon.Blood analyses showed marked eosinophilia(eosinophils 1760/mm3,total leukocytes 6850/mm3).Initial treatment with furosemide 20 mg/d and prednisolone 25 mg/d relieved these symptoms.However,the patient subsequently experienced localised epileptic seizures characterized by bilateral eyelid twitching and eyes rolling upwards,without generalized convulsions,and respiratory arrest occurred.Electroencephalography showed spikes and waves.Non-contrast magnetic resonance imaging of the brain showed extensive periventricular hyperintensity.With administration of levetiracetam 1000 mg/d the epileptic seizures disappeared.However,the patient’s consciousness remained impaired,and her pneumonia worsened again.Two weeks later,she died of pneumonia.CONCLUSION HES symptoms are variable and atypical,and the level and timing of eosinophilia and organ damage are often discordant.展开更多
Objective: To report cases of neurocysticercosis(NCC) from three neighboring districts of Andhra Pradesh state in India where NCC burden was never explored before.Methods: A total of 160 patients presenting with recen...Objective: To report cases of neurocysticercosis(NCC) from three neighboring districts of Andhra Pradesh state in India where NCC burden was never explored before.Methods: A total of 160 patients presenting with recent onset seizures were recruited from neurology, general medicine, and pediatric outpatient clinics of a local major tertiary care teaching hospital serving above districts during the period 2011–2014. Brain imaging was performed in all the above cases. A commercial immunoglobulin G-ELISA kit(sensitivity = 85%; specificity = 94%) was employed for the serological diagnosis of NCC.Results: The recruited patients presented with generalized, simple partial, and complex partial seizures(55%, 31.25% and 13.75% respectively). NCC was diagnosed in 44 of160(27.5%) seizure cases based on imaging characteristics, and a positive serum antibody ELISA. No association was detected between seropositivity with the number and location of the lesion(s) in the brain.Conclusions: The possible potentiality of NCC could be identified as an underlying cause of the recent onset of seizures in this region as explored in the present study. It is recommended that NCC should be suspected as one of the major differential in every recent onset seizure with or without a radio imaging supportive diagnosis, especially in areas endemic for taeniasis/cysticercosis.展开更多
Febrile seizures （FSs） are the most common convulsions in childhood. Studies have demonstrated a significant relationship between a history of prolonged FSs during early childhood and temporal sclerosis, which is re...Febrile seizures （FSs） are the most common convulsions in childhood. Studies have demonstrated a significant relationship between a history of prolonged FSs during early childhood and temporal sclerosis, which is responsible for intractable mesial temporal lobe epilepsy. It has been shown that interleukin-1β （IL-1β） is intrinsically involved in the febrile response in children and in the generation of FSs. We summarize the gene polymorphisms, changes of IL-1β levels and the putative role of IL-1β in the generation of FSs. IL-1β could play a role either in enhancing or in reducing neural excitability. If the enhancing and reducing effects are balanced, an FS does not occur. When the enhancing effect plays the leading role, an FS is generated. A mild imbalance can cause simple FSs while a severe imbalance can cause complex FSs and febrile status epilepticus. Therefore, anti-IL-1β therapy may help to treat FSs.展开更多
BACKGROUND ACTA2 gene is a specific gene that encodes actinα2.Multisystem smooth muscle dysfunction syndrome(MSMDS)is a multisystem disease characterized by aortic and cerebrovascular lesions caused by ACTA2 gene mut...BACKGROUND ACTA2 gene is a specific gene that encodes actinα2.Multisystem smooth muscle dysfunction syndrome(MSMDS)is a multisystem disease characterized by aortic and cerebrovascular lesions caused by ACTA2 gene mutations.There have been many reports of cardiac,pulmonary and cerebrovascular lesions caused by MSMDS;however,few studies have focused on seizures caused by MSMDS.CASE SUMMARY Our patient was a girl aged 7 years and 8 mo with recurrent cough,asthma and seizures for 7 years.She was diagnosed with severe pneumonia,congenital heart disease,cardiac insufficiency,and malnutrition in the local hospital.Cardiac ultrasonography revealed congenital heart disease,patent ductus arteriosus(with a diameter of 0.68 cm),left coronary arteriectasis,patent oval foramen(0.12 cm),tricuspid and pulmonary regurgitation,and pulmonary hypertension.Cerebral magnetic resonance imaging and magnetic resonance angiography indicated stiffness in the brain vessels,together with multiple aberrant signaling shadows in bilateral paraventricular regions.A heterozygous mutation(c.536G>A)was identified in the ACTA2 gene,resulting in generation of p.R179H.Finally,the girl was diagnosed with MSMDS combined with epilepsy.The patient had 4 episodes of seizures before treatment,and no onset of seizure was reported after oral administration of sodium valproate for 1 year.CONCLUSION MSMDS has a variety of clinical manifestations and unique cranial imaging features.Cerebrovascular injury and white matter injury may lead to seizures.Gene detection can confirm the diagnosis and prevent missed diagnosis or misdiagnosis.展开更多
Febrile seizures（FSs） occur commonly in children aged from 6 months to 5 years. Complex（repetitive or prolonged） FSs, but not simple FSs, can lead to permanent brain modification. Human infants and immature rodent...Febrile seizures（FSs） occur commonly in children aged from 6 months to 5 years. Complex（repetitive or prolonged） FSs, but not simple FSs, can lead to permanent brain modification. Human infants and immature rodents that have experienced complex FSs have a high risk of subsequent temporal lobe epilepsy. However, the causes of FSs and the mechanisms underlying the subsequent epileptogenesis remain unknown. Here, we mainly focus on two major questions concerning FSs： how fever triggers seizures, and how epileptogenesis occurs after FSs. The risk factors responsible for the occurrence of FSs and the epileptogenesis after prolonged FSs are thoroughly summarized and discussed. An understanding of these factors can provide potential therapeutic targets for the prevention of FSs and also yield biomarkers for identifying patients at risk of epileptogenesis following FSs.展开更多
Gender differences are involved in many neurological disorders including epilepsy. However, little is known about the effect of gender difference on the risk of epilepsy in adults with a specific early pathological st...Gender differences are involved in many neurological disorders including epilepsy. However, little is known about the effect of gender difference on the risk of epilepsy in adults with a specific early pathological state such as complex febrile seizures（FSs） in infancy. Here we used a well-established complex FS model in rats and showed that：（1） the susceptibility to seizures induced by hyperthermia, pentylenetetrazol（PTZ）, and maximal electroshock（MES） was similar in male and female rat pups, while males were more susceptible to PTZ- and MES-induced seizures than age-matched females in normal adult rats;（2） adult rats with complex FSs in infancy acquired higher seizure susceptibility than normal rats; importantly, female FS rats were more susceptible to PTZ and MES than male FS rats; and（3） the protein expression of interleukin-1β, an infl ammatory factor associated with seizure susceptibility, was higher in adult FS females than in males, which may reflect a gender-difference phenomenon of seizure susceptibility. Our results provide direct evidence that the acquired seizure susceptibility after complex FSs is gender-dependent.展开更多
Epilepsy, characterized by spontaneous recurrent seizures （SRS）, is a serious and common neurological disorder afflicting an estimated 1% of the population worldwide. Animal experiments, especially those utilizing s...Epilepsy, characterized by spontaneous recurrent seizures （SRS）, is a serious and common neurological disorder afflicting an estimated 1% of the population worldwide. Animal experiments, especially those utilizing small laboratory rodents, remain essential to understanding the fundamental mechanisms underlying epilepsy and to prevent, diagnose, and treat this disease. While much attention has been focused on epileptogenesis in animal models of epilepsy, there is little discussion on SRS, the hallmark of epilepsy. This is in part due to the technical difficulties of rigorous SRS detection. In this review, we comprehensively summarize both genetic and acquired models of SRS and discuss the methodology used to monitor and detect SRS in mice and rats.展开更多
AIM: To review the clinical response to levetiracetam(LEV) in neonatal seizure management in intensive care unit.METHODS: Medical records of neonates who received LEV from January 2009 to August 2014 were reviewed. Th...AIM: To review the clinical response to levetiracetam(LEV) in neonatal seizure management in intensive care unit.METHODS: Medical records of neonates who received LEV from January 2009 to August 2014 were reviewed. Their demographic data, clinical characteristics, etiology, seizures, electroencephalograms, response to treatment and outcome were noted. Literature review of use of LEV in neonates were also performed via Pub Med and EMBASE with keywords- "neonates", "seizures", "epilepsy" and "LEV" up to Sep 2014 and retrieved the publications. The response rate to LEV was compared.RESULTS: Twelve neonates were identified during the study period. All patients received phenobarbitone loading prior to consideration of LEV. Seven(58%) and nine(75%) achieved seizure freedom 24 h and 72 h after LEV was added, both clinically and electrographically. No serious adverse effects were associated with LEV use. From the literature, there are total 144 neonates reported to have used LEV. The overall results suggested that LEV could control up to 90% of neonatal seizures.CONCLUSION: LEV was found to be relatively safe and efficacious in treating neonatal seizures, but might not work well in the most severe hypoxic ischemic encephalopathy.展开更多
Background: Salivatory seizures are a singularly rare condition, which can occur both in idiopathic and symptomatic epilepsies. Objectives: To describe and discuss the case of an adolescent patient with sleep-trigger...Background: Salivatory seizures are a singularly rare condition, which can occur both in idiopathic and symptomatic epilepsies. Objectives: To describe and discuss the case of an adolescent patient with sleep-triggered “pure” salivatory seizures associated with a subtle cortical malformation of the right parietal cortex. Case report: Herein, we report a 17-year-old female who started to present salivatory paroxysms, which occasionally secondarily generalized, shortly after falling asleep, at the age of eight years. Video-electroencephalographic monitoring with scalp electrodes failed to show any epileptiform activity during the several recorded clinical events. Brain MRI and curvilinear reconstruction revealed, in the three orthogonal planes, a subtle cortical thickening, limited to a single gyrus in the right parietal cortex, suggestive of a focal cortical malformation. After antiepileptic drug therapy was optimized, the patient became seizure-free. Conclusion: An epilepsy diagnosis should be pursued in patients presenting isolated, paroxysmal hypersalivation, despite possible negative scalp EEG studies.展开更多
Early brain development after birth is extremely dynamic,suggest!ng that potential functional changes occur during this period.In this study,the maximal electroshock seizure threshold(MEST)was used to explore the elec...Early brain development after birth is extremely dynamic,suggest!ng that potential functional changes occur during this period.In this study,the maximal electroshock seizure threshold(MEST)was used to explore the electrophysiological variation among three developmental stages in young mice(no more than 5 weeks old).The induced electroshock seizure(ES)behavior of early post natal mice(1-2-weeks old)differed from that during weaning(3 weeks old)and early puberty(4-5-weeks old).Thus,we further explored their respective characteristic responses to the ES parameters.When the stimulation current(SC)was limited to 4.0 mA,only the 1-2-week-old mice were induced to exhibit ES behavior at voltages of 30 V and 40 V,indicating they were more sensitive to maximal electroshock seizure(MES)(response to lower voltage).展开更多
BACKGROUND： Studies have demonstrated that in vitro cultured cortical neurons from embryonic rats can produce spontaneous recurrent epileptiform discharges following transient Mg^2＋-free extracellular solution cultu...BACKGROUND： Studies have demonstrated that in vitro cultured cortical neurons from embryonic rats can produce spontaneous recurrent epileptiform discharges following transient Mg^2＋-free extracellular solution culture. OBJECTIVE： To explore gammaminobutyric acid A receptor （GABAAR）γ 2 subunit expression following Mg^2＋-free-induced seizures in cultured developing neurons. DESIGN, TIME AND SETTING： Cellular and molecular biology. The in vitro experiment was performed at the Department of Pediatrics, Second Xiangya Hospital of Central Southern University between January 2007 and February 2008. MATERIALS： Cortical neurons of Wistar rats on gestational days 16-17 were used. Normal extracellular solution （pH 7.3） consisted of NaCl 145 mmol/L, KCl 2.5 mmol/L, HEPES l0 mmol/L, MgC12 1 mmol/L, CaC12 2 mmol/L, glucose 10 mmol/L, and glycine 0.01 mmol/L. In addition, there was no MgCl2 in the Mg^2＋-free extracellular solution. METHODS： Cortical neurons cultured for 6 days were exposed to normal extracellular solution （control group） and Mg^2＋-free media （Mg^2＋-free group） respectively for 3 hours, followed by continuous culture in DMEM solution. MAIN OUTCOME MEASURES： On days 1, 7 and 12 after Mg^2＋-free treatment, real-time RT-PCR, immunochemistry, and flow cytometry were used to detect GABAAR 3/2 subunit expression. RESULTS： Compared with the control group, GABAAR γ-positive cells decreased significantly on days 1 and 7 after Mg^2＋-free treatment （P 〈 0.01）, but significantly increased on day 12 （P 〈 0.01 ）. GABAAR γ2 subunit mRNA expression decreased significantly at 7 days Mg^2＋-free treatment when measured by real-time RT-PCR compared with the control group （P 〈 0.05）. CONCLUSION： GABAAR γ2 subunit expression is modified following Mg-free-induced seizures in cultured developing neurons. This indicates the possibility that abnormal GABAA receptor expression might play an important role in development of neuronal injury.展开更多
基金supported by the Natural Science Foundation of Fujian Province,No.2020J02027the National Natural Science Foundation of China,No.31970461the Foundation of NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate,Fujian Maternity and Child Health Hospital,No.2022-NHP-05(all to WC).
文摘Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.
基金Supported by The Zhejiang Provincial Health Commission,No.2022KY1391.
文摘BACKGROUND Nikethamide,a respiratory stimulant,is used to treat hypoxemia caused by coronavirus disease 2019(COVID-19),but it carries a risk of convulsions.Magnesium sulfate(MgSO_(4)),a seizure inhibitor,might serve as a rescue agent against nikethamide-induced seizures.AIM To investigate the therapeutic effect of MgSO_(4)on nikethamide-induced seizures in COVID-19 patients through animal experiments,providing experimental support for the clinical application of MgSO_(4)in preventing and treating seizures caused by nikethamide.METHODS Forty mice were randomly divided into four groups:(1)Physiological saline;(2)Low-dose MgSO_(4)(50 mg/kg);(3)Medium-dose MgSO_(4)(100 mg/kg);and(4)High-dose MgSO_(4)(200 mg/kg).After 15 minutes of intraperitoneal injection of different doses of MgSO_(4)or an equal volume of physiological saline,the mice were injected with nikethamide(250 mg/kg).RESULTS Compared to the normal saline group,all doses of MgSO_(4)significantly prolonged the seizure latency and reduced the severity of convulsions.However,they also extended the duration of seizures and correspondingly increased survival time(P<0.05).The incidence of seizures and mortality rate in the MgSO_(4)-treated groups were significantly lower than those in the normal saline group(P<0.05).CONCLUSION MgSO_(4)can prevent and treat seizures caused by nikethamide in mice.This finding has implications for the application of MgSO_(4)in treating and preventing seizures caused by nikethamide in COVID-19 treatment.
基金Open access funding provided by The Science,Technology&Innovation Funding Authority(STDF)in coop eration with The Egyptian Knowledge Bank(EKB).
文摘Objective:The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics.We investigated the role of endothelial progenitor cells(EPCs)in a pentylenetetrazole(PTZ)-induced rat seizure model.A selected panel of long noncoding RNAs(lncRNAs),which maintain an elaborate balance in brain neural regulatory networks as well as the autophagy pathway,was also targeted.Methods:The impact of intravenously administered EPCs on PTZ-induced kindling in rats was evaluated by measuring the expression of neuronal damage markers,neurotrophic factors,and relevant lncRNA genes.Rat behavior was assessed using Y-maze test and open field test(OFT).Results:EPCs mitigated seizure associated neurological damage and reversed PTZ-induced working memory and locomotor activity deficits,as evidenced by improved performance in the Y-maze test and OFT.EPC treatment reversed the downregulation of the expression of the lncRNAs Evf2,Pnky,Dlx1,APF,HOTAIR,and FLJ11812.EPCs also boosted vascular endothelial growth factor(VEGF)expression.The ameliorative effect achieved by EPCs was comparable to that produced by valproate.Conclusions:These findings indicate that EPCs ameliorate kindling epileptic seizures and their associated abnormalities and that the effect of EPCs may be mediated via the upregulation of certain regulatory lncRNAs.
基金Supported by Four"Batches"Innovation Project of Invigorating Medical Through Science and Technology of Shanxi Province,No.2023XM016.
文摘BACKGROUND Non-ketotic hyperglycaemic(NKH)seizures are a rare neurological complication of diabetes caused by hyperglycaemia in non-ketotic and non-hyperosmotic states.The clinical characteristics of NKH seizures are atypical and lack unified diagnostic criteria,leading to potential misdiagnoses in the early stages of the disease.CASE SUMMARY This report presents a rare case of NKH seizures in a 52-year-old male patient with a history of type 2 diabetes mellitus.We performed comprehensive magnetic resonance imaging(MRI)studies at admission,12 d post-admission,and 20 d post-discharge.The imaging techniques included contrast-enhanced head MRI,T2-weighted imaging(T2WI),fluid-attenuated inversion recovery(FLAIR),diffusion-weighted imaging,susceptibility-weighted imaging,magnetic reso-nance spectroscopy(MRS),and magnetic resonance venography.At the time of admission,T2WI and FLAIR of the cranial MRI showed that the left parieto-occipital cortex had gyrus-like swelling and high signal,and subcortical stripes had low signal.MRS showed a reduced N-acetylaspartate peak and increased creatine and choline peaks in the affected areas.A follow-up MRI 20 d later showed that the swelling and high signal of the left parieto-occipital cortex had disappeared,and the low signal of the subcortex had disappeared.CONCLUSION This case study provides valuable insights into the potential pathogenesis,diagnosis,and treatment of NKH seizures.The comprehensive MRI findings highlight the potential utility of various MRI sequences in diagnosing and characterizing NKH seizures.
文摘BACKGROUND Seizures are one of the most common neurological complications encountered in the intensive care unit(ICU).They can occur in the background of exacerbation of a known neurological disease or secondary to non-neurological conditions such as sepsis and metabolic disturbances.However,there is a paucity of literature on the incidence and pattern of new-onset seizures in ICUs.AIM To study the incidence and patterns of new-onset seizures in patients admitted to the medical ICU.METHODS This was a prospective,multicenter,observational study performed in two tertiary care centers in Hyderabad,India over a period of 1 year.Patients upon ICU admission,who developed new-onset generalized tonic clonic seizures(GTCS),were enrolled.Those with a pre-existing seizure disorder,acute cerebrovascular accident,head injury,known structural brain lesions,or chronic liver disease were excluded as they have a higher likelihood of developing seizures.All enrolled patients were subjected to biochemical routines,radiological imaging of either computed tomography or magnetic resonance imaging,and other relevant laboratory tests as per clinical suspicion according to the protocol,and their data were recorded.Statistical analyses were conducted using descriptive statistics,χ^(2) tests,and linear regression.RESULTS A total of 61 of 2522 patients developed GTCS.Among all etiologies of seizures,metabolic causes were most frequent(35%)followed by infective causes(27%)and others(new-onset structural,drug withdrawal,druginduced,toxicology-related,and miscellaneous factors).Logistic regression analysis showed that increased sodium and calcium levels were associated with a lower likelihood of developing seizures.CONCLUSION This study identified the etiology of new-onset seizures developing in critically ill patients admitted to the ICU.These findings highlight the need for targeted monitoring of those at risk of developing seizures.
文摘Introduction: Seizures are one of the most common neurological complications in the infant period. The aim of our study was to describe the epidemiological, clinical, therapeutic and prognostic features of seizures in infants at the Albert Royer Children’s Hospital (Senegal). Materials and Methods: This was a retrospective, descriptive study from 1 January 2012 to 30 September 2018 of infants aged 0 days to 2 months who presented with seizures. Results: The hospital rate was 8.5%. Almost all the mothers (99.1%) had undergone at least 3 antenatal visits. Urogenital infection, gestational arterial hypertension and funicular anomalies were the main pregnancy-related pathologies. Delivery was vaginal in the majority of cases (80.9%). Most infants (43.6%) had not cried at birth. The majority of infants (63%) were born at term. Trophicity was normal in 68% of cases. The average age of the infants was 6.7 days. The main causes of seizures were hypoxic-ischemic encephalopathy (48.7%), metabolic disturbances (48.1%) and central ոеrvοսѕ system infections (15.6%). Phenobarbital was the 1st-line anticonvulsant. The case fatality rate was 39.5%. The main sequela observed were delayed psychomotor development (20.6%). Conclusion: Optimal management of infant seizures requires early diagnosis and etiological treatment by improving the quality of perinatal care to ensure better management of risk factors, as well as increasing the availability of neuroimaging equipment.
基金Key Health Science and Technology Development Project of Nanjing City,Jiangsu Province,No.ZKX19038.
文摘BACKGROUND The SETD1B gene is instrumental in human intelligence and nerve development.Mutations in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders,seizures,and language delay.CASE SUMMARY This study aimed to analyze the clinical manifestations and treatment of three patients suffering from mental retardation,epilepsy,and language delay resulting from a new mutation in the SETD1B gene.Three individuals with these symptoms were selected,and their clinical symptoms,gene test results,and treatment were analyzed.This article discusses the impact of the SETD1B gene mutation on patients and outlines the treatment approach.Among the three patients(two females and one male,aged 8,4,and 1,respectively),all exhibited psychomotor retardation,attention deficit,and hyperactivity disorder,and two had epilepsy.Antiepileptic treatment with sodium tripolyvalproate halted the seizures in the affected child,although mental development remained somewhat delayed.Whole exome sequencing revealed new mutations in the SETD1B gene for all patients,specifically with c.5473C>T(p.Arg1825trp),c.4120C>T(p.Gln1374*,593),c.14_15insC(p.His5Hisfs*33).CONCLUSION Possessing the SETD1B gene mutation may cause mental retardation accompanied by seizures and language delay.Although the exact mechanism is not fully understood,interventions such as drug therapy,rehabilitation training,and family support can assist patients in managing their symptoms and enhancing their quality of life.Furthermore,genetic testing supplies healthcare providers with more precise diagnostic and therapeutic guidance,informs families about genetic disease risks,and contributes to understanding disease pathogenesis and drug research and development.
文摘Objective Measuring the serum concentrations of adrenocorticotropic hormone （ACTH） and cortisol in epileptic seizures during sleep to investigate their link to the EEG changes. Methods Pre-surgical evaluation was performed by videoEEG monitoring using 24 channel recording. Thirty six epilepsy patients could be attributed to two groups： 28 patients had spontaneous seizures, and the other 8 patients whose seizures were induced by bemegride. Another 11 persons with confirmed psychogenic non-epileptic seizures （PNES） served as control group. Blood samples were obtained at five points： wake （08：00 a.m.）, sleep （00：00 a.m.）, and shortly before, during and after an epileptic seizure. The serum ACTH and cortisol were measured and analyzed by chemiluminescent immunoassay. Results The levels of ACTH and cortisol in serum underwent significant changes： declining below the average sleep-level shortly before seizures, increasing during seizures, and far above the average wake-level after seizures （P 〈 0.001）. Such changes did not occur in the control group （P 〉 0.05）. The ACTH and cortisol levels had no significant difference between spontaneous group and bemegride-induced group （P 〉 0.05）. Conclusion The serum concentrations of ACTH and cortisol during sleep seizures are linked with pre-ictal and ictal EEG changes in epilepsy patients.
文摘As a leading cause for morbidity and mortality in young adults,traumatic brain injury（TBI）,along with the poorly understood TBI-related seizures inducing their predispositions,pose a major health and socioeconomic problem in the world（Huang,2013）.
文摘BACKGROUND Hypereosinophilic syndrome(HES)is a condition characterized by increased eosinophil proliferation in the bone marrow,as well as tissue eosinophilia,often causing organ damage.The cause of the disease is unknown.Initial symptoms include fatigue,cough,shortness of breath,myalgia,angioedema,fever,and pneumonia.In addition to the respiratory symptoms,damage to the central nervous system can lead to severe seizures.Here,we report a case with pneumonia and complex partial seizures secondary to HES.CASE SUMMARY A 94-year-old woman was admitted to our hospital for heart failure and bloody stools.After admission,she also showed symptoms of pneumonia.Non-contrast computed tomography of the chest showed pleural effusion and infiltrative shadows.Lower gastrointestinal endoscopy showed multiple ulcers in the sigmoid colon.Blood analyses showed marked eosinophilia(eosinophils 1760/mm3,total leukocytes 6850/mm3).Initial treatment with furosemide 20 mg/d and prednisolone 25 mg/d relieved these symptoms.However,the patient subsequently experienced localised epileptic seizures characterized by bilateral eyelid twitching and eyes rolling upwards,without generalized convulsions,and respiratory arrest occurred.Electroencephalography showed spikes and waves.Non-contrast magnetic resonance imaging of the brain showed extensive periventricular hyperintensity.With administration of levetiracetam 1000 mg/d the epileptic seizures disappeared.However,the patient’s consciousness remained impaired,and her pneumonia worsened again.Two weeks later,she died of pneumonia.CONCLUSION HES symptoms are variable and atypical,and the level and timing of eosinophilia and organ damage are often discordant.
基金Partially supported by the Indian Council of Medical Research Ad-hoc Research Grant(IRIS ID:2010-10530)
文摘Objective: To report cases of neurocysticercosis(NCC) from three neighboring districts of Andhra Pradesh state in India where NCC burden was never explored before.Methods: A total of 160 patients presenting with recent onset seizures were recruited from neurology, general medicine, and pediatric outpatient clinics of a local major tertiary care teaching hospital serving above districts during the period 2011–2014. Brain imaging was performed in all the above cases. A commercial immunoglobulin G-ELISA kit(sensitivity = 85%; specificity = 94%) was employed for the serological diagnosis of NCC.Results: The recruited patients presented with generalized, simple partial, and complex partial seizures(55%, 31.25% and 13.75% respectively). NCC was diagnosed in 44 of160(27.5%) seizure cases based on imaging characteristics, and a positive serum antibody ELISA. No association was detected between seropositivity with the number and location of the lesion(s) in the brain.Conclusions: The possible potentiality of NCC could be identified as an underlying cause of the recent onset of seizures in this region as explored in the present study. It is recommended that NCC should be suspected as one of the major differential in every recent onset seizure with or without a radio imaging supportive diagnosis, especially in areas endemic for taeniasis/cysticercosis.
基金supported by the National Natural Science Foundation of China(81100970, 81171127)
文摘Febrile seizures （FSs） are the most common convulsions in childhood. Studies have demonstrated a significant relationship between a history of prolonged FSs during early childhood and temporal sclerosis, which is responsible for intractable mesial temporal lobe epilepsy. It has been shown that interleukin-1β （IL-1β） is intrinsically involved in the febrile response in children and in the generation of FSs. We summarize the gene polymorphisms, changes of IL-1β levels and the putative role of IL-1β in the generation of FSs. IL-1β could play a role either in enhancing or in reducing neural excitability. If the enhancing and reducing effects are balanced, an FS does not occur. When the enhancing effect plays the leading role, an FS is generated. A mild imbalance can cause simple FSs while a severe imbalance can cause complex FSs and febrile status epilepticus. Therefore, anti-IL-1β therapy may help to treat FSs.
基金Zhejiang Medical and Health Science and Technology Program,No.2020KY327 and No.2017KY660.
文摘BACKGROUND ACTA2 gene is a specific gene that encodes actinα2.Multisystem smooth muscle dysfunction syndrome(MSMDS)is a multisystem disease characterized by aortic and cerebrovascular lesions caused by ACTA2 gene mutations.There have been many reports of cardiac,pulmonary and cerebrovascular lesions caused by MSMDS;however,few studies have focused on seizures caused by MSMDS.CASE SUMMARY Our patient was a girl aged 7 years and 8 mo with recurrent cough,asthma and seizures for 7 years.She was diagnosed with severe pneumonia,congenital heart disease,cardiac insufficiency,and malnutrition in the local hospital.Cardiac ultrasonography revealed congenital heart disease,patent ductus arteriosus(with a diameter of 0.68 cm),left coronary arteriectasis,patent oval foramen(0.12 cm),tricuspid and pulmonary regurgitation,and pulmonary hypertension.Cerebral magnetic resonance imaging and magnetic resonance angiography indicated stiffness in the brain vessels,together with multiple aberrant signaling shadows in bilateral paraventricular regions.A heterozygous mutation(c.536G>A)was identified in the ACTA2 gene,resulting in generation of p.R179H.Finally,the girl was diagnosed with MSMDS combined with epilepsy.The patient had 4 episodes of seizures before treatment,and no onset of seizure was reported after oral administration of sodium valproate for 1 year.CONCLUSION MSMDS has a variety of clinical manifestations and unique cranial imaging features.Cerebrovascular injury and white matter injury may lead to seizures.Gene detection can confirm the diagnosis and prevent missed diagnosis or misdiagnosis.
基金supported by the National Natural Science Foundation of China (91332202 and 81503045)
文摘Febrile seizures（FSs） occur commonly in children aged from 6 months to 5 years. Complex（repetitive or prolonged） FSs, but not simple FSs, can lead to permanent brain modification. Human infants and immature rodents that have experienced complex FSs have a high risk of subsequent temporal lobe epilepsy. However, the causes of FSs and the mechanisms underlying the subsequent epileptogenesis remain unknown. Here, we mainly focus on two major questions concerning FSs： how fever triggers seizures, and how epileptogenesis occurs after FSs. The risk factors responsible for the occurrence of FSs and the epileptogenesis after prolonged FSs are thoroughly summarized and discussed. An understanding of these factors can provide potential therapeutic targets for the prevention of FSs and also yield biomarkers for identifying patients at risk of epileptogenesis following FSs.
基金supported by the National Natural Science Foundation of China (91332202,81201007,and 81302749)the Doctoral Fund of the Ministry of Education of China (20120101120070)the China Postdoctoral Science Foundation (2013M531476)
文摘Gender differences are involved in many neurological disorders including epilepsy. However, little is known about the effect of gender difference on the risk of epilepsy in adults with a specific early pathological state such as complex febrile seizures（FSs） in infancy. Here we used a well-established complex FS model in rats and showed that：（1） the susceptibility to seizures induced by hyperthermia, pentylenetetrazol（PTZ）, and maximal electroshock（MES） was similar in male and female rat pups, while males were more susceptible to PTZ- and MES-induced seizures than age-matched females in normal adult rats;（2） adult rats with complex FSs in infancy acquired higher seizure susceptibility than normal rats; importantly, female FS rats were more susceptible to PTZ and MES than male FS rats; and（3） the protein expression of interleukin-1β, an infl ammatory factor associated with seizure susceptibility, was higher in adult FS females than in males, which may reflect a gender-difference phenomenon of seizure susceptibility. Our results provide direct evidence that the acquired seizure susceptibility after complex FSs is gender-dependent.
基金supported by the American Epilepsy Society Fellowship(2016)
文摘Epilepsy, characterized by spontaneous recurrent seizures （SRS）, is a serious and common neurological disorder afflicting an estimated 1% of the population worldwide. Animal experiments, especially those utilizing small laboratory rodents, remain essential to understanding the fundamental mechanisms underlying epilepsy and to prevent, diagnose, and treat this disease. While much attention has been focused on epileptogenesis in animal models of epilepsy, there is little discussion on SRS, the hallmark of epilepsy. This is in part due to the technical difficulties of rigorous SRS detection. In this review, we comprehensively summarize both genetic and acquired models of SRS and discuss the methodology used to monitor and detect SRS in mice and rats.
基金Supported by Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee(CREC Ref.),No.2014.072
文摘AIM: To review the clinical response to levetiracetam(LEV) in neonatal seizure management in intensive care unit.METHODS: Medical records of neonates who received LEV from January 2009 to August 2014 were reviewed. Their demographic data, clinical characteristics, etiology, seizures, electroencephalograms, response to treatment and outcome were noted. Literature review of use of LEV in neonates were also performed via Pub Med and EMBASE with keywords- "neonates", "seizures", "epilepsy" and "LEV" up to Sep 2014 and retrieved the publications. The response rate to LEV was compared.RESULTS: Twelve neonates were identified during the study period. All patients received phenobarbitone loading prior to consideration of LEV. Seven(58%) and nine(75%) achieved seizure freedom 24 h and 72 h after LEV was added, both clinically and electrographically. No serious adverse effects were associated with LEV use. From the literature, there are total 144 neonates reported to have used LEV. The overall results suggested that LEV could control up to 90% of neonatal seizures.CONCLUSION: LEV was found to be relatively safe and efficacious in treating neonatal seizures, but might not work well in the most severe hypoxic ischemic encephalopathy.
文摘Background: Salivatory seizures are a singularly rare condition, which can occur both in idiopathic and symptomatic epilepsies. Objectives: To describe and discuss the case of an adolescent patient with sleep-triggered “pure” salivatory seizures associated with a subtle cortical malformation of the right parietal cortex. Case report: Herein, we report a 17-year-old female who started to present salivatory paroxysms, which occasionally secondarily generalized, shortly after falling asleep, at the age of eight years. Video-electroencephalographic monitoring with scalp electrodes failed to show any epileptiform activity during the several recorded clinical events. Brain MRI and curvilinear reconstruction revealed, in the three orthogonal planes, a subtle cortical thickening, limited to a single gyrus in the right parietal cortex, suggestive of a focal cortical malformation. After antiepileptic drug therapy was optimized, the patient became seizure-free. Conclusion: An epilepsy diagnosis should be pursued in patients presenting isolated, paroxysmal hypersalivation, despite possible negative scalp EEG studies.
基金supported by the National Natural Science Foundation of China(81403191)Yunnan Provincial Natural Science Foundation(2018FB118,2015FA004,and KKSY201626001)
文摘Early brain development after birth is extremely dynamic,suggest!ng that potential functional changes occur during this period.In this study,the maximal electroshock seizure threshold(MEST)was used to explore the electrophysiological variation among three developmental stages in young mice(no more than 5 weeks old).The induced electroshock seizure(ES)behavior of early post natal mice(1-2-weeks old)differed from that during weaning(3 weeks old)and early puberty(4-5-weeks old).Thus,we further explored their respective characteristic responses to the ES parameters.When the stimulation current(SC)was limited to 4.0 mA,only the 1-2-week-old mice were induced to exhibit ES behavior at voltages of 30 V and 40 V,indicating they were more sensitive to maximal electroshock seizure(MES)(response to lower voltage).
基金the National Natural Science Foundation of China,No.30400483
文摘BACKGROUND： Studies have demonstrated that in vitro cultured cortical neurons from embryonic rats can produce spontaneous recurrent epileptiform discharges following transient Mg^2＋-free extracellular solution culture. OBJECTIVE： To explore gammaminobutyric acid A receptor （GABAAR）γ 2 subunit expression following Mg^2＋-free-induced seizures in cultured developing neurons. DESIGN, TIME AND SETTING： Cellular and molecular biology. The in vitro experiment was performed at the Department of Pediatrics, Second Xiangya Hospital of Central Southern University between January 2007 and February 2008. MATERIALS： Cortical neurons of Wistar rats on gestational days 16-17 were used. Normal extracellular solution （pH 7.3） consisted of NaCl 145 mmol/L, KCl 2.5 mmol/L, HEPES l0 mmol/L, MgC12 1 mmol/L, CaC12 2 mmol/L, glucose 10 mmol/L, and glycine 0.01 mmol/L. In addition, there was no MgCl2 in the Mg^2＋-free extracellular solution. METHODS： Cortical neurons cultured for 6 days were exposed to normal extracellular solution （control group） and Mg^2＋-free media （Mg^2＋-free group） respectively for 3 hours, followed by continuous culture in DMEM solution. MAIN OUTCOME MEASURES： On days 1, 7 and 12 after Mg^2＋-free treatment, real-time RT-PCR, immunochemistry, and flow cytometry were used to detect GABAAR 3/2 subunit expression. RESULTS： Compared with the control group, GABAAR γ-positive cells decreased significantly on days 1 and 7 after Mg^2＋-free treatment （P 〈 0.01）, but significantly increased on day 12 （P 〈 0.01 ）. GABAAR γ2 subunit mRNA expression decreased significantly at 7 days Mg^2＋-free treatment when measured by real-time RT-PCR compared with the control group （P 〈 0.05）. CONCLUSION： GABAAR γ2 subunit expression is modified following Mg-free-induced seizures in cultured developing neurons. This indicates the possibility that abnormal GABAA receptor expression might play an important role in development of neuronal injury.
