Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

SCN1A rs6732655A/T polymorphism:Diagnostic and therapeutic insights for drug-resistant epilepsy

BACKGROUND A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs,resulting in heightened mortality rates,psychosocial challenges,and a diminished quality of life.Genetic factors,particularly within the SCN1A gene,and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases.In this extended study,we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response.AIM To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response.METHODS The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases.We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique.The diagnostic performance of interleukin(IL)-1β,IL-6,and high mobility group box 1(HMGB1)protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis.RESULTS AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy.Serum biomarkers IL-6,IL1βand HMGB1 demonstrated diagnostic potential,with cutoff values of 4.63 pg/mL,59.52 pg/mL and 7.99 ng/mL,respectively,offering valuable tools for epilepsy management.Moreover,specific genotypes(AA and AT)were found to be linked to the elevated levels of IL-1βand IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy.CONCLUSION SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk.These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance.

The role of axon guidance molecules in the pathogenesis of epilepsy

Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target novel cellular and molecular mechanisms and mechanisms of action. Increasing evidence suggests that axon guidance molecules play a role in the structural and functional modifications of neural networks and that the dysregulation of these molecules is associated with epilepsy susceptibility. In this review, we discuss the essential role of axon guidance molecules in neuronal activity in patients with epilepsy as well as the impact of these molecules on synaptic plasticity and brain tissue remodeling. Furthermore, we examine the relationship between axon guidance molecules and neuroinflammation, as well as the structural changes in specific brain regions that contribute to the development of epilepsy. Ample evidence indicates that axon guidance molecules, including semaphorins and ephrins, play a fundamental role in guiding axon growth and the establishment of synaptic connections. Deviations in their expression or function can disrupt neuronal connections, ultimately leading to epileptic seizures. The remodeling of neural networks is a significant characteristic of epilepsy, with axon guidance molecules playing a role in the dynamic reorganization of neural circuits. This, in turn, affects synapse formation and elimination. Dysregulation of these molecules can upset the delicate balance between excitation and inhibition within a neural network, thereby increasing the risk of overexcitation and the development of epilepsy. Inflammatory signals can regulate the expression and function of axon guidance molecules, thus influencing axonal growth, axon orientation, and synaptic plasticity. The dysregulation of neuroinflammation can intensify neuronal dysfunction and contribute to the occurrence of epilepsy. This review delves into the mechanisms associated with the pathogenicity of axon guidance molecules in epilepsy, offering a valuable reference for the exploration of therapeutic targets and presenting a fresh perspective on treatment strategies for this condition.

EFFECTS ON ENDOCRINAL FUNCTION TREATED WITH ACUPUNCTURE BASED ON QIJIE THEROY IN EPILEPSY PATIENTS

Objective To explore the effects on endocrinal function treated with acupuncture based on Qijie （the pathway of qi） theory in epilepsy patients. Methods A total of 60 epilepsy patients were randomly divided into acupuncture and medication group （n--30）, and single medication group （n = 30）. Both groups were taken antiepileptic drugs, sodium valproate regularly. The acupoints of Fengfu（风府 GV 16）,TiEmzhu （天柱 BL 10） and Renying （人迎 ST 9） were selected as major points according to Qijie theory （气街理论） in acupuncture and medication group. The plasma levels of cortisol （CORT）, estrogen （E2）, progesterone （Prog）, pituitary prolactin （PRL）, and epilepsy score were observed successively in both enrolled groups in pre-treatment and post-treatment. The outcomes were statistically analyzed. Results The effective rate was 96.7% in either group, and there was no significant differences; the epilepsy score was （13. 584.01） in pre- treatment and （7.86 ___4.90） in post-treatment in acupuncture and medication group and those in single medi- cation group were （12.97 ± 3. 91） and （7. 86 ± 4.90） respectively, indicating apparent improvement （P〈O. 05）. The increase of CORT in acupuncture and medication group indicated significant difference in post-treatment compared with that in single medication group （P = 0.046）. The differences of E2, PRL, Prog in post-treatment in two groups showed no statistical significance （P〉0. 05）. More effects had been a- chieved in acupuncture and medication group on endocrinal function and controlling epileptic seizures in epilepsy patients. Conclusion Acupuncture treatment based on Qijie theory is effective on improving endocrinal function in epilepsy patients.

Analysis of the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal epilepsy

Objective:To detect the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal lobe epilepsy(NFLE).Methods:Blood samples were collected from 215 Southern Han Chinese patients with NFLE and 200 healthy Southern Han Chinese control subjects.Genomic DNA was extracted,and CHRNA7 whole genome exons were amplified by the polymerase chain reaction and subjected to Sanger sequencing.Results:No CHRNA7 gene mutation was detected in all of the NFLE patients.However,five single nucleotide polymorphisms(SNPs)in sporadic cases were found,located in exons 5,6.and 7 of the CHRNA7 gene.Among them,c.690G>A and c.698A>G are known SNPs,while c.370G>A,c.654C>T,and c.497-498delTG were newly discovered SNPs.These SNPs were also found in some of the healthy controls.Conclusions:No CHRNA7 gene mutation was identified in Southern Han Chinese patients with NFLE.The CHRNA7 gene is probably not responsible for NFLE in this population.

Effects of topiramate versus other antiepileptic drugs on the cognitive function of patients with epilepsy

BACKGROUND： Only very large dose of topiramate has neurotoxicity, indicating that topiramate has low neurotoxicity and high safety. The residual rate of topiramate is affected by many cognitive-related adverse effects. Patients who take topiramate often accompany with thought slowness, difficulty in finding words, dyscalculia, blunt reaction, attention decreasing, memory deterioration, etc. OBJECTIVE： To compare the effects of topiramate with traditional anti-epileptic drugs （including carbamazepine and Valproic acid （VPA） on cognitive function of patients with epilepsy. DESIGN： Observational experiment, self-control and intergroup comparison. SETTING： Sichuan Academy of Medical Science. PARTICIPANTS： Eighty-seven inpatients and outpatients with newly diagnosed epilepsy who received preliminary diagnosis and follow-up in the Department of Neurology, Sichuan People＇s Hospital between January 2004 and June 2006 were involved in this survey. They were diagnosed according to disease history and electroencephalogram （EEG）. The onset type was diagnosed following the definition of epilepsy and epileptic syndrome in 1989 International Anti-epileptic League. The involved patients and their relatives were informed of detection and therapeutic regimen. The patients were assigned into two groups according to table of random digit： traditional antiepileptic drugs group （AEDs group, n =44） and topiramate （TPM） group （n =43）. METHODS： （1）Among the patients in AEDs group, carbamazepine was the first choice for 21 patients with partial seizures or partial secondarily generalized seizures, and VPA for 23 patients with generalized seizures. The initial dose of carbamazepine was 300 mg/d, and that of VPA was 500 mg/d. Patients in the TPM group took TPM with the initial dose of 25 mg/d, increased by 25 mg/d each week to target dose 150 mg/d within 8 weeks. （2） Curative effect was graded into 4 degrees： markedly effective, effective, ineffective and aggravated. Total effective rate was calculated. （3） Cognitive function of patients was tested before and 6 months after administration by using Wechsler Adult Intelligence Scale（WAIS） or Wechsler Intelligence Scale for Children （WISC, Chinese edition）, （Higher scores indicated better cognitive function）, Stroop color word interference, test of memory of past numbers, test of telling the names of fruits and vegetables within 1 minute （Shorter time for reading word, telling color and memory of past numbers demonstrated better cognitive function. Less errors in reading words, telling colors and memory of past numbers, numbering and telling the names of fruits and vegetables within 1 minute indicated better cognitive function）, etc. totally 22 items. （4） t test and paired t test were used for measurement data. MAIN OUTCOME MEASURES： Clinical curative effects and adverse reactions as well as neurological tests. RESULTS： Eighty-four pationts praticipated final analysis and 3 dropped out. （1） Inthe AEDS group and TPM group, total effective rate was 86% and 99%, respectively. （2） In the AEDs group, there were no significant changes in the scores of each test of WIS before and after treatment （P 〉 0.05）. In the TPM group, total IQ, word scores, verbal IQ and digit span scores were significantly decreased （ t =2.097 - 4.423, P 〈 0.05 - 0.01 ） .Following treatment, the time for reading word and telling color for patients in the AEDs group was prolonged in Stroop color interference test （ t = - 2.304, - 2.454, P 〈 0.05 ）, and time for reading word and memory of past numbers for patients in the topiramate group was significantly prolonged （ t = - 3.054, 2.272, P 〈 0.01, 0.05 ）. （3）There were no significant differences in scores of WIS before and after treatment in AEDs group and TPM group （P 〉 0.05）. Following treatment, verbal IQ, word scores, total IQ, digit span of patients in the TPM group were significantly lower than those in the AEDs group （t =2.052 - 3.297, P 〈 0.05- 0.01 ） .There were no significant differences in Stroop color word interference, memory of past numbers and telling the names of fruits and vegetables within 1 minute before and after treatment in AEDs group and TPM group （P 〉 0.05）. CONCLUSION： （1） Moderate and small doses of both TPM and AEDs may lead to mild cognitive function impairment of patients, mainly presenting delayed reaction and decreased sensitivity. （2）TPM mainly influences attention, language comprehension ability and fluency, while AEDs cause delayed reaction easily, but influence executive function mainly.

MicroRNAs in mouse and rat models of experimental epilepsy and potential therapeutic targets

Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.

Epilepsy versus non-epileptic attack disorder: A diagnostic and therapeutic challenge

Epilepsy and non-epileptic attack disorder (NEAD) share a vast number of clinical features, however the aetiology and management are very different. Video-EEG is the gold standard diagnostic tool and relies on the occurrence of seizure activity during assessment to make a diagnosis. Added complexity arises from the co-existence of epilepsy and NEAD, occurring in a significant proportion of patients. Comprehensive assessment and investigation is therefore required to prevent gross mistreatment in this diagnostically difficult subgroup. We present a case of NEAD with co-existing epilepsy and the challenges that this may present in clinical practice.

Valproic acid therapy decreases serum 25-hydroxyvitamin D level in female infants and toddlers with epilepsy-a pilot longitudinal study

To evaluate if valproic acid(VPA)therapy is associated with vitamin D deficiency among infants and toddlers with epilepsy,a cross-sectional clinical study was conducted in 25 children with epilepsy taking VPA.Blood levels of calcium,phosphorus,alkaline phosphatase,and 25-hydroxy vitamin D[25(OH)D]and plasma VPA level were measured at 1-to 3-month intervals.At the initial and final measurements,vitamin D deficiency or insufficiency was recognized in 8(32%)and 12(42%),respectively.In girls,a decreasing trend in serum25(OH)D levels(P<0.05)was observed.Polytherapy had a significant negative effect on the longitudinal change of 25(OH)D(P<0.05)in girls.In conclusion,our study indicates that a high proportion of girls after VPA therapy had hypovitaminosis D.

Astrocytic Kir4.1 potassium channels as a novel therapeutic target for epilepsy and mood disorders

Astrocytic Kir4.1 channels and spatial potassium buffering：Astrocytes play a crucial role in maintaining the structural and functional integrity of the brain,which includes formation of the blood-brain barrier,maintenance of water and ion homeostasis,metabolism of neurotransmitters and secretion of various neuroactive molecules.

CLINICAL STUDY ON TREATMENT OF INFANTILE PRIMARY EPILEPSY WITH ACUPOINT CATGUT-IMPLANTATION THERAPY

Aim: To observe the therapeutic effect of acupoint catgut implantation therapy in the treatment of infantile primary epilepsy. Methods: A total of 63 cases of primary epilepsy children were randomly divided into medication group (n=32) and acupoint catgut implantation group (n=31) and treated respectively with Sodium Valproate 5-10 mg/kg/d and catgut implantation at Changqiang (GV 1), Jiuwei (CV 15), bilateral Xinshu (BL 15) and bilateral Zusanli (ST 36). Results: Following 60 days of treatment, the abnormal changes of electroencephlogram (EEG), the seizure frequency and duration and clinical symptoms were improved apparently in comparison with those of pre treatment, but no significant differences were found between the two groups (P>0.05). There was a significant difference between two groups in the cure rate of the short term effect (P<0.05), with the therapeutic effect of the treatment group being superior to that of medication group. Conclusion: Acupoint catgut implantation therapy has a good therapeutic effect in the treatment of primary infantile epilepsy.

Correlation between human seizure-related gene 6 variants and idiopathic generalized epilepsy in a Southern Chinese Han population

This study sought to analyze the genotype and gene mutations of human seizure-related gene 6 in 98 patients with idiopathic generalized epilepsy （non-febrile seizures）, who were selected from three generations of the Chinese Han population living in Shanghai, Zhejiang Province, Wuxi of Jiangsu Province, and Jiangxi Province of Southern China. Twenty-six patients＇ parents were available as a first-degree relatives group and 100 biologically unrelated healthy controls were collected as the control group. Based on the age of onset and seizure type, the patients were divided into six subgroups. Polymerase chain reaction and DNA direct sequencing analysis showed that the most frequent mutations c. 1249dupC （p.Gly418Argfx31 ） and c.1636A 〉 G （p.Thr546Ala） were detected in some idiopathic generalized epilepsy patients and tl^eir asymptomatic first-degree relatives （30.6% vs. 19.2% and 11.2% vs. 26.9%）. A novel mutation c.1807G 〉A （p.Val603Met） was found in a patient with late-onset idiopathic generalized epilepsy. There was no significant difference in the incidence of these three mutations among the different subgroups of idiopathic generalized epilepsy and controls. Thus, further analysis of a larger population is needed to confirm the assumption that human seizure-related gene 6 is a susceptibility gene for idiopathic generalized epilepsy with various sub-syndromes.

Problems of Rational Therapy for Epilepsy during Pregnancy

Epilepsy is one of the most frequent neurological disorders. In these circumstances, more than 25% of the patients are women of reproductive age. The aim of our research was to analyze the effectiveness and safety of antiepileptic therapy in women with epilepsy during pregnancy and to analyze the pregnancies’ outcomes. We included in our research 121 pregnancies of 101 women aged at the moment of childbearing about 26.9 ± 4.57 years old. Idiopathic forms of epilepsy were predominant among all causes—47.1% (р < 0.01). Of all cases, 65.4% remained seizure-free from generalized tonic-clonic seizures (GTCS), including 69.6% of all idiopathic epilepsy cases and 68.6% among symptomatic ones. The antiepileptic drugs (AED) dosages were exceeding teratogenic level at the moment of conception in 54.7% of the cases. Worse control of epileptic seizures was associated with Benzobarbital (66.7%) and Lamotrigine (50.0%). Women with epilepsy did not receive specialized neurological therapy before conception in most cases, which leaded to the usage of AED teratogenic doses and less effectiveness of AED during pregnancy. It is necessary to plan the pregnancy and prescribe rational treatment for epilepsy starting at the stage of planning and during gestation in order to obtain a better seizures control and to decrease congenital disorders risk in fetus.

Treadmill exercise improves hippocampal neural plasticity and relieves cognitive deficits in a mouse model of epilepsy

Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.

Profound Hypothermia Secondary to Clobazam Use in Epilepsy: A Novel Association

Clobazam, a 1-5 benzodiazepine, was introduced in the 1970s for the treatment of anxiety and agitation. Antiepileptic properties were recognized, and efficacy in a number of epilepsy syndromes was demonstrated in humans, with good tolerance. Recent reviews are generally favorable, with a relative minimum of medication-related side effects. However, a number of benzodiazepines have been associated with causing hypothermia. To date, this side effect has not been reported with clobazam. We report two cases of profound hypothermia associated with the use of this medication for the treatment of epilepsy. Both children had significant cerebral dysgenesis and were developmentally impaired, but neither had experienced hypothermia before. Temperature dysregulation was resolved with medication withdrawal after an extensive work-up for alternative causes. Hypothermia should be considered as a possible side effect of clobazam, although the exact mechanism is unknown. Appropriate monitoring of temperature is appropriate, and precautions should be offered by caregivers.

Flexible,high-density,laminated ECoG electrode array for high spatiotemporal resolution foci diagnostic localization of refractory epilepsy

High spatiotemporal resolution brain electrical signals are critical for basic neuroscience research and high-precision focus diagnostic localization,as the spatial scale of some pathologic signals is at the submillimeter or micrometer level.This entails connecting hundreds or thousands of electrode wires on a limited surface.This study reported a class of flexible,ultrathin,highdensity electrocorticogram(ECoG)electrode arrays.The challenge of a large number of wiring arrangements was overcome by a laminated structure design and processing technology improvement.The flexible,ultrathin,high-density ECoG electrode array was conformably attached to the cortex for reliable,high spatial resolution electrophysiologic recordings.The minimum spacing between electrodes was 15μm,comparable to the diameter of a single neuron.Eight hundred electrodes were prepared with an electrode density of 4444 mm^(-2).In focal epilepsy surgery,the flexible,high-density,laminated ECoG electrode array with 36 electrodes was applied to collect epileptic spike waves inrabbits,improving the positioning accuracy of epilepsy lesions from the centimeter to the submillimeter level.The flexible,high-density,laminated ECoG electrode array has potential clinical applications in intractable epilepsy and other neurologic diseases requiring high-precision electroencephalogram acquisition.

Effects of lamotrigine + sodium valproate therapy on the nerve cell nutrition and apoptosis status as well as inflammatory response in patients with intractable epilepsy

Objective: To investigate the effects of lamotrigine + sodium valproate therapy on the nerve cell nutrition and apoptosis as well as inflammatory response in patients with intractable epilepsy. Methods: A total of 70 patients with intractable epilepsy who were treated in our hospital between August 2013 and October 2016 were divided into routine group (n=35) and study group (n=35) by random number table method, routine group received sodium valproate therapy and study group received lamotrigine combined with sodium valproate therapy. The differences in serum levels of neurotrophy indexes, nerve apoptosis indexes and inflammatory factors were compared between the two groups before and after treatment. Results: Before treatment, there was no statistically significant difference in serum levels of neurotrophy indexes, nerve apoptosis indexes and inflammatory factors between the two groups. After treatment, serum BDNF and NGF levels of study group were higher than those of routine group;serum Bcl-2, Fas and FasL levels of study group were lower than those of routine group whereas Bax level was higher than that of routine group;serum IL-1β, IL-6 and PGE2 levels of study group were lower than those of routine group. Conclusion: Lamotrigine combined with sodium valproate therapy can effectively increase the neurotrophy, inhibit the nerve apoptosis and reduce the systemic inflammatory response in patients with intractable epilepsy.

Effects of Chaotic Epilepsy Therapeutic Equipment on the Bemagle induced Epilepsy Attack in Rats

Objective The CH9417 Anti epilepsy Instrument was designed according to chaotic theory. The goal of this study was to evaluate its therapeutic effect of anti epilepsy.Methods The epilepsy animal model was established by using Bemagle in rats. Two treatment groups and one control group were used, 15 Spradue Dawley rats for each group. All animals were treated with CH9417 Anti epilepsy Instrument for 20 min each time twice a day for five days as one course. The behavioral changes of epilepsy onset were observed and the syndrome was divided into 0 5 stage. The total therapeutic duration was three courses.Results The results suggested that the latency of Bemagle induced epilepsy episode was significantly prolonged in both 0.1 mA and 0.05 mA treatment groups. In the 3rd course, the latent time was (1.70±0.9) min for control group and (3 97±2 32) min, (8 75±3.58) min for groups of 0.05 mA and 0.1 mA treatment, respectively. The latent time of epilepsy wave in EEG was also prolonged. \;

Aberrant adult neurogenesis in intractable epilepsy:can GABAergic progenitor transplantation normalize this process?

Temporal lobe epilepsy(TLE) is a common type of focal epilepsy characterized by seizure foci within the temporal lobes.While surgical resection of the foci is an established and effective approach for controlling seizures,both temporal lobes cannot be removed,due to their prominent roles in learning and memory.Additionally,seizures induce changes to the temporal lobes that contribute to hyperexcitability,including mossy fiber sprouting,astrogliosis.

Astrocyte chloride,excitatory-inhibitory balance and epilepsy

Excitation and inhibition are at the core of brain function and malfunction.To sustain the activity of neuronal networks over time and space,glutamatergic excitation is balanced by GABAergic inhibition.The equipoise of excitation and inhibition,known as the excitation/inhibition(E/I)balance,is crucial for proper brain function.The E/I balance is highly dynamic and shifts across different brain states:wakefulness primarily augments excitatory activity,while sleep promotes a decrease in excitation and an increase in inhibition(Bridi et al.,2020).Neuronal activity during various brain states is primarily regulated by neurotransmitters(Schiemann et al.,2015),alongside non-synaptic mechanisms that operate on a slower timescale.The non-synaptic mechanisms are many,with the ionic composition of the extracellular space playing a significant role;altering extracellular ion concentrations affects sleep,arousal,electroencephalogram patterns,and behavioral states(Ding et al.,2016).