Regulation of specific abnormal calcium signals in the hippocampal CA1 and primary cortex M1 alleviates the progression of temporal lobe epilepsy

Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.

Cognitive Disorders, Depression and Anxiety in Temporal Lobe Epilepsy: An Overview

Partial epilepsies, originating in a specific brain region, affect about 60% of adults with epilepsy. Temporal lobe epilepsy (TLE) is the most prevalent subtype within this category, often necessitating surgical intervention due to its refractoriness to antiepileptic drugs (AEDs). Hippocampal sclerosis, a common underlying pathology, often exacerbates the severity by introducing cognitive and emotional challenges. This review delves deeper into the cognitive profile of TLE, along with the risk factors for cognitive disorders, depression, and anxiety in this population.

MicroRNAs as potential biomarkers in temporal lobe epilepsy and mesial temporal lobe epilepsy

Temporal lobe epilepsy is the most common form of focal epilepsy in adults,accounting for one third of all diagnosed epileptic patients,with seizures originating from or involving mesial temporal structures such as the hippocampus,and many of these patients being refractory to treatment with anti-epileptic drugs.Temporal lobe epilepsy is the most common childhood neurological disorder and,compared with adults,the symptoms are greatly affected by age and brain development.Diagnosis of temporal lobe epilepsy relies on clinical examination,patient history,electroencephalographic recordings,and brain imaging.Misdiagnosis or delay in diagnosis is common.A molecular biomarker that could distinguish epilepsy from healthy subjects and other neurological conditions would allow for an earlier and more accurate diagnosis and appropriate treatment to be initiated.Among possible biomarkers of pathological changes as well as potential therapeutic targets in the epileptic brain are micro RNAs.Most of the recent studies had performed micro RNA profiling in body fluids such as blood plasma and blood serum and brain tissues such as temporal cortex tissue and hippocampal tissue.A large number of micro RNAs were dysregulated when compared to healthy controls and with some overlap between individual studies that could serve as potential biomarkers.For example,in adults with temporal lobe epilepsy,possible biomarkers are miR-199a-3p in blood plasma and miR-142-5p in blood plasma and blood serum.In adults with mesial temporal lobe epilepsy,possible biomarkers are miR-153 in blood plasma and miR-145-3p in blood serum.However,in many of the studies involving patients who receive one or several anti-epileptic drugs,the influence of these on micro RNA expression in body fluids and brain tissues is largely unknown.Further studies are warranted with children with temporal lobe epilepsy and consideration should be given to utilizing mouse or rat and non-human primate models of temporal lobe epilepsy.The animal models could be used to confirm micro RNA findings in human patients and to test the effects of targeting specific micro RNAs on disease progression and behavior.

Activation of medial septum cholinergic neurons restores cognitive function in temporal lobe epilepsy

Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in tempo ral lobe epile psy.However,their role in the cognitive impairment of temporal lobe epilepsy remains unclear.In this study,we found that patients with temporal lobe epile psy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory,but had no impairment in nonverbal memory.The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tra cts measured by diffusion tensor imaging.In a mouse model of chronic temporal lobe epilepsy induced by kainic acid,the number of medial septum choline rgic neurons was reduced and acetylcholine release was reduced in the hippocampus.Furthermore,selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice,and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid-and kindling-induced epile psy models.These res ults suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.

'Hippocampal innate inflammatory gliosis only'-the future role of surgery in a novel temporal lobe epilepsy syndrome

Epilepsy is one of the most common neurological conditions affecting more than 50 million people worldwide(https://www.who.int/news-room/fact-sheets/detail/epilepsy).Despite numerous antiseizure medications(ASM),approximately 30%of all patients will develop drug-resistant epile psy(DRE).DRE leads to devastating health and socioeconomic consequences(Luoni et al.,2011).

DIAGNOSTIC VALUE OF INTERICTAL DIFFUSION-WEIGHTED IMAGING IN EVALUATION OF INTRACTABLE TEMPORAL LOBE EPILEPSY

Objective To explore the ability of interictal diffusion-weighted imaging(DWI)to localize the temporal lobe of seizure origin and to predict postoperative seizure control in patients with temporal lobe epilepsy(TLE).Methods Twenty-seven patients with intractable TLE considered for surgery and 19 healthy volunteers were studied with conventional magnetic resonance imaging(MRI)and DWI.Apparent diffusion coefficients(ADCs)of bilateral hippocampi in both TLE patients and control subjects were obtained.Lateralization to either temporal lobe with hippocampal ADC was based on the threshold values derived from ±1SD of right/left ratios in normal subjects.And the postoperative pathology was reviewed.Results Hippocampal ADCs were higher on the side of surgery compared with those on the contralateral side as well as the ipsilateral side in control subjects [resected side(109.8±7.3)×10-5 cm2/s,contralateral side(91.7±4.7)×10-5 cm2/s,control subjects(81.6±5.2)×10-5 cm2/s,all P<0.01].Right/left hippocampal ADC ratio and conventional MRI lateralized to the operated temporal lobe in 21 of 27(77.8%)and in 18 of 27(66.7%)patients.Lateralization to the surgical side was not associated with postoperative seizure control with right/left hippocampal ADC ratio(P>0.05).Conclusions Conventional MRI is a sensitive method to detect hippocampal sclerosis.Accuracy of the right/left hippocampal ADC ratio for lateralizing to the side of surgery is very high,but it isn't a better predictor of surgical outcome.

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.

Anomalous expression of chloride transporters in the sclerosed hippocampus of mesial temporal lobe epilepsy patients

The Na＋-K＋-CI- cotransporter 1 and K＋-CI- cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophysiological mechanisms of mesial temporal lobe epilepsy. Imbalance in the relative expression of these two proteins can lead to a collapse of CI- homeostasis, resulting in a loss of gamma-aminobutyric acid-ergic inhibition and even epileptiform discharges. In this study, we investigated the expression of Na＋-K＋-CI- cotransporter 1 and K＋-CI- cotransporter 2 in the sclerosed hippocampus of patients with mesial temporal lobe epilepsy, using western blot analysis and immunohistochemistry. Compared with the histologically normal hippocampus, the sclerosed hippocampus showed increased Na＋-K＋-Cl- cotransporter 1 expression and decreased K＋-CI- cotransporter 2 expression, especially in CA2 and the dentate gyrus. The change was more prominent for the Na＋-K＋-CI- cotransporter 1 than for the K＋-CI- cotransporter 2. These experimental findings indicate that the balance between intracellular and extracellular chloride may be disturbed in hippocampal sclerosis, contributing to the hyperexcitability underlying epileptic seizures. Changes in Na＋-K＋-CI-cotransporter 1 expression seems to be the main contributor. Our study may shed new light on possible therapies for patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

Increased expression of Notch1 in temporal lobe epilepsy: animal models and clinical evidence

Temporal lobe epilepsy is associated with astrogliosis. Notchl signaling can induce astrogliosis in glioma. However, it remains unknown whether Notchl signaling is involved in the pathogenesis of epilepsy. This study investigated the presence of Notchl, hairy and enhancer of split-l, and glial fibrillary acidic protein in the temporal neocortex and hippocampus of lithium-pilocar- pine-treated rats. The presence of Notchl and hairy and enhancer of split-1 was also explored in brain tissues of patients with intractable temporal lobe epilepsy. Quantitative electroencephalo- gram analysis and behavioral observations were used as auxiliary measures. Results revealed that the presence of Notchl, hairy and enhancer of split-l, and glial fibriUary acidic protein were en- hanced in status epilepticus and vehicle-treated spontaneous recurrent seizures rats, but remain unchanged in the following groups： control, absence of either status epilepticus or spontaneous recurrent seizures, and zileuton-treated spontaneous recurrent seizures. Compared with patient control cases, the presences of Notch1 and hairy and enhancer of split- 1 were upregulated in the temporal neocortex of patients with intractable temporal lobe epilepsy. Therefore, these results suggest that Notchl signaling may play an important role in the onset of temporal lobe epilepsy via astrogliosis. Furthermore, zileuton may be a potential therapeutic strategy for temporal lobe epilepsy by blocking Notchl signaling.

Posterior quadrantic disconnection maintains the activity of isolated temporal-parietal-occipital nerve tissue: neuroprotective measures in the surgical treatment of epilepsy

Extensive lesions involving the posterior quadrant of the cerebral hemisphere （temporal, parietal, and occipital lobes） induce intractable epilepsy. These patients are potential candidates for surgical treatmenttu. Maintenance of isolated nerve tissue activity after surgery plays a crucial role in the neuroprotective effects of neurosurgery treatment. Disconnection surgery of the posterior quadrant is used to completely isolate nerve fibers, while blood supply at the isolated lobes is maintained. Subsequently, cavities caused by cystic or necrotic nerve tissues should be reduced as much as possible,

Spatio-temporal Expression Study of Phosphorylated 70-kDa Ribosomal S6 Kinase (p70S6k) in Mesial Temporal Lobe Epilepsy

Objective To determine the spatio-temporal expression of p70S6k activation in hippocampus in mesial temporal lobe epilepsy. Methods Temporal lobe epilepsy model was established by stereotaxically unilateral and intrahip-pocampal injection of kainite acid (KA) in adult male C57BL/6 mice. Latent and chronic epileptogenesis were represented by mice 5 days after KA injection (n=5) and mice 5 weeks after KA injection (n=8), respectively. Control mice (n=5) were injected with saline. Immunohistochemical assays were performed on brain sections of the mice. Results Hippocampus both ipsilateral and contralateral to the KA injection displayed significantly up-regulated pS6 immunoreactivity in dispersed granule cells in 5-day and 5-week model mice. Conclusion The activation of p70S6k is mainly located in the dentate gyrus in KA-induced mouse model of temporal lobe epilepsy, indicating that the activation may be related with the disperse degree and hypertrophy of granule cells.

Research on Medial Temporal Lobe Epilepsy by Combining Structural and Functional MRI

Epilepsy is a common neurological disorder, and its electrophysiology characteristic is abnormally high excitability and synchronization of the neural activity. This paper focuses on the study of medial temporal lobe epilepsy with hippocampal sclerosis. The hippocampus plays an important role in short-term memory. However, little is known about the connectivity between hippocampal structures and adjacent brain regions. The functional and structural connectivity between patients and controls was investigated by using the techniques of functional magnetic resonance imaging and diffusion tensor imaging in the paper. Three pairs of ROIs related to working memory from BOLD-fMRI data were chosen. These ROIs were registrated from MNI space to individual space and the fiber bundle between two ROIs were traced in the DTI images. The results show that the number of fiber bundle of patients reduce among these ROIs, such as left hippocampus and right hippocampus, left hippocampus and left thalamus, left hippocampus and left frontal lobe and so on. And the number of fiber bundle of patients increase among these ROIs, such as left thalamus and right thalamus, right hippocampus and right thalamus. And the FA values of the fiber bundles of patients in some regions related to left hippocampus decrease. The cause of abnormal functional and structural connections due to the damage of hippocampus in medial temporal lobe epilepsy is studied from a new perspective.

Effects of low-frequency repetitive transcranial magnetic stimulation on electroencephalogram and seizure frequency in 15 patients with temporal lobe epilepsy following dipole source localization

BACKGROUND： Low-frequency repetitive transcranial magnetic stimulation （rTMS） has been shown to significantly reduce epileptiform discharges and control clinical seizures in intractable epilepsy patients. The location of epileptic foci and magnetic stimulation sites remain uncertain. The effects of rTMS on electroencephalogram and seizure remain unclear in epileptic patients following dipole source localization. OBJECTIVE： To investigate the effects of low-frequency rTMS on electroencephalogram and seizure in temporal lobe epilepsy patients after dipole source localization. DESIGN, TIME AND SETTING： The randomized, controlled study was performed at the outpatient clinic Department of Neurology, Hospital Affiliated to North Sichuan Medical College from December 2003 to February 2007. PARTICIPANTS： A total of 30 temporal lobe epilepsy patients, comprising 19 males and 11 females, aged 1749 years, presented with epileptiform discharges and were enrolled for this study. Disease course ranged between 1-6 years, with 1-5 seizures per month. Imaging examinations revealed 11 patients with structural changes in the brain. The patients were randomly and equally assigned into drug treatment and transcranial magnetic stimulation （TMS） groups. METHODS： Patients in the drug treatment group were orally treated with carbamazepine. Patients in the TMS group received oral carbamazepine treatment of and TMS. A Maglite-r25 magnetic stimulator （Dantec Dynamics, Denmark） was used to stimulate epileptic foci in the temporal lobe following electroencephalogram dipole localization （1 Hz, 90% threshold intensity, at a stimulation frequency of 500 times, once a day, for 7 days）. MAIN OUTCOME MEASURES： At 30 days after TMS, seizure frequency and rate of epileptiform discharges were observed in patients from both groups. Therapeutic safety was investigated during treatment. RESULTS： Within 30 days of treatment, there were no significant differences in seizure frequency between the TMS group （1.5 ± 0.3） seizures and the drug treatment group [（1.9± 0.4） seizures] （P 〉 0.05）. The rate of epileptiform discharges [27% （4/15）] was significantly less in the TMS group than in the drug treatment group [73% （11/15）] （P 〈 0.05）. During TMS, five patients suffered from transient mild headache, but were completely relieved within 2 hours. CONCLUSION： Low-frequency rTMS exhibited inhibitory effects on epileptiform discharges over a short period of time, and decreased seizure frequency to some degree. Results from the present study suggested that low-frequency rTMS is safe.

METABOLIC ABNORMALITIES IN MESIAL TEMPORAL LOBE EPILEPSY PATIENTS DEPICTED BY PROTON MR SPECTROSCOPY USING A 3.0T MR SCANNER

Objective To evaluate metabolic abnormalities in patients with mesial temporal lobe epilepsy （MTLE） with proton magnetic resonance spectroscopy （MRS） using a 3.0T MR scanner. Methods Sixty-three patients （32 women and 31 men） with diagnosed MTLE underwent diagnostic MR imaging （MRI） and proton MRS using a 3.0T MR scanner. The clinical history and interictal epileptiform discharges （IEDs） were recorded. Sixteen healthy volunteers served as control. The results of proton MRS were compared with the findings of electroencephalogram and structural MRI findings. Results Twenty-seven of the 63 patients with MTLE showed unilateral hippocampal sclerosis, and 9 showed bilateral hippocampal sclerosis. The concentration ratio of N-acytelaspartate （NAA） / [ creatine （ Cr ） ＋ choline （Cho） ] in the hippocampal region of MTLE patients （0. 64±0. 07） was significantly lower than control （0. 80±0. 05, P = 0.023）. In the patients with unilateral hippocampal sclerosis, NAA/（Cr ＋ Cho） in the hippocampal region ipsilateral to the sclerotic hippocampus （0.56±0.06） was significantly lower than the ratio in the contralateral hippocampal region （0.69±0.07, P 〈 0. 001 ）. There was significant difference in hippocampal NAA/（ Cr ＋ Cho） between the refractory patients and the non-refractory patients （0. 64±0. 05 vs.0.71±0. 07, P =0. 04）. Forty-five patients were lateralized by IEDs, while 49 patients were lateralized by metabolite ratio. And lateralization determined by proton MRS and IEDs was concordant in 33 patients. Conclusions MRS as a noninvasive tool adds helpful metabolite information to routine MRI in evaluation of MTLE. The method is well established and should be a routine clinical application in the investigation of epilepsy.

Molecular typing of familial temporal lobe epilepsy

The pathogenesis of temporal lobe epilepsy(TLE)was originally considered to be acquired.However,some reports showed that TLE was clustered in some families,indicating a genetic etiology.With the popularity of genetic testing technology,eleven different types of familial TLE(FTLE),including ETL1-ETL11,have been reported,of which ETL9-ETL11 had not yet been included in the OMIM database.These types of FTLE were caused by different genes/Loci and had distinct characteristics.ETL1,ETL7 and ETL10 were characterized by auditory,visual and aphasia seizures,leading to the diagnosis of familial lateral TLE.ETL2,ETL3 and ETL6 showed prominent autonomic symptom and automatism with or without hippocampal abnormalities,indicating a mesial temporal origin.Febrile seizures were common in FTLEs such as ETL2,ETL5,ETL6 and ETL11.ETL4 was diagnosed as occipitotemporal lobe epilepsy with a high incidence of migraine and visual aura.Considering the diversity and complexity of the symptoms of TLE,neurologists enquiring about the family history of epilepsy should ask whether the relatives of the proband had experienced unnoticeable seizures and whether there is a family history of other neurological diseases carefully.Most FTLE patients had a good prognosis with or without anti-seizure medication treatment,with the exception of patients with heterozygous mutations of the CPA6 gene.The pathogenic mechanism was diverse among these genes and spans disturbances of neuron development,differentiation and synaptic signaling.In this article,we describe the research progress on eleven different types of FTLE.The precise molecular typing of FTLE would facilitate the diagnosis and treatment of FTLE and genetic counseling for this disorder.

Cross-frequency network analysis of functional brain connectivity in temporal lobe epilepsy

In this study, we investigate the cross-frequency coupling and functional brain networks in the subjects with temporal lobe epilepsy(TLE) using interictal EEG signals. The phase to phase synchronization within and across frequency bands is calculated and a significant difference between the epilepsy and control groups is observed. Compared with the controls,the epilepsy patients exhibit a stronger within-frequency coupling(WFC) within theta and beta bands, and shows a stronger cross-frequency coupling(CFC) in the delta–alpha and theta–alpha band pairs, but a weakened CFC in alpha–beta band pairs. The weakened coupling between alpha and high frequency band reflects a suppression of phase modulation between the brain regions related to epilepsy. Moreover, WFC and CFC are positively correlated, which is higher in the patients relative to controls. We further reconstruct functional brain connectivity and find that both WFC and CFC networks show small-world properties. For the epilepsy, the small-world efficiency is enhanced in the CFC networks in delta–alpha and theta–alpha band pairs, whereas weakened between alpha and beta bands, which suggests a shift away from the optimal operating point in the epileptic brain with a new balance between WFC and CFC. Our results may help us to understand the important role of information communication across different frequency bands and shed new light on the study of pathology of epilepsy.

Prodynorphin Gene Promoter Polymorphism and Temporal Lobe Epilepsy:A Meta-analysis

Previous studies have reported the association of prodynorphin（PDYN） promoter polymorphism with temporal lobe epilepsy（TLE） susceptibility,but the results remain inconclusive. To further precisely evaluate this association,we performed a meta-analysis. Published studies of TLE and PDYN polymorphism up to February 2015 were identified. Subgroup analysis by TLE subtype was performed. Moreover,sensitivity,heterogeneity,and publication bias were also analyzed. Seven case-control studies were finally included in this meta-analysis with 875 TLE cases and 1426 controls. We did not find synthetic evidence of association between PDYN promoter polymorphism and TLE susceptibility（OR=1.184,95% CI： 0.873–1.606,P=0.277）. Similar results were also obtained in non-familial-risk TLE subgroup. However,in the familial-risk TLE subgroup analysis,a significant association was observed（OR=1.739,95% CI： 1.154–2.619,P=0.008）. In summary,this meta-analysis suggests that PDYN gene promoter polymorphism might contribute to familial-risk TLE.

Subicular pyramidal neurons gate drug resistance in temporal lobe epilepsy

OBJECTIVE To understand the underlying mechanisms of drug resistant temporal lobe epilepsy(TLE).METHODS In vivo and vitro electrophysiology,optogenetics and chemogenetics were used in a classic multi-drug resistant TLE model.RESULTS Subicular pyramidal neuron activity was not inhibited by the anti-epileptic drug phenytoin in drug resistant rats.This phenomenon was specific to the subiculum,but did not involve surrounding temporal lobe regions.Selective inhibition of subicular pyramidal neurons by both optogenetics and chemogenetics reversed drug resistance.In contrast,selective activation of subicular pyramidal neurons directly induced drug resistance in drug responsive rats.Furthermore,long-term low frequency stimulation at the subiculum,which is clinically feasible,inhibited the activity of subicular pyramidal neurons and reversed drug resistance.CONCLUSION Subicular pyramidal neurons might be a key ″ switch″ mediating drug resistance in TLE and represent a new potential target for more precise treatment of drug resistant TLE.

Effects of D2 receptor antagonist haloperidol on hippocampal neuronal apoptosis in a rat model of temporal epilepsy

BACKGROUND： Dopamine receptors are divided into D1 and D2 subgroups. It has been reported that D2 receptors resist neural toxicity induced by excitatory amino acids and muscarine, and also alleviate epilepsy attacks following pilocarpine treatment. However, it has not yet been established whether D2 receptors regulate temporal epilepsy. OBJECTIVE： To observe the effects of the D2 antagonist haloperidol on hippocampal neuronal apoptosis and electrical brain activity in a rat model of kainic acid-induced temporal epilepsy. DESIGN, TIME AND SETTING： Randomized grouping and histopathological study were performed at the Neurology Medicine Institute of Zhujiang Hospital, Southern Medical University from August to December 2004. MATERIALS： Twenty-five adult, male, Sprague Dawley rats were selected for the present study. Kainic acid （Sigma, USA） was injected into the right lateral ventricle to establish models of temporal epilepsy. A PowerLah multiplying channel eleetrophysiolograph was provided by AD Instruments, Australia. METHODS： The rats were randomly divided into 5 groups （n = 5）： control, model, haloperidol hippocampus, haloperidol striatum, and haloperidol substantia nigra. Temporal epilepsy was established in all rats except the control group. Haloperidol was slowly injected into the hippocampus, striatum and substantia nigra, respectively, in three different injection groups. Normal saline was injected into the right lateral ventricle of the control rats. MAIN OUTCOME MEASURES： Hippocampal apoptosis was observed on the day 3 of treatment using TUNEL staining. Changes in electroencephalogram at 0, 0.5, 2, 6, and 12 hours following treatment onset were observed using a PowerLab multiplying channel electrophysiolograph. Animal behaviors were classified according to the Racine criteria. RESULTS： Twenty-five rats were included in the final analysis. Seizures did not occur in the control group. In the model group, 10 minutes after kainic acid injection to the lateral cerebral ventricle, epilepsy seizures occurred and reached a peak within one hour. Hippocampal neuronal apoptosis occurred following epilepsy, in particular on day 3. Following haloperidol injection, hippocampal neuronal apoptosis increased, in particular in the haloperidol hippocampus group, and was significantly greater than the model group （P 〈 0.05）. CONCLUSION： Results suggested that D2 receptors inhibited temporal epilepsy. The hippocampal D2 receptors exhibited the strongest influence on temporal epilepsy in the hippocampus, followed by the suhstantia nigra and the striatum.

Association between serotonin transporter gene polymorphisms and non-lesional temporal lobe epilepsy in a Chinese Han population

Serotonin （5-hydroxytryptamine, 5-HT） influences the cortical and subcortical excitatory/inhibitory balance and participates in the pathophysiological processes of epilepsy. The serotonin transporter （5-HTT） is the most important factor in serotonin inactivation. We tested whether 5-HTT polymorphisms are involved in the pathogenesis of epilepsy in Chinese Han population. We did not find a significant difference in the frequencies of genotypes and alleles in the 5-HTT gene-linked poLymorphic region （5-H-I-FLPR） in patients with non-lesional temporal lobe epilepsy and normal controls （P〉 0.05）. Frequencies of the 5-H1-1- intron 2 variable number tandem repeat （5-HTTVNTR） 12/12 genotype and allele 12 were higher in the patients with non-lesional temporal lobe epilepsy than normal controls （P 〈 0.01）. The odds ratio of affecting non-lesional temporal lobe epilepsy was 1.435 （95% Cl, 1.096 1.880） in patients carrying allele 12 （P 〈 0.05）. Although the 5-HTTLPR may not be a genetic locus of non-lesional temporal lobe epilepsy in Chinese Hart population, allele 12 in the 5-HTTVNTR may correlate with non-lesional temporal lobe epilepsy. The Stin2.12 allele and 12/12 genotype could be predisposing to non-lesional temporal lobe epilepsy.