Occurrence Of Spontaneous Seizures Research Articles

A comprehensive overview on phytomedicines as an upcoming/emerging candidate for the management of epilepsy

Background: The word "epilepsy" refers to a category of chronic CNS illnesses characterised by spontaneous occurrence of seizures, which are typically accompanied by loss of consciousness and uncontrollable shaking of the body (convulsions). Epilepsy is one of the most commonly occurring non-communicable neurological disorder that affects people of all age groups. By preventing discharge and inducing hypnosis, anticonvulsant medications are used to manage convulsions. The medication used for the therapy includes phenytoin (PHT), diazepam, valproate (VPA), levetiracetam, etc. These medications have brand-new effectiveness ranges and brand-new side effects. They also represent a significant cost increase. Herbal medicine, which has its roots in ancient civilizations, involves the use of medicinal plants to treat diseases and promote overall well-being. Although the widespread use of herbal medicine as an antiepileptic, there is little solid data supporting the effectiveness and safety of the majority of herbs. Additionally, the herbal remedy needs to pass a rigorous, evidence-based review. As herbal drugs are derived from natural sources, they are often considered safer than synthetic drugs. Therefore, there is a growing interest in exploring the potential of herbal medicine for treating neurodegenerative diseases such as Parkinson's disease. Due to their lower adverse effects, herbal medications are becoming more and more popular for the adjuvant treatment of epilepsy.
 Objective: The objective of this article is to investigate whether herbal medications have potential as a treatment option for Parkinsonism, and to provide a clear understanding of the current state of research on this topic.
 Keywords: Convulsion, epilepsy, herbal treatment, seizures, phytoconstituents, herbal medicine, GABA.

Personalized Real-Time Federated Learning for Epileptic Seizure Detection.

Epilepsy is one of the most prevalent paroxystic neurological disorders. It is characterized by the occurrence of spontaneous seizures. About 1 out of 3 patients have drug-resistant epilepsy, thus their seizures cannot be controlled by medication. Automatic detection of epileptic seizures can substantially improve the patient's quality of life. To achieve a high-quality model, we have to collect data from various patients in a central server. However, sending the patient's raw data to this central server puts patient privacy at risk and consumes a significant amount of energy. To address these challenges, in this work, we have designed and evaluated a standard federated learning framework in the context of epileptic seizure detection using a deep learning-based approach, which operates across a cluster of machines. We evaluated the accuracy and performance of our proposed approach on the NVIDIA Jetson Nano Developer Kit based on the EPILEPSIAE database, which is one of the largest public epilepsy datasets for seizure detection. Our proposed framework achieved a sensitivity of 81.25%, a specificity of 82.00%, and a geometric mean of 81.62%. It can be implemented on embedded platforms that complete the entire training process in 1.86 hours using 344.34 mAh energy on a single battery charge. We also studied a personalized variant of the federated learning, where each machine is responsible for training a deep neural network (DNN) to learn the discriminative electrocardiography (ECG) features of the epileptic seizures of the specific person monitored based on its local data. In this context, the DNN benefitted from a well-trained model without sharing the patient's raw data with a server or a central cloud repository. We observe in our results that personalized federated learning provides an increase in all the performance metric, with a sensitivity of 90.24%, a specificity of 91.58%, and a geometric mean of 90.90%.

Seizure progression triggered by IQSEC3 loss is mitigated by reducing activated microglia in mice.

IQSEC3, a guanine nucleotide exchange factor for ADP-ribosylation factors (ARF-GEFs) is specifically expressed at GABAergic synapses, and its loss increases seizure susceptibility in mice. However, the contribution of microglia to initiation and/or progression of seizures in IQSEC3-deficient mice has not been investigated. In the current study, we show that mice with hippocampal dentate gyrus (DG)-specific IQSEC3 knockdown (KD) exhibit microglial activation and death of DG granule cell. Furthermore, treatment of IQSEC3-KD mice with minocycline, an inhibitor of microglial activation, blocks DG granule neuron cell death and the occurrence of spontaneous seizures without affecting GABAergic synapse deficits or loss of somatostatin. Our results suggest that microglial activation is involved in a subset of IQSEC3-KD-induced epileptogenesis stages, and that its regulation could be an alternative strategy for managing epilepsy.

Adversarial Representation Learning for Robust Patient-Independent Epileptic Seizure Detection.

Epilepsy is a chronic neurological disorder characterized by the occurrence of spontaneous seizures, which affects about one percent of the worlds population. Most of the current seizure detection approaches strongly rely on patient history records and thus fail in the patient-independent situation of detecting the new patients. To overcome such limitation, we propose a robust and explainable epileptic seizure detection model that effectively learns from seizure states while eliminates the inter-patient noises. A complex deep neural network model is proposed to learn the pure seizure-specific representation from the raw non-invasive electroencephalography (EEG) signals through adversarial training. Furthermore, to enhance the explainability, we develop an attention mechanism to automatically learn the importance of each EEG channels in the seizure diagnosis procedure. The proposed approach is evaluated over the Temple University Hospital EEG (TUH EEG) database. The experimental results illustrate that our model outperforms the competitive state-of-the-art baselines with low latency. Moreover, the designed attention mechanism is demonstrated ables to provide fine-grained information for pathological analysis. We propose an effective and efficient patient-independent diagnosis approach of epileptic seizure based on raw EEG signals without manually feature engineering, which is a step toward the development of large-scale deployment for real-life use.

Silencing MicroRNA-134 Alleviates Hippocampal Damage and Occurrence of Spontaneous Seizures After Intraventricular Kainic Acid-Induced Status Epilepticus in Rats.

Epilepsy is a disorder of abnormal brain activity typified by spontaneous and recurrent seizures. MicroRNAs (miRNAs) are short non-coding RNAs, critical for the post-transcriptional regulation of gene expression. MiRNA dysregulation has previously been implicated in the induction of epilepsy. In this study, we examined the effect of silencing miR-134 against status epilepticus (SE). Our results showed that level of miR-134 was significantly up-regulated in rat brain after Kainic acid (KA)-induced SE. TUNEL staining showed that silencing miR-134 alleviated seizure-induced neuronal apoptosis in the CA3 subfield of the hippocampus. Western blot showed that a miR-134 antagonist suppressed lesion-induced endoplasmic reticulum (ER) stress and apoptosis related expression of CHOP, Bim and Cytochrome C, while facilitated the expression of CREB at 24 h post KA-induced lesion in the hippocampus. Consistently, silencing miR-134 significantly diminished loss of CA3 pyramidal neurons using Nissl staining as well as reducing aberrant mossy fiber sprouting (MFS) in a rat epileptic model. In addition, the results of EEG and behavior analyses showed seizures were alleviated by miR-134 antagonist in our experimental models. These results suggest that silencing miR-134 modulates the epileptic phenotype by upregulating its target gene, CREB. This in turn attenuates oxidative and ER stress, inhibits apoptosis, and decreases MFS long term. This indicates that silencing miR-134 might be a promising intervention for the treatment of epilepsy.

Long-Term Effects of Myoinositol on Behavioural Seizures and Biochemical Changes Evoked by Kainic Acid Induced Epileptogenesis.

Epilepsy is one of the most devastating neurological diseases and despite significant efforts there is no cure available. Occurrence of spontaneous seizures in epilepsy is preceded by numerous functional and structural pathophysiological reorganizations in the brain—a process called epileptogenesis. Treatment strategies targeting this process may be efficient for preventing spontaneous recurrent seizures (SRS) in epilepsy, or for modification of disease progression. We have previously shown that (i) myoinositol (MI) pretreatment significantly decreases severity of acute seizures (status epilepticus: SE) induced by kainic acid (KA) in experimental animals and (ii) that daily post-SE administration of MI for 4 weeks prevents certain biochemical changes triggered by SE. However it was not established whether such MI treatment also exerts long-term effects on the frequency of SRS. In the present study we have shown that, in KA-induced post-SE epilepsy model in rats, MI treatment for 28 days reduces frequency and duration of behavioural SRS not only during the treatment, but also after its termination for the following 4 weeks. Moreover, MI has significant effects on molecular changes in the hippocampus, including mi-RNA expression spectrum, as well as mRNA levels of sodium-MI transporter and LRRC8A subunit of the volume regulated anionic channel. Taken together, these data suggest that molecular changes induced by MI treatment may counteract epileptogenesis. Thus, here we provide data indicating antiepileptogenic properties of MI, which further supports the idea of developing new antiepileptogenic and disease modifying drug that targets MI system.

Calpain activation and neuronal death during early epileptogenesis

Epilepsy is a brain disorder characterized by a predisposition to suffer epileptic seizures. Acquired epilepsy might be the result of brain insults like head trauma, stroke, brain infection, or status epilepticus (SE) when one of these triggering injuries starts a transformative process known as epileptogenesis. There is some data to suggest that, during epileptogenesis, seizures themselves damage the brain but there is no conclusive evidence to demonstrate that spontaneous recurrent seizures themselves injure the brain. Our recent evidence indicates that calpain overactivation might be relevant for epileptogenesis. Here, we investigated if spontaneous recurrent seizures that occur during an early period of epileptogenesis show any correlation with the levels of calpain activation and/or expression. In addition, we also investigated a possible association between the occurrence of spontaneous seizures and increased levels of cell death, gliosis and inflammation (typical markers associated with epileptogenesis). We found that the number of spontaneous seizures detected prior to sample collection was correlated with altered calpain activity and expression. Moreover, the levels of hippocampal neurodegeneration were also correlated with seizure occurrence. Our findings suggest that, at least during early epileptogenesis, there is a correlation between seizure occurrence, calpain activity and neurodegeneration. Thus, this study opens the possibility that aberrant calpain reactivation by spontaneous seizures might contribute to the manifestation of future spontaneous seizures.

T-cell infiltration into the perilesional cortex is long-lasting and associates with poor somatomotor recovery after experimental traumatic brain injury

T-lymphocyte (T-cell) invasion into the brain parenchyma is a major consequence of traumatic brain injury (TBI). However, the role of T-cells in the post-TBI functional outcome and secondary inflammatory processes is unknown. We explored the dynamics of T-cell infiltration into the cortex after TBI to establish whether the infiltration relates to post-injury functional impairment/recovery and progression of the secondary injury. TBI was induced in rats by lateral fluid-percussion injury, and the acute functional impairment was assessed using the neuroscore. Animals were killed between 1-90 d post-TBI for immunohistochemical analysis of T-cell infiltration (CD3), chronic macrophage/microglial reaction (CD68), blood-brain barrier (BBB) dysfunction (IgG), and endophenotype of the cortical injury. Furthermore, the occurrence of spontaneous seizures and spike-and-wave discharges were assessed using video-electroencephalography. The number of T-cells peaked at 2-d post-TBI, and then dramatically decreased by 7-d post-TBI (5% of 2-d value). Unexpectedly, chronic T-cell infiltration at 1 or 3 months post-TBI did not correlate with the severity of chronic inflammation (p > 0.05) or BBB dysfunction (p > 0.05). Multiple regression analysis indicated that inflammation and BBB dysfunction is associated with 48% of the perilesional T-cell infiltration even at the chronic time-point (r = 0.695, F = 6.54, p < 0.05). The magnitude of T-cell infiltration did not predict the pathologic endophenotype of cortical injury, but the higher the number of T-cells in the cortex, the poorer the recovery index based on the neuroscore (r = - 0.538, p < 0.05). T-cell infiltration was not associated with the number or duration of age-related spike-and-wave discharges (SWD). Nevertheless, the higher the number of SWD, the poorer the recovery index (r = - 0.767, p < 0.5). These findings suggest that acute infiltration of T-cells into the brain parenchyma after TBI is a contributing factor to poor post-injury recovery.

Neonatal Seizure Models to Study Epileptogenesis

Current therapeutic strategies for epilepsy include anti-epileptic drugs and surgical treatments that are mainly focused on the suppression of existing seizures rather than the occurrence of the first spontaneous seizure. These symptomatic treatments help a certain proportion of patients, but these strategies are not intended to clarify the cellular and molecular mechanisms underlying the primary process of epilepsy development, i.e., epileptogenesis. Epileptogenic changes include reorganization of neural and glial circuits, resulting in the formation of an epileptogenic focus. To achieve the goal of developing “anti-epileptogenic” drugs, we need to clarify the step-by-step mechanisms underlying epileptogenesis for patients whose seizures are not controllable with existing “anti-epileptic” drugs. Epileptogenesis has been studied using animal models of neonatal seizures because such models are useful for studying the latent period before the occurrence of spontaneous seizures and the lowering of the seizure threshold. Further, neonatal seizure models are generally easy to handle and can be applied for in vitro studies because cells in the neonatal brain are suitable for culture. Here, we review two animal models of neonatal seizures for studying epileptogenesis and discuss their features, specifically focusing on hypoxia-ischemia (HI)-induced seizures and febrile seizures (FSs). Studying these models will contribute to identifying the potential therapeutic targets and biomarkers of epileptogenesis.

An on demand macaque model of mesial temporal lobe seizures induced by unilateral intra hippocampal injection of penicillin

PurposeOur objective was to propose a new on demand non-human primate model of mesial temporal lobe seizures suitable for pre-clinical innovative therapeutic research. MethodsFive macaques were stereotaxically implanted unilaterally with a deep recording electrode in the hippocampus. For each experiment, penicillin was injected into the hippocampus and animals were monitored during five consecutive hours. A total of 12–27 experiments with a mean cumulative dose of 162644 ± 70190 UI of penicillin have been performed per animal Injections were repeated at least once a week over a period of 98-276 days. The time-course of electro-clinical seizures and the response to diazepam have been quantified from, respectively, 84 and 11 experiments randomly selected. To evaluate brain injury produced by several penicillin injections and to characterize the changes occurring into the hippocampus, we performed an histological analysis, including neuronal nuclei and glial fibrillary acid protein immunostaining and electron microscopy. ResultsAfter each penicillin injection, we observed that the electro-clinical characteristics were reproducible among non-human primates and experiments. Seizures duration was stable (29.60 ± 6.62 s) and the frequency of seizures reached a plateau with about 3 seizures/20 min during 180 min and that could be useful to test new treatments. Diazepam did not modify the course of the seizures. Hippocampal sclerosis was found similar to that encountered in epileptic patients with a neuronal loss and a glial cells proliferation. Electron microscopy analysis of CA1 revealed a decreased number of synapses and a large amount of glial fibrillary filaments in the injected hippocampus. Interestingly, this on-demand model of seizure, turned into a chronic model with spontaneous occurrence of seizures after a cumulative amount ranging from 119 to 145 KIU of penicillin injected. ConclusionThe present study shows that an on-demand model of mesial temporal lobe seizure can be developed by intra-hippocampal injection of penicillin. The seizures are reproducible, stable and resistant to diazepam. Brain damages are confined to the hippocampus with similar features to that found in human mesial temporal lobe epilepsy. This model reproduces the symptomatogenic and the irritative zone usually seen in human MTLE, with the additional advantage of having a clear delineation of the epileptogenic zone. However, the mechanism of actions of the penicillin as a proconvulsant agent does not replicate all of the much more complex physiological and cellular mechanisms that are involved in human epilepsy and represent a limitation of our study that one must be aware of.

Increased expression of (immuno)proteasome subunits during epileptogenesis is attenuated by inhibition of the mammalian target of rapamycin pathway.

Inhibition of the mammalian target of rapamycin (mTOR) pathway reduces epileptogenesis in various epilepsy models, possibly by inhibition of inflammatory processes, which may include the proteasome system. To study the role of mTOR inhibition in the regulation of the proteasome system, we investigated (immuno)proteasome expression during epileptogenesis, as well as the effects of the mTOR inhibitor rapamycin. The expression of constitutive (β1, β5) and immunoproteasome (β1i, β5i) subunits was investigated during epileptogenesis using immunohistochemistry in the electrical post-status epilepticus (SE) rat model for temporal lobe epilepsy (TLE). The effect of rapamycin was studied on (immuno)proteasome subunit expression in post-SE rats that were treated for 6 weeks. (Immuno)proteasome expression was validated in the brain tissue of patients who had SE or drug-resistant TLE and the effect of rapamycin was studied in primary human astrocyte cultures. In post-SE rats, increased (immuno)proteasome expression was detected throughout epileptogenesis in neurons and astrocytes within the hippocampus and piriform cortex and was most evident in rats that developed a progressive form of epilepsy. Rapamycin-treated post-SE rats had reduced (immuno)proteasome protein expression and a lower number of spontaneous seizures compared to vehicle-treated rats. (Immuno)proteasome expression was also increased in neurons and astrocytes within the human hippocampus after SE and in patients with drug-resistant TLE. In vitro studies using cultured human astrocytes showed that interleukin (IL)-1β-induced (immuno)proteasome gene expression could be attenuated by rapamycin. Because dysregulation of the (immuno)proteasome system is observed before the occurrence of spontaneous seizures in rats, is associated with progression of epilepsy, and can be modulated via the mTOR pathway, it may represent an interesting novel target for drug treatment in epilepsy.

RNA sequencing of synaptic and cytoplasmic Upf1-bound transcripts supports contribution of nonsense-mediated decay to epileptogenesis

The nonsense mediated decay (NMD) pathway is a critical surveillance mechanism for identifying aberrant mRNA transcripts. It is unknown, however, whether the NMD system is affected by seizures in vivo and whether changes confer beneficial or maladaptive responses that influence long-term outcomes such the network alterations that produce spontaneous recurrent seizures. Here we explored the responses of the NMD pathway to prolonged seizures (status epilepticus) and investigated the effects of NMD inhibition on epilepsy in mice. Status epilepticus led to increased protein levels of Up-frameshift suppressor 1 homolog (Upf1) within the mouse hippocampus. Upf1 protein levels were also higher in resected hippocampus from patients with intractable temporal lobe epilepsy. Immunoprecipitation of Upf1-bound RNA from the cytoplasmic and synaptosomal compartments followed by RNA sequencing identified unique populations of NMD-associated transcripts and altered levels after status epilepticus, including known substrates such as Arc as well as novel targets including Inhba and Npas4. Finally, long-term video-EEG recordings determined that pharmacologic interference in the NMD pathway after status epilepticus reduced the later occurrence of spontaneous seizures in mice. These findings suggest compartment-specific recruitment and differential loading of transcripts by NMD pathway components may contribute to the process of epileptogenesis.

Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channels in Epilepsy.

Epilepsy is a common brain disorder characterized by the occurrence of spontaneous seizures. These bursts of synchronous firing arise from abnormalities of neuronal networks. Excitability of individual neurons and neuronal networks is largely governed by ion channels and, indeed, abnormalities of a number of ion channels resulting from mutations or aberrant expression and trafficking underlie several types of epilepsy. Here, we focus on the hyperpolarization-activated cyclic nucleotide-gated ion (HCN) channels that conduct Ih current. This conductance plays complex and diverse roles in the regulation of neuronal and network excitability. We describe the normal function of HCN channels and discuss how aberrant expression, assembly, trafficking, and posttranslational modifications contribute to experimental and human epilepsy.

Discriminating preictal and interictal brain states in intracranial EEG by sample entropy and extreme learning machine

BackgroundEpilepsy is one of the most common neurological disorders approximately one in every 100 people worldwide are suffering from it. Uncontrolled epilepsy poses a significant burden to society due to associated healthcare cost to treat and control the unpredictable and spontaneous occurrence of seizures. The objective of this research is to develop and present a novel classification framework that is utilised to discriminate interictal and preictal brain activities via quantitative analysis of electroencephalogram (EEG) recordings. New methodSample entropy-based features were extracted in parallel from 6 intracranial EEG channels, and then these features were fed to the extreme learning machine model for classification. Performance was evaluated on the basis of sensitivity and specificity and validation was performed using stratified cross-validation approach. ResultsThe proposed method can correctly distinguish interictal and preictal EEGs with a sensitivity of 86.75% and a specificity of 83.80%, on average, across 21 patients and 6 epileptic seizure origins. Comparison with existing methodCompared with traditional variance-based feature extraction, the proposed SampEn-based feature extraction method not only shows a significant improvement in the accuracy, but also has higher classification robustness and stability in terms of the much lower standard errors of classification accuracies across different evaluation periods. In addition, the proposed classification framework runs around 20 times faster than the support vector machine model during testing. ConclusionsThe high accuracy and efficiency of the proposed method makes it feasible to extend it to the development of a real-time EEG-based brain monitoring system for epileptic seizure prediction.

Pharmacological characterization of an antisense knockdown zebrafish model of Dravet syndrome: inhibition of epileptic seizures by the serotonin agonist fenfluramine.

Dravet syndrome (DS) is one of the most pharmacoresistant and devastating forms of childhood epilepsy syndromes. Distinct de novo mutations in the SCN1A gene are responsible for over 80% of DS cases. While DS is largely resistant to treatment with existing anti-epileptic drugs, promising results have been obtained in clinical trials with human patients treated with the serotonin agonist fenfluramine as an add-on therapeutic. We developed a zebrafish model of DS using morpholino antisense oligomers (MOs) targeting scn1Lab, the zebrafish ortholog of SCN1A. Zebrafish larvae with an antisense knockdown of scn1Lab (scn1Lab morphants) were characterized by automated behavioral tracking and high-resolution video imaging, in addition to measuring brain activity through local field potential recordings. Our findings reveal that scn1Lab morphants display hyperactivity, convulsive seizure-like behavior, loss of posture, repetitive jerking and a myoclonic seizure-like pattern. The occurrence of spontaneous seizures was confirmed by local field potential recordings of the forebrain, measuring epileptiform discharges. Furthermore, we show that these larvae are remarkably sensitive to hyperthermia, similar to what has been described for mouse models of DS, as well as for human DS patients. Pharmacological evaluation revealed that sodium valproate and fenfluramine significantly reduce epileptiform discharges in scn1Lab morphants. Our findings for this zebrafish model of DS are in accordance with clinical data for human DS patients. To our knowledge, this is the first study demonstrating effective seizure inhibition of fenfluramine in an animal model of Dravet syndrome. Moreover, these results provide a basis for identifying novel analogs with improved activity and significantly milder or no side effects.

Astrocyte-neuronal interactions in epileptogenesis.

Pentylenetetrazol, kainic acid, or pilocarpine can be used to induce seizures in animal models of epilepsy. The present Review describes disturbances in astrocyte-neuron interactions in the acute, latent, and chronic phases analyzed by magnetic resonance spectroscopy of brain tissue extracts from rats injected with [1-(13)C]glucose and [1,2-(13)C]acetate. The most consistent change after onset of seizures was the decrease in (13)C labeling of glutamate (GLU) from [1-(13) C]glucose regardless of brain area, severity, or duration of the period with seizures and toxin used. In most cases this decrease was accompanied by a reduction in glutamine (GLN) labeling from [1-(13)C]glucose, presumably as a direct consequence of the reduction in labeling of GLU and the GLU-GLN cycle. Amounts of GLN were never changed. Reduction in the content of N-acetyl aspartate (NAA) was first detectable some time after status epilepticus but before the occurrence of spontaneous seizures. This decrease can be an indication of neuronal death and/or mitochondrial impairment and might indicate beginning gliosis. It is known that gliosis occurs in the chronic phase of temporal lobe epilepsy in hippocampus, but astrocyte metabolism appears normal in this phase, indicating that the gliotic astrocytes have a somewhat reduced metabolism per volume. A decrease in (13)C labeling of GLU from [1-(13)C]glucose is a very sensitive measure for the onset of epileptogenesis, whereas reduction of NAA is first detectable later. In the chronic phases of the hippocampal formation, astrocyte metabolism is upregulated given that the number of neurons is reduced.

Hypothermia did not prevent epilepsy following experimental status epilepticus

In epilepsy research, one of the major challenges is to prevent or at least mitigate development of epilepsy following acquired brain insult by early therapeutic interventions. So far, all pharmacological antiepileptogenic treatment approaches were largely unsuccessful in clinical trials and in experimental animal studies. In a well-established rat model of chronic epilepsy following self-sustaining status epilepticus (SSSE), we assessed the antiepileptogenic properties of 3-h-cooling induced directly after the end of SSSE. Occurrence of spontaneous seizures and seizure severity up to 8 weeks after SSSE were compared with normothermic SSSE controls. Furthermore, electrophysiological parameters assessing inhibition and excitation in the dentate gyrus were assessed at multiple time points. Post SSSE hypothermia did not prevent the occurrence of seizures in any animal. Eight weeks after SSSE, Racine motor seizures trended to be less severe following cooling (4.0±0.6) compared with normothermic controls (4.8±0.2) but the difference was not significant when testing for multiple comparisons. Early loss of inhibition that is typically seen following SSSE was somewhat attenuated in cooled animals 3h after SSSE as expressed by smaller paired-pulse ratios (PPR; 0.16±0.21) compared with normothermic controls (0.54±0.21) but difference was not significant either. Latency between stimulus artefact and excitatory post-synaptic potential 3h after SSSE, reciprocally reflecting neuronal excitation, was higher in animals that underwent hypothermia (8.29±2.45ms) compared with controls (4.82±0.66ms), difference was not significant after correction for multiple comparisons. In summary, the current experiments were not able to demonstrate prevention or mitigation of epileptogenesis with immediate short-term cooling following SSSE.

Herbal and synthetic approaches for the treatment of epilepsy

The term epilepsy is collectively designated for a group of chronic central nervous system disorders characterized by spontaneous occurrence of seizures generally associated with the loss of consciousness and body movements (convulsions). Anticonvulsant drugs are used to control the convulsions by inhibiting the discharge and then producing hypnosis. Various synthetic drugs, viz. phenytoin (PHT), diazepam, valproate (VPA), leviteracetam, etc., are used for the treatment. These agents have a new spectrum of efficacy and novel adverse effects. They also represent an enormous escalation of costs. At present, herbal therapies are tried by patients in developing as well as developed countries for control of seizures or adverse effects from antiepileptic drugs, or for general health maintenance. There are number of synthetic drugs available for treatment of epilepsy in modern therapy, but the major disadvantage being faced is their chronic side effects. Treatment of epilepsy with herbal drugs as adjuvant seems to be more beneficial and is gaining more popularity due to their fewer side effects.

Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects

Temporal lobe epilepsy is a common, chronic neurologic disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have important roles in the pathogenesis of neurologic disorders. In models of prolonged, injurious seizures (status epilepticus) and in experimental and human epilepsy, we found up-regulation of miR-134, a brain-specific, activity-regulated miRNA implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21%, and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus reduced the later occurrence of spontaneous seizures by over 90% and mitigated attendant pathologic features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure suppressant and neuroprotective actions; whether these represent anticonvulsant or truly antiepileptogenic effects requires additional experimentation.

Pilocarpine-induced temporal lobe epilepsy in the rat is associated with increased dopamine neuron activity

Temporal lobe epilepsy (TLE) is defined as the occurrence of spontaneous seizures that involve the limbic system, with the hippocampal formation and associated structures being central to the most prevalent refractory form of adult focal epilepsy. TLE is often associated with psychotic features resembling the hallucinations and delusions that occur with schizophrenia. Given evidence that the ventral hippocampus plays an important role in the maintenance of temporal lobe seizures, we investigated whether an animal model of TLE using intrahippocampal injection of pilocarpine induces alterations in mesolimbic dopamine neuron activity. We found that in 60% of rats in which pilocarpine induced seizure activity, there was a significant increase in the number of dopamine neurons firing per electrode track. Furthermore, this occurred in concert with an increase in amphetamine-stimulated locomotor activity. Both observations are similar to those observed in a rodent developmental model of psychosis. Therefore, as in animal models of schizophrenia, TLE-associated psychosis is probably due to abnormal hippocampal overdrive of dopamine neuron activity.