Temporal lobe epilepsy

…as a new approach in the treatment of temporal lobe epilepsy (TLE), one of the most common types of drug-resistant epilepsy. While this approach is promising, its application in animal models has proven to be a challenge. This can be attributed to the numerous parameters involved in both the optogenetic stimulation setup and the neuronal environment. These are difficult to investigate and optimize in limited in vivo experiments. Therefore, an in silico approach was developed by refitting the double two-st

Temporal lobe epilepsy (TLE) arises mostly due to an initial injury. Certain stimuli can make a normal brain prone to repeated, spontaneous seizures via a process called epileptogenesis. The aim of this study is to examine the plasma metabolomics profile in TLE-induced rats to find feasible biomarkers that can distinguish phases of epileptogenesis. Status epilepticus (SE) was induced by low-dose-repetitive-lithium chloride–pilocarpine hydrocholoride intraperitoneal injections. Control groups just received saline injections. Blood samples were collected 48 hours, 7 days and 6 weeks after SE, re

Temporal lobe epilepsy (TLE), the most common form of DRE, is associated with enhanced glutamate receptor-mediated hyperexcitability in the temporal lobe structures. The mechanism of regulation of aberrant glutamatergic activity in TLE is still elusive. Sema 3F regulates the AMPA receptor surface expression in post-synapse. In this study, we investigated the contribution of semaphorin3F (SEMA 3F) to glutamatergic synaptic activity in TLE rats' hippocampus and anterior temporal lobe (ATL). synaptic transmission in the hippocampus and ATL. Golgi-Cox staining was conducted to visualize alteration

Epilepsy, a neurological disorder affecting approximately 60 million individuals globally, poses a significant medical challenge with a substantial unmet need. Temporal lobe epilepsy is the most prevalent form, often triggered by traumatic incidents or status epilepticus (SE), resulting in hippocampal damage characterized by neuronal loss, astro- and microgliosis and neuroinflammation preceding the spontaneous recurrent seizures. Recently, an AAV-PHP.B-GFAP-interleukin-2 (IL-2) gene therapy exhibited impressive neuroprotective and anti-inflammatory effects in mouse models of traumatic brain in

Noradrenaline is released via volume transmission from axons originating in the locus coeruleus and released into the parenchyma to be detected by both neurons and astrocytes. Noradrenergic α-1 receptors are Gq-coupled receptors that induce intracellular calcium release from the endoplasmic reticulum as a key pathway for astrocyte calcium signalling. Due to interactions between astrocytes and synapses including their known roles in structural isolation of synapses, metabolic support, potassium buffering and gliotransmitter release, fluctuations of intracellular calcium in astrocytes can influe

Astrocytic dysfunctions have increasingly been recognized as a significant element in epilepsy pathophysiology. The prominent expression of connexin channels is one of the key features of astrocytes, essential for their extensive intercellular coupling. It is currently debated whether astrocytic connexins have pro- or anti-epileptic effects. The existence of two types of connexins, namely Cx30 and Cx43, which display different properties as well as several functions beyond gap junction formation, such as hemichannel constituents or signaling elements, further makes it more complex to investig

Temporal lobe epilepsy (TLE) is one of the most prevalent neurological disorders, affecting 1-3% people worldwide. As this type of epilepsy is often refractory to anticonvulsant drugs, it is crucial to advance the understanding of the mechanisms that underlie its pathophysiology. The endocannabinoid system (ECS) protects nerve cells through the cannabinoid CB1 receptor regulation of the glutamatergic neuronal excitability. As TLE patients frequently show changes in the ECS, in this study we analyze the impact of the status epilepticus in the hippocampus four weeks after administraton of the pr

Microglia seem able to alter the excitatory/inhibitory balance in temporal lobe epilepsy (TLE). Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) enable cell-specific modulation. We aim to investigate whether Gi-DREADD-based modulation of microglia reduces the amount of spontaneous recurrent seizures (SRS) in a mouse model of TLE.CX3CR1CreERT2/CreERT2 mice were crossed with R26LSL-Gi-DREADD/LSL-Gi-DREADD mice to obtain CX3CR1CreERT2/+:R26LSL-Gi-DREADD/+ and CX3CR1CreERT2/+:R26+/+ mice, as controls. Tamoxifen was administered to induce Gi-DREADD expression in CX3CR1+ cells. F

Background: In temporal lobe epilepsy, seizures tend to occur at preferential times of the day. This timing of seizures may result from the sleep-wake history (process S) and/or from the circadian rhythm (process C). We aimed at disentangling their contributions to timing limbic seizures in the hippocampal kainic acid mouse model. Methods: Using 16 depth-electrodes, we recorded limbic seizures in epileptic mice (n=24) exposed to different chronobiological paradigms over months: 1)12h:12h light-dark cycle (LD), 2) gentle sleep deprivation (GSD), 3) continuous dim red light (DD), 4) continuous l

Temporal lobe epilepsy (TLE) is a focal epilepsy often refractory to anti-epileptic medications. Hippocampal sclerosis and lesions in the temporal cortex are associated to mesial TLE and neocortical TLE, respectively. In both cases, histopathological alterations in other areas have been reported. Here, we investigated the possible correlation between lesioned location and severity of the epileptic syndrome.Status epilepticus (SE) was induced by pilocarpine injection in Sprague-Dawley rats and was terminated 30 minutes later by ketamine/diazepam. Two weeks later, rats were implanted with depth

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. Though available anticonvulsants achieve a full seizure control for two-thirds of the TLE patients, one third does not respond sufficiently to these drugs and resection of the seizure area is the best possible treatment for them. One way to improve this is to identify key regulatory ion channels in excitatory synaptic function. Here, we investigated the ultrastructural localization of I) P/Q-type voltage-gated calcium channels (Cav2.1) at the presynaptic site triggering vesicle release and II) AMPA receptors mediating the

Aims: Temporal lobe epilepsy is a neurological disorder characterised by the occurrence of spontaneous seizures. Current treatment methods consist of anti-epileptic drugs, resective surgery or neuromodulation each with significant risks and/or side-effects. Responsive neuromodulation could provide a solution by providing spatial and temporal specificity. In this study, we evaluated whether seizures could be detected with a self-designed embedded system and terminated through activation of the WiChR opsin in the intrahippocampal kainic acid mouse model of temporal lobe epilepsy.Methods: Mice we

Temporal lobe epilepsy (TLE) is characterized by spontaneous recurrent seizures poorly controlled by antiseizure medications in over 30% of patients. The current study aims to investigate the most epileptogenic areas in a TLE animal model using high-density EEG.Sprague Dawley male rats were injected intraperitoneally with pilocarpine to induce the status epilepticus (SE) terminated 30 minutes later by ketamine/diazepam. Two weeks later animals were implanted with epidural electrodes in the frontal cortex and depth electrodes in several temporal areas. Video-EEG recordings (24h, >3 days/week

…observed in patients suffering from temporal lobe epilepsy (TLE) which brings neurodegeneration into association with an increased risk of epileptic seizures. This study aimed to provide pilot data on the possible relationship between excitability and neurodegeneration. Electrical activity was recorded at 37°C using the multielectrode array (MEA) technique in cerebral organoids prepared from induced pluripotent stem c

…causes of Sudden Unexpected Death in Epilepsy (SUDEP). Apnea in SUDEP is characterised by prologued hypercapnia with severe hypoventilation. We propose that this implies an impairment at the level of central CO2 chemoreception (CCR) drive for breathing which is coupled with cardiodysregulation. CCR can be quantified with ventilatory response to hypercapnic challenge and has not been previously studied in a chronic model of temporal lobe epilepsy, in which SUDEP may be obs

The post status epilepticus (SE) model is one of the most helpful animal models for epilepsy research. In many cases it closely mimics the clinical signs of temporal lobe epilepsy in humans. Although behavioral, electrophysiological and molecular alterations following SE have been extensively studied, corresponding structural changes remain less well explored. However, to optimize the treatment of epilepsy and complications of SE, it is essential to know how effectively they prevent seizure-induced neuronal damage. In the present study, we elucidate ultrastructural changes and quantitative alt

…are implicated in schizophrenia and temporal lobe epilepsy pathogenesis, however limited research has been done with respect to their role in epilepsy. Our study on HA-Nrg1-tg mice that overexpress the cysteine-rich domain of NRG1-type III, revealed diverse recurrent epileptic seizures characterized by spike and wave discharges (SWDs) in the cortex and thalamus. Seizure expression varied among animals, with slow (4 – 5 Hz) and/or fast (6 - 8 Hz) SWDs present. Slow 4-5 Hz SWDs occurred during passive wakefulness and were abundant du

…excitability in the context of temporal lobe epilepsy. We discovered that PTPRN facilitates NaV1.2 sodium channel en

Temporal lobe epilepsy (TLE) is one of the most common forms of drug-resistant epilepsy and its precise etiology is still unknown making it imperative to understand the molecular pathways contributing to the disease. It is, therefore, crucial to study the therapeutic targets and signalling pathways involved in the treatment of this disease. Pyk2 has previously been shown to be activated in stress-mediated pathways in the brain. Consequently, we hypothesized that Pyk2 activation might contribute to the pathogenesis of the disease. A pilocarpine model of TLE was used to examine p-Pyk2Tyr402 prot

The adenosine A1 receptor (A1R) is a promising therapeutic target in epilepsy by mediating neuronal inhibition. In this study, we investigated whether A1R signaling is still functional in the intrahippocampal kainic acid (IHKA) mouse model for temporal lobe epilepsy (TLE). Moreover, we evaluated the feasibility of spatial selective inhibition of specific hippocampal subregions through photopharmacology. Electrically evoked field postsynaptic potentials (fPSPs) were recorded in the CA1 and DG of acute hippocampal slices. The effect of adding 40 nM of the A1R agonist N6cyclopentyladenosine (CPA)

Temporal lobe epilepsy (TLE) is a neurological disorder associated with spontaneously recurrent seizures with about 30% of the patients exhibiting pharmacoresistant. Thus, it is imperative to understand the molecular mechanisms underlying the pathogenesis of TLE to develop an effective treatment strategy. Several neurological disorders are associated with Histone deacetylase 4 (HDAC4) dysregulation, but its specific molecular substrates and the precise mechanism by which it contributes to TLE are unknown. Thus, in our study, we used the lithium-pilocarpine model of TLE and samples resected fro

…robotic technology in patients with temporal lobe epilepsy (TLE). Network analysis was performed using multimodal MRI from TLE patients (n=22) and healthy subjects (n=20). Five tests with the Kinarm robot were used to evaluate five cognitive domains. Four graph theory metrics were computed to characterize structural networks. Structural and cognitive phenotypes were identified using an unsupervised learning algorithm, and the association between them evaluated. Three cognitive clusters were identifie

…Using tissue resected from 13 temporal lobe epilepsy patients, we perform multicellular patch-clamp based microcircuit analysis (n=80 recordings) to characterize synaptic connectivity in the human hippocampa

…is known to drive the development of temporal lobe epilepsy (TLE) after a precipitating brain insult. Although long non-coding RNAs (lncRNAs) are key modulators of RNA processing, their functional involvement in epilepsy pathogenesis remains largely unexplored. Here, we perform the first comprehensive profiling study of lncRNAs during epileptogenesis and assess their utility as novel drug targets. Methods: To study lncRNA dysregulation, Next Generation Sequencing was performed on hippocampal tissue collected during