High Frequency Oscillations (>250Hz) Outnumber Interictal Spikes in Preclinical Studies of Alzheimer's Disease.

Unlabelled: Interictal spikes (IIS) and seizures are well-documented in Alzheimer's disease (AD). IIS typically outnumber seizures, supporting their role as a prominent EEG biomarker in AD. In preclinical models, we showed that high frequency oscillations (HFOs>250Hz) also occur, but it is currently unknown how HFOs compare to IIS.

Interictal spikes in Alzheimer's disease: Preclinical evidence for dominance of the dentate gyrus and cholinergic control by the medial septum.

Interictal spikes (IIS) are a common type of abnormal electrical activity in Alzheimer's disease (AD) and preclinical models. The brain regions where IIS are largest are not known but are important because such data would suggest sites that contribute to IIS generation. Because hippocampus and cortex exhibit altered excitability in AD models, we asked which areas dominate the activity during IIS along the cortical-CA1-dentate gyrus (DG) dorso-ventral axis.

Reduced Cholecystokinin-Expressing Interneuron Input Contributes to Disinhibition of the Hippocampal CA2 Region in a Mouse Model of Temporal Lobe Epilepsy.

A significant proportion of temporal lobe epilepsy (TLE) patients experience drug-resistant seizures associated with mesial temporal sclerosis, in which there is extensive cell loss in the hippocampal CA1 and CA3 subfields, with a relative sparing of dentate gyrus granule cells and CA2 pyramidal neurons (PNs). A role for CA2 in seizure generation was suggested based on findings of a reduction in CA2 synaptic inhibition (Williamson and Spencer, 1994) and the presence of interictal-like spike activity in CA2 in resected hippocampal tissue from TLE patients (Wittner et al., 2009).

Levetiracetam Pharmacokinetics and Brain Uptake in a Lateral Fluid Percussion Injury Rat Model.

Post-traumatic epilepsy (PTE) occurs in some patients after moderate/severe traumatic brain injury (TBI). Although there are no approved therapies to prevent epileptogenesis, levetiracetam (LEV) is commonly given for seizure prophylaxis due to its good safety profile. This led us to study LEV as part of the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) Project.

Interictal Spikes in Alzheimer's Disease: Preclinical Evidence for Dominance of the Dentate Gyrus and Cholinergic Control by Medial Septum.

Highlights: Interictal spikes (IIS) occur in 3 mouse lines with Alzheimer's disease featuresIIS in all 3 mouse lines were most frequent during rapid eye movement (REM) sleepThe dentate gyrus showed larger IIS and earlier current sources vs. CA1 or cortexChemogenetic silencing of medial septum (MS) cholinergic neurons reduced IIS during REMMS silencing did not change REM latency, duration, number of bouts or theta power.

Unlabelled: Interictal spikes (IIS) are a common type of abnormal electrical activity in Alzheimer's disease (AD) and preclinical models.

Hippocampal area CA2 controls seizure dynamics, interictal EEG abnormalities and social comorbidity in mouse models of temporal lobe epilepsy.

Unlabelled: Temporal lobe epilepsy (TLE) is characterized by spontaneous recurrent seizures, abnormal activity between seizures, and impaired behavior. CA2 pyramidal neurons (PNs) are potentially important because inhibiting them with a chemogenetic approach reduces seizure frequency in a mouse model of TLE. However, whether seizures could be stopped by timing inhibition just as a seizure begins is unclear.

High-frequency oscillations (250-500 Hz) in animal models of Alzheimer's disease and two animal models of epilepsy.

Objective: To test the hypothesis that high-frequency oscillations (HFOs) between 250 and 500 Hz occur in mouse models of Alzheimer's disease (AD) and thus are not unique to epilepsy.

Methods: Experiments were conducted in three mouse models of AD: Tg2576 mice that simulate a form of familial AD, presenilin 2 knock-out (PS2KO) mice, and the Ts65Dn model of Down's syndrome. We recorded HFOs using wideband (0.

Robust chronic convulsive seizures, high frequency oscillations, and human seizure onset patterns in an intrahippocampal kainic acid model in mice.

Intrahippocampal kainic acid (IHKA) has been widely implemented to simulate temporal lobe epilepsy (TLE), but evidence of robust seizures is usually limited. To resolve this problem, we slightly modified previous methods and show robust seizures are common and frequent in both male and female mice. We employed continuous wideband video-EEG monitoring from 4 recording sites to best demonstrate the seizures.

Region-specific Effects of Early-life Status Epilepticus on the Adult Hippocampal CA3 - Medial Entorhinal Cortex Circuitry In vitro: Focus on Interictal Spikes and Concurrent High-frequency Oscillations.

Convulsive status epilepticus (SE) in immature life is often associated with lasting neurobiological changes. We provoked SE by pentylenetetrazole in postnatal day 20 rat pups and examined communication modalities between the temporal hippocampus and medial entorhinal cortex (mEC) in vitro. After a minimum of 40 days post-SE, we prepared combined temporal hippocampal - medial entorhinal cortex (mEC) slices from conditioned (SE) and naïve (N) adult rats and recorded 4-aminopyridine-induced spontaneous epileptiform interictal-like discharges (IED) simultaneously from CA3 and mEC layer V-VI.

Climate change and epilepsy: Insights from clinical and basic science studies.

Climate change is with us. As professionals who place value on evidence-based practice, climate change is something we cannot ignore. The current pandemic of the novel coronavirus, SARS-CoV-2, has demonstrated how global crises can arise suddenly and have a significant impact on public health.

In search of antiepileptogenic treatments for post-traumatic epilepsy.

Post-traumatic epilepsy (PTE) is diagnosed in 20% of individuals with acquired epilepsy, and can impact significantly the quality of life due to the seizures and other functional or cognitive and behavioral outcomes of the traumatic brain injury (TBI) and PTE. There is no available antiepileptogenic or disease modifying treatment for PTE. Animal models of TBI and PTE have been developed, offering useful insights on the value of inflammatory, neurodegenerative pathways, hemorrhages and iron accumulation, calcium channels and other target pathways that could be used for treatment development.

Immature Status Epilepticus: In Vitro Models Reveal Differences in Cholinergic Control and HFO Properties of Adult CA3 Interictal Discharges in Temporal vs Septal Hippocampus.

We have earlier demonstrated that a Status Epilepticus (SE) during CNS development has long-lasting effects on cholinergic neurotransmission, detectable in vitro and in vivo. In this work, we aimed to localize changes in temporal (T) vs septal (S) hippocampus and to correlate adult CA3 interictal epileptiform discharge (IED) frequency changes to those of Ripples (R) and Fast Ripples (FR) of the High-Frequency Oscillations (HFOs). Spontaneous IEDs were induced by bathing slices in Mg-free ACSF or in 4-Aminopyridine (4-AP, 50 µM) and data were analyzed separately for each model.