Epilepsy



Epilepsy Research

A seizure is an episode of increased or irregular electrical activity in the brain. Seizures can happen in both humans and other animals, of all ages, and can be due to a variety of factors; including but not limited to, chronic early life stress (Dubé et al,. 2015), a genetic predisposition, developmental disorders, infectious disease, injury or nerve agent exposure.  In many cases the cause is of unknown origins.  Seizures can occur throughout the brain (generalized) or only in a single hemisphere or location (partial or focal).  They can present as a single event or exhibit  recurrent characteristics (epilepsy). The symptoms can vary, depending on type, location and severity.  Some of these signs can include a strange feeling or sensation as precursory (prodromal) symptoms, freezing or zoning out, loss of consciousness and violent or rhythmic muscle contractions.  The long term effects can include histopathological alterations in various brain regions (Curia et al., 2008),  abnormalities in sleep (Suntsova et al., 2009) and neuropsychiatric disorders (Loughman et al., 2017, Epilepsy Behav.).

Types of Seizure

Seizures can be generalized, partial or complex partial.  Generalized seizures affect a large portion of the brain, but not always the entire brain and are characterized by loss of consciousness.  Generalized seizures can present as generalized tonic-clonic seizures, i.e. grand mal seizures, displaying severe motoric exacerbation or as petit-mal seizures with less severe or no motor components. Childhood absence epilepsy is a petit-mal example characterized by 3 Hz spike-wave discharges (SWD) in humans. An example of a related genetic model of generalized absence epilepsy  in rats is the WAG/Rij rat model.  Similar to what is observed in children, this model shows evidence of SWDs  accompanied by a freezing behavior (Nersesyan et al., 2004). 

In contrast to generalized seizures, partial (focal) seizures often occur in a single hemisphere or brain region and can be further categorized into simple partial and complex partial seizure.  While in simple partial seizures consciousness remains intact, complex partial seizures regularly exhibit an impairment of consciousness  The rat pilocarpine (chemical) model of medial (mesial) temporal lobe epilepsy (mTLE) is an important and well-established example of a complex partial limbic epilepsy model in rats. In humans, temporal lobe epilepsy is among the most common as well.

Electrophysiological and motoric seizure Characteristics 

Depending on the model or chemical compound used, abnormal activity in the brain may present itself in various ways.  Those models include genetic, pharmacological and electrical induced-epilepsy.

According to a review by Dr. D’Ambrosio and Dr. Miller, seizure can vary in duration and may be defined as motor or non-motor because only detected by EEG analysis.

Seizure Models

The purpose of a model is to mimic a condition, disease or illness and/or predict efficacy or adverse effect of a treatment for a specific disease, condition or illness. Ideally, animal models should meet the criteria of construct validity (quantitative, degree of similarity of the pathology), face validity (description of the pathology e.g. similar behavior) and predictive validity (manipulation induce similar effects: e.g. pharmacological treatment). A number of models in several species have been characterized and are used to unravel underlying etiology and pathophysiology, to test antiepileptic drugs or the increased susceptibility to seizure (the lowering of a seizure threshold).  Seizure/epilepsy models can be genetic or induced in normal animals.  Genetic models of seizure are further separated by spontaneous and reflex seizure (seizure caused by a stimulus such as sound).  Alternatively, seizure can be induced in normal animals through electrical or chemical means and these induced seizures can be acute, chronic or spontaneous/recurrent (Löscher, 2011).  New models are constantly in development to more accurately portray and treat seizures which are at present resistant to existing anti-epileptic drugs. We have created this table to provide you with more information regarding the various species and applications that have been studied in seizure research.

Click here for a list of seizure models and proposed EEG placement.

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Epilepsy articles citing DSI in Google Scholar



Small Animal Implantable Telemetry System – The system is composed of receiver plates (placed below the cage). The signals are then routed through a matrix (MX2) interface into a PC for real time signal collection using network standards (Router and Switch).

Learn more about mouse and small animal telemetry specifications from DSI.

System image


Large Animal Implantable Telemetry System (PhysioTel Digital) – The system is composed of receiver plates placed in the cage that allow group housing of animals and larger cages. The signal are then routed through a matrix interface into a PC for real time signal collection using network standards (Router and Switch).

Learn more about large animal telemetry specifications from DSI.



Hardwired Monitoring System – DSI’s hardwired solutions provide a minimally invasive method to offer continuous measurement (EEG, EMG, EOG, etc.) during central nervous system studies with small animals.  Hardwired solutions allow the use of a tether solution to monitor up to 12 EEG/EMG channels with higher input bandwidths (0.05 Hz to 20 kHz).    

A setup would include use of electrodes, wires, and commutators (researcher’s choice). EEG and/or EMG signals from this tethered approach are brought into DSI’s Ponemah software platform by the use of digital signal conditioners/amplifiers.

Learn more about Signal Conditioners and accessory PODS from DSI.

Hardwired_EEG+Headstage


NeuroScore Software – After data acquisition has taken place, DSI’s NeuroScore™ software can be used to efficiently analyze chronic data sets common to neuroscience studies.  This modular platform offers sleep scoring, seizure detection, video synchronization, and batch processing capabilities. 

Learn more about NeuroScore software from DSI.

Neuroscore, Seizure


References

Authier, S., et al. “Video-electroencephalography in conscious non human primate using radiotelemetry and computerized analysis: Refinement of a safety pharmacology model”. Journal of Pharmacological and Toxicological Methods, 60.1 (2009): 88-93.

Bassett, Leanne, et al. “Telemetry video-electroencephalography (EEG) in rats, dogs and non-human primates: Methods in follow-up safety pharmacology seizure liability assessments”. Journal of Pharmacological and Toxicological Methods,  70.3 (2014): 230-240.

Cho, Kyung-Ok, et al. “Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline”. Nature Communications, 6.6606 (2015).

Curia, Giulia, et al. “The pilocarpine model of temporal lobe epilepsy”. Neuroscience Methods, 172 (2008): 143-157.

Dubé, Céline M., et al. “Hyper-excitability and epilepsy generated by chronic early-life stress”. Neurobiology of Stress, 2 (2015):10-19.

D’Ambrosio, Raimondo, et al. “What is an epileptic seizure? Unifying definitions in clinical practice and animal research to develop novel treatments.” Epilepsy Currents, 10.3 (2010): 61-66.

Dürmüller, Niklaus, et al. “The use of the dog electroencephalogram (EEG) in safety pharmacology to evaluate proconvulsant risk”. Journal of Pharmacological and Toxicological Methods, 56 (2007): 234-238.

Jackson, J. Hughlings “On the anatomical investigation of epilepsy and epileptiform convulsions.” The British Medical Journal, May 10, 1873: 531-533.

Joosen, Marloes J. A., et al. “Treatment efficacy in a soman-poisoned guinea pig model: added value of physostigmine”. Organ Toxicity and Mechanisms, 85 (2011): 227-237.

Krook-Magnuson, et al. “On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy”. Nature Communications, 10.1038 (2013).

Löscher, Wolfgang. “Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs”. Seizure, 20 (2011): 359-368.

Moraes, M. F. D, et. al. “A comprehensive electrographic and behavioral analysis of generalized tonic-clonic seizures of GEPR-9s”. Brain Research, 1033 (2005): 1-12.

Nersesyan, Hrachya, et al. “Dynamic fMRI and EEG Recordings During Spike-Wave Seizures and Generalized Tonic-Clonic Seizures in WAG/Rij Rats”. Journal of Cerebral Blood Flow and Metabolism, 24 (2004): 589-599.

Suntsova, N., et al. “A role for the preoptic sleep-promoting system in absence epilepsy”. Neurobiology of Disease, 36.1 (2009): 126-141.

Tse, Karen, et al. “Advantages of Repeated Low Dose against Single High Dose of Kainate in C57BL/6J Mouse Model of Status Epilepticus: Behavioral and Electroencephalographic Studies”.  PLoS ONE, 9.5 (2014): e96622.

Weiergräber, Marco, et al. “Electrocorticographic and deep intracerebral EEG recording in mice using a telemetry system.” Brain Research Protocols, 14 (2005): 154-164