Epilepsy is one of the most common neurological diseases as it affects approximately 50 million people worldwide.1 Often the cause of a seizure is unknown, but they can occur in relation to genetics, chronic stress in childhood, developmental disorders, traumatic brain injury, exposure to nerve agents, or infectious disease.2 Treatment for epilepsy primarily includes anti-seizure medications or surgical procedures. However, current anti-seizure medications can come with serious side effects including “fatigue, dizziness, weight gain, loss of bone density, skin rashes, loss of coordination, speech problems, cognitive issues, depression, suicidal thoughts/behaviors, and the inflammation of certain organs”.2 In some cases, surgical procedures can also lead to reduced cognitive abilities.2 There are promising therapies on the rise which, although invasive, may have less side effects. These include vagus nerve and deep brain stimulation. Some studies have also shown an anti-epileptic effect of a ketogenic diet. Research continues to better understand the causes of epilepsy and identify more effective treatment options.
Animal Models of Epilepsy
There are two methods of creating an animal model of epilepsy. The animals can either be bred with a genetic predisposition to epilepsy, or it can be induced in a normal animal by electrical or chemical methods. Genetic models of seizure are further separated by spontaneous and reflex seizure (seizure caused by a stimulus such as sound). Induced seizures can be acute, chronic, or spontaneous/recurrent. 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 have been characterized in several species and are used to unravel underlying etiology and pathophysiology, evaluate anti-epileptic drugs, or test the increased susceptibility to seizure (the lowering of a seizure threshold). New models are constantly in development to more accurately portray and treat seizures which are at present resistant to existing anti-epileptic drugs. The primary methods of studying epilepsy in animal models are EEG measurement and video monitoring.
Sample of Publications Citing Use of DSI Solutions
mGluR5 Modulation of Behavioral and Epileptic Phenotypes in a Mouse Model of Tuberous Sclerosis Complex
Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder and those who have it also experience cognitive and attention deficits, hyperactivity, epilepsy, and autism spectrum disorder (ASD). This study aimed to test the therapeutic utility of metabotropic glutamate receptor 5 (mGluR5) for ASD and TSC. The research team used a mutant mouse model that demonstrated disease-related phenotypes including ASD behavioral symptoms and epilepsy. They used DSI’s ETA-F10 telemetry implant to measure EEG and NeuroScore™ software for automatic seizure detection. The results showed that the inhibition of mGluR5 corrects hyperactivity and seizures, confirming its therapeutic potential.3
Pharmacogenetics of KCNQ channel activation in 2 potassium channelopathy mouse models of epilepsy
Current anti-seizure medications do not work for everyone and, as mentioned above, often come with significant side effects. This study aimed to examine the efficacy of the KCNQ channel activation therapy in preventing seizures and neurocardiac dysfunction. Using a tether, commutator, and DSI signal conditioners for hardwired applications, investigators were able to measure EEG and ECG simultaneously in mouse models of both severe and mild epilepsy. Using Ponemah software, they were able to identify spontaneous seizures and cardiovascular events. The two mouse models experienced different behavioral and physiological responses to the KCNQ activation. These results suggest a role for genetics in drug efficacy and potentially warrants limiting the utility of KCNQ modulation to a method of preventing neurocardiac dysfunction in epilepsy.4
DSI Solutions for Epilepsy Research
Video-EEG
DSI systems offer the flexibility to monitor EEG and synchronize it with video recording for seizure detection and confirmation. EEG can be monitored continuously in conscious, freely moving animals with telemetry or tethered (hardwired) solutions. Telemetry offers the flexibility to incorporate other endpoints of interest including blood pressure, ECG, blood glucose, temperature, and activity in animals ranging in size from mouse to primate. It is also ideal for animal welfare and data integrity as human interaction is minimized. Hardwired systems offer a minimally invasive method of continuously monitoring biopotentials (typically EEG, EMG, or ECG) in small animal models, and uses digital signal conditioners/amplifiers to bring signals into the Ponemah software. Noldus Media Recorder software is integrated into Ponemah, allowing for easy synchronization of physiologic and video data.
NeuroScore
In addition to data acquisition solutions, DSI offers analysis software. Designed to efficiently analyze large, continuous data sets common to seizure studies, the modular NeuroScore platform provides the power and consistency required for CNS research applications.
The spike train detector is designed primarily for seizure detection from EEG waveforms. The detector scans the waveform for repeating spike activity using amplitude-based criteria. Events are visually displayed within the waveform allowing for manual editing and confirmation. Several parameters including the spike train duration and number of spikes can be displayed per event or summarized over longer time intervals.
The video synchronization module imports video data acquired in Ponemah and synchronizes it with the physiologic waveforms, allowing playback in real-time or fast speed. This allows you to view the subjects’ behavior to validate or further classify detected seizure events.
To learn more about DSI’s solutions for epilepsy research, schedule a free consultation with us today!
References
1World Health Organization. (2019). “Epilepsy”. https://www.who.int/news-room/fact-sheets/detail/epilepsy
2Mayo Clinic Staff. (2019). “Epilepsy”. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/epilepsy/diagnosis-treatment/drc-20350098
3Kelly E, Schaeffer SM, Dhamne SC, Lipton JO, Lindemann L, Honer M, Jaeschke G, Super CE, Lammers SHT, Modi ME, Silverman JL, Dreier JR, Kwiatkowski DJ, Rotenberg A, Sahin M. (2018). “mGluR5 Modulation of Behavioral and Epileptic Phenotypes in a Mouse Model of Tuberous Sclerosis Complex”. Neuropsychopharmacology, 43, 1457-1465. https://www.nature.com/articles/npp2017295
4Vanhoof‐Villalba SL, Gautier NM, Mishra V, Glasscock, E. (2018). “Pharmacogenetics of KCNQ channel activation in 2 potassium channelopathy mouse models of epilepsy”. Epilepsia, 59(2), 358-368. https://onlinelibrary.wiley.com/doi/full/10.1111/epi.13978