In recognition of International Epilepsy Awareness Day, we’re celebrating some of the incredible work being performed by researchers around the world to address the causes, side-effects, and treatment options for epilepsy.
At ADInstruments, we’re lucky to be part of an ever-growing community of researchers performing cutting-edge experiments. Learn more about their work below!
Finding New Drug Treatments - The Anticonvulsant Drug Development (ADD) Program
The team at the Anticonvulsant Drug Development (ADD) Program, a lab within the University of Utah, is hard at work testing new compounds to treat epilepsy. It’s an intensive job, with blinded trials lasting for months at a time to amass the data needed to push a compound on to the next stage of drug development or end its journey altogether.
ADD uses spontaneous seizure models in rats and mice to replicate epilepsy. “Traditionally, the way drugs were screened was usually to induce a seizure either electrically or chemically. You would give the drug beforehand, then induce the seizure and ask: ‘Did my drug block that seizure?’,” ADD Associate Director, Dr. Cameron Metcalf says, “But as we’ve expanded our ability to identify new targets and better validate new drugs, we are also looking at seizures as they occur spontaneously in various contexts… it’s a more clinically relevant seizure type, and it better models what happens in people.”
Find out more about the ADD team:
On-Demand Webinar: Evaluation of Novel Therapies Using Spontaneous Seizure Models
Improving pre-clinical epilepsy screening with Kaha Telemetry
Streamlining Seizure Detection with Kaha Telemetry
Basic Research Into The Underpinnings of Seizure Activity - The Granger Group
The Granger Group are exploring synaptic and cellular physiology. In a recent publication, they investigated the efficacy of PSAM4-GlyR, a synthetic chloride-permeable ion channel, activated by the ligand uPSEM817. In vitro experiments demonstrated that activation of PSAM4-GlyR reduced neuronal excitability by shunting depolarizing currents, leading to fewer action potentials. Organotypic slices of the hippocampus also showed a decrease in epileptiform activity, including reduced burst frequency and peak amplitudes. However, in vivo administration of uPSEM817 in a mouse model of temporal lobe epilepsy did not significantly reduce electrographic seizures, though there was a trend toward reduced seizures.
Read more basic research into the underpinnings of seizure activity:
- Chemogenetics with PSAM4-GlyR decreases excitability and epileptiform activity in epileptic hippocampus - PubMed
- Activated astrocytes attenuate neocortical seizures in rodent models through driving Na+-K+-ATPase | Nature Communications
- Integrin-KCNB1 potassium channel complexes regulate neocortical neuronal development and are implicated in epilepsy | Cell Death & Differentiation
- Discrete subicular circuits control generalization of hippocampal seizures | Nature Communications
The Physical Impacts of Seizures - Oxford Neuroscience
Sudden Unexpected Death in Epilepsy (SUDEP) is an unpredictable killer. With no known mechanism of action, it is unclear why and how it happens, and who might be at risk. What we do know is that generalized tonic-clonic seizures, and heart arrhythmia during seizures, are associated with SUDEP. It is likely that heart and respiratory problems are the cause of SUDEP and that repeated seizures may lead to fatal arrhythmias.
Professor John Jeffreys and his team explored the cardiac impact of recurrent seizures in a rat model, developing a clearer pathophysiology of these potentially fatal arrhythmias. Five animals were monitored for seven full weeks using implanted Kaha Dual Biopotential Telemeters, providing constant electrocardiogram (ECG) and cortical electroencephalogram (ECoG) data.
During a seizure, it was common for the telemeters to record tachycardic readings. The significantly increased heart rate could continue for more than 10 minutes after the seizure was over. As the experiment went on, the rats’ resting heart rates increased, showing lasting stress on their hearts outside of each seizure event. The severity of this effect was related to the severity of the seizure. If the rat had a Racine Class 5 seizure, a full motor seizure, the impact of their cardiac function was significantly worse than if they’d had a more mild seizure.
Read more about the physical impacts of seizures:
The Neuroprosthetic Baroreflex, Hypertension after Stroke, and the Cardiac Impacts of Epilepsy
More information about using ADInstruments products for epilepsy research:
ADInstruments Epilepsy Research Brochure »
Kaha Telemetry Neurophysiology Guide »
