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Epilepsy affects millions worldwide, yet developing effective antiepileptic drugs (AEDs) remains a complex challenge. At Neuroservices-Alliance, we leverage Microelectrode Array (MEA) technology to provide highly precise, in vitro models for AED profiling. Using 4-aminopyridine (4-AP) and 0 Mg²⁺ models, our approach replicates epileptiform discharges (EDs)—enabling researchers to assess drug efficacy, seizure risk, and compound safety with unparalleled accuracy. 

• ED correspond to a massive and synchronous discharge of a group of neurons over a large brain area, in the absence of any electrical stimulation (see nearby an example of 4-AP-induced ED in a hippocampal slice in vitro).
• ED are observed in the EEG of 90% of patients suffering of epilepsy, whereas they are observed in less than 5% of in the EEG of non-epileptic patients.
• Comparable ED can be observed in hippocampal slices exposed to certain pro-convulsive compounds.
• ED can be reduced or suppressed by anti-epileptic drugs (AED) in vivo as well as in vitro.

Methods used

ED detection

The raw data is filtered using a low-pass Butterworth filter (second order, cutoff at 20 Hz) to remove high-frequency components such as single action potentials, isolating the local field potentials (LFPs) that represent the synchronized activity of neuronal populations, such as epileptiform discharges (EDs). A threshold is then set to detect EDs, capturing both positive and negative peaks from the filtered signal.

Electrode validation

To ensure electrode reliability (discard silent or noisy electrodes), each electrode must display ED activity during the pro-epileptic aCSF period and be inhibited after TTX application. Validated electrodes are then averaged for each slice, with each slice considered an individual sample (n).

Data presentation

ED rates and amplitudes (normalized or not) are typically averaged in 60-second bins. Values (± SEM) are plotted over time, and scatter plots can be generated at different time points for comparison and statistical analysis. 

4-AP & 0 Mg2+ models

• 4-Aminopyridine (4-AP) is widely used in Epilepsy models, in vitro, in vivo and clinically. 4-AP is a non-selective voltage-dependent K⁺ channel blocker, that inhibits intrinsic neuronal potassium currents. By disrupting the normal repolarization process, 4-AP prolongs the depolarized state of the neuron, making it more susceptible to repetitive firing and facilitating the generation of synchronized discharges that result in epileptiform activity.
• Zero magnesium aCSF release NMDA receptor enhancing excitability and facilitating synchronized firing, that can be coupled with High K⁺ concentration that reduces the electrochemical gradient for potassium across the membrane promoting sustained depolarization leading to epileptiform discharges.

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