A pentylenetetrazole-induced kindling zebrafish larval model for evoked recurrent seizures

Abstract

Background:Transient pentylenetetrazol (PTZ) treatment on zebrafish larvae has been widely accepted a promising animal model for human epilepsy. However, this model is not ideal due to its acuteness and lack of recurrent seizures, which are the key feature of epilepsy in human disease. It is important to develop a more sensitive zebrafish model for epilepsy with well-controlled, predictable, recurrent seizures. New Method:The new method includes an experimental setup and a treatment protocol. The setup tracks the locomotion activity of up to 48 larvae simultaneously, while a visual stimulus can be presented to each of the 48 animals individually. The protocol treated the larvae through a water bath in 5 mM PTZ while being stimulated with rotating grating stimuli for 1 hour/day from 5 to 7 days postfertilization. Results:The setup captured the locomotion activity of zebrafish larvae during visual stimulation. The new protocol generated recurrent responses after flashing lights 4 hours post PTZ treatment. The effects could be suppressed by the anti-epileptic drug valproic acid. The characteristics of the visual stimulus play a major role in this kindling model. Comparisons with Existing Methods:We compared the proposed method with the transient PTZ model and confirmed that the flashing-light-evoked recurrent seizure is a new feature in addition to the transient changes. Conclusions:The new method generated non-drug-triggered predictable recurrent seizures in response to intermittent photic stimulation in zebrafish larvae and may serve as a sensitive method for anti-epileptic drug screening or a new research protocol in epilepsy research. Baraban, 2015; Liu and Baraban, 2019). In the acute seizure zebrafish model, lower concentrations of pentylenetetrazol (PTZ) merely evoked seizure-like behavior, such as increased locomotion activity (Stage I and II) and clonus-like convulsion (Stage III), which can be evoked only in the presence of high concentrations of PTZ (15 mM). Once Stage III is evoked in 2005; Grone and

THE ZEBRAFISH ANIMAL MODEL (Danio rerio) USED FOR DIFFERENT THERAPEUTIC APPROACHES FOR THE SUPPRESSION OF EPILEPTIC CRISIS: A SYSTEMATIC REVIEW

“…The effects can be suppressed by the antiepileptic medicine valproic acid. The characteristics of visual stimuli play an important role in this new model (4).…”

“…The new method generated predictable recurrent seizures not triggered by drugs in response to intermittent photic stimulation in zebrafish larvae and can serve as a sensitive method for screening for antiepileptic drugs or a new research protocol in epilepsy research (4).…”

“…However, this treatment is only effective in treating seizures and not the underlying epileptic disorder. In addition, ASDs usually cause adverse effects and one third of people with epilepsy develop drug resistance (4).…”

A current perspective on the relevance of nano and microplastics in the neurodevelopmental disorders: further relevance for metabolic, gastrointestinal, oxidative stress-related and zebrafish studies

“…Studies using zebrafish have opened up new perspectives as it turned out that recurrent light-sensitive effects (23) and some parameters increased with exposures to PTZ concentrations that led to the cumulative frequency of the score, the intensity of seizures and their severity, latency to onset, mortality rate (6,24) all opening avenues of research for new genetic markers of epilepsy in zebrafish (25).…”