Systematic Review of Experimental Deep Brain Stimulation in Rodent Models of Epilepsy

Objectives: Deep brain stimulation (DBS) is an established neuromodulatory technique for treating drug-resistant epilepsy. Despite its widespread use in carefully selected patients, the mechanisms underlying the antiseizure effects of DBS remain unclear. Herein, we provide a detailed overview of the current literature pertaining to experimental DBS in rodent models of epilepsy and identify relevant trends in this field. Materials and Methods: A systematic review was conducted using the PubMed MEDLINE database, following PRISMA guidelines. Data extraction focused on study characteristics, including stimulation protocol, seizure and behavioral outcomes, and reported mechanisms of action. Results: Of the 1788 resultant articles, 164 were included. The number of published articles has grown exponentially in recent decades. Most studies used chemically or electrically induced models of epilepsy. DBS targeting the anterior nucleus of the thalamus, hippocampal formation, or amygdala was most extensively studied. Effective stimulation parameters were identified, and novel stimulation designs were explored, such as closed-loop and unstructured stimulation approaches. Common mechanisms included synaptic modulation through the depression of excitatory neurotransmission and inhibitory release of GABA. At the network level, antiseizure effects were associated with the desynchronization of neural networks, characterized by decreased low-frequency oscillations. Conclusions: Rodent models have significantly advanced the understanding of disease pathophysiology and the development of novel therapies. However, fundamental questions remain regarding DBS mechanisms, optimal targets, and parameters. Further research is necessary to improve DBS therapy and tailor treatment to individual patient circumstances.