Abstracts

Systematic Review of Deep Brain Stimulation in Rodent Models of Epilepsy

Abstract number : 1.045
Submission category : 1. Basic Mechanisms / 1D. Mechanisms of Therapeutic Interventions
Year : 2023
Submission ID : 395
Source : www.aesnet.org
Presentation date : 12/2/2023 12:00:00 AM
Published date :

Authors :
Presenting Author: Rafi Matin, B.Sc – University of Toronto, The Hospital for Sick Children

Kristina Zhang, BMSc – PhD Student, Ibrahim lab, Neuroscience & Mental Health, Institute of Medical Science, The Hospital for Sick Children, University of Toronto; Carolina Gorodetsky, carolina.gorodetsky@sickkids.ca – Pediatric Neurologist, Neuroscience and Mental Health, Division of Neurology, The Hospital for Sick Children; Flavia Venetucci Gouveia, PhD – Postdoctoral Research Fellow, Ibrahim Lab, Neurosciences & Mental Health, The Hospital for Sick Children; George Ibrahim, MD, PhD, FRCSC, FAANS, FACS – Abe Bresver Chair in Functional Neurosurgery, Associate Professor, Senior Scientist, Department of Surgery, Program in Neuroscience and Mental Health, The Hospital for Sick Children, University of Toronto

Rationale: Approximately one-third of patients with epilepsy continue to experience debilitating seizures despite the best available medical treatments.1 Deep brain stimulation (DBS), a neuromodulation technique involving the electrical stimulation of deep brain regions through surgically inserted electrodes, is a promising treatment for seizures in patients with refractory epilepsy.2 Although DBS has yielded promising clinical results, the underlying neurobiological mechanisms of treatment are not well understood, preventing the development of more personalized treatments.3 Tightly controlled preclinical experiments in rodent models of epilepsy have provided valuable insight on the underlying neurobiological mechanisms of DBS. Here, we performed a systematic review to assess the literature on DBS in rodent models of epilepsy and synthesize the current knowledge to gain insights for future studies.

1Sultana, B. et al. Incidence and Prevalence of Drug-Resistant Epilepsy: A Systematic Review and
Meta-analysis. Neurology 96, 805–817 (2021).
2Klinger, N. & Mittal, S. Deep brain stimulation for seizure control in drug-resistant epilepsy. Neurosurg. Focus
45, (2018).
3Lozano AM, Lipsman N, Bergman H, Brown P, Chabardes S, Chang JW, et al. Deep brain stimulation: current challenges and future directions. Nat Rev Neurol. 2019; 15(3):148–60.

Methods:
This systematic review was performed in accordance with PRISMA guidelines. A literature search was performed on the PubMed MEDLINE (National Library of Medicine) database for original articles published in English, reporting deep brain stimulation in rodent models of epilepsy using the following search terms: “epilepsy,” “DBS,” “deep brain stimulation,” “rat,” and “mouse”. The records identified were uploaded to the Covidence systematic review software for further screening. Data extraction followed focusing on the effects of DBS in rodent models of epilepsy, targeted brain regions, and stimulation parameters used.

Results:
The systematic search yielded 1726 records imported to Covidence for screening. After duplicates were removed (n=225), 1501 studies screened against title and abstract, resulting in the exclusion of 1393 studies. Full text screening followed with the final inclusion of 91 studies (rat: n=83, mouse: n=8) (Fig. 1, 2A). DBS had positive effects on seizure activity in 89% of studies (Fig. 2B). Twenty-six brain regions were targeted with DBS, with the anterior thalamic nucleus, hippocampal formation, and amygdala targeted most frequently (Fig. 2C). A wide range of stimulation schedules and parameters were employed (Fig. 2D).

Conclusions:
Our systematic review reveals the beneficial effects of DBS on seizure activity and highlights the variable effects of stimulation target and parameters on treatment outcome. Future studies are necessary to determine if these data are translatable to the clinical population. Overall, this review summarizes the current knowledge on anatomical targets and stimulation parameters that are associated with the therapeutic benefits of DBS in rodent models.

Funding: Ontario Graduate Scholarship
CIHR Canada Graduate Scholarship (Master’s)

Basic Mechanisms