Non-Invasive Vagus Nerve Stimulation Improves Brain Lesion Volume and Neurobehavioral Outcomes in a Rat Model of Traumatic Brain Injury

Authors

Afshin A. Divani, Department of Neurology, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
Pascal Salazar, Canon Medical Informatics, Inc., Minnetonka, Minnesota, USA
Hafiz A. Ikram, Department of Neurology, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
Erik Taylor, Department of Radiology, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
Colin M. Wilson, Department of Radiology, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
Yirong Yang, Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
Javad Mahmoudi, Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Alina Seletska, Department of Neurology, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
Karen S. SantaCruz, Department of Pathology, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
Michel T. Torbey, Department of Neurology, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
Eric J. Liebler, electroCore, Inc., Rockaway, New Jersey, USA
Olga A. Bragina, Lovelace Biomedical Research Institute, Albuquerque, New Mexico, USA
Russel A. Morton, Department of Neuroscience, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
Denis E. Bragin, Lovelace Biomedical Research Institute, Albuquerque, New Mexico, USA

Document Type

Article

Publication Date

7-1-2023

Abstract

Traumatic brain injury (TBI) continues to be a major cause of death and disability worldwide. This study assessed the effectiveness of non-invasive vagus nerve stimulation (nVNS) in reducing brain lesion volume and improving neurobehavioral performance in a rat model of TBI. Animals were randomized into three experimental groups: (1) TBI with sham stimulation treatment (Control), (2) TBI treated with five lower doses (2-min) nVNS, and (3) TBI treated with five higher doses (2 × 2-min) nVNS. We used the gammaCore nVNS device to deliver stimulations. Magnetic resonance imaging studies were performed 1 and 7 days post-injury to confirm lesion volume. We observed smaller brain lesion volume in the lower dose nVNS group compared with the control group on days 1 and 7. The lesion volume for the higher dose nVNS group was significantly smaller than either the lower dose nVNS or the control groups on days 1 and 7 post-injury. The apparent diffusion coefficient differences between the ipsilateral and contralateral hemispheres on day 1 were significantly smaller for the higher dose (2 × 2 min) nVNS group than for the control group. Voxel-based morphometry analysis revealed an increase in the ipsilateral cortical volume in the control group caused by tissue deformation and swelling. On day 1, these abnormal volume changes were 13% and 55% smaller in the lower dose and higher dose nVNS groups, respectively, compared with the control group. By day 7, nVNS dampened cortical volume loss by 35% and 89% in the lower dose and higher dose nVNS groups, respectively, compared with the control group. Rotarod, beam walking, and anxiety performances were significantly improved in the higher-dose nVNS group on day 1 compared with the control group. The anxiety indices were also improved on day 7 post-injury compared with the control and the lower-dose nVNS groups. In conclusion, the higher dose nVNS (five 2 × 2-min stimulations) reduced brain lesion volume to a level that further refined the role of nVNS therapy for the acute treatment of TBI. Should nVNS prove effective in additional pre-clinical TBI models and later in clinical settings, it would have an enormous impact on the clinical practice of TBI in both civilian and military settings, as it can easily be adopted into routine clinical practice.

Publisher

Mary Ann Liebert

Publication Title

Journal of neurotrauma

ISSN

1557-9042

Volume

40

Issue

13-14

First Page

1481

Last Page

1494

DOI

10.1089/neu.2022.0153

Recommended Citation

Divani AA, Salazar P, Ikram HA, Taylor E, Wilson CM, Yang Y, Mahmoudi J, Seletska A, SantaCruz KS, Torbey MT, Liebler EJ, Bragina OA, Morton RA, Bragin DE. Non-Invasive Vagus Nerve Stimulation Improves Brain Lesion Volume and Neurobehavioral Outcomes in a Rat Model of Traumatic Brain Injury. J Neurotrauma. 2023 Jul;40(13-14):1481-1494. doi: 10.1089/neu.2022.0153. Epub 2023 May 17. PMID: 36869619; PMCID: PMC10294566.