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Vagus Nerve Stimulation and Other Neuromodulation Methods for Treatment of Traumatic Brain Injury

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Abstract

The objective of this paper is to review the current literature regarding the use of vagus nerve stimulation (VNS) in preclinical models of traumatic brain injury (TBI) as well as discuss the potential role of VNS along with alternative neuromodulation approaches in the treatment of human TBI. Data from previous studies have demonstrated VNS-mediated improvement following TBI in animal models. In these cases, VNS was observed to enhance motor and cognitive recovery, attenuate cerebral edema and inflammation, reduce blood brain barrier breakdown, and confer neuroprotective effects. Yet, the underlying mechanisms by which VNS enhances recovery following TBI remain to be fully elucidated. Several hypotheses have been offered including: a noradrenergic mechanism, reduction in post-TBI seizures and hyper-excitability, anti-inflammatory effects, attenuation of blood–brain barrier breakdown, and cerebral edema. We present other potential mechanisms by which VNS acts including enhancement of synaptic plasticity and recruitment of endogenous neural stem cells, stabilization of intracranial pressure, and interaction with the ghrelin system. In addition, alternative methods for the treatment of TBI including deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation, and focused ultrasound stimulation are discussed. Although the primary source data show that VNS improves TBI outcomes, it remains to be determined if these findings can be translated to clinical settings.

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Abbreviations

BBB:

Blood–brain barrier

CAP:

Compound action potential

DBS:

Deep brain stimulation

FDA:

Food and Drug Administration

FPI:

Fluid percussion injury

FUS:

Focused ultrasound stimulation

GABA:

Gamma aminobutyric acid

GAD:

Glutamic acid decarboxylase

HIFU:

High intensity focused ultrasound

ICP:

Intracranial pressure

IL:

Interleukin

LC:

Locus coeruleus

LTD:

Long-term depression

LTP:

Long-term potential

NMDA:

N-methyl d-aspartate

TBI:

Traumatic brain injury

tDCS:

Transcranial direct current stimulation

TMS:

Transcranial magnetic stimulation

TNF:

Tumor necrosis factor

tTMS:

Repetitive TMS

t-VNS:

Transcutaneous VNS

VNS:

Vagus nerve stimulation

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Authors and Affiliations

  1. Department of Neurology, University of Minnesota, 420 Delaware Street S.E., MMC 295, Minneapolis, MN, 55455, USA

    Daniel Neren, Salam P. Bachour & Afshin A. Divani

  2. Medical School, Twin Cites Campus, University of Minnesota, Minneapolis, MN, USA

    Daniel Neren

  3. Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA

    Matthew D. Johnson & Afshin A. Divani

  4. Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis, MN, USA

    Wynn Legon

  5. Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

    Geoffrey Ling

  6. Department of Neurological Surgery, University of Minnesota, Minneapolis, MN, USA

    Afshin A. Divani

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  1. Daniel Neren
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  2. Matthew D. Johnson
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  3. Wynn Legon
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  4. Salam P. Bachour
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Correspondence to Afshin A. Divani.

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Neren, D., Johnson, M.D., Legon, W. et al. Vagus Nerve Stimulation and Other Neuromodulation Methods for Treatment of Traumatic Brain Injury. Neurocrit Care 24, 308–319 (2016). https://doi.org/10.1007/s12028-015-0203-0

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