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Defining Experimental Variability in Actuator-Driven Closed Head Impact in Rats

  • S.I. : 50Th Anniversary Reviews
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Abstract

Traumatic brain injury (TBI) is a world-wide health challenge that lacks tools for diagnosis and treatment. There is a need for translational preclinical models to effectively design clinical tools, however, the diversity of models is a barrier to reproducible studies. Actuator-driven closed head impact (AD-CHI) models have translational advantages in replicating the pathophysiological and behavioral outcomes resulting from impact TBI. The main advantages of AD-CHI protocols include versatility of impact parameters such as impact angle, velocity, depth, and dwell time with the ability to interchange tip types, leading to consistent outcomes without the need for craniectomy. Sources of experimental variability within AD-CHI rat models are identified within this review with the aim of supporting further characterization to improve translational value. Primary areas of variability may be attributed to lack of standardization of head stabilization methods, reporting of tip properties, and performance of acute neurological assessments. AD-CHI models were also found to be more prevalently used among pediatric and repeated TBI paradigms. As this model continues to grow in use, establishing the relationships between impact parameters and associated injury outcomes will reduce experimental variability between research groups and encourage meaningful discussions as the community moves towards common data elements.

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Abbreviations

A:

Length of apnea test

ACHI:

Awake closed head injury

AD-CHI:

Actuator-driven closed head impact

AP:

Anterior–posterior

BBB:

Blood–brain-barrier

BM:

Barnes maze test

BW:

Beam walk test

CCI:

Controlled cortical impact

CDEs:

Common data elements

EPM:

Elevated plus maze test

F:

Female

FST:

Forced swim test

LA:

Locomotor activity test

LDB:

Light–dark box test

LE:

Long Evans rats

M:

Male

MPS:

Maximum principal strain

ML:

Medial–lateral

MWM:

Morris water maze

NLR:

Novel location recognition

NOR:

Novel object recognition

OFT:

Open field test

P:

Pain Reflex test

P#:

Post-natal day #

RR:

Loss of righting reflex test

SD:

Sprague Dawley rats

SD-T:

Transgenic Sprague Dawley rats

SPT:

Sucrose preference test

TBI:

Traumatic brain injury

VF:

Von Frey test

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Acknowledgments

The authors would like to thank the Traumatic Nerve Technologies (TNT) laboratory at Virginia Tech for their support.

Conflict of interest

The authors disclose no conflicts of interest.

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Author notes

    Authors and Affiliations

    1. Graduate Program in Translational Biology, Medicine and Health, Virginia Tech, Blacksburg, VA, USA

      Caiti-Erin Talty

    2. School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA, USA

      Carly Norris

    3. Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA, USA

      Pamela VandeVord

    4. Veterans Affairs Medical Center, Salem, VA, USA

      Pamela VandeVord

    Author notes

    1. Caiti-Erin Talty and Carly Norris have contributed equally to this work and are co-first authors.

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      Talty, CE., Norris, C. & VandeVord, P. Defining Experimental Variability in Actuator-Driven Closed Head Impact in Rats. Ann Biomed Eng 50, 1187–1202 (2022). https://doi.org/10.1007/s10439-022-03012-0

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