Conditioned Contextual Freezing is A Neurobehavioral Biomarker of Axonal Injury Indicated by Reduced Fractional Anisotropy in A Mouse Model of Blast-Induced Mild Traumatic Brain Injury

Craig Weiss, Frances R. Lendacki, Paul H. Rigby, Alice M. Wyrwicz, John F Disterhoft, Joachim Spiess*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Mild Traumatic Brain Injury (TBI) is an important public health problem generated by closed head injury. This study is focused on the impact of blast-induced mild TBI on auditory trace and delay fear conditioning, models of declarative and non-declarative memory, respectively, and the correlation of conditioned freezing and fractional anisotropy, a measure of axonal state. A supersonic helium pressure wave was generated by a shock tube to blast 8 week old male mice on Day 1 for 1.4 msec with an incident pressure of 16 psi, corresponding to a reflected pressure of 56.5 psi at the mouse head. On Day 3, the mice were subjected to auditory trace- or delay- fear conditioning. On Day 4, contextual freezing in the trained context, and pre-cue and cued freezing in a novel context were determined. After cardiac perfusion on Day 5, ex vivo images were obtained with diffusion tensor imaging at 14.1 Tesla. We observed that delay fear conditioning prevented or reversed the decrease in fractional anisotropy in both the medial and lateral corpus callosum suggesting axonal stabilization of potentially behavioral therapeutic significance. Moderately strong and statistically significant Pearson correlations were found between fractional anisotropy and contextual freezing in the medial and lateral corpus callosum of blasted and sham-blasted delay- or trace- fear conditioned mice. Thus, contextual freezing is a neurobehavioral biomarker for axonal injury in mild TBI and is a reliable and high-throughput behavioral assay for the evaluation of potential therapeutics to treat mild TBI.

Original languageEnglish (US)
JournalShock
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Brain Concussion
Anisotropy
Freezing
Biomarkers
Fear
Wounds and Injuries
Corpus Callosum
Pressure
Closed Head Injuries
Helium
Diffusion Tensor Imaging
Cues
Shock
Public Health
Perfusion
Head
Therapeutics
Conditioning (Psychology)

Keywords

  • declarative memory
  • delay fear conditioning
  • non-declarative memory
  • post-concussion syndrome (PCS)
  • posttraumatic stress disorder (PTSD)
  • trace fear conditioning

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Cite this

@article{818de949cf514c8e9fb6a39ab05c35bd,
title = "Conditioned Contextual Freezing is A Neurobehavioral Biomarker of Axonal Injury Indicated by Reduced Fractional Anisotropy in A Mouse Model of Blast-Induced Mild Traumatic Brain Injury",
abstract = "Mild Traumatic Brain Injury (TBI) is an important public health problem generated by closed head injury. This study is focused on the impact of blast-induced mild TBI on auditory trace and delay fear conditioning, models of declarative and non-declarative memory, respectively, and the correlation of conditioned freezing and fractional anisotropy, a measure of axonal state. A supersonic helium pressure wave was generated by a shock tube to blast 8 week old male mice on Day 1 for 1.4 msec with an incident pressure of 16 psi, corresponding to a reflected pressure of 56.5 psi at the mouse head. On Day 3, the mice were subjected to auditory trace- or delay- fear conditioning. On Day 4, contextual freezing in the trained context, and pre-cue and cued freezing in a novel context were determined. After cardiac perfusion on Day 5, ex vivo images were obtained with diffusion tensor imaging at 14.1 Tesla. We observed that delay fear conditioning prevented or reversed the decrease in fractional anisotropy in both the medial and lateral corpus callosum suggesting axonal stabilization of potentially behavioral therapeutic significance. Moderately strong and statistically significant Pearson correlations were found between fractional anisotropy and contextual freezing in the medial and lateral corpus callosum of blasted and sham-blasted delay- or trace- fear conditioned mice. Thus, contextual freezing is a neurobehavioral biomarker for axonal injury in mild TBI and is a reliable and high-throughput behavioral assay for the evaluation of potential therapeutics to treat mild TBI.",
keywords = "declarative memory, delay fear conditioning, non-declarative memory, post-concussion syndrome (PCS), posttraumatic stress disorder (PTSD), trace fear conditioning",
author = "Craig Weiss and Lendacki, {Frances R.} and Rigby, {Paul H.} and Wyrwicz, {Alice M.} and Disterhoft, {John F} and Joachim Spiess",
year = "2019",
month = "1",
day = "1",
doi = "10.1097/SHK.0000000000001424",
language = "English (US)",
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Conditioned Contextual Freezing is A Neurobehavioral Biomarker of Axonal Injury Indicated by Reduced Fractional Anisotropy in A Mouse Model of Blast-Induced Mild Traumatic Brain Injury. / Weiss, Craig; Lendacki, Frances R.; Rigby, Paul H.; Wyrwicz, Alice M.; Disterhoft, John F; Spiess, Joachim.

In: Shock, 01.01.2019.

Research output: Contribution to journalArticle

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T1 - Conditioned Contextual Freezing is A Neurobehavioral Biomarker of Axonal Injury Indicated by Reduced Fractional Anisotropy in A Mouse Model of Blast-Induced Mild Traumatic Brain Injury

AU - Weiss, Craig

AU - Lendacki, Frances R.

AU - Rigby, Paul H.

AU - Wyrwicz, Alice M.

AU - Disterhoft, John F

AU - Spiess, Joachim

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N2 - Mild Traumatic Brain Injury (TBI) is an important public health problem generated by closed head injury. This study is focused on the impact of blast-induced mild TBI on auditory trace and delay fear conditioning, models of declarative and non-declarative memory, respectively, and the correlation of conditioned freezing and fractional anisotropy, a measure of axonal state. A supersonic helium pressure wave was generated by a shock tube to blast 8 week old male mice on Day 1 for 1.4 msec with an incident pressure of 16 psi, corresponding to a reflected pressure of 56.5 psi at the mouse head. On Day 3, the mice were subjected to auditory trace- or delay- fear conditioning. On Day 4, contextual freezing in the trained context, and pre-cue and cued freezing in a novel context were determined. After cardiac perfusion on Day 5, ex vivo images were obtained with diffusion tensor imaging at 14.1 Tesla. We observed that delay fear conditioning prevented or reversed the decrease in fractional anisotropy in both the medial and lateral corpus callosum suggesting axonal stabilization of potentially behavioral therapeutic significance. Moderately strong and statistically significant Pearson correlations were found between fractional anisotropy and contextual freezing in the medial and lateral corpus callosum of blasted and sham-blasted delay- or trace- fear conditioned mice. Thus, contextual freezing is a neurobehavioral biomarker for axonal injury in mild TBI and is a reliable and high-throughput behavioral assay for the evaluation of potential therapeutics to treat mild TBI.

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