A novel closed-body model of spinal cord injury caused by high-pressure air blasts produces extensive axonal injury and motor impairments

Nobel del Mar, Xinyu von Buttlar, Angela S. Yu, Natalie H. Guley, Anton Reiner, Marcia Honig

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Diffuse axonal injury is thought to be the basis of the functional impairments stemming from mild traumatic brain injury. To examine how axons are damaged by traumatic events, such as motor vehicle accidents, falls, sports activities, or explosive blasts, we have taken advantage of the spinal cord with its extensive white matter tracts. We developed a closed-body model of spinal cord injury in mice whereby high-pressure air blasts targeted to lower thoracic vertebral levels produce tensile, compressive, and shear forces within the parenchyma of the spinal cord and thereby cause extensive axonal injury. Markers of cytoskeletal integrity showed that spinal cord axons exhibited three distinct pathologies: microtubule breakage, neurofilament compaction, and calpain-mediated spectrin breakdown. The dorsally situated axons of the corticospinal tract primarily exhibited microtubule breakage, whereas all three pathologies were common in the lateral and ventral white matter. Individual axons typically demonstrated only one of the three pathologies during the first 24. h after blast injury, suggesting that the different perturbations are initiated independently of one another. For the first few days after blast, neurofilament compaction was frequently accompanied by autophagy, and subsequent to that, by the fragmentation of degenerating axons. TuJ1 immunolabeling and mice with YFP-reporter labeling each revealed more extensive microtubule breakage than did βAPP immunolabeling, raising doubts about the sensitivity of this standard approach for assessing axonal injury. Although motor deficits were mild and largely transient, some aspects of motor function gradually worsened over several weeks, suggesting that a low level of axonal degeneration continued past the initial wave. Our model can help provide further insight into how to intervene in the processes by which initial axonal damage culminates in axonal degeneration, to improve outcomes after traumatic injury. Importantly, our findings of extensive axonal injury also caution that repeated trauma is likely to have cumulative adverse consequences for both brain and spinal cord.

Original languageEnglish (US)
Pages (from-to)53-71
Number of pages19
JournalExperimental Neurology
Volume271
DOIs
StatePublished - Sep 1 2015

Fingerprint

Air Pressure
Spinal Cord Injuries
Axons
Spinal Cord
Microtubules
Wounds and Injuries
Intermediate Filaments
Pathology
Diffuse Axonal Injury
Brain Concussion
Blast Injuries
Spectrin
Pyramidal Tracts
Calpain
Autophagy
Motor Vehicles
Accidents
Sports
Thorax
Brain

All Science Journal Classification (ASJC) codes

  • Neurology
  • Developmental Neuroscience

Cite this

A novel closed-body model of spinal cord injury caused by high-pressure air blasts produces extensive axonal injury and motor impairments. / del Mar, Nobel; von Buttlar, Xinyu; Yu, Angela S.; Guley, Natalie H.; Reiner, Anton; Honig, Marcia.

In: Experimental Neurology, Vol. 271, 01.09.2015, p. 53-71.

Research output: Contribution to journalArticle

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