Behavioral and anatomical consequences of repetitive mild thoracic spinal cord contusion injury in the rat

Exp Neurol. 2014 Jul;257:57-69. doi: 10.1016/j.expneurol.2014.04.016. Epub 2014 Apr 28.

Abstract

Moderate and severe spinal cord contusion injuries have been extensively studied, yet much less is known about mild injuries. Mild contusions result in transient functional deficits, proceeding to near-complete recovery, but they may render the spinal cord vulnerable to future injuries. However, to date there have been no appropriate models to study the behavioral consequences, anatomical changes, and susceptibility of a mild contusion to repeated injuries, which may occur in children as well as adults during competitive sport activities. We have developed a novel mild spinal cord contusion injury model characterized by a sequence of transient functional deficits after the first injury and restoration to near-complete motor and sensory function, which is then followed up by a second injury. This model can serve not only to study the effects of repeated injuries on behavioral and anatomical changes, but also to examine the relationship between successive tissue damage and recovery of function. In the present study, we confirmed that mild thoracic spinal cord contusion, utilizing the NYU impactor device, resulted in localized tissue damage, characterized by a cystic cavity and peripheral rim of spared white matter at the injury epicenter, and rapid functional recovery to near-normal levels utilizing several behavioral tests. Repeated injury after 3weeks, when functional recovery has been completed, resulted in worsening of both motor and sensory function, which did not recover to prior levels. Anatomical analyses showed no differences in the volumes of spared white matter, lesion, or cyst, but revealed modest extension of lesion area rostral to the injury epicenter as well as an increase in inflammation and apoptosis. These studies demonstrate that a mild injury model can be used to test efficacy of treatments for repeated injuries and may serve to assist in the formulation of policies and clinical practice regarding mild SCI injury and spinal concussion.

Keywords: Anatomical analysis; Behavioral analysis; Repeated CNS injury; Spinal cord injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism
  • Analysis of Variance
  • Animals
  • Calcium-Binding Proteins / metabolism
  • Carrier Proteins / metabolism
  • Contusions / complications
  • Disease Models, Animal
  • Ectodysplasins / metabolism
  • Exploratory Behavior
  • Female
  • Gene Expression Regulation
  • Locomotion / physiology*
  • Microfilament Proteins / metabolism
  • Muscle Strength
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / physiology*
  • Spinal Cord Injuries / etiology
  • Spinal Cord Injuries / pathology*
  • Spinal Cord Injuries / physiopathology*
  • Time Factors

Substances

  • Actins
  • Aif1 protein, rat
  • Calcium-Binding Proteins
  • Carrier Proteins
  • Ectodysplasins
  • Microfilament Proteins