Kinematic and kinetic gait analysis to evaluate functional recovery in thoracic spinal cord injured rats

https://doi.org/10.1016/j.neubiorev.2018.12.027Get rights and content

Highlights

  • Several methods have been developed to analyze locomotion in the rat model after SCI.

  • Kinematic parameters can allow detection of subtle deficits in gait following SCI.

  • With ground reaction forces it is possible to identify gait compensatory mechanisms.

  • The use of multiple kinematic and kinetic parameters is crucial for future studies.

Abstract

The recovery of walking function following spinal cord injury (SCI) is of major importance to patients and clinicians. In experimental SCI studies, a rat model is widely used to assess walking function, following thoracic spinal cord lesion. In an effort to provide a resource which investigators can refer to when seeking the most appropriate functional assay, the authors have compiled and categorized the behavioral assessments used to measure the deficits and recovery of the gait in thoracic SCI rats. These categories include kinematic and kinetic measurements. Within this categorization, we discuss the advantages and disadvantages of each type of measurement. The present review includes the type of outcome data that they produce, the technical difficulty and the time required to potentially train the animals to perform them, and the need for expensive or highly specialized equipment. The use of multiple kinematic and kinetic parameters is recommended to identify subtle deficits and processes involved in the compensatory mechanisms of walking function after experimental thoracic SCI in rats.

Introduction

Spinal cord injury (SCI) has a high prevalence in the entire world (Singh et al., 2014). This disease may result in permanent loss of motor, sensory, and autonomic function caused by initial mechanical lesion and secondary tissue damage. Despite advances have taken place over the past decade, recovering the capacity to walk remains a dream for most patients. Animal models are widely used in translational research for SCI in humans. The rat has become the favorite animal for testing various treatment strategies in SCI research and different lesion techniques have been developed to mimic human spinal cord lesions (Kim et al., 2017; Kozuka et al., 2016; Nicola et al., 2017).

In experimental SCI studies, one of the most used methods is the contusion technique, which produces a typical picture of secondary spinal cord damage and closely mimics the situation in humans (Beaumont et al., 2009; Iannotti et al., 2011; Koopmans et al., 2009; Ramu et al., 2007). With this model, since not all spinal tracts are disrupted, residual function persists to some degree and several motor and sensory tests have been developed in order to quantify remaining activity in the spinal cord (Jin et al., 2014; Zhao et al., 2016). An accurate evaluation of the spared and regenerating nervous tissue can be obtained by morphological methods, however, the most important factor on predicting SCI recovery is the evaluation of functional outcome, which can determine the lesion location and severity, and give information on the integrity of specific motor and sensory pathways (Basso, 2004). Rat models of contusive thoracic SCI allow the isolation and study of white matter deficits, namely spastic paralysis below the injury and sensory loss/chronic pain (Gensel et al., 2006; Wang et al., 2015). Since the most obvious functional consequence of injuries at the thoracic level is the loss of hindlimb motor function (Anderson et al., 2005) and due to the reliability and reproducibility of thoracic SCI models and behavioral tests, this kind of model has been widely used in spinal cord research (Bhimani et al., 2017; Muir and Webb, 2000).

Depending on the type of data collected, functional evaluation tests can be classified as: endpoint measures, in which a behavior is scored upon reaching a specific goal (Fagoe et al., 2016); kinematic analysis, including continuous kinematic analysis (Couto et al., 2008) and qualitative tests describing a particular movement; kinetic measurements, which quantify the amount of force produced by the hindlimbs (Howard et al., 2000); and electrophysiological measurements, which detect and measure muscle or sensory system activity (Gad et al., 2015; Keller et al., 2018).

Several methods have been developed to improve analyses of locomotion in rats after thoracic experimental SCI. Locomotion scoring systems are widely applied to evaluate motor function (Caudle et al., 2015; Morita et al., 2016). With this kind of method, it is possible to estimate spinal cord damage without compensatory behavior (Basso et al., 1995), as opposed to endpoints tests, in which the results cannot provide any information concerning how the task was performed (Whishaw et al., 1997). With advancement of new technology, such as computed gait analysis and force plate kinetics, important information about locomotion has allowed a better understanding of functional recovery after SCI (Couto et al., 2008; Howard et al., 2000).

This literature review aims to describe the advances in kinematic and kinetic assessments to evaluate locomotion in thoracic spinal cord injured rats with the goal of accelerating the translation of discoveries from the bench to the bedside and eventually to therapeutic practices that improve the quality of life in SCI patients, namely the capacity to walk.

We selected references by searching PubMed for manuscripts published in English between January 1, 1978, and August 20, 2018, using the term “rat” and assorted combinations of the following terms: “spinal cord injury” “gait analysis”, “locomotion”. “kinematics”, “kinetics”, “functional recovery”, “ground reaction forces” and “footprint analysis”. We examined the reference lists within original research and review articles for additional references. We finalized the reference list on the basis of originality and relevance to the scope of this Review. Data on kinematic and kinetic assessments to evaluate locomotion in thoracic spinal cord injured rats are summarized in Table 1.

Section snippets

Kinematic measures

Kinematic techniques include any method that describes and quantifies the movement of the whole body or body segments relative to each other and/or to an external frame of reference. In SCI research, several kinematic methods have been used to assess functional recovery including ordinal locomotor rating scales and continuous kinematic data (Basso et al., 1995; Couto et al., 2008; Osuna-Carrasco et al., 2016).

Kinetic measurements

Kinetics is the area of biomechanics concerned with forces and can be applied to rats by using force-transducing platforms that quantify forces exerted by these animals when moving over surfaces or objects (Muir and Whishaw, 1999a, b; Muir and Whishaw, 2000).

Force-transducing platforms include three-axis piezoelectric force transducers, charge amplifiers, signal conditioning boards, and a computer-based data acquisition system (Howard et al., 2000). When measuring forces during overground

Final considerations

Recovery of locomotor function after SCI underlies a complex process where many factors contribute to a gain in walking function. Kinematic methods provide important information about walking function in SCI. Despite modern equipment and advanced technology used for studies on gait analysis, the BBB scale is still the most common functional assessment method used in SCI. Locomotor rating scales may be insufficient in providing quantitative and detailed assessment of locomotion behavior in

Author disclosure statement

The authors declare that they have no competing financial interests.

References (101)

  • C. Escobar-Corona et al.

    Electroacupuncture improves gait locomotion, H-reflex and ventral root potentials of spinal compression injured rats

    Brain Res. Bull.

    (2017)
  • R.M. Evans et al.

    ScoreCentre: a computer program to assist with collection and calculation of BBB locomotor scale data

    J. Neurosci. Methods

    (2010)
  • V.M. Filipe et al.

    Effect of skin movement on the analysis of hindlimb kinematics during treadmill locomotion in rats

    J. Neurosci. Methods

    (2006)
  • M.A. Freeman et al.

    The movement of the normal tibio-femoral joint

    J. Biomech.

    (2005)
  • P. Gad et al.

    Electrophysiological mapping of rat sensorimotor lumbosacral spinal networks after complete paralysis

    Prog. Brain Res.

    (2015)
  • T. Gorska et al.

    Changes in forelimb-hindlimb coordination after partial spinal lesions of different extent in the rat

    Behav. Brain Res.

    (2013)
  • G. Guízar-Sahagún et al.

    Spontaneous and induced aberrant sprouting at the site of injury is irrelevant to motor function outcome in rats with spinal cord injury

    Brain Res.

    (2004)
  • T.G. Hampton et al.

    Gait dynamics in trisomic mice: quantitative neurological traits of Down syndrome

    Physiol. Behav.

    (2004)
  • D.E. Handley et al.

    A force plate system for measuring low-magnitude reaction forces in small laboratory animals

    Physiol. Behav.

    (1998)
  • J.E. Hillyer et al.

    A new measure of hindlimb stepping ability in neonatally spinalized rats

    Behav. Brain Res.

    (2009)
  • C.S. Howard et al.

    Functional assessment in the rat by ground reaction forces

    J. Biomech.

    (2000)
  • R.E. Hruska et al.

    Quantitative aspects of normal locomotion in rats

    Life Sci.

    (1979)
  • C.A. Iannotti et al.

    A combination immunomodulatory treatment promotes neuroprotection and locomotor recovery after contusion SCI

    Exp. Neurol.

    (2011)
  • Y. Jin et al.

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

    Exp. Neurol.

    (2014)
  • K. Klapdor et al.

    A low-cost method to analyse footprint patterns

    J. Neurosci. Methods

    (1997)
  • G.C. Koopmans et al.

    Acute rolipram/thalidomide treatment improves tissue sparing and locomotion after experimental spinal cord injury

    Exp. Neurol.

    (2009)
  • J. Kuerzi et al.

    Task-specificity vs. ceiling effect: step-training in shallow water after spinal cord injury

    Exp. Neurol.

    (2010)
  • S. Li et al.

    Transgenic inhibition of Nogo-66 receptor function allows axonal sprouting and improved locomotion after spinal injury

    Mol. Cell. Neurosci.

    (2005)
  • H. Majczynski et al.

    Comparison of two methods for quantitative assessment of unrestrained locomotion in the rat

    J. Neurosci. Methods

    (2007)
  • D.M. McTigue et al.

    The PPAR gamma agonist Pioglitazone improves anatomical and locomotor recovery after rodent spinal cord injury

    Exp. Neurol.

    (2007)
  • G.A.S. Metz et al.

    Efficient testing of motor function in spinal cord injured rats

    Brain Res.

    (2000)
  • T. Morita et al.

    Intravenous infusion of mesenchymal stem cells promotes functional recovery in a model of chronic spinal cord injury

    Neuroscience

    (2016)
  • G.D. Muir et al.

    Complete locomotor recovery following corticospinal tract lesions: measurement of ground reaction forces during overground locomotion in rats

    Behav. Brain Res.

    (1999)
  • F.D. Nicola et al.

    Neuroprotector effect of stem cells from human exfoliated deciduous teeth transplanted after traumatic spinal cord injury involves inhibition of early neuronal apoptosis

    Brain Res.

    (2017)
  • L.P. Osuna-Carrasco et al.

    Quantitative analysis of hindlimbs locomotion kinematics in spinalized rats treated with Tamoxifen plus treadmill exercise

    Neuroscience

    (2016)
  • J.E. Pereira et al.

    A comparison analysis of hindlimb kinematics during overground and treadmill locomotion in rats

    Behav. Brain Res.

    (2006)
  • J.E. Pereira et al.

    Methylprednisolone fails to improve functional and histological outcome following spinal cord injury in rats

    Exp. Neurol.

    (2009)
  • J. Ramu et al.

    Cortical reorganization in NT3-treated experimental spinal cord injury: functional magnetic resonance imaging

    Exp. Neurol.

    (2007)
  • E. Redondo-Castro et al.

    Quantitative assessment of locomotion and interlimb coordination in rats after different spinal cord injuries

    J. Neurosci. Methods

    (2013)
  • K.G. Sharp et al.

    A re-assessment of the effects of treatment with a non-steroidal anti-inflammatory (ibuprofen) on promoting axon regeneration via RhoA inhibition after spinal cord injury

    Exp. Neurol.

    (2013)
  • N. Silva et al.

    A cost-effective instrumented walkway for measuring ground reaction forces in rats to assess gait pattern

    Measurement

    (2017)
  • M. von Euler et al.

    Motor performance score: a new algorithm for accurate behavioral testing of spinal cord injury in rats

    Exp. Neurol.

    (1996)
  • R.E. von Leden et al.

    (18)F-FDG-PET imaging of rat spinal cord demonstrates altered glucose uptake acutely after contusion injury

    Neurosci. Lett.

    (2016)
  • H. Wang et al.

    Treadmill training induced lumbar motoneuron dendritic plasticity and behavior recovery in adult rats after a thoracic contusive spinal cord injury

    Exp. Neurol.

    (2015)
  • I.Q. Whishaw et al.

    Analysis of limb use by control rats and unilateral DA-depleted rats in the Montoya staircase test: movements, impairments and compensatory strategies

    Behav. Brain Res.

    (1997)
  • J.K. Wong et al.

    One day of motor training with amphetamine impairs motor recovery following spinal cord injury

    Exp. Neurol.

    (2012)
  • N. Xu et al.

    A sensitive and reliable test instrument to assess swimming in rats with spinal cord injury

    Behav. Brain Res.

    (2015)
  • O. Alluin et al.

    Kinematic study of locomotor recovery after spinal cord clip compression injury in rats

    J. Neurotrauma

    (2011)
  • O. Alluin et al.

    Examination of the combined effects of chondroitinase ABC, growth factors and locomotor training following compressive spinal cord injury on neuroanatomical plasticity and kinematics

    PLoS One

    (2014)
  • M. Ballermann et al.

    Adaptations in the walking pattern of spinal cord injured rats

    J. Neurotrauma

    (2006)
  • Cited by (11)

    View all citing articles on Scopus
    View full text