Abstract
Functional recovery is the ultimate goal of research into experimental therapy for spinal cord injury (SCI). The effective use of animal models of SCI requires functional assessment methods that can be reliably repeated in different laboratories. The aim of this chapter is to describe some key features of behavioural methodology which inform our laboratory’s decisions regarding appropriate assessments in rat models of SCI. These include recognition of the type of data being measured, assurance of appropriate sampling methods to improve reliability, and considerations of the animals’ motivation during completion of the behavioural tasks. We then illustrate these principles with methods used in our laboratory, a major emphasis of which has been biomechanical analysis of limb action during overground locomotion. We also describe analysis of skilled limb movements during more challenging tasks such as ladder locomotion and forelimb pellet retrieval. Our focus throughout is on objective quantitative assessment of movement that can be reliably used to assess functional capabilities in rat SCI models under different lesion or treatment conditions.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Sedy J, Urdzikova L, Jendelova P, Sykova E (2008) Methods for behavioral testing of spinal cord injured rats. Neurosci Biobehav Rev 32:550–580
Muir GD, Webb AA (2000) Mini-review: assessment of behavioural recovery following spinal cord injury in rats. Eur J Neurosci 12:3079–3086
Goldberger ME, Bregman BS, Vierck-CJ J, Brown M (1990) Criteria for assessing recovery of function after spinal cord injury: behavioral methods. Exp Neurol 107:113–117
Kunkel BE, Dai HN, Bregman BS (1993) Methods to assess the development and recovery of locomotor function after spinal cord injury in rats. Exp Neurol 119:153–164
Wrathall JR (1992) Behavioral endpoint measures for preclinical trials using experimental models of spinal cord injury. J Neurotrauma 9:165–167
Basso DM (2004) Behavioral testing after spinal cord injury: congruities, complexities, and controversies. J Neurotrauma 21:395–404
Sharp KG, Flanagan L, Yee KM, Steward O (2011) A re-assessment of a combinatorial treatment involving Schwann cell transplants and elevation of cyclic AMP on recovery of motor function following thoracic spinal cord injury in rats. Exp Neurol in press
Webb AA, Muir GD (2005) Sensorimotor behaviour following incomplete cervical spinal cord injury in the rat. Behav Brain Res 165:147–159
Cheng H, Almstrom S, Gimenez LL, Chang R, Ove OS, Hoffer B, Olson L (1997) Gait analysis of adult paraplegic rats after spinal cord repair. Exp Neurol 148:544–557
Basso DM, Beattie MS, Bresnahan JC (1995) A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 12:1–21
Kanagal SG, Muir GD (2008) The differential effects of cervical and thoracic dorsal funiculus lesions in rats. Behav Brain Res 187:379–386
Webb AA, Muir GD (2002) Compensatory locomotor adjustments of rats with cervical or thoracic spinal cord hemisections. J Neurotrauma 19:239–256
Sandrow-Feinberg HR, Zhukareva V, Santi L, Miller K, Shumsky JS, Baker DP, Houle JD (2010) PEGylated interferon-beta modulates the acute inflammatory response and recovery when combined with forced exercise following cervical spinal contusion injury. Exp Neurol 223:439–451
Martinez M, Brezun JM, Bonnier L, Xerri C (2009) A new rating scale for open-field evaluation of behavioral recovery after cervical spinal cord injury in rats. J Neurotrauma 26:1043–1053
Anderson KD, Sharp KG, Hofstadter M, Irvine KA, Murray M, Steward O (2009) Forelimb locomotor assessment scale (FLAS): novel assessment of forelimb dysfunction after cervical spinal cord injury. Exp Neurol 220:23–33
Timoszyk WK, Nessler JA, Acosta C, Roy RR, Edgerton VR, Reinkensmeyer DJ, de LR (2005) Hindlimb loading determines stepping quantity and quality following spinal cord transection. Brain Res 1050:180–189
Cha J, Heng C, Reinkensmeyer DJ, Roy RR, Edgerton VR, de Leon RD (2007) Locomotor ability in spinal rats is dependent on the amount of activity imposed on the hindlimbs during treadmill training. J Neurotrauma 24:1000–1012
Magnuson DS, Smith RR, Brown EH, Enzmann G, Angeli C, Quesada PM, Burke D (2009) Swimming as a model of task-specific locomotor retraining after spinal cord injury in the rat. Neurorehabil Neural Repair 23:535–545
Smith RR, Brown EH, Shum-Siu A, Whelan A, Burke DA, Benton RL, Magnuson DS (2009) Swim training initiated acutely after spinal cord injury is ineffective and induces extravasation in and around the epicenter. J Neurotrauma 26:1017–1027
Smith RR, Shum-Siu A, Baltzley R, Bunger M, Baldini A, Burke DA, Magnuson DS (2006) Effects of swimming on functional recovery after incomplete spinal cord injury in rats. J Neurotrauma 23:908–919
Webb AA, Muir GD (2003) Unilateral dorsal column and rubrospinal tract injuries affect overground locomotion in the unrestrained rat. Eur J Neurosci 18:412–422
Muir GD, Webb AA, Kanagal S, Taylor L (2007) Dorsolateral cervical spinal injury differentially affects forelimb and hindlimb action in rats. Eur J Neurosci 25:1501–1510
Kanagal SG, Muir GD (2008) Effects of combined dorsolateral and dorsal funicular lesions on sensorimotor behaviour in rats. Exp Neurol 214:229–239
Kanagal SG, Muir GD (2009) Task-dependent compensation after pyramidal tract and dorsolateral spinal lesions in rats. Exp Neurol 216:193–206
Martin P, Bateson P (2007) Measuring Behaviour, an introductory guide. Cambridge University Press, Cambridge, UK
Kerlinger FN (1986) Foundations of Behavioral Research. Holt, Rinehart and Winston, Inc., New York
Metz GA, Whishaw IQ (2002) Cortical and subcortical lesions impair skilled walking in the ladder rung walking test: a new task to evaluate fore- and hindlimb stepping, placing, and co-ordination. J Neurosci Methods 115:169–179
Metz GA, Whishaw IQ (2009) The ladder rung walking task: a scoring system and its practical application. J Vis Exp
Basso DM, Beattie MS, Bresnahan JC, Anderson DK, Faden AI, Gruner JA, Holford TR, Hsu CY, Noble LJ, Nockels R, Perot PL, Salzman SK, Young W (1996) MASCIS evaluation of open field locomotor scores: effects of experience and teamwork on reliability. Multicenter Animal Spinal Cord Injury Study. J Neurotrauma 13:343–359
Schallert T, Fleming SM, Leasure JL, Tillerson JL, Bland ST (2000) CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury. Neuropharmacology 39:777–787
Whishaw IQ, Pellis SM (1990) The structure of skilled forelimb reaching in the rat: a proximally driven movement with a single distal rotatory component. Behav Brain Res 41:49–59
McKenna JE, Whishaw IQ (1999) Complete compensation in skilled reaching success with associated impairments in limb synergies, after dorsal column lesion in the rat. J Neurosci 19:1885–1894
Grillner S (1975) Locomotion in vertebrates: central mechanisms and reflex interaction. Physiol Rev 55:247–304
Grillner S, Wallen P (1985) Central pattern generators for locomotion, with special reference to vertebrates. Annu Rev Neurosci 8:233–261
Armstrong DM (1986) Supraspinal contributions to the initiation and control of locomotion in the cat. Prog Neurobiol 26:273–361
Muir GD, Whishaw IQ (2000) Red nucleus lesions impair overground locomotion in rats: a kinetic analysis. Eur J Neurosci 12:1113–1122
Muir GD, Whishaw IQ (1999) Ground reaction forces in locomoting hemi-parkinsonian rats: a definitive test for impairments and compensations. Exp Brain Res 126:307–314
Kanagal SG, Muir GD (2007) Bilateral dorsal funicular lesions alter sensorimotor behaviour in rats. Exp Neurol 205:513–524
Webb AA, Muir GD (2004) Course of motor recovery following ventrolateral spinal cord injury in the rat. Behav Brain Res 155:55–65
Winter DA (1990) Biomechanics and Motor Control of Human Movement. John Wiley and Sons, Inc, New York
Biewener AA, Full RJ (1992) Force platform and kinematic analysis. In: Biewener AA (ed) Biomechanics: Structures and Systems. Oxford University Press, Oxford, pp 45–73
Couto PA, Filipe VM, Magalhaes LG, Pereira JE, Costa LM, Melo-Pinto P, Bulas-Cruz J, Mauricio AC, Geuna S, Varejao AS (2008) A comparison of two-dimensional and three-dimensional techniques for the determination of hindlimb kinematics during treadmill locomotion in rats following spinal cord injury. J Neurosci Methods 173:193–200
Fischer MS, Schilling N, Schmidt M, Haarhaus D, Witte H (2002) Basic limb kinematics of small therian mammals. J Exp Biol 205:1315–1338
Pereira JE, Cabrita AM, Filipe VM, Bulas-Cruz J, Couto PA, Melo-Pinto P, Costa LM, Geuna S, Mauricio AC, Varejao AS (2006) A comparison analysis of hindlimb kinematics during overground and treadmill locomotion in rats. Behav Brain Res 172:212–218
Thota AK, Watson SC, Knapp E, Thompson B, Jung R (2005) Neuromechanical control of locomotion in the rat. J Neurotrauma 22:442–465
Johnson WL, Jindrich DL, Roy RR, Reggie E, V (2008) A three-dimensional model of the rat hindlimb: musculoskeletal geometry and muscle moment arms. J Biomech 41:610–619
Wehner T, Wolfram U, Henzler T, Niemeyer F, Claes L, Simon U (2010) Internal forces and moments in the femur of the rat during gait. J Biomech 43:2473–2479
Soblosky JS, Colgin LL, Chorney-Lane D, Davidson JF, Carey ME (1997) Ladder beam and camera video recording system for evaluating forelimb and hindlimb deficits after sensorimotor cortex injury in rats. J Neurosci Methods 78:75–83
Jeffery ND, Blakemore WF (1997) Locomotor deficits induced by experimental spinal cord demyelination are abolished by spontaneous remyelination. Brain 120 (Pt 1):27–37
Schallert T, Woodlee MT (2005) Orienting and Placing. In: Whishaw IQ, Kolb B (eds) The behavior of the laboratory rat: a handbook with tests. Oxford University Press, Oxford, pp 129–140
IQ, O’Connor WT, Dunnett SB (1986) The contributions of motor cortex, nigrostriatal dopamine and caudate-putamen to skilled forelimb use in the rat. Brain 109 (Pt 5):805–843
Whishaw IQ, Pellis SM, Gorny BP (1992) Skilled reaching in rats and humans: evidence for parallel development or homology. Behav Brain Res 47:59–70
Soblosky JS, Song JH, Dinh DH (2001) Graded unilateral cervical spinal cord injury in the rat: evaluation of forelimb recovery and histological effects. Behav Brain Res 119:1–13
Schrimsher GW, Reier PJ (1992) Forelimb motor performance following cervical spinal cord contusion injury in the rat. Exp Neurol 117:287–298
Schrimsher GW, Reier PJ (1993) Forelimb motor performance following dorsal column, dorsolateral funiculi, or ventrolateral funiculi lesions of the cervical spinal cord in the rat. Exp Neurol 120:264–276
Whishaw IQ, Gorny B, Sarna J (1998) Paw and limb use in skilled and spontaneous reaching after pyramidal tract, red nucleus and combined lesions in the rat: behavioral and anatomical dissociations. Behav Brain Res 93:167–183
Whishaw IQ, Whishaw P, Gorny B (2008) The structure of skilled forelimb reaching in the rat: a movement rating scale. J Vis Exp
Diener PS, Bregman BS (1998) Fetal spinal cord transplants support the development of target reaching and coordinated postural adjustments after neonatal cervical spinal cord injury. J Neurosci 18:763–778
Metz GA, Whishaw IQ (2000) Skilled reaching an action pattern: stability in rat (Rattus norvegicus) grasping movements as a function of changing food pellet size. Behav Brain Res 116:111–122
Miklyaeva EI, Whishaw IQ (1996) Hemi-Parkinson analogue rats display active support in good limbs versus passive support in bad limbs on a skilled reaching task of variable height. Behav Neurosci 110:117–125
Miklyaeva EI, Castaneda E, Whishaw IQ (1994) Skilled reaching deficits in unilateral dopamine-depleted rats: impairments in movement and posture and compensatory adjustments. J Neurosci 14:7148–7158
Whishaw IQ (2005) Prehension. In: Whishaw IQ, Kolb B (eds) The behavior of the laboratory rat; a handbook with tests. Oxford University Press, Oxford, pp 162–170
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Muir, G.D., Prosser-Loose, E.J. (2011). Assessing Spinal Cord Injury. In: Lane, E., Dunnett, S. (eds) Animal Models of Movement Disorders. Neuromethods, vol 62. Humana Press. https://doi.org/10.1007/978-1-61779-301-1_21
Download citation
DOI: https://doi.org/10.1007/978-1-61779-301-1_21
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-300-4
Online ISBN: 978-1-61779-301-1
eBook Packages: Springer Protocols