Advertisement

Neurobehavioral Assessments of Spinal Cord Injury

  • Jed S. Shumsky
  • John D. Houlé
Protocol
Part of the Springer Protocols Handbooks book series (SPH)

Abstract

Experimental spinal cord injuries can be categorized as being mild, moderate, or severe, based upon the extent of tissue damage and the severity of functional deficit incurred. The level of injury and unilateral or bilateral nature of an injury also greatly impact upon whether deficits involve single or multiple limbs. Having these features in mind, the investigator is directed towards performing the appropriate neurobehavioral tests to assess the functional capabilities of injured animals before and after therapeutic interventions have been applied. An ideal test should use quantitative methods that can provide some insight into the physiological mechanisms involved in functional recovery.

Key words

Somatosensory testing Behavioral assessment Locomotion Spinal cord injury, Functional recovery 

References

  1. 1.
    Metz GA, Merkler D, Dietz V, Schwab ME, Fouad K (2000) Efficient testing of motor function in spinal cord injured rats. Brain Res 883:165–177PubMedCrossRefGoogle Scholar
  2. 2.
    Basso DM (2004) Behavioral testing after spinal cord injury: congruities, complexities, and controversies. J Neurotrauma 21:395–404CrossRefGoogle Scholar
  3. 3.
    Sedý J, Urdzíková L, Jendelová P, Syková E (2008) Methods for behavioral testing of spinal cord injured rats. Neurosci Biobehav Rev 32:550–580PubMedCrossRefGoogle Scholar
  4. 4.
    Schallert T, Tillerson JL (1999) Intervention strategies for degeneration of dopamine neurons in Parkinsonism: optimizing behavioral assessment of outcome. In: Emerich DF (ed) Innovative models of CNS diseases. Humana Press, Clifton NJGoogle Scholar
  5. 5.
    Basso DM, Beattie ME, Bresnahan JC (1995) A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 12:1–21PubMedCrossRefGoogle Scholar
  6. 6.
    Basso DM, Beattie ME, Bresnahan JC (1996) Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol 139:244–256PubMedCrossRefGoogle Scholar
  7. 7.
    Nothias JM, Mitsui T, Shumsky JS, Fischer I, Antonacci MD, Murray M (2005) Combined effects of neurotrophin secreting transplants, exercise, and serotonergic drug challenge improve function in spinal rats. Neurorehab Neural Repair 19:296–312Google Scholar
  8. 8.
    Kao T, Shumsky JS, Jacob-Vadakot S, Himes BT, Murray M, Moxon KA (2006) Role of the 5-HT2C receptor for improving weight supported stepping in adult rats spinalized as neonates. Brain Res 1112:159–168Google Scholar
  9. 9.
    Miya D, Tessler A, Giszter S, Mori F, Murray M (1997) Fetal transplants alter the development of function after spinal cord transection in newborn rats. J Neurosci 17:4856–4872PubMedGoogle Scholar
  10. 10.
    Kim D, Murray M, Simansky KJ (2001) The serotonergic 5-HT(2C) agonist m-chlorophenylpiperazine increases weight-supported locomotion without development of tolerance in rats with spinal transections. Exp Neurol 169:496–500PubMedCrossRefGoogle Scholar
  11. 11.
    Stackhouse SK, Shibayama M, Bowes M, Murray M (1997) Fetal tissue transplants improve hindlimb function in adult spinal rats. Soc Neurosci Abstr 23:906Google Scholar
  12. 12.
    Belanger M, Drew T, Provencher J, Rossignol S (1996) A comparison of treadmill locomotion in adult cats before and after spinal transection. J Neurophysiol 76:471–491PubMedGoogle Scholar
  13. 13.
    de Leon RD, Tamaki H, Hodgson JA, Roy RR, Edgerton VR (1999) Hindlimb locomotor and postural training modulates glycinergic inhibition in the spinal cord of the adult spinal cat. J Neurophysiol 82:359–369PubMedGoogle Scholar
  14. 14.
    Brustein E, Rossignol S (1998) Recovery of locomotion after ventral and ventrolateral spinal lesions in the cat. I. Deficits and adaptive mechanisms. J Neurophysiol 80:1245–1267PubMedGoogle Scholar
  15. 15.
    Howland DR, Bregman BS, Tessler A, Goldberger ME (1995) Transplants enhance locomotion in neonatal kittens whose spinal cords are transected: a behavioral and anatomical study. Exp Neurol 135:123–145PubMedCrossRefGoogle Scholar
  16. 16.
    Shumsky JS, Tobias CA, Tumolo M, Long WD, Giszter SF, Murray M (2003) Delayed transplantation of fibroblasts genetically modified to secrete BDNF and NT-3 into a spinal cord injury site is associated with limited recovery of function. Exp Neurol 184:114–130PubMedCrossRefGoogle Scholar
  17. 17.
    Hargreaves K, Dubner R, Brown F, Flores C, Joris J (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32:77–88PubMedCrossRefGoogle Scholar
  18. 18.
    Christensen MD, Everhart AW, Pickelman JT, Hulsebosch CE (1996) Mechanical and thermal allodynia in chronic central pain following spinal cord injury. Pain 68:97–107PubMedCrossRefGoogle Scholar
  19. 19.
    Yezierski RP, Liu S, Ruenes GL, Kajander KJ, Brewer KL (1998) Excitotoxic spinal cord injury: behavioral and morphological characteristics of a central pain model. Pain 75:141–155PubMedCrossRefGoogle Scholar
  20. 20.
    Hutchinson KJ, Gómez-Pinilla F, Crowe MJ, Ying Z, Basso DM (2004) Three exercise paradigms differentially improve sensory recovery after spinal cord contusion in rats. Brain 127:1403–1414PubMedCrossRefGoogle Scholar
  21. 21.
    Mitsui T, Kakizaki H, Shibata T, Tanaka H, Matsuoka I, Koyanagi T (2003) Transplanted immortalized neural stem cells into injured spinal cord promote recovery of voiding function in rats. J Urology 170:1421–1425CrossRefGoogle Scholar
  22. 22.
    Mitsui T, Fischer I, Shumsky JS, Murray M (2005) Transplants of fibroblasts expressing BDNF and NT-3 promote recovery of bladder function following spinal contusion injury in rats. Exp Neurol 194:410–431PubMedCrossRefGoogle Scholar
  23. 23.
    Yoshiyama M, Nezu FM, Yokoyama O, De Groat WC, Chancellor MB (1999) Changes in micturition after spinal cord injury in conscious rats. Urology 54:923–933CrossRefGoogle Scholar
  24. 24.
    Cao Y, Shumsky JS, Sabol MA, Kushner RA, Tessler A, Strittmatter S, Hamers FPT, Lee DHS, Rabacchi SA, Murray M (2008) Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat. Neurorehab Neural Repair 22:262–278Google Scholar
  25. 25.
    Hamers FP, Lankhorst AJ, van Laar TJ, Veldhuis WB, Gispen WH (2001) Automated quantitative gait analysis during overground locomotion in the rat: its application to spinal cord contusion and transection injuries. J Neurotrauma 18:187–201PubMedCrossRefGoogle Scholar
  26. 26.
    Koopmans GC, Deumens R, Honig WM, Hamers FP, Steinbusch HW, Joosten EA (2005) The assessment of locomotor function in spinal cord injured rats: the importance of objective analysis of coordination. J Neurotrauma 22:214–225PubMedCrossRefGoogle Scholar
  27. 27.
    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 18:763–778Google Scholar
  28. 28.
    Grill R, Murai K, Blesch A, Gage FH, Tuszynski MH (1997) Cellular delivery of neurotrophin-3 promotes corticospinal axonal growth and partial recovery after spinal cord injury. J Neurosci 17:5560–5572PubMedGoogle Scholar
  29. 29.
    Smith RR, Burke DA, Baldini AD, Shum-Siu A, Baltzley R, Bunger M, Magnuson DS (2006) The Louisville Swim Scale: a novel assessment of hindlimb function following spinal cord injury in adult rats. J Neurotrauma 23:1654–1670Google Scholar
  30. 30.
    Liu Y, Kim D, Himes BT, Chow S, Murray M, Tessler A, Fischer I (1999) Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons and recovery of forelimb function. J Neuroscience 19:4370–4387Google Scholar
  31. 31.
    Kim D, Schallert T, Liu Y, Browarak T, Nayeri N, Tessler A, Fischer I, Murray M (2001) Transplantation of genetically modified fibroblasts expressing BDNF in adult rats with a subtotal hemisection improves specific motor and sensory functions. Neurorehab Neural Repair 15:141–150CrossRefGoogle Scholar
  32. 32.
    Cabe PA, Tilson HA, Mitchell CL, Dennis R (1978) A simple recording grip strength device. Pharmacol Biochem Behav 8:101–102PubMedCrossRefGoogle Scholar
  33. 33.
    Meyer OA, Tilson HA, Byrd WC, Riley MT (1979) A method for the routine assessment of fore- and hindlimb grip strength of rats and mice. Neurobehav Toxicol 1:233–236PubMedGoogle Scholar
  34. 34.
    Anderson KD, Gunawan A, Steward O (2007) Spinal pathways involved in the control of forelimb motor function in rats. Exp Neurol 206:318–331Google Scholar
  35. 35.
    Schallert T, Upchurch M, Lobaugh N, Farrar SB, Spirduso WW, Gilliam P, Vaughn D, Wilcox RE (1982) Tactile extinction: distinguishing between sensorimotor and motor asymmetries in rats with unilateral nigrostriatal damage. Pharmacol Biochem Behav 16:455–462PubMedCrossRefGoogle Scholar
  36. 36.
    Schallert T, Upchurch M, Wilcox RE, Vaughn DM (1983) Posture-independent sensorimotor analysis of inter-hemispheric receptor asymmetries in neostriatum. Pharmacol Biochem Behav 18:753–759PubMedCrossRefGoogle Scholar
  37. 37.
    Schallert T, Hernandez TD, Barth TM (1986) Recovery of function after brain damage: severe and chronic disruption by diazepam. Brain Res 379:104–111PubMedCrossRefGoogle Scholar
  38. 38.
    Barth TM, Jones TA, Schallert T (1990) Functional subdivisions of the rat somatic sensorimotor cortex. Behav Brain Res 39:73–95PubMedCrossRefGoogle Scholar
  39. 39.
    Whishaw IQ, Pellis SM, Gorny BP (1992) Medial frontal cortex lesions impair the aiming component of rat reaching. Behav Brain Res 50:93–104PubMedCrossRefGoogle Scholar
  40. 40.
    Whishaw IQ, Pellis SM, Gorny B, Kollo B, Tetzlaff W (1993) Proximal and distal impairments in rat forelimb use in reaching follow unilateral pyramidal tract lesions. Behav Brain Res 56:59–76PubMedCrossRefGoogle Scholar
  41. 41.
    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 19:1885–1894PubMedGoogle Scholar
  42. 42.
    Stackhouse SK, Murray M, Shumsky JS (2008) The effect of cervical dorsolateral funiculotemy on reach-to-grasp function in the rat. J Neurotrauma 25:1039–1047PubMedCrossRefGoogle Scholar
  43. 43.
    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. Behav Brain Res 93:167–183PubMedCrossRefGoogle Scholar
  44. 44.
    Li Y, Field PM, Raisman G (1997) Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science 277:2000–2002PubMedCrossRefGoogle Scholar
  45. 45.
    Hyland BI, Jordan VMB (1997) Muscle activity during forelimb reaching movements in rats. Behav Brain Res 85:175–186PubMedCrossRefGoogle Scholar
  46. 46.
    Ballermann M, Tompkins G, Whishaw IQ (2000) Skilled forelimb reaching for pasta guided by tactile input in the rat as measured by accuracy, spatial adjustments, and force. Behav Brain Res 109:49–57PubMedCrossRefGoogle Scholar
  47. 47.
    Ballermann M, McKenna J, Whishaw IQ (2001) A grasp-related deficit in tactile discrimination following dorsal column lesion in the rat. Brain Res Bull 54:237–242PubMedCrossRefGoogle Scholar
  48. 48.
    Montoya CP, Campbell-Hope LJ, Pemberton KD, Dunnett SB (1991) The “staircase test”: a measure of independent forelimb reaching and grasping abilities in rats. J Neurosci 36:219–228Google Scholar
  49. 49.
    Schallert T, Woodlee MT, Fleming SM (2002) Disentangling multiple types of recovery from brain injury. In: Krieglstein J, Klump S (eds) Pharmacology of cerebral ischemia. Stuttgart, Medpharm Scientific Publishers, pp 201–216Google Scholar
  50. 50.
    Schallert T, Woodlee MT (2005) Orienting and placing. In: Whishaw IQ, Kolb B (eds) The behavior of the laboratory rat. New York, Oxford University Press, pp 129–140Google Scholar
  51. 51.
    Edgerton VR, Kim SJ, Ichiyama RM, Gerasimenko YP, Roy RR (2006) Rehabilitative therapies after spinal cord injury. J Neurotrauma 23:560–570PubMedCrossRefGoogle Scholar
  52. 52.
    Houle JD, Morris K, Skinner RD, Garcia-Rill E, Peterson CA (1999) Effects of fetal spinal cord tissue transplants and cycling exercise on the soleus muscle in spinalized rats. Muscle Nerve 22:846–856PubMedCrossRefGoogle Scholar
  53. 53.
    Sandrow-Feinberg HR, Izzi J, Shumsky JS, Zhukareva V, Houle JD (2009) Forced exercise as a rehabilitation strategy after unilateral cervical spinal cord contusion injury. J Neurotrauma 26:721–731PubMedCrossRefGoogle Scholar
  54. 54.
    de Leon RD, Hodgson JA, Roy RR, Edgerton VR (1999) Retention of hindlimb stepping ability in adult spinal cats after the cessation of step training. J Neurophysiol 81:85–94PubMedGoogle Scholar
  55. 55.
    Edgerton VR, de Leon RD, Harkema SJ (2001) Topical review: retraining the injured spinal cord. J Physiol (Lond) 533:15–22Google Scholar
  56. 56.
    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. Neurorehab Neural Repair 23:535–545Google Scholar
  57. 57.
    Smith RR, Shum-Siu A, Baltzley R, Bunger M, Baldini R, Burke DA, Magnuson DS (2006) Effects of swimming on functional recovery after incomplete spinal cord injury in rats. J Neuro-trauma 23:908–919PubMedCrossRefGoogle Scholar
  58. 58.
    Skinner RD, Houle JD, Reese NB, Berry CL, Garcia-Rill E (1996) Effects of exercise and fetal spinal cord implants on the H-reflex in chronically spinalized adult rats. Brain Res 729:127–131PubMedCrossRefGoogle Scholar
  59. 59.
    Beaumont E, Houle JD, Peterson CA, Gardiner PF (2004) Passive exercise and fetal spinal cord transplant both help to restore motoneuronal properties after spinal cord transection in rats. Muscle Nerve 29:234–242PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Neurobiology and Anatomy, The Spinal Cord Research CenterDrexel University College of MedicinePhiladelphiaUSA

Personalised recommendations