title: Evaluation of Five Tests for Sensitivity to Functional Deficits following Cervical or Thoracic Dorsal Column Transection in the Rat.
abstract: The dorsal column lesion model of spinal cord injury targets sensory fibres which originate from the dorsal root ganglia and ascend in the dorsal funiculus. It has the advantages that fibres can be specifically traced from the sciatic nerve, verifiably complete lesions can be performed of the labelled fibres, and it can be used to study sprouting in the central nervous system from the conditioning lesion effect. However, functional deficits from this type of lesion are mild, making assessment of experimental treatment-induced functional recovery difficult. Here, five functional tests were compared for their sensitivity to functional deficits, and hence their suitability to reliably measure recovery of function after dorsal column injury. We assessed the tape removal test, the rope crossing test, CatWalk gait analysis, and the horizontal ladder, and introduce a new test, the inclined rolling ladder. Animals with dorsal column injuries at C4 or T7 level were compared to sham-operated animals for a duration of eight weeks. As well as comparing groups at individual timepoints we also compared the longitudinal data over the whole time course with linear mixed models (LMMs), and for tests where steps are scored as success/error, using generalized LMMs for binomial data. Although, generally, function recovered to sham levels within 2-6 weeks, in most tests we were able to detect significant deficits with whole time-course comparisons. On the horizontal ladder deficits were detected until 5-6 weeks. With the new inclined rolling ladder functional deficits were somewhat more consistent over the testing period and appeared to last for 6-7 weeks. Of the CatWalk parameters base of support was sensitive to cervical and thoracic lesions while hind-paw print-width was affected by cervical lesion only. The inclined rolling ladder test in combination with the horizontal ladder and the CatWalk may prove useful to monitor functional recovery after experimental treatment in this lesion model.
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, an Institute of the Royal Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Nitish D
authors.initials: ND
authors.lastname: Fagoe
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, an Institute of the Royal Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Callan L
authors.initials: CL
authors.lastname: Attwell
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, an Institute of the Royal Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Ruben
authors.initials: R
authors.lastname: Eggers
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, an Institute of the Royal Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Lizz
authors.initials: L
authors.lastname: Tuinenbreijer
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, an Institute of the Royal Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Dorette
authors.initials: D
authors.lastname: Kouwenhoven
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, an Institute of the Royal Academy of Arts and Sciences, Amsterdam, The Netherlands.|Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Verhaagen
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, an Institute of the Royal Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Matthew R J
authors.initials: MR
authors.lastname: Mason
mesh_terms: D000818:Animals; D066193:Cervical Cord / Q000293:injuries / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D020233:Gait Disorders, Neurologic / Q000175:diagnosis / Q000503:physiopathology; D005727:Ganglia, Spinal / Q000293:injuries / Q000503:physiopathology; D009416:Nerve Regeneration; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function; D013116:Spinal Cord / Q000503:physiopathology*; D066148:Spinal Cord Dorsal Horn / Q000293:injuries / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000175:diagnosis / Q000503:physiopathology*; D016138:Walking