Abstract
In rodents and nonhuman primates subjected to spinal cord lesion, neutralizing the neurite growth inhibitor Nogo-A has been shown to promote regenerative axonal sprouting and functional recovery. The goal of the present report was to re-examine the data on the recovery of the primate manual dexterity using refined behavioral analyses and further statistical assessments, representing secondary outcome measures from the same manual dexterity test. Thirteen adult monkeys were studied; seven received an anti-Nogo-A antibody whereas a control antibody was infused into the other monkeys. Monkeys were trained to perform the modified Brinkman board task requiring opposition of index finger and thumb to grasp food pellets placed in vertically and horizontally oriented slots. Two parameters were quantified before and following spinal cord injury: (i) the standard ‘score’ as defined by the number of pellets retrieved within 30 s from the two types of slots; (ii) the newly introduced ‘contact time’ as defined by the duration of digit contact with the food pellet before successful retrieval. After lesion the hand was severely impaired in all monkeys; this was followed by progressive functional recovery. Remarkably, anti-Nogo-A antibody-treated monkeys recovered faster and significantly better than control antibody-treated monkeys, considering both the score for vertical and horizontal slots (Mann–Whitney test: P = 0.05 and 0.035, respectively) and the contact time (P = 0.008 and 0.005, respectively). Detailed analysis of the lesions excluded the possibility that this conclusion may have been caused by differences in lesion properties between the two groups of monkeys.
Highlights
In the adult mammalian central nervous system, lesions lead to persistent motor and sensory deficits and the severity of these deficits is often correlated with the location and size of the injury
In three of thirteen monkeys (Mk-CS, Mk-CC and Mk-AF), an intracortical microstimulation mapping of the M1 hand area was conducted on both hemispheres (Schmidlin et al, 2004, 2005), a procedure which may have partly reduced the recovery of their manual dexterity
Our initial statistical comparison of score between the two groups of monkeys was univariate, taking into account only the score without considering the variability of the extent of the lesion (Freund et al, 2006a)
Summary
In the adult mammalian central nervous system, lesions lead to persistent motor and sensory deficits and the severity of these deficits is often correlated with the location and size of the injury. Expanding upon data previously reported in rats, adult nonhuman primates were subjected to spinal cord injury and treated with a neutralizing antibody against Nogo-A They exhibited enhanced functional recovery, in parallel with increased sprouting in the CS tract, both caudal and rostral to the lesion site (in macaques: Freund et al, 2006a, 2007; see Fouad et al, 2004 for anti-Nogo-A-enhanced regeneration of CS tract in marmosets subjected to spinal cord lesion). These studies emphasize the feasibility and importance of using adult nonhuman primate models of spinal cord injury as a precursor to clinical trials in humans (Lemon & Griffiths, 2005; Courtine et al, 2007), especially considering the more similar organization of the CS system between nonhuman primates and humans (as compared to rats; see Nudo & Frost, 2006)
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