Anti‐Nogo‐A antibody treatment promotes recovery of manual dexterity after unilateral cervical lesion in adult primates – re‐examination and extension of behavioral data

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 antiNogo-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.

Representation of motor habit in a sequence of repetitive reach and grasp movements performed by macaque monkeys: Evidence for a contribution of the dorsolateral prefrontal cortex

“…For the present investigation, the motor performances at the modified Brinkman board task e static e and the rotating Brinkman board task e moving either clockwise or counterclockwise e were analysed. These two tasks were described in more detail in previous studies (Brinkman and Kuypers, 1973;Brinkman, 1984;Liu and Rouiller, 1999;Freund et al, 2009;Kaeser et al, 2010Kaeser et al, , 2011Schmidlin et al, 2011) and can be seen on the following web page: http://www.unifr.ch/neuro/rouiller/ research/brink.php. For each monkey, the performance of the left hand and the right hand were analysed separately.…”

Behavioral Assessment of Manual Dexterity in Non-Human Primates

“…For the CT, as an increase reflects a deficit, the functional recovery expressed in % is the ratio of the median pre-lesion CT (plateau) divided by the median post-lesion CT at plateau * 100. The effect of treatments post-lesion, demonstrated based on the test 1, are illustrated in detail in previous reports from this laboratory 14,15,17 . A further analysis may address the issue of the strategy, namely the temporal sequence of slots visited by the monkey (Figure 4B).…”

“…As previously reported1 4,15 , these tasks represent the behavioral basis to investigate whether the spontaneous recovery from a lesion of the cervical cord may be enhanced with a specific treatment aimed at promoting axonal regeneration (Figure 8).…”

“…The four behavioral tests illustrated above (Figure 1) have been used extensively in our laboratory in the context of studies aimed at investigating the functional recovery from lesion of the cervical spinal cord (Figure 2A) or of the motor cortex ( Figure 2B), in absence or in presence of a treatment applied to enhance the spontaneous recovery [12][13][14][15][16][17][18][19] .…”

Dynamic Motor Compensations with Permanent, Focal Loss of Forelimb Force after Cervical Spinal Cord Injury

“…10 The loss and recovery of forelimb motor function has been studied in several models of cervical SCI in rats, 4,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] cats, [28][29][30] and primates. [31][32][33][34][35] All those studies demonstrated some extent of spontaneous motor function recovery, albeit with persisting deficits as a consequence of interruption of descending axonal tracts or segmental neuronal death. Despite these advances, there is still a need of cervical SCI models in which motor performance is comprehensively assessed in the long term to determine the motor components that show recovery and to link the chronic deficits with the neuroanatomical damage.…”