Abstract
In spinal cord injured adult mammals, neutralizing the neurite growth inhibitor Nogo‐A with antibodies promotes axonal regeneration and functional recovery, although axonal regeneration is limited in length. Neurotrophic factors such as BDNF stimulate neurite outgrowth and protect axotomized neurons. Can the effects obtained by neutralizing Nogo‐A, inducing an environment favorable for axonal sprouting, be strengthened by adding BDNF? A unilateral incomplete hemicord lesion at C7 level interrupted the main corticospinal component in three groups of adult macaque monkeys: control monkeys (n = 6), anti‐Nogo‐A antibody‐treated monkeys (n = 7), and anti‐Nogo‐A antibody and BDNF‐treated monkeys (n = 5). The functional recovery of manual dexterity was significantly different between the 3 groups of monkeys, the lowest in the control group. Whereas the anti‐Nogo‐A antibody‐treated animals returned to manual dexterity performances close to prelesion ones, irrespective of lesion size, both the control and the anti‐Nogo‐A/BDNF animals presented a limited functional recovery. In the control group, the limited spontaneous functional recovery depended on lesion size, a dependence absent in the combined treatment group (anti‐Nogo‐A antibody and BDNF). The functional recovery in the latter group was significantly lower than in anti‐Nogo‐A antibody‐treated monkeys, although the lesion was larger in three out of the five monkeys in the combined treatment group.
Highlights
In adult mammals, following spinal cord injury (SCI), transected axons do not regenerate, resulting in persistent and often severe motor and sensory deficits
The aim of the present study was to investigate, in adult macaque monkeys subjected to SCI at cervical level whether the addition of BDNF can enhance the extent of functional recovery of manual dexterity prompted by anti‐Nogo‐A antibody treatment administered alone
The present report is an extension of a previous study,[8] which demonstrated that an intrathecal treatment with the anti‐Nogo‐A antibody led to enhanced functional recov‐ ery of manual dexterity in adult macaques, as compared to control antibody‐treated monkeys, following hemisection of the cervical spinal cord
Summary
In adult mammals, following spinal cord injury (SCI), transected axons do not regenerate, resulting in persistent and often severe motor and sensory deficits. The aim of the present study was to investigate, in adult macaque monkeys subjected to SCI at cervical level whether the addition of BDNF can enhance the extent of functional recovery of manual dexterity prompted by anti‐Nogo‐A antibody treatment administered alone (see Appendix S1 for rationale). In our model of SCI in macaques, anti‐Nogo‐A antibody treatment administered alone yielded nearly complete functional recovery,[6,8] preventing to detect an improvement of functional recovery if BDNF is added to the treatment (ceiling effect) For this reason, in the present study, the strategy was to generate larger size SCI in order to produce a more extensive and extra deficit of manual dexterity. The alternative hypothesis, considering some reported ad‐ verse effects of combining the 2 treatments (see above), is that functional recovery from SCI is reduced as compared to single anti‐Nogo‐A antibody treatment, especially if the cervical lesion is larger than in monkeys treated with anti‐Nogo‐A antibody alone
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