(C) Representation of the dorsal column fasciculi and the consecutive steps for image analyses using imageJ software

(C) Representation of the dorsal column fasciculi and the consecutive steps for image analyses using imageJ software. Abbreviations: Cu.N., cuneate nucleus; DCN, dorsal column nuclei; Gr.N., gracile nucleus; T.Cu., tractus cuneatus; T.Gr., tractus gracilis. Secondly, the aim was to verify that this same C7-C8 spinal cord hemi-section does Brucine not affect the primary sensory axons terminating in the cuneate nucleus, originating from the ipsilesional thumb and index finger (Figure 1). dorsal funiculus, resulted in an ipsilesional lower extent of the inputs from the toes in the gracile nuclei, not modified by the combined treatment. SCI at C7-C8 level did not affect the bilateral balance of primary inputs to the cuneate nuclei, neither in absence nor in presence of the combined treatment. MCI targeted to the hand area did not impact on the primary inputs to the cuneate nuclei in 2 untreated monkeys. After MCI, the administration of anti-Nogo-A antibody resulted in a slight bilateral asymmetrical extent of cutaneous inputs to the cuneate nuclei, with a larger extent ipsilesionally. Overall, remote effects following MCI or SCI have not been observed at the DCN level, except possibly after MCI and anti-Nogo-A antibody treatment. strong class=”kwd-title” Keywords: Spinal cord injury, motor cortex lesion, brain-derived neurotrophic factor, Nogo-A antibody therapy, motor control, transganglionic anterograde tracing Significance Statement Primary cutaneous inputs from toes to the gracile nuclei were reduced ipsilaterally after C7-C8 hemisection. No effect on the primary cutaneous inputs from fingers to the cuneate nuclei after C7-C8 hemisection or unilateral motor cortex lesions. Treatment combining BDNF and anti-Nogo-A antibody did not interfere with the primary cutaneous inputs after C7-C8 hemisection. Slightly larger Brucine extent of ipsilesional cutaneous inputs to the cuneate nuclei after motor cortex lesion and anti-Nogo-A Brucine antibody treatment. Introduction Anatomical reorganizations of the somatosensory pathways resulting from motor system injury remain largely unexplored. Rare studies have reported the possible effects of motor system lesion around the somatosensory system.1,2 As the first relay of the ascending sensory inputs, the dorsal column nuclei (DCN) might be sensitive to remote effects following injury affecting the motor system at the cortical or at the spinal cord level. Due to the extent of the cortical and subcortical interconnections, remote effects in other distant areas can be observed following restricted cortical injury,3 possibly in line with the concept of connectional diaschisis.4,5 Although the cortico-nuclear projections to DCN originate predominantly from the somatosensory cortex,6 anatomical and electrophysiological studies have evidenced the existence of projections from the motor cortex and particularly from the primary motor cortex (M1).6-10 Considering not only the cortical contingent, injury of the motor system at the cortical or at the spinal cord level might result in connectional changes at a distance from the incoming cutaneous inputs to the cuneate nucleus originating from the hand behaviorally affected by the lesion. Following injury of the central nervous system, 2 main approaches have been proposed to promote axonal regrowth and/or sprouting, either by making the environment permissive to axonal growth or by increasing the level of neurotrophic molecules promoting intrinsic axonal growth. First, based on the characterization of the highly inhibitory properties of the Nogo-A protein in the spinal cord myelin sheath,11 numerous studies showed the beneficial potentials of blocking this molecule and its signaling pathways to promote functional recovery and neural repair in case of spinal cord injury or stroke,12-18 Treatment with an antibody against Nogo-A promotes functional recovery from spinal cord or motor cortex injuries, enhancing sprouting of corticospinal19 and lesioned sensory axons20 promoting reorganization of territories close and distant to the lesion site in rodent,21-25 in non-human primate19,26-32 and potentially in human. 33 This anti-Nogo-A antibody treatment has also induced more remote effects, such as the regeneration of lesioned pyramidal projections to the sensory DCN in the brainstem after pyramidotomy in rodent.22 Secondly, there has been a large interest in the regeneration promoting role of neurotrophic factors, such as brain derived neurotrophic factor (BDNF),34 in case of central nervous system injury. BDNF exhibits a promoting role in the survival of axotomized axons, regeneration of injured fibers, Rabbit Polyclonal to Actin-pan plasticity, myelination, and functional recovery.35,36 It has been highlighted that BDNF can potentiate axonal regrowth alone37 and also in combination with different molecules.38 It currently appears that optimal regeneration may well require the application of combined therapies involving several complementary molecules.39 In the context of SCI,.