RESUMEN

Motor cortical areas from both hemispheres play a role during functional recovery after a unilateral spinal cord injury (SCI). However, little is known about the morphologic and phenotypical differences that a SCI could trigger in corticospinal (CS) neurons of the ipsilesional and contralesional hemisphere. Using an SMI-32 antibody which specifically labeled pyramidal neurons in cortical Layers V, we investigated the impact of a unilateral cervical cord lesion on the rostral part (F6) and caudal part (F3) of the supplementary motor area (SMA) in both hemispheres of eight adult macaque monkeys compared with four intact control monkeys. We observed in F3 (but not in F6) interindividual variable and adaptive interhemispheric asymmetries of SMI-32-positive Layer V neuronal density and dendritic arborization, which are strongly correlated with the extent of the SCI as well as the duration of functional recovery, but not with the extent (percentage) of functional recovery.

Asunto(s)

Corteza Motora , Traumatismos de la Médula Espinal , Animales , Haplorrinos , Macaca , Recuperación de la Función

RESUMEN

A restricted lesion of the hand area in the primary motor cortex (M1) leads to a deficit of contralesional manual dexterity, followed by an incomplete functional recovery, accompanied by plastic changes in M1 itself and in other cortical areas on both hemispheres. Using the marker SMI-32 specific to pyramidal neurons in cortical layers III and V, we investigated the impact of a focal unilateral M1 lesion (hand representation) on the rostral part (F6) and caudal part (F3) of the supplementary motor area (SMA) in both hemispheres in nine adult macaque monkeys compared with four intact control monkeys. The M1 lesion induced a consistent interhemispheric asymmetry in density of SMI-32-positive neurons in F3 layer V (statistically significant in 8 of 9 lesioned monkeys), highly correlated with the lesion volume and with the duration of functional recovery, but not with the extent of functional recovery itself. Such interhemispheric asymmetry was neither present in the intact monkeys, as expected, nor in F6 in all monkeys. In addition, the M1 lesion also impacted on the basal dendritic arborization of F3 layer V neurons. Neuronal density was clearly less affected by the M1 lesion in F3 layer III compared with layer V. We interpret the remote effect of M1 lesion onto the density of SMI-32-positive neurons and dendritic arborization in the SMAs bilaterally as the consequence of multiple factors, such as changes of connectivity, diaschisis and various mechanisms involved in cortical plasticity underlying the functional recovery from the M1 lesion.SIGNIFICANCE STATEMENT The motor system of macaque monkeys, in addition to be similarly organized as in humans, is a good candidate to study the impact of a focal lesion of the main contributor to voluntary movements, the primary motor cortex (M1), on non-primary motor cortical areas also involved in manual dexterity, both at behavioral and structural levels. Our results show that a unilateral permanent lesion of M1 hand area in nine monkeys affects the interhemispheric balance of the number of SMI-32-positive pyramidal neurons in the cortical layer V of the supplementary motor area, in a way strongly correlated to the lesion volume and duration of the incomplete functional recovery.

Asunto(s)

Lateralidad Funcional/fisiología , Corteza Motora/patología , Corteza Motora/fisiología , Destreza Motora/fisiología , Desempeño Psicomotor/fisiología , Factores de Edad , Animales , Craneotomía/métodos , Macaca fascicularis , Macaca mulatta , Corteza Motora/citología

RESUMEN

In the context of an autologous adult neural cell ecosystem (ANCE) transplantation study, four intact adult female macaque monkeys underwent a unilateral biopsy of the dorsolateral prefrontal cortex (dlPFC) to provide the cellular material needed to obtain the ANCE. Monkeys were previously trained to perform quantitative motor (manual dexterity) tasks, namely, the "modified-Brinkman board" task and the "reach and grasp drawer" task. The aim of the present study was to extend preliminary data on the role of the prefrontal cortex in motor habit and test the hypothesis that dlPFC contributes to predict the grip force required when a precise level of force to be generated is known beforehand. As expected for a small dlPFC biopsy, neither the motor performance (score) nor the spatiotemporal motor sequences were affected in the "modified-Brinkman board" task, whereas significant changes (mainly decreases) in the maximal grip force (force applied on the drawer knob) were observed in the "reach and grasp drawer" task. The present data in the macaque monkey related to the prediction of grip force are well in line with the previous fMRI data reported for human subjects. Moreover, the ANCE transplantation strategy (in the case of stroke or Parkinson's disease) based on biopsy in dlPFC does not generate unwanted motor consequences, at least as far as motor habit and motor performance are concerned in the context of a sequential grasping a small objects, which does not require the development of significant force levels.

Asunto(s)

Habituación Psicofisiológica/fisiología , Fuerza de la Mano/fisiología , Actividad Motora/fisiología , Corteza Prefrontal/fisiología , Desempeño Psicomotor/fisiología , Animales , Femenino , Lateralidad Funcional , Procesamiento de Imagen Asistido por Computador , Macaca fascicularis , Imagen por Resonancia Magnética , Corteza Prefrontal/diagnóstico por imagen , Rango del Movimiento Articular/fisiología

RESUMEN

In adult macaque monkeys subjected to an incomplete spinal cord injury (SCI), corticospinal (CS) fibers are rarely observed to grow in the lesion territory. This situation is little affected by the application of an anti-Nogo-A antibody which otherwise fosters the growth of CS fibers rostrally and caudally to the lesion. However, when using the Sternberger monoclonal-incorporated antibody 32 (SMI-32), a marker detecting a non-phosphorylated neurofilament epitope, numerous SMI-32-positive (+) fibers were observed in the spinal lesion territory of 18 adult macaque monkeys; eight of these animals had received a control antibody infusion intrathecally for 1 month after the injury, five animals an anti-Nogo-A antibody, and five animals received an anti-Nogo-A antibody together with brain-derived neurotrophic factor (BDNF). These fibers occupied the whole dorso-ventral axis of the lesion site with a tendency to accumulate on the ventral side, and their trajectories were erratic. Most of these fibers (about 87%) were larger than 1.3 µm and densely SMI-32 (+) stained. In the undamaged spinal tissue, motoneurons form the only large population of SMI-32 (+) neurons which are densely stained and have large diameter axons. These data therefore suggest that a sizeable proportion of the fibers seen in the lesion territory originate from motoneurons, although fibers of other origins could also contribute. Neither the presence of the antibody neutralizing Nogo-A alone, nor the presence of the antibody neutralizing Nogo-A combined with BDNF influenced the number or the length of the SMI-32 (+) fibers in the spinal lesion area. In summary, our data show that after a spinal cord lesion in adult monkeys, the lesion site is colonized by fibers, a large portion of which presumably originate from motoneurons.

Asunto(s)

Proteínas de la Mielina/inmunología , Fibras Nerviosas/fisiología , Regeneración Nerviosa/fisiología , Recuperación de la Función/fisiología , Traumatismos de la Médula Espinal/patología , Animales , Anticuerpos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/uso terapéutico , Proteoglicanos Tipo Condroitín Sulfato/metabolismo , Modelos Animales de Enfermedad , Femenino , Inyecciones Espinales , Macaca , Masculino , Proteínas de la Mielina/metabolismo , Fibras Nerviosas/efectos de los fármacos , Regeneración Nerviosa/efectos de los fármacos , Proteínas de Neurofilamentos/metabolismo , Proteínas Nogo , Recuperación de la Función/efectos de los fármacos , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/fisiopatología

RESUMEN

The present study describes in primates the effects of a spinal cord injury on the number and size of the neurons in the magnocellular part of the red nucleus (RNm), the origin of the rubrospinal tract, and evaluates whether a neutralization of Nogo-A reduces the lesioned-induced degenerative processes observed in RNm. Two groups of monkeys were subjected to unilateral section of the spinal cord affecting the rubrospinal tract; one group was subsequently treated with an antibody neutralizing Nogo-A; the second group received a control antibody. Intact animals were also included in the study. Counting neurons stained with a monoclonal antibody recognizing non-phosphorylated epitopes on neurofilaments (SMI-32) indicated that their number in the contralesional RNm was consistently inferior to that in the ipsilesional RNm, in a proportion amounting up to 35%. The lesion also induced shrinkage of the soma of the neurons detected in the contralesional RNm. Infusing an anti-Nogo-A antibody at the site of the lesion did not increase the proportion of SMI-32 positive rubrospinal neurons in the contralesional RNm nor prevent shrinkage.

Asunto(s)

Anticuerpos Monoclonales/farmacología , Proteínas de la Mielina/antagonistas & inhibidores , Neuronas/patología , Tractos Piramidales/patología , Núcleo Rojo/patología , Traumatismos de la Médula Espinal/patología , Animales , Axotomía , Vértebras Cervicales , Lateralidad Funcional/fisiología , Humanos , Macaca , Proteínas de Neurofilamentos/efectos de los fármacos , Proteínas Nogo

RESUMEN

The effects of a unilateral interruption of the dorsolateral funiculus at cervical level on the survival of neurons in the motor cortex were investigated in macaque monkeys. The lesion was made on the left side at the transition region between the 7(th) and 8(th) cervical segments, above the motoneurons controlling hand muscles. As a result, the homolateral hand became paretic, although an incomplete recovery of manual dexterity took place during 2 months post-lesion. A quantitative anatomical assessment of pyramidal neurons in layer V was performed in the hindlimb area of the primary motor cortex and in the supplementary motor area (SMA proper). The pyramidal neurons were visualized using the marker SMI-32 and thus included the subpopulation of corticospinal neurons. These quantitative data demonstrated that the vast majority of the axotomized corticospinal (CS) neurons did not degenerate. Rather, their somata shrank, compared to the opposite hemisphere or to intact monkeys. This conclusion is in contrast to some previous studies in monkeys that argued for a substantial degeneration of motor cortex neurons as a result of transection of the corticospinal tract; yet in agreement with others that concluded the survival of most CS neurons. The survival of the majority of CS axotomized neurons is also consistent with the observation of numerous CS axons 1 mm above the cervical hemisection.

Asunto(s)

Corteza Motora/fisiopatología , Tractos Piramidales/lesiones , Tractos Piramidales/fisiopatología , Degeneración Retrógrada/fisiopatología , Traumatismos de la Médula Espinal/fisiopatología , Médula Espinal/fisiopatología , Animales , Anticuerpos , Axones/patología , Axones/fisiología , Axones/ultraestructura , Axotomía , Biomarcadores/metabolismo , Recuento de Células , Muerte Celular/fisiología , Tamaño de la Célula , Supervivencia Celular/fisiología , Vértebras Cervicales , Lateralidad Funcional/fisiología , Mano/inervación , Mano/fisiopatología , Macaca mulatta , Corteza Motora/patología , Neuronas Motoras/patología , Paresia/etiología , Paresia/patología , Paresia/fisiopatología , Células Piramidales/patología , Tractos Piramidales/patología , Recuperación de la Función/fisiología , Degeneración Retrógrada/etiología , Degeneración Retrógrada/patología , Médula Espinal/patología , Traumatismos de la Médula Espinal/patología , Factores de Tiempo

RESUMEN

We report the observation of the spatial decay of the long range surface plasmon mode using optical second harmonic generation. The surface wave is excited at 1.06 microm with prism coupling in a multilayer geometry consisting of a quartz crystal substrate, a thin silver film, and an index-matched liquid. From the asymmetry in the reflected second harmonic profile a decay length of 0.8 mm is determined. This value is a factor of 3 smaller than that predicted due to the effect of surface roughness scattering on the propagation of the long range surface plasmon mode.