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Motor cortex electrical stimulation augments sprouting of the corticospinal tract and promotes recovery of motor function.

Carmel JB, Martin JH - Front Integr Neurosci (2014)

Bottom Line: Reversible inactivation of the stimulated motor cortex reinstated the impairment demonstrating the importance of the stimulated system to recovery.Motor cortex electrical stimulation is an effective approach to promote spouting of spared CST axons.By optimizing activity-dependent sprouting in animals, we could have an approach that can be translated to the human for evaluation with minimal delay.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Weill Cornell Medical College New York, NY, USA ; Department of Pediatrics, Weill Cornell Medical College New York, NY, USA ; Brain and Mind Research Institute, Weill Cornell Medical College New York, NY, USA ; Burke Medical Research Institute White Plains, NY, USA.

ABSTRACT
The corticospinal system-with its direct spinal pathway, the corticospinal tract (CST) - is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout, and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST sprouting from the unaffected hemisphere. We discovered that 10 days of electrical stimulation of either the spared CST or motor cortex induces CST axon sprouting that partially reconstructs the lost CST. Stimulation also leads to sprouting of the cortical projection to the magnocellular red nucleus, where the rubrospinal tract originates. Coordinated outgrowth of the CST and cortical projections to the red nucleus could support partial re-establishment of motor systems connections to the denervated spinal motor circuits. Stimulation restores skilled motor function in our animal model. Lesioned animals have a persistent forelimb deficit contralateral to pyramidotomy in the horizontal ladder task. Rats that received motor cortex stimulation either after acute or chronic injury showed a significant functional improvement that brought error rate to pre-lesion control levels. Reversible inactivation of the stimulated motor cortex reinstated the impairment demonstrating the importance of the stimulated system to recovery. Motor cortex electrical stimulation is an effective approach to promote spouting of spared CST axons. By optimizing activity-dependent sprouting in animals, we could have an approach that can be translated to the human for evaluation with minimal delay.

No MeSH data available.


Related in: MedlinePlus

Motor cortex stimulation causes robust outgrowth to the magnocellular red nucleus. Heatmaps showing corticorubral axon density in the magnocellular red nucleus after injury alone (A) and injury plus stimulation (B). Color scales apply to both (A,B). Note the axon length scales are different on the two sides to show the full range on each side. (C) Schematic organization of corticorubral system and stimulation. Outgrowth to the contralateral nucleus (right) could improve motor control on the impaired side through the re-crossed rubrospinal tract. Modified from Carmel et al. (2013).
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Figure 4: Motor cortex stimulation causes robust outgrowth to the magnocellular red nucleus. Heatmaps showing corticorubral axon density in the magnocellular red nucleus after injury alone (A) and injury plus stimulation (B). Color scales apply to both (A,B). Note the axon length scales are different on the two sides to show the full range on each side. (C) Schematic organization of corticorubral system and stimulation. Outgrowth to the contralateral nucleus (right) could improve motor control on the impaired side through the re-crossed rubrospinal tract. Modified from Carmel et al. (2013).

Mentions: We also tested the effects of cortical stimulation on outgrowth to important brain stem targets. We were particularly interested in determining if motor cortex stimulation augmented corticorubral outgrowth into the magnocellular red nucleus, which gives rise to the rubrospinal tract (see Figure 4C). Like the spinal cord, motor cortex stimulation produced massive (3- to 5-fold) increase in axon density (Figures 4A and 4B). In addition, we observed a selective increase in the density of corticorubral axon terminations in the presumed forelimb region of the contralateral magnocellular red nucleus (Figure 4B; arrow), which projects to the affected side of the spinal cord. Thus, coordinated outgrowth in the spinal cord and red nucleus could support partial re-establishment of motor systems connections to the denervated spinal motor circuits. Selective inactivation of each of these pathways will be important to determine the relative contribution of each to the reparative effects of motor cortex stimulation.


Motor cortex electrical stimulation augments sprouting of the corticospinal tract and promotes recovery of motor function.

Carmel JB, Martin JH - Front Integr Neurosci (2014)

Motor cortex stimulation causes robust outgrowth to the magnocellular red nucleus. Heatmaps showing corticorubral axon density in the magnocellular red nucleus after injury alone (A) and injury plus stimulation (B). Color scales apply to both (A,B). Note the axon length scales are different on the two sides to show the full range on each side. (C) Schematic organization of corticorubral system and stimulation. Outgrowth to the contralateral nucleus (right) could improve motor control on the impaired side through the re-crossed rubrospinal tract. Modified from Carmel et al. (2013).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061747&req=5

Figure 4: Motor cortex stimulation causes robust outgrowth to the magnocellular red nucleus. Heatmaps showing corticorubral axon density in the magnocellular red nucleus after injury alone (A) and injury plus stimulation (B). Color scales apply to both (A,B). Note the axon length scales are different on the two sides to show the full range on each side. (C) Schematic organization of corticorubral system and stimulation. Outgrowth to the contralateral nucleus (right) could improve motor control on the impaired side through the re-crossed rubrospinal tract. Modified from Carmel et al. (2013).
Mentions: We also tested the effects of cortical stimulation on outgrowth to important brain stem targets. We were particularly interested in determining if motor cortex stimulation augmented corticorubral outgrowth into the magnocellular red nucleus, which gives rise to the rubrospinal tract (see Figure 4C). Like the spinal cord, motor cortex stimulation produced massive (3- to 5-fold) increase in axon density (Figures 4A and 4B). In addition, we observed a selective increase in the density of corticorubral axon terminations in the presumed forelimb region of the contralateral magnocellular red nucleus (Figure 4B; arrow), which projects to the affected side of the spinal cord. Thus, coordinated outgrowth in the spinal cord and red nucleus could support partial re-establishment of motor systems connections to the denervated spinal motor circuits. Selective inactivation of each of these pathways will be important to determine the relative contribution of each to the reparative effects of motor cortex stimulation.

Bottom Line: Reversible inactivation of the stimulated motor cortex reinstated the impairment demonstrating the importance of the stimulated system to recovery.Motor cortex electrical stimulation is an effective approach to promote spouting of spared CST axons.By optimizing activity-dependent sprouting in animals, we could have an approach that can be translated to the human for evaluation with minimal delay.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Weill Cornell Medical College New York, NY, USA ; Department of Pediatrics, Weill Cornell Medical College New York, NY, USA ; Brain and Mind Research Institute, Weill Cornell Medical College New York, NY, USA ; Burke Medical Research Institute White Plains, NY, USA.

ABSTRACT
The corticospinal system-with its direct spinal pathway, the corticospinal tract (CST) - is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout, and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST sprouting from the unaffected hemisphere. We discovered that 10 days of electrical stimulation of either the spared CST or motor cortex induces CST axon sprouting that partially reconstructs the lost CST. Stimulation also leads to sprouting of the cortical projection to the magnocellular red nucleus, where the rubrospinal tract originates. Coordinated outgrowth of the CST and cortical projections to the red nucleus could support partial re-establishment of motor systems connections to the denervated spinal motor circuits. Stimulation restores skilled motor function in our animal model. Lesioned animals have a persistent forelimb deficit contralateral to pyramidotomy in the horizontal ladder task. Rats that received motor cortex stimulation either after acute or chronic injury showed a significant functional improvement that brought error rate to pre-lesion control levels. Reversible inactivation of the stimulated motor cortex reinstated the impairment demonstrating the importance of the stimulated system to recovery. Motor cortex electrical stimulation is an effective approach to promote spouting of spared CST axons. By optimizing activity-dependent sprouting in animals, we could have an approach that can be translated to the human for evaluation with minimal delay.

No MeSH data available.


Related in: MedlinePlus