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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

Corticospinal tracts in the intact rodent and after unilateral pyramidotomy. (A) The corticospinal tracts originating in each hemisphere are shown, together with their callosal interconnections. The corticospinal tract axons descend in the dorsal, lateral, and ventral columns; most descend in the dorsal columns. Note that each hemisphere gives rise to dense contralateral and sparse ipsilateral spinal terminations. (B) Unilateral pyramidal tract lesion (pyramidotomy) eliminates all corticospinal tract axons from one hemisphere. What remains on the affected side are sparse terminations from the ipsilateral motor cortex.
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Figure 1: Corticospinal tracts in the intact rodent and after unilateral pyramidotomy. (A) The corticospinal tracts originating in each hemisphere are shown, together with their callosal interconnections. The corticospinal tract axons descend in the dorsal, lateral, and ventral columns; most descend in the dorsal columns. Note that each hemisphere gives rise to dense contralateral and sparse ipsilateral spinal terminations. (B) Unilateral pyramidal tract lesion (pyramidotomy) eliminates all corticospinal tract axons from one hemisphere. What remains on the affected side are sparse terminations from the ipsilateral motor cortex.

Mentions: The CST is a primarily crossed pathway, with 80–95% of the axons terminating on the contralateral side (Figure 1). The sparse ipsilateral termination largely reflects “double crossing” of CST axons, first in the pyramid and then in the segmental spinal cord, as well as some axons that descend ipsilaterally in the white matter (Rosenzweig et al., 2009). While sparse in the rodent (Brosamle and Schwab, 2000), the ipsilateral CST is more robust in primates (Rosenzweig et al., 2009), especially to the cervical spinal cord, suggesting that the ipsilateral CST is a good target for promoting its connections. The CST is the direct spinal path from motor cortex; there are also indirect paths that relay in brain stem motor centers, especially the red nucleus and the reticular formation (Jankowska and Edgley, 2006).


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

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

Corticospinal tracts in the intact rodent and after unilateral pyramidotomy. (A) The corticospinal tracts originating in each hemisphere are shown, together with their callosal interconnections. The corticospinal tract axons descend in the dorsal, lateral, and ventral columns; most descend in the dorsal columns. Note that each hemisphere gives rise to dense contralateral and sparse ipsilateral spinal terminations. (B) Unilateral pyramidal tract lesion (pyramidotomy) eliminates all corticospinal tract axons from one hemisphere. What remains on the affected side are sparse terminations from the ipsilateral motor cortex.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Corticospinal tracts in the intact rodent and after unilateral pyramidotomy. (A) The corticospinal tracts originating in each hemisphere are shown, together with their callosal interconnections. The corticospinal tract axons descend in the dorsal, lateral, and ventral columns; most descend in the dorsal columns. Note that each hemisphere gives rise to dense contralateral and sparse ipsilateral spinal terminations. (B) Unilateral pyramidal tract lesion (pyramidotomy) eliminates all corticospinal tract axons from one hemisphere. What remains on the affected side are sparse terminations from the ipsilateral motor cortex.
Mentions: The CST is a primarily crossed pathway, with 80–95% of the axons terminating on the contralateral side (Figure 1). The sparse ipsilateral termination largely reflects “double crossing” of CST axons, first in the pyramid and then in the segmental spinal cord, as well as some axons that descend ipsilaterally in the white matter (Rosenzweig et al., 2009). While sparse in the rodent (Brosamle and Schwab, 2000), the ipsilateral CST is more robust in primates (Rosenzweig et al., 2009), especially to the cervical spinal cord, suggesting that the ipsilateral CST is a good target for promoting its connections. The CST is the direct spinal path from motor cortex; there are also indirect paths that relay in brain stem motor centers, especially the red nucleus and the reticular formation (Jankowska and Edgley, 2006).

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