Reticulospinal and corticospinal axon regeneration after complete spinal cord injury


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A Master's thesis.
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Master (thesis) (master)
Reticulospinal and corticospinal axon regeneration after complete spinal cord injury
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Université de Lausanne, Faculté de biologie et médecine
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Neuroprosthetic rehabilitation demonstrated that significant functional benefit could be
achieved with lumbosacral neuromodulation in both human and animal models of spinal
cord injury. It promoted the recovery of voluntary leg movements through the
reorganization of residual reticulospinal and propriospinal projections pathways.
However, in case of complete spinal cord injuries (SCI), which isolate the circuits under
the lesion from any supraspinal control, the outcome of neuroprosthetic rehabilitation is
still not sufficient. Indeed, it will require the restoration of robust regrowth and
sprouting of several types of axons across the injury. Axons fail to regrow across spinal
lesions because of different inhibitory mechanisms. It has been demonstrated that this
spontaneous axon regeneration failure can be reversed by i) stimulating the neuronal
intrinsic growth capacity using viral technology, ii) remodeling the lesion core with
growth factors, in order to create a more permissive environment, and iii) guiding axons
with chemo-attractive molecules across and beyond the SCI site. It was thus
demonstrated that propriospinal axons are able to regrow and build a robust
descending bridge across complete SCIs when the needed facilitators are provided.
However, this robust propriospinal bridging failed to promote functional recovery by
itself. It might be explained by an insufficient descending motor control partly
supported by other systems such as the reticulospinal tract (RtST) and the corticospinal
tract (CST). Therefore we wanted to study the regenerative potential of the RtST and
CST pathways. The RtST arises from the brainstem and reaches for the spinal cord
acting as relay for descending motor cortical commands. The CST is the main descending
motor cortical command arising from the primary motor cortex.
In the present study, we applied the same strategy to enhance sprouting and regrowth
of reticulospinal and corticospinal neurons across anatomically complete SCI. We first
activated the neuronal intrinsic growth capacity of both tracts using viral technology.
The lesion environment was then remodeled with growth factors, delivered using a
biocompatible hydrogel. Finally, we established chemical axon guidance using chemoattractant
molecules. These interventions were delivered with a spatiotemporal profile
corresponding to the axon growth sequence during development. We did not obtain any
CST regeneration, due to the severe crush injury model inducing extensive CST axons
degeneration probably caused by ischemic phenomenon. Regarding the RtST, we
obtained significant reticulospinal regeneration into the lesion core with some fibers
growing across the lesion reaching the healthy caudal tissue. This regeneration
remained limited though as compared with the propriospinal results indicating the
importance of identifying complementary strategies to increase the density of the
regenerated tract and to attract the axons in the healthy tissue below the SCI. Our
ultimate goal is to restore anatomical communications across complete SCI and promote
their functional integration using neuroprosthetic rehabilitation program.
Spinal cord injury, Reticulospinal tract, Corticospinal tract, Axon regeneration, Neuronal growth program
Create date
03/09/2019 10:03
Last modification date
08/09/2020 6:08
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