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Commonalities of axonal repair: understanding tract diversities & molecules involvment
Commonalities of axonal repair: understanding tract diversities & molecules involvment
There was in 2019 in the USA alone over 17 000 new cases of spinal cord injury and close to 300 000 patients in total. This life-threatening condition isn’t only traumatic and devastating for patients and their family, it is as well an enormous financial burden. Patients suffering spinal cord injury will lose the ability to move and feel below the level of the injury, making them either paraplegic or tetraplegic. Complete lesions, where no tissue is spared will impair the patient for life with no chance of recovery without medical intervention. Even if incomplete lesions leave the possibility of some level of recovery, the path is long and sometimes unsuccessful. This recovery was shown to rely on remodeling of cut axons away from the scar tissue in both motor and sensory systems. In order to reach recovery, the cut axons will have to sprout and reach a suitable target, that will then convey the inputs previously lost. The motor pathways have been studied for decades because of their prevalence and importance in injured patients, but always more reports inform on the necessity to recover both motor and sensory inputs in order to regain full motricity. The purpose of this thesis was to look how sensory axons remodel following dorsal column lesion and if, like in the motor system, formation of a detour circuit allowed functional recovery. First, we investigated how DRG axons remodel following dorsal column lesion and observed significant increase in DRG sprouting in the grey matter of the spinal cord 3 weeks after injury persisting at 12 weeks. When we looked at the localization of DRG collaterals, we saw an increase of boutons in the dorsal and ventral layers of the spinal cord, leading to the search and discovery of DRG neurons’ target: the cuneate nucleus projecting neurons. The study of contacts between DRG and cuneate nucleus projecting neurons showed an increase of contacts 3 weeks post lesion of DRG collaterals on cuneate nucleus projecting neurons as well as an overall increase of number of contacts onto single neurons at both 3 and 12 weeks. Then, the characterization of these relay neurons presented new insights on possible molecular cues implicated in recovery in sensory tracts as an increase in contact onto parvalbumine and glutamate expressing cuneate nucleus neurons was found. Finally, study of the spontaneous recovery using behavioral testing showed recovery of proprioceptive inputs 3 weeks after dorsal column lesion, validated by a relesion experiment. To summarize, with this thesis, we aimed to better understand the detour circuit formation in the sensory system following dorsal column lesion. The characterization of the relay neurons might allow to find a therapeutic target for patients lacking sensory recovery.
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Granier, Charlène
2021
English
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Granier, Charlène (2021): Commonalities of axonal repair: understanding tract diversities & molecules involvment. Dissertation, LMU München: Graduate School of Systemic Neurosciences (GSN)
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Abstract

There was in 2019 in the USA alone over 17 000 new cases of spinal cord injury and close to 300 000 patients in total. This life-threatening condition isn’t only traumatic and devastating for patients and their family, it is as well an enormous financial burden. Patients suffering spinal cord injury will lose the ability to move and feel below the level of the injury, making them either paraplegic or tetraplegic. Complete lesions, where no tissue is spared will impair the patient for life with no chance of recovery without medical intervention. Even if incomplete lesions leave the possibility of some level of recovery, the path is long and sometimes unsuccessful. This recovery was shown to rely on remodeling of cut axons away from the scar tissue in both motor and sensory systems. In order to reach recovery, the cut axons will have to sprout and reach a suitable target, that will then convey the inputs previously lost. The motor pathways have been studied for decades because of their prevalence and importance in injured patients, but always more reports inform on the necessity to recover both motor and sensory inputs in order to regain full motricity. The purpose of this thesis was to look how sensory axons remodel following dorsal column lesion and if, like in the motor system, formation of a detour circuit allowed functional recovery. First, we investigated how DRG axons remodel following dorsal column lesion and observed significant increase in DRG sprouting in the grey matter of the spinal cord 3 weeks after injury persisting at 12 weeks. When we looked at the localization of DRG collaterals, we saw an increase of boutons in the dorsal and ventral layers of the spinal cord, leading to the search and discovery of DRG neurons’ target: the cuneate nucleus projecting neurons. The study of contacts between DRG and cuneate nucleus projecting neurons showed an increase of contacts 3 weeks post lesion of DRG collaterals on cuneate nucleus projecting neurons as well as an overall increase of number of contacts onto single neurons at both 3 and 12 weeks. Then, the characterization of these relay neurons presented new insights on possible molecular cues implicated in recovery in sensory tracts as an increase in contact onto parvalbumine and glutamate expressing cuneate nucleus neurons was found. Finally, study of the spontaneous recovery using behavioral testing showed recovery of proprioceptive inputs 3 weeks after dorsal column lesion, validated by a relesion experiment. To summarize, with this thesis, we aimed to better understand the detour circuit formation in the sensory system following dorsal column lesion. The characterization of the relay neurons might allow to find a therapeutic target for patients lacking sensory recovery.