Increased target reinnervation by rescued cervical motoneurons after ventral root avulsion the effects of spinal cord-brachialis plexus reconnection and riluzole treatment /
Although adult motoneurons do not die if their axons are injured at some distance from the cell body, they are vulnerable to injury inflicted on the axons close to the cell body. Ventral root avulsion injury induces death of the vast majority of the affected adult motoneurons. However, some of these...
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| További közreműködők: | |
| Dokumentumtípus: | Disszertáció |
| Megjelent: |
2019-06-24
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| Kulcsszavak: | avulsion; delayed nerve grafting; motoneuron; reinnervation; riluzole; ventral root |
| Tárgyszavak: | |
| doi: | 10.14232/phd.10083 |
| mtmt: | 31267811 |
| Online Access: | http://doktori.ek.szte.hu/10083 |
| Tartalmi kivonat: | Although adult motoneurons do not die if their axons are injured at some distance from the cell body, they are vulnerable to injury inflicted on the axons close to the cell body. Ventral root avulsion injury induces death of the vast majority of the affected adult motoneurons. However, some of these cells can be rescued if the avulsed ventral root or a peripheral nerve graft is inserted into the spinal cord. The freshly injured axons of the motoneurons can enter this conduit and are able to grow along the way to the muscles originally innervated by the damaged motoneurons. The neuroprotective effect of riluzole has also been previously proven on the injured motoneurons: they can be rescued even if they have no possibility to regenerate their axons. Here we investigated the strategies that could be used to rescue injured motoneurons and compared their effects. The cervical 7th ventral root (C7) was avulsed and several therapeutic approaches were applied to induce the survival and regeneration of injured motoneurons. Avulsion of the root without reimplantation resulted in very low numbers of surviving motoneurons (65 ± 7.5 SEM), while treatment of the injured motoneurons with riluzole, a potent presynaptic glutamate release inhibitor resulted in significantly higher numbers of surviving motoneurons (637 ± 25.5 SEM). When the C7 ventral root was reimplanted or a peripheral nerve implant was used to guide the regenerating axons to a muscle considerable numbers of motoneurons sent their axons into the vacated endoneural sheaths (211 ± 14.8 SEM and 274 ± 27.8 SEM, respectively). Much greater numbers of axons regenerated when reimplantation was followed by riluzole treatment (573 ± 8.6 SEM). Avulsion and immediate reconnection of the motoneuron pool to the spinal nerve resulted in moderate reinnervation of the spinal nerve (281± 23 SEM retrogradely labelled motoneurons), while treatment of the injured motoneurons with riluzole yielded considerably higher numbers of reinnervating motoneurons (548± 18 SEM). The clinical relevance of our study is given by the brachial plexus injuries that involve the complete or partial avulsion of one or more cervical ventral roots. These injuries can be treated successfully only if satisfactory numbers of motoneurons remain alive following such an injury at the time of reconstructive surgery. In order to that we designed the next step in our study to investigate the capacity of injured motoneurons rescued by riluzole pretreatment to reinnervate denervated forelimb muscles in a model where surgical reconnection with a peripheral nerve graft between the affected spinal cord segment and the C7 spinal nerve was established immediately or with 1 and 3-week-delay after avulsion. Reconnection of the motor pool with the C7 spinal nerve with 1-week-delay allowed fewer motor axons to reinnervate their targets in control and riluzole-treated animals (159± 21 vs 395 ± 16 SEM). A clinically relevant 3-week-delay in reconnection further reduced the number of reinnervating motoneurons (76±22 SEM), but riluzole pretreatment still enabled a significant number of rescued motoneurons (396±17 SEM) to regenerate their axons into the C7 spinal nerve. These results show that adult motoneurons damaged by a brachial plexus injury can be rescued by riluzole treatment even if they cannot regenerate their axons. Reinnervation of the peripheral targets can also be achieved by providing a peripheral conduit for the motoneurons and the extent of reinnervation can be further improved with riluzole treatment. Motoneurons rescued by riluzole are able to reinnervate their targets even if they are provided with a conduit several weeks after the primary injury. This finding suggests that rescuing injured motoneurons with riluzole in patients who suffered a brachial plexus avulsion injury may provide an available pool of surviving motoneurons for late reconnection/reimplantation surgeries. Amennyiben egy motonueuron axonja a sejttestől távol sérül azt a motoneuron túléli, a sejttesthez közeli sérülések azonban a neuron pusztulását okozzák. A gerincvelő mellső gyökerének kitépése - avulziója - az érintett motoneuronok nagy többségének pusztulásával jár. Jelen munka során meg kívántuk határozni a cervikális gerinvelői gyök avulzióját követően károsodott motoneuronok túlélésének és különbőző vezetőcsatornákba történő regenerációjának feltételeit, az avulziót követően azon riluzollal kezelt motoneuronok számát, melyek célhoz vezető csatorna hiányában is hosszú távon túlélhetnek illetve azt, hogy avulziót követően egy vagy három hetes késést követő perifériás ideg graft - mint vezetőcsatorna - beültetése esetén a riluzollal megmentett C7 szegmentumban lévő motoneuronok képesek-e morfológiailag és funkcionálisan is sikeresen reinnerválni a plexus brachiálist és a denervált izmokat. A tanulmányban bizonyítottuk, hogy a gerincvelői gyök avulzióját követően pusztulásra ítélt motoneuronok megmenthetők. A károsodott neuronok sejthalála megelőzhető riluzollal akkor is, ha a kiszakított gyökér reimplantációjára nem kerül sor, reimplantáció esetén pedig a megmentett motoneuronok képesek axonregenerációra a reimplantált gyökéren keresztül |
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