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 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

Increased Survival and Reinnervation of Cervical Motoneurons by Riluzole after Avulsion of the C7 Ventral Root

Although adult motoneurons do not die if their axons are injured at some distance from the cell body, they are unable to survive injury caused by ventral root avulsion. Some of the injured motoneurons can be rescued if the ventral root is re-inserted into the spinal cord. Brachial plexus injuries that involve the complete or partial avulsion of one or more cervical ventral roots can be treated successfully only if satisfactory numbers of motoneurons remain alive following such an injury at the time of reconstructive surgery. Here we investigated the various strategies that could be used to rescue injured rat cervical motoneurons. The seventh cervical ventral root (C7) was avulsed and various therapeutic approaches were applied to induce motoneuronal survival and regeneration. Avulsion of the root without reimplantation resulted in very low numbers of surviving motoneurons (65 ± 8 SEM), while treatment of the injured motoneurons with riluzole resulted in high numbers of surviving motoneurons (637 ± 26 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 regenerated their axons (211 ± 15 SEM and 274 ± 28 SEM, respectively). Much greater numbers of axons regenerated when reimplantation was followed by riluzole treatment (573 ± 9 SEM). These results show that injured adult motoneurons can be rescued by riluzole treatment, even if they cannot regenerate their axons. Reinnervation of the peripheral targets can also be further improved with riluzole treatment

Changing the treatment to reduce complication rate in open tibial fractures

Complications of open tibial fractures have been found to be very frequent after application of monotherapies (external fixator, plate, intramedullary nailing). The use of combined therapy has improved our results. We treated 658 patients for open tibial fractures over a course of 15 years. Plating was the method of treatment in the initial phase, and then external fixators and unreamed tibial nails (UTN) were used as a monotherapy. In the last ten years the option of a combined therapy was at our disposal, namely, changing the method of treatment. Monotherapy was performed in 352 cases, and 270 patients were treated in a combined manner. The rate of septic complications could be reduced with the combined therapy from 15.5% to 6.6%, the rate of bone healing disorders from 31.6% to 8.7%, and that of amputations from 4.9% to 0.7%. Elaboration of therapeutic tactics and their consistent application increases the healing potential of open tibial fractures. During this 15 year period, our therapeutic concepts have changed, whereby gradual, combined therapy models were initiated, increasing the advantages and decreasing the disadvantages of the different methods