Spinal Root Avulsion Injury Research Articles

Microtubule stabilization promoted axonal regeneration and functional recovery after spinal root avulsion.

A spinal root avulsion injury disconnects spinal roots with the spinal cord. The rampant motoneuron death, inhibitory CNS/PNS transitional zone (TZ) for axonal regrowth and limited regeneration speed together lead to motor dysfunction. Microtubules rearrange to assemble a new growth cone and disorganized microtubules underline regeneration failure. It has been shown that microtubule-stabilizing drug, Epothilone B, enhanced axonal regeneration and attenuated fibrotic scaring after spinal cord injury. Here, we are reporting that after spinal root avulsion+ re-implantation in adult rats, EpoB treatment improved motor functional recovery and potentiated electrical responses of motor units. It facilitated axons to cross the TZ and promoted more and bigger axons in the peripheral nerve. Neuromuscular junctions were reformed with better preserved postsynaptic structure, and muscle atrophy was prevented by EpoB administration. Our study showed that EpoB was a promising therapy for promoting axonal regeneration after peripheral nerve injury.

The Effects of Minocycline on Spinal Root Avulsion Injury in Rat Model.

The neuroprotective role of minocycline in the treatment of brachial plexus injury is controversial. To study the neuroprotective effect of minocycline via different routes in adult Sprague Dawley rats with brachial plexus injury. The C7 nerve roots of the animals were avulsed via an anterior extravertebral approach. Traction force was used to transect the ventral motor nerve roots at the preganglionic level. Intraperitoneal and intrathecal minocycline (50 mg/kg for the first week and 25 mg/kg for the second week) were administered to promote motor healing. The spinal cord was harvested six weeks after the injury, and structural changes following the avulsion injury and pharmacological intervention were analysed. Motor neuron death and microglial proliferation were observed after the administration of minocycline via two different routes (intraperitoneal and intrathecal) following traumatic avulsion injury of the ventral nerve root. The administration of intraperitoneal minocycline reduced the microglia count but increased the motor neuron count. Intrathecal minocycline also reduced the microglial count, with a greater reduction than in the intraperitoneal group, but it decreased the motor neuron count. Intraperitoneal minocycline increased motor neuron survival by inhibiting microglial proliferation following traumatic avulsion injury of the nerve root. The inhibitory effect was augmented by the use of intrathecal minocycline, in which the targeted drug delivery method increased the bioavailability of the therapeutic agent. However, motor neuron survival was impaired at a higher concentration of minocycline via the intrathecal route due to the more efficient method of drug delivery. Microglial suppression via minocycline can have both beneficial and damaging effects, with a moderate dose being beneficial as regards motor neuron survival but a higher dose proving neurotoxic due to impairment of the glial response and Wallerian degeneration, which is a pre-requisite for regeneration.

Vascular changes associated with spinal root avulsion injury

This paper has investigated the hypothesis that spinal root avulsion (SRA) injury produces alterations in blood flow that contribute to avulsion injury induced pain-like behaviour in rodents. Photoplethysmography (PPG) is an established way of assessing blood flow in the central nervous system (CNS) and laser Doppler flowmetry (LDF) is the most widely used technique for measuring tissue perfusion. Using an established model of SRA injury that produces mechanical hypersensitivity, the PPG and LDF signals were recorded in animals 2 weeks post-injury and compared to naive recordings. PPG and LDF measurements were assessed on the ipsilateral and contralateral sides of the spinal cord rostral and caudal to the avulsion injury and at the level of the injury. Two weeks after injury, a time when vascular blood vessel endothelial markers are known to be decreased, no significant changes were seen in the spinal cord blood flow (SCBF) above, at, or below the injury site or when comparing the ipsilateral vs. contralateral side. Assessment of oxygenation levels again revealed no significant differences between naive and spinal root injured animals along the rostrocaudal axis (i.e., above, at, and below the site of injury or its equivalent on the contralateral side). From these experiments it is concluded that SRA does not significantly alter blood flow or tissue oxygen levels and so ischemia may play a less prominent role in avulsion injury induced pain.

Ventral root re-implantation is better than peripheral nerve transplantation for motoneuron survival and regeneration after spinal root avulsion injury

BackgroundPeripheral nerve (PN) transplantation and ventral root implantation are the two common types of recovery operations to restore the connection between motoneurons and their target muscles after brachial plexus injury. Despite experience accumulated over the past decade, fundamental knowledge is still lacking concerning the efficacy of the two microsurgical interventions.MethodsThirty-eight adult female Sprague–Dawley rats were divided into 5 groups. Immediately following root avulsion, animals in the first group (n = 8) and the second group (n = 8) received PN graft and ventral root implantation respectively. The third group (n = 8) and the fourth group (n = 8) received PN graft and ventral root implantation respectively at one week after root avulsion. The fifth group received root avulsion only as control (n = 6). The survival and axonal regeneration of severed motoneurons were investigated at 6 weeks post-implantation.ResultsRe-implantation of ventral roots, both immediately after root avulsion and in delay, significantly increased the survival and regeneration of motoneurons in the avulsed segment of the spinal cord as compared with PN graft transplantation.ConclusionsThe ventral root re-implantation is a better surgical repairing procedure than PN graft transplantation for brachial plexus injury because of its easier manipulation for re-implanting avulsed ventral roots to the preferred site, less possibility of causing additional damage and better effects on motoneuron survival and axonal regeneration.

Neurotrophic Factor Treatment After Spinal Root Avulsion Injury

Spinal root avulsion injury causes motoneuron death and immediate loss of sensory and motor functions. Surgical intervention such as reimplantation of avulsed root is proven useful to restore neural circuitry of spinal cord and targeted muscles. Yet, additional strategies are required for faster and better functional recovery which is overall unsatisfactory. Accumulating evidences in animal studies, particularly in peripheral nerve injuries, demonstrated the effectiveness of neurotrophic factors in rescuing injured motoneurons and promoting axon regeneration. It is, however, important to recognize the differences between peripheral nerve and avulsion injury. In this review, we will briefly describe the changes in motoneurons after avulsion and provides a comprehensive list of neurotrophic factors which are known to exert neuroprotective effects on motoneurons. We will include recent studies on trophic factors for motoneuron survival and regeneration in peripheral nerve and avulsion injuries. We will also discuss the potential use of trophic factors in the context of avulsion injuries.

Restoration of sensory function and lack of long-term chronic pain syndromes after brachial plexus injury in human neonates.

Obstetric complications are a common cause of brachial plexus injuries in neonates. Failure to restore sensation leads to trophic injuries and poor limb function. It is not known whether the infant suffers chronic neuropathic or spinal cord root avulsion pain; in adults, chronic pain is usual after spinal root avulsion injuries, and this is often intractable. The plexus is repaired surgically in severe neonatal injures; if no spontaneous recovery has occurred by 3 months, and if neurophysiological investigations point to poor prognosis, then nerve trunk injures are grafted, while spinal cord root avulsion injuries are treated by transferring an intact neighbouring nerve (e.g. intercostal) to the distal stump of the damaged nerve, in an attempt to restore sensorimotor function. Using a range of non-invasive quantitative measures validated in adults, including mechanical, thermal and vibration perception thresholds, we have assessed for the first time sensory and cholinergic sympathetic function in 24 patients aged between 3 and 23 years, who had suffered severe brachial plexus injury at birth. While recovery of function after spinal root avulsion was related demonstrably to surgery, there were remarkable differences from adults, including excellent restoration of sensory function (to normal limits in all dermatomes for at least one modality in 16 out of 20 operated cases), and evidence of exquisite CNS plasticity, i.e. perfect localization of restored sensation in avulsed spinal root dermatomes, now presumably routed via nerves that had been transferred from a distant spinal region. Sensory recovery exceeded motor or cholinergic sympathetic recovery. There was no evidence of chronic pain behaviour or neuropathic syndromes, although pain was reported normally to external stimuli in unaffected regions. We propose that differences in neonates are related to later maturation of injured fibres, and that CNS plasticity may account for their lack of long-term chronic pain after spinal root avulsion injury.

Sodium channel beta1 and beta2 subunits parallel SNS/PN3 alpha-subunit changes in injured human sensory neurons.

Voltage-gated sodium channels consist of a pore-containing alpha-subunit and one or more auxiliary beta-subunits, which may modulate channel function. We previously demonstrated that sodium channel SNS/PN3 alpha-subunits were decreased in human sensory cell bodies after spinal root avulsion injury, and accumulated at injured nerve terminals in pain states. Using specific antibodies for immunohistochemistry, we have now detected sodium channel beta1 and beta2 subunits in sensory cell bodies within control human postmortem sensory ganglia (78% of small/medium (< or = 50 microm) and 68% of large (> or = 50 microm) cells); their changes in cervical sensory ganglia after avulsion injury paralleled those described for SNS/PN3 alpha-subunits. Our results suggest that alpha- and beta-subunits share common regulatory mechanisms, but present distinct targets for novel analgesics.