Treatment Of Brachial Plexus Avulsion Research Articles

Microarray analysis of potential biomarkers of brachial plexus avulsion caused neuropathic pain in male rat

The present study aimed to investigate the expression of mRNA in the brachial plexus avulsion neuropathic pain model and analyze biological functions. Microarray mRNA assay and reverse transcriptase quantitative polymerase chain reaction (RT-PCR) were conducted. The whole blood was collected from two groups for Microarray mRNA analysis. The predicted mRNA targets were studied by gene ontology analysis and pathway analysis. We identified 3 targeted mRNAs, including PIK3CB, HRAS, and JUN. The results showed that PIK3CB, HRAS, and JUN gene expression was increased in the control group but decreased in the neuropathic pain group. These findings indicate that certain genes may be important biomarkers for the potential targets for the prevention and treatment of brachial plexus avulsion caused neuropathic pain.

Comparison of Different In Vivo Animal Models of Brachial Plexus Avulsion and Its Application in Pain Study.

Brachial plexus injuries (BPIs) are high-energy trauma that can result in serious functional problems in the affected upper extremities, and brachial plexus avulsion (BPA) could be considered the most severe type of them. The booming occurrence rate of BPA brings up devastating impact on patients' life. Complications of muscle atrophy, neuropathic pain, and denervation-associated psychological disorders are major challenges in the treatment of BPA. Animal models of BPA are good vehicles for this kind of research. Full understanding of the current in vivo BPA models, which could be classified into anterior approach avulsion, posterior approach avulsion, and closed approach avulsion groups, could help researchers select the appropriate type of models for their studies. Each group of the BPA model has its distinct merits and demerits. An ideal BPA model that can inherit the advantages and make up for the disadvantages is still required for further exploration.

Localised delivery of quercetin by thermo-sensitive PLGA-PEG-PLGA hydrogels for the treatment of brachial plexus avulsion

Accumulating evidence indicates that oxidative stress and inflammation are implicated in brachial plexus avulsion (BPA). Quercetin has anti-inflammatory, anti-oxidant, anti-apoptotic, and neuroprotective properties. This study investigated the therapeutic efficacy of a temperature-sensitive poly(D,L-lactide-co-glycolide)-poly(ethylene-glycol)-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel sustained-release system of quercetin in BPA. In situ injections of the hydrogel loaded with different concentrations of quercetin were conducted in a rat model of BPA. Significantly reduced reactive oxygen species and interleukin-6 levels in the injured spinal cord 24 h post-surgery, increased number of anterior horn motor and functional neurons in the spinal cord 6 weeks post-surgery, thickened biceps muscle fibres and enlarged endplate area with clear structure, reduced demyelinated peripheral nerves, and significantly increased Terzis grooming test scores were found in the groups with 50 or 100 mg/mL quercetin-loaded hydrogels compared with the control and blank hydrogel groups. In conclusion, the temperature-sensitive quercetin loaded PLGA-PEG-PLGA hydrogel sustained-release system can alleviate oxidative damage and inflammation in the spinal cord, increase neuron survival rate, and promote nerve regeneration and motor function recovery in rats with early BPA. The findings suggest that this drug-loaded hydrogel has potential applications in the clinical treatment of BPA.

Berberine enhances survival and axonal regeneration of motoneurons following spinal root avulsion and re-implantation in rats

Brachial plexus avulsion (BPA) occurs when the spinal nerve roots are pulled away from the surface of the spinal cord and disconnects neuronal cell body from its distal downstream axon, which induces massive motoneuron death, motor axon degeneration and de-innervation of targeted muscles, thereby resulting in permanent paralysis of motor functions in the upper limb. Avulsion injury triggers oxidative stress and intense local neuroinflammation at the lesioned site, leading to the death of most motoneurons. Berberine (BBR), a natural isoquinoline alkaloid derived from medicinal herbs of Berberis and Coptis species, has been reported to possess neuro-protective, anti-inflammatory and anti-oxidative effects in various animal models of central nervous system (CNS)-related disorders. In this study, we aimed to investigate the effect of BBR on motoneuron survival and axonal regeneration following spinal root avulsion plus re-implantation in rats. Our results indicated BBR significantly accelerated motor function recovery in the forelimb as revealed by the increased Terzis grooming test score, facilitated motor axon regeneration as evidenced by the elevated number of Fluoro-Gold-labeled and P75-positive regenerative motoneurons. The survival of motoneurons was notably promoted by BBR administration presented with boosted ChAT-immunopositive and neutral red-stained neurons. BBR treatment efficiently alleviated muscle atrophy, attenuated functional motor endplates loss in biceps and prevented the reduction of motor axons in the musculocutaneous nerve. Additionally, BBR treatment markedly mitigated the avulsion-induced neuroinflammation via inhibiting microglial and astroglial reactivity, up-regulated the expression of antioxidative indicator Cu/Zn SOD, and down-regulated the levels of nNOS, 3-NT, lipid peroxidation and NF-κB, as well as promoted SIRT1, PI3K and Akt activation. Collectively, BBR might be a promising therapy to assist re-implantation surgery for the treatment of BPA.

Collateral sprouting axons of end-to-side nerve coaptation in the avulsion of ventral branches of the C5-C6 spinal nerves in the brachial plexus.

This study assessed the collateral sprouting in avulsion of the ventral branches of the C5 and C6 spinal nerves treated by coaptation of these nerves to the C7 spinal nerve on the brachial plexus of rabbits. Thirty-six New Zealand rabbits were randomly divided into four groups: end-to-side coaptation (ESN) (n = 12), side-to-side coaptation (SSN) (n = 12), direct neurorrhaphy (end-to-end) (EEN) (n = 6) and no coaptation (n = 6). The operations were performed on the left brachial plexus. The contralateral, non-operated right brachial plexi were used as the control group. The groups were compared using morphological, electrophysiological and behavioral methods. The follow-up duration was 20 weeks. Significant differences were observed in all parameters when the experimental groups were compared with the control group and the no coaptation group. The histology of axonal regeneration after ESN, but not after SSN, was comparable to that after EEN. There were no significant differences in the electrophysiological, behavioral assessment or G-ratio parameters between the ESN and EEN groups. There were significant differences in the behavioral assessment, G-ratio and the histomorphometric parameters between the SSN and EEN groups, which disagreed with the electrophysiological results. Sensory axon collateral sprouting was more rapid than motor axon collateral sprouting. The electrophysiological, histomorphometric and behavioral results obtained using end-to-side coaptation of ventral branches of the C5 and C6 spinal nerves to the C7 spinal nerve in the brachial plexi of rabbits confirm the occurrence of collateral sprouting at this level. After further research is performed to confirm the results of this study, end-to-side coaptation might emerge as an alternative method in the treatment of brachial plexus avulsion.

Survival of Injured Spinal Motoneurons in Adult Rat upon Treatment with Glial Cell Line–Derived Neurotrophic Factor at 2 Weeks but Not at 4 Weeks after Root Avulsion

We conducted a study of whether treatment with glial cell line-derived neurotrophic factor (GDNF) initiated at 2 or 4 weeks after spinal-root avulsion could promote survival and regulate neuronal nitric oxide synthase (nNOS) expression in adult rat spinal motoneurons. By 6 weeks after root avulsion, the treatment given at 2 weeks not only increased motoneuron survival (86.1% vs. 27.9%), but also reversed the atrophy of injured motoneurons and increased their somatic size (101.3% vs. 52.9%) in comparison to the untreated control group of animals. All surviving motoneurons in the GDNF-treated group showed immunoreactivity for choline acetyltransferase. In contrast, GDNF treatment at 4 weeks post-injury failed to promote motoneuron survival (33.1% vs. 27.9%) at 6 weeks compared to the control group. Both the 2- and 4-week post-injury treatments downregulated nNOS expression. This finding suggests that injured adult motoneurons die shortly (a few weeks in the rat) after root avulsion injury, but can be saved from degeneration by treatment within the proper time frame after injury, which in the case of GDNF treatment in rats, appears to be within 2 weeks of the avulsion injury of the spinal root. These findings provide useful information for choosing the best time frame for the potential clinical treatment of brachial plexus avulsion.

Phrenic nerve transfer in the treatment of brachial plexus avulsion: an experimental study of nerve regeneration and muscle morphology in rats.

The regeneration of motor and sensory neurons and the morphological changes of the target muscle after phrenic nerve transfer were investigated in adult rats. Six months following nerve transfer, 326.0 +/- 16.31 phrenic motoneurons regenerated into musculocutaneous nerve, which is not different from the normal number of phrenic motoneurons. The regenerated motoneurons exhibited a 14% nonsignificant hypertrophy. Of the dorsal root ganglia (DRG) neurons, 255.8 +/- 45.26 regenerated, which was significantly lower than the number of normal phrenic DRG neurons. The regenerated phrenic DRG neurons showed a 24% close-to-significant atrophy. The target muscle fiber morphology changed considerably after reinnervation. The present results suggest that the phrenic nerve has very good regenerative ability in terms of its motoneurons and a relatively insufficient sensory neuronal regeneration.