scholarly journals Injury-Induced HSP27 Expression in Peripheral Nervous Tissue Is Not Associated with Any Alteration in Axonal Outgrowth after Immediate or Delayed Nerve Repair

2021 ◽  
Vol 22 (16) ◽  
pp. 8624
Author(s):  
Lena Stenberg ◽  
Derya Burcu Hazer Rosberg ◽  
Sho Kohyama ◽  
Seigo Suganuma ◽  
Lars B. Dahlin

We investigated injury-induced heat shock protein 27 (HSP27) expression and its association to axonal outgrowth after injury and different nerve repair models in healthy Wistar and diabetic Goto-Kakizaki rats. By immunohistochemistry, expression of HSP27 in sciatic nerves and DRG and axonal outgrowth (neurofilaments) in sciatic nerves were analyzed after no, immediate, and delayed (7-day delay) nerve repairs (7- or 14-day follow-up). An increased HSP27 expression in nerves and in DRG at the uninjured side was associated with diabetes. HSP27 expression in nerves and in DRG increased substantially after the nerve injuries, being higher at the site where axons and Schwann cells interacted. Regression analysis indicated a positive influence of immediate nerve repair compared to an unrepaired injury, but a shortly delayed nerve repair had no impact on axonal outgrowth. Diabetes was associated with a decreased axonal outgrowth. The increased expression of HSP27 in sciatic nerve and DRG did not influence axonal outgrowth. Injured sciatic nerves should appropriately be repaired in healthy and diabetic rats, but a short delay does not influence axonal outgrowth. HSP27 expression in sciatic nerve or DRG, despite an increase after nerve injury with or without a repair, is not associated with any alteration in axonal outgrowth.

2019 ◽  
Vol 184 (11-12) ◽  
pp. e937-e944 ◽  
Author(s):  
Laurent Mathieu ◽  
Georges Pfister ◽  
James Charles Murison ◽  
Christophe Oberlin ◽  
Zoubir Belkheyar

Abstract Missile injuries of the sciatic nerve are frequently encountered in modern violent conflicts. Gunshot and fragment wounds may cause large nerve defects, for which management is challenging. The great size of the sciatic nerve, in both diameter and length, explains the poor results of nerve repair using autografts or allografts. To address this issue, we used a simple technique consisting of a direct suture of the sciatic nerve combined with knee flexion for 6 weeks. Despite a published series showing that this procedure gives better results than sciatic nerve grafting, it remains unknown or underutilized. The purpose of this cases study is to highlight the efficiency of direct sciatic nerve coaptation with knee flexed through three cases with missile injuries at various levels. At the follow-up of two years, all patients were pain free with a protective sensory in the sole and M3+ or M4 gastrocnemius muscles, regardless of the injury level. Recovery was also satisfying in the fibular portion, except for the very proximal lesion. No significant knee stiffness was noticed, including in a case suffering from an associated distal femur fracture. Key points to enhance functional recovery are early nerve repair (as soon as definitive bone fixation and stable soft-tissue coverage are achieved) and careful patient selection.


Neurosurgery ◽  
2008 ◽  
Vol 62 (3) ◽  
pp. 656-663 ◽  
Author(s):  
Willem Pondaag ◽  
Alain Gilbert

Abstract OBJECTIVE Options for nerve repair are limited in brachial plexus lesions with multiple root avulsions because an insufficient number of proximal nerve stumps are available to serve as lead-out for nerve grafts. End-to-side nerve repair might be an alternative surgical technique for repair of such severe lesions. In this technique, an epineurial window is created in a healthy nerve, and the distal stump of the injured nerve is coapted to this site. Inconsistent results of end-to-side nerve repairs in traumatic nerve lesions in adults have been reported in small series. This article evaluates the results of end-to-side nerve repair in obstetric brachial plexus lesions and reviews the literature. METHODS A retrospective analysis was performed of 20 end-to-side repairs in 12 infants. Evaluation of functional recovery of the target muscle was performed after at least 2 years of follow up (mean, 33 mo). RESULTS Five repairs failed (25%). Seven times (35%) good function (Medical Research Council at least 3) of the target muscle occurred in addition to eight partial recoveries (40%). In the majority of patients, however, the observed recovery cannot be exclusively attributed to the end-to-side repair. The reinnervation may be based on axonal outgrowth through grafted or neurolyzed adjacent nerves. It seems likely that recovery was solely based on the end-to-side repair in only two patients. No deficits occurred in donor nerve function. CONCLUSION This study does not convincingly show that the end-to-side nerve repair in infants with an obstetric brachial plexus lesion is effective. Its use cannot be recommended as standard therapy.


2010 ◽  
Vol 24 (8) ◽  
pp. 730-735 ◽  
Author(s):  
Chia-Chou Yeh ◽  
Yu-Ching Lin ◽  
Fuu-Jen Tsai ◽  
Chih-Yang Huang ◽  
Chun-Hsu Yao ◽  
...  

Background. The timing of electrical stimulation (ES) after peripheral nerve transection may enhance axonal regeneration and functional recovery. Objective. The authors examined whether percutaneous ES at 1 mA and 2 Hz affects regeneration between the proximal and distal nerve stumps. Methods. Four groups of adult rats were subjected to sciatic nerve section followed by repair using silicone rubber conduits across a 10-mm gap. All groups received ES for 15 minutes every other day for 2 weeks. Stimulation was initiated on day 1 following the nerve repair for group A, day 8 for group B, and day 15 for group C. The control group D received no ES. Results. At 6 weeks after surgery in groups B and C, histological evaluations showed a significantly higher number of regenerated myelinated fibers in the sciatic nerve, and the electrophysiological results showed higher levels of reinnervation with relatively larger mean values of amplitudes, durations, and areas of compound muscle action potentials compared with A and D. Conclusion. A short delay in the onset of ES may improve the recovery of a severe peripheral nerve injury, which should be considered as a way of augmenting rehabilitative approaches.


2017 ◽  
Vol 42 (3) ◽  
pp. E2 ◽  
Author(s):  
Zachary C. Gersey ◽  
S. Shelby Burks ◽  
Kim D. Anderson ◽  
Marine Dididze ◽  
Aisha Khan ◽  
...  

OBJECTIVE Long-segment injuries to large peripheral nerves present a challenge to surgeons because insufficient donor tissue limits repair. Multiple supplemental approaches have been investigated, including the use of Schwann cells (SCs). The authors present the first 2 cases using autologous SCs to supplement a peripheral nerve graft repair in humans with long-term follow-up data. METHODS Two patients were enrolled in an FDA-approved trial to assess the safety of using expanded populations of autologous SCs to supplement the repair of long-segment injuries to the sciatic nerve. The mechanism of injury included a boat propeller and a gunshot wound. The SCs were obtained from both the sural nerve and damaged sciatic nerve stump. The SCs were expanded and purified in culture by using heregulin β1 and forskolin. Repair was performed with sural nerve grafts, SCs in suspension, and a Duragen graft to house the construct. Follow-up was 36 and 12 months for the patients in Cases 1 and 2, respectively. RESULTS The patient in Case 1 had a boat propeller injury with complete transection of both sciatic divisions at midthigh. The graft length was approximately 7.5 cm. In the postoperative period the patient regained motor function (Medical Research Council [MRC] Grade 5/5) in the tibial distribution, with partial function in peroneal distribution (MRC Grade 2/5 on dorsiflexion). Partial return of sensory function was also achieved, and neuropathic pain was completely resolved. The patient in Case 2 sustained a gunshot wound to the leg, with partial disruption of the tibial division of the sciatic nerve at the midthigh. The graft length was 5 cm. Postoperatively the patient regained complete motor function of the tibial nerve, with partial return of sensation. Long-term follow-up with both MRI and ultrasound demonstrated nerve graft continuity and the absence of tumor formation at the repair site. CONCLUSIONS Presented here are the first 2 cases in which autologous SCs were used to supplement human peripheral nerve repair in long-segment injury. Both patients had significant improvement in both motor and sensory function with correlative imaging. This study demonstrates preliminary safety and efficacy of SC transplantation for peripheral nerve repair.


1993 ◽  
Vol 136 (3) ◽  
pp. 431-438 ◽  
Author(s):  
H. Shindo ◽  
M. Tawata ◽  
T. Onaya

ABSTRACT We have investigated the relationship between cyclic nucleotides and nerve function in the sciatic nerve of rats made diabetic with streptozotocin. Cyclic AMP (cAMP) content in the sciatic nerves of diabetic rats was significantly (P < 0·05) lower than in those of normal rats, while cyclic GMP content did not differ between the two groups. Administration of the stable prostacyclin analogue iloprost or dibutyryl cyclic AMP (dbcAMP) significantly (P<0·05) restored the cAMP content in the sciatic nerves and motor nerve conduction velocity, which reflects nerve function. There was a positive correlation between cAMP content in the sciatic nerves and motor nerve conduction velocity in both normal and diabetic rats. Endoneurial preparations of sciatic nerves obtained from normal rats were incubated in Krebs–Ringer bicarbonate buffer containing d-glucose (30 or 5·5 mmol/l). Cyclic AMP accumulation was significantly (P<0·05) suppressed in the buffer containing 30 mmol d-glucose/l compared with that containing 5·5 mmol/l. Iloprost (P<0·05) and dbcAMP (P<0·01) increased cAMP accumulations in the tissues incubated in buffer containing both 5·5 and 30 mmol d-glucose/l. When non-metabolizing hexoses, such as l-glucose or 3-O-methylglucose instead of d-glucose were used, cAMP accumulations at 30 mmol hexose/1 were not significantly different from those at 5·5 mmol/l. Cyclic AMP phosphodiesterase activity in the sciatic nerves of diabetic rats did not change compared with that in nerves from normal rats. Although not significant, mean ATP content in the sciatic nerves of diabetic rats was about 30% lower than that in nerves of normal rats. Basal, iloprost-stimulated and forskolin-stimulated adenylate cyclase activities in the sciatic nerves of diabetic rats were significantly (P<0·05) reduced when compared with those of control rats. We therefore conclude that reduction of cAMP content in peripheral nerves may be involved in the pathogenesis of diabetic neuropathy and is mainly caused by the impairment of adenylate cyclase activity in the diabetic state. Journal of Endocrinology (1993) 136, 431–438


2016 ◽  
Vol 2016 ◽  
pp. 1-11
Author(s):  
Pengsong Liu ◽  
Yuanyuan Bian ◽  
Hong Zhang ◽  
Aiming Jia

Ischemia and hypoxia are important physiological changes in diabetic peripheral neuropathy (DPN). Chinese herbal medicine prescription Tangkuei Decoction for Frigid Extremities (TDFE) is useful for increasing blood flow. To help determine whether TDFE could protect the peripheral nerves of diabetic patients from the degeneration caused by high blood glucose, TDFE was administered to streptozotocin-induced diabetic rats for 6 or 12 weeks. Plantar thermal stimulation reaction time thresholds, sciatic nerve conduction velocities, and the levels of HIF-1αmRNA, HIF-1αprotein, VEGF protein, and the endothelial marker vWF in sciatic nerves were measured at the end of the sixth and twelfth weeks. The thermal thresholds and sciatic nerve conduction velocities of the rats differed after 12 weeks, and the sciatic nerves of the diabetic rats that were given TDFE displayed higher levels of HIF-1αprotein, VEGF protein, and HIF-1αmRNA than those of the diabetic model rats. The results at 6 weeks differed from those at 12 weeks. These results suggest that the early preventive application of TDFE effectively delayed the development of DPN and that TDFE increased HIF-1αmRNA levels in the sciatic nerves of diabetic rats through 12 weeks of treatment.


Author(s):  
Manochehr Safari ◽  
Niloofar Aldaghi ◽  
Hamid Reza Sameni ◽  
Mohammad Reza Aldaghi

Objective: Alteration in the basement membrane proteins maybe associated with diabetic neuropathy. Fibronectin is one of the most important components of peripheral nerves basement membrane. In this study we investigated the effects of insulin administration on prevention of alteration in fibronectin contents of sciatic nerve in diabetic rats. Materials and Methods: Twenty-four wistar rats were divided into control, diabetic and diabetic with insulin treatment groups. Three months after diabetes induction, we measured blood glucose level, body weight and then expression of fibronectin in sciatic nerves of rats were evaluated by real time polymerase chain reaction (PCR) and immunohistochemical study. Results: Intensity of fibronectin immunoreactivity in the perineurium and endoneurium of sciatic nerves significantly increased in diabetic without treatment group compared to control group (P-value< 0.001). Conclusion: This finding suggested that diabetic neuropathy resulted in increased of fibronectin contents in sciatic nerves of rats.  


2019 ◽  
Author(s):  
Jesse E Bucksot ◽  
Andrew J Wells ◽  
Kimiya C Rahebi ◽  
Vishnoukumaar Sivaji ◽  
Mario Romero-Ortega ◽  
...  

AbstractThe majority of available systems for nerve stimulation use circumferential stimulation electrodes inside an insulating cuff, which produce largely uniform current density within the nerve. Flat stimulation electrodes that contact only one side of the nerve may provide advantages including simpler implantation, ease of production, and more resistance to mechanical failure. However, it is possible that the flat configuration will yield inefficient fiber recruitment due to a less uniform current distribution within the nerve. Here we tested the hypothesis that flat electrodes will require higher current amplitude to achieve effective stimulation than circumferential designs. Computational modeling and in vivo experiments were performed to evaluate fiber recruitment in different nerves and different species using a variety of electrode designs. Initial results demonstrated similar fiber recruitment in the rat vagus and sciatic nerves with a standard circumferential cuff electrode and a cuff electrode modified to approximate a flat configuration. Follow up experiments comparing true flat electrodes to circumferential electrodes on the rabbit sciatic nerve confirmed that fiber recruitment was equivalent between the two designs. These findings demonstrate that flat electrodes represent a viable design for nerve stimulation that may provide advantages over the current circumferential designs for applications in which the goal is uniform activation of the nerve.


2021 ◽  
Vol 22 (13) ◽  
pp. 7146
Author(s):  
Derya Burcu Hazer Rosberg ◽  
Baki Hazer ◽  
Lena Stenberg ◽  
Lars B. Dahlin

Reconstruction of nerve defects is a clinical challenge. Autologous nerve grafts as the gold standard treatment may result in an incomplete restoration of extremity function. Biosynthetic nerve conduits are studied widely, but still have limitations. Here, we reconstructed a 10 mm sciatic nerve defect in healthy rats and analyzed nerve regeneration in poly (e-caprolactone) (PCL) conduits longitudinally divided by gold (Au) and gold-cobalt oxide (AuCoO) nanoparticles embedded in poly-propylene poly-ethylene glycol (PPEG) membranes (AuPPEG or AuCoOPPEG) and compared it with unmodified PPEG-membrane and hollow PCL conduits. After 21 days, we detected significantly better axonal outgrowth, together with higher numbers of activated Schwann cells (ATF3-labelled) and higher HSP27 expression, in reconstructed sciatic nerve and in corresponding dorsal root ganglia (DRG) in the AuPPEG and AuCoOPPEG groups; whereas the number of apoptotic Schwann cells (cleaved caspase 3-labelled) was significantly lower. Furthermore, numbers of activated and apoptotic Schwann cells in the regenerative matrix correlated with axonal outgrowth, whereas HSP27 expression in the regenerative matrix and in DRGs did not show any correlation with axonal outgrowth. We conclude that gold and cobalt-oxide nanoparticle modified membranes in conduits improve axonal outgrowth and increase the regenerative performance of conduits after nerve reconstruction.


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