Sensory reinnervation of muscle spindles after repair of tibial nerve defects using autogenous vein grafts

Motor reinnervation after repair of tibial nerve defects using autologous vein grafts in rats has previously been reported, but sensory reinnervation after the same repair has not been fully investigated. In this study, partial sensory reinnervation of muscle spindles was observed after repair of lO-mm left tibial nerve defects using autologous vein grafts with end-to-end anasto- mosis in rats, and functional recovery was confirmed by electrophysiological studies. There were no significant differences in the number, size, or electrophysiological function of reinnervated muscle spindles between the two experimental groups. These findings suggest that repair of short nerve defects with autologous vein grafts provides comparable results to immediate end-to-end anastomosis in terms of sensory reinnervation of muscle spindles.

Effects of targeted muscle reinnervation on spinal cord motor neurons in rats following tibial nerve transection

Targeted muscle reinnervation(TMR)is a surgical procedure used to transfer residual peripheral nerves from amputated limbs to targeted muscles,which allows the target muscles to become sources of motor control information for function reconstruction.However,the effect of TMR on injured motor neurons is still unclear.In this study,we aimed to explore the effect of hind limb TMR surgery on injured motor neurons in the spinal cord of rats after tibial nerve transection.We found that the reduction in hind limb motor function and atrophy in mice caused by tibial nerve transection improved after TMR.TMR enhanced nerve regeneration by increasing the number of axons and myelin sheath thickness in the tibial nerve,increasing the number of anterior horn motor neurons,and increasing the number of choline acetyltransferase-positive cells and immunofluorescence intensity of synaptophysin in rat spinal cord.Our findings suggest that TMR may enable the reconnection of residual nerve fibers to target muscles,thus restoring hind limb motor function on the injured side.

Isolated tibial nerve injury: a rare presentation

Tibial nerve injury is rare and is always associated with other injuries due to its close association with the other structures.We present a rare case of isolated injury to the tibial nerve where the nerve was avulsed from the middle third of the leg,but all other structures were intact.The nerve was reconstructed with sural nerve grafts.The patient recovered sensation of the sole twelve months following the reconstruction and was able to maintain a normal gait and is living normal life.The results of nerve repairs in lower limbs in general have been poor.The treatment options for such an interesting case are discussed along with the management and outcome of the presented patient.

The anatomical,electrophysiological and histological observations of muscle contraction units in rabbits:a new perspective on nerve injury and regeneration

In the conventional view a muscle is composed of intermediate structures before its further division into microscopic muscle fibers.Our experiments in mice have confirmed this intermediate structure is composed of the lamella cluster formed by motor endplates,the innervating nerve branches and the corresponding muscle fibers,which can be viewed as an independent structural and functional unit.In this study,we verified the presence of these muscle construction units in rabbits.The results showed that the muscular branch of the femoral nerve sent out 4–6 nerve branches into the quadriceps and the tibial nerve sent out 4–7 nerve branches into the gastrocnemius.When each nerve branch of the femoral nerve was stimulated from the most lateral to the medial,the contraction of the lateral muscle,intermediate muscle and medial muscle of the quadriceps could be induced by electrically stimulating at least one nerve branch.When stimulating each nerve branch of the tibial nerve from the lateral to the medial,the muscle contraction of the lateral muscle 1,lateral muscle 2,lateral muscle 3 and medial muscle of the gastrocnemius could be induced by electrically stimulating at least one nerve branch.Electrical stimulation of each nerve branch resulted in different electromyographical waves recorded in different muscle subgroups.Hematoxylin-eosin staining showed most of the nerve branches around the neuromuscular junctions consisted of one individual neural tract,a few consisted of two or more neural tracts.The muscles of the lower limb in the rabbit can be subdivided into different muscle subgroups,each innervated by different nerve branches,thereby allowing much more complex muscle activities than traditionally stated.Together,the nerve branches and the innervated muscle subgroups can be viewed as an independent structural and functional unit.This study was approved by the Animal Ethics Committee of Peking University People’s Hospital(approval No.2019 PHE027)on October 20,2019.

Peripheral nerve repair by conduits made of human hair keratin: An experimental study

Objective: To explore the method to repair injured peripheral nerve using conduits made of human hair keratin (HHK). Methods: The tibial nerves of rabbits were transected leaving a gap 10 mm in length between the 2 severed ends, which were either routinely sutured or bridged using HHK nerve conduits. Electro-physiological , anatomical and histological examinations were performed at different time postoperatively. Results: Electrophysiological study showed more obvious improvement in the neural function recovery in rabbits with HHK conduits bridging as compared with that in rabbits with routine suture. In the former group, HHK conduits were gradually degraded and absorbed with large amount of myelinated nerve fibers and Schwann cells regenerated around HHK conduits. In the latter group, however, the nerve tissues around the suture were degenerated and replaced by connective tissues. Conclusion: HHK may induce the regeneration of the nerve fibers and provides an ideal approach to repair nerve damages.

Non-invasive transcutaneous electrical stimulation in the treatment of overactive bladder

We reviewed the literature on transcutaneous electrical nerve stimulation(TENS)used as a therapy for overactive bladder(OAB)symptoms,with a particular focus on:stimulation site,stimuli parameters,neural structures thought to be targeted,and the clinical and urodynamic outcomes achieved.The majority of studies used sacral or tibial nerve stimulation.The literature suggests that,whilst TENS therapy may have neuromodulation effects,patient are unlikely to benefit to a significant extent from a single application of TENS and indeed clear benefits from acute studies have not been reported.In long-term studies there were differences in the descriptions of stimulation intensity,strategy of the therapy,and positioning of the electrodes,as well as in the various symptoms and pathology of the patients.Additionally,most studies were uncontrolled and hence did not evaluate the placebo effect.Little is known about the underlying mechanism by which these therapies work and therefore exactly which structures need to be stimulated,and with what parameters.There is promising evidence for the efficacy of a transcutaneous stimulation approach,but adequate standardisation of stimulation criteria and outcome measures will be necessary to define the best way to administer this therapy and document its efficacy.

Treating Urinary Incontinence with Electrical Stimulus: A Review

Urinary incontinence markedly affects women’s quality of life. There are several methods to mitigate or reduce this problem such as medication, surgery, or exercises. Of various types of urinary incontinence, overactive bladder consists of one category, which is often resistant to various treatments. Electrical stimulation methods have been considered a treatment option of overactive bladder. We here briefly summarize various treatment options for urinary incontinence, with special reference to the role of electrical stimulation methods for this disease. Electrical stimulation methods include vaginal electrical stimulation (VES), posterior tibial nerve stimulation (PTNS) and sacral nerve stimulation (SNS). The three methods have shown good results, and these findings will contribute to achieving a better quality of life for patients.

APPLICATION OF PRE－AND POSTOPERATIVE SOMATOSENSORY EVOKED POTENTIALS OF DIASTEMATOMYELIA

Conical somatosensory evoked potential(CSEP) examination of posterior tibial nerve was performed Pre-and postoperatively smong 20 patients with diastematomyelia and 20 normal people as control group at the same time.The results indicated CSEP changes were statistically significant between patients and normal people(P< 0.05);postoperative P40, Peak latencies and amplitudes changed significantly and CSEPs had apparent difference in bilateral lower extremities among preoperative patients.This shows that CSEP is an objective,sensitive and reliable diagnostic tool that may be used to judge the severity of neural damage and evaluate the surgical results.

Electrical neuromodulation therapy for inflammatory bowel disease

Inflammatory bowel disease(IBD)is an inflammatory disease of the gastrointestinal(GI)tract.It has financial and quality of life impact on patients.Although there has been a significant advancement in treatments,a considerable number of patients do not respond to it or have severe side effects.Therapeutic approaches such as electrical neuromodulation are being investigated to provide alternate options.Although bioelectric neuromodulation technology has evolved significantly in the last decade,sacral nerve stimulation(SNS)for fecal incontinence remains the only neuromodulation protocol commonly utilized use for GI disease.For IBD treatment,several electrical neuromodulation techniques have been studied,such as vagus NS,SNS,and tibial NS.Several animal and clinical experiments were conducted to study the effectiveness,with encouraging results.The precise underlying mechanisms of action for electrical neuromodulation are unclear,but this modality appears to be promising.Randomized control trials are required to investigate the efficacy of intrinsic processes.In this review,we will discuss the electrical modulation therapy for the IBD and the data pertaining to it.

Sacral neuromodulation and peripheral nerve stimulation in patients with anal incontinence:an overview of techniques,complications and troubleshooting

Sacral neuromodulation(SNM)therapy has revolutionized the management of many forms of anal incontinence,with an expanded use and a medium-term efficacy of 75%overall.This review discusses the technique of SNM therapy,along with its complications and troubleshooting and a discussion of the early data pertaining to peripheral posterior tibial nerve stimulation in incontinent patients.Future work needs to define the predictive factors for neurostimulatory success,along with the likely mechanisms of action of their therapeutic action.

Preparation and application of rat myostatin antiserum

Objective To prepare and identify a polyclonal antibody against rat myostatin and investigate myostatin expression in the rat atrophic gastrocnemius muscle after tibial nerve crush. Methods The purified fusion protein was used as antigen to immunize rabbits for the preparation of polyclonal antibody. The polyclonal antibody of the protein was measured by enzyme linked immunosorbent assay （ELISA）, western-blot and immunochemistry. Myostatin protein expression levels in normal and atrophic gastrocnemius muscle were detected by western-blot and immunochemistry assays. Results The GST-myostatin had a purity of 96% and possessed high titer and specificity. The level of myostatin in gastrocnemius muscle significantly increased one week after tibial nerve crush, reached the peak on day 14, and then returned to normal level on day 28. Conclusion We have successfully made antiserum of rat myostatin and found that the expression level of myostatin protein in the gastrocnemius after tibial nerve crush-induced atrophy was time-dependent. This study provides an experimental basis to clarify the possible role of myostatin during skeletal muscle atrophy.

Mechanosensitive Ion Channel TMEM63A Gangs Up with Local Macrophages to Modulate Chronic Post-amputation Pain

Post-amputation pain causes great sufering to amputees,but still no efective drugs are available due to its elusive mechanisms.Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump efectively relieves the phantom pain aficting patients after amputation.This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain(CPAP).However,the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery.In this study,we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infltrated into the dorsal root ganglion(DRG)neurons worked synergistically to promote CPAP.Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG,and the expression of TMEM63A increased signifcantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer(TNT).Behavioral tests showed that the mechanical,heat,and cold sensitivity were not afected in the Tmem63a-/-mice in the naïve state,suggesting the basal pain was not afected.In the infammatory and post-amputation state,the mechanical allodynia but not the heat hyperalgesia or cold allodynia was signifcantly decreased in Tmem63a-/-mice.Further study showed that there was severe neuronal injury and macrophage infltration in the DRG,tibial nerve,residual stump,and the neuromalike structure of the TNT mouse model,Consistent with this,expression of the pro-infammatory cytokines TNFα,IL-6,and IL-1βall increased dramatically in the DRG.Interestingly,the deletion of Tmem63a signifcantly reduced the macrophage infltration in the DRG but not in the tibial nerve stump.Furthermore,the ablation of macrophages signifcantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model,indicating an interaction between nociceptors and macrophages,and that these two factors gang up together to regulate the formation of CPAP.This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.