Number Of Myelinated Nerve Fibers Research Articles

The Exploratory Study of the PTEN-AKT/mTOR Signaling Pathway in the Corresponding Dorsal Root Ganglion during Compensatory Repair via Small Gap Amplification in Sciatic Nerve Injury.

Peripheral nerve injury is a challenging orthopedic issue in clinical management that often leads to limb dysfunction or even disability in severe cases. A thorough exploration of the repair process of peripheral nerve injury and the underlying mechanism contributes to formulate more effective therapeutic strategies. In the present study, we established a sciatic nerve transection injury model in Sprague-Dawley (SD) rats. A 12-week compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis was then performed via sleeve jointing the proximal common peroneal nerve to the distal tibial nerve and common peroneal nerve, with a 2 mm interval. Compensatory repair via small gap amplification was observed via gross observation of nerve specimen, osmic acid staining, and electrophysiological stimulation of sciatic nerve branches of the tibial and common peroneal nerve. Rat limbs were observed, and the functional recovery of effector muscles of the gastrocnemius and tibialis anterior muscles was assessed through weighing the muscle wet weight, Hematoxylin and Eosin (H&E) staining, and muscle strength detection. H&E staining, Masson staining, and toluidine blue staining were performed to observe the morphological changes of the dorsal root ganglion. Positive expressions of key proteins involved in the Phosphatase and tensin homologue deleted on chromosome ten (PTEN)-protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, including PTEN, AKT, mTOR, Toll-like receptor 4 (TLR4), and Caspase9 in the dorsal root ganglion during compensatory repair of sciatic nerve after injury via small gap amplification, were detected by immunohistochemical staining. It is found that the compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing effectively restored the continuity, number of myelinated nerve fibers, and nerve conduction velocity. It promoted toe abduction recovery, improved muscle fiber morphology and increased the wet weight and muscle strength of the gastrocnemius muscle and tibialis anterior muscle. Moreover, it increased the number of neurons and nerve fibers, and improved their morphology. Downregulated PTEN, TLR4, and Caspase9 in the dorsal root ganglia and upregulated AKT and mTOR were observed after small gap amplification than those of the transection injury group, which were closer to those of the control group. Compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing can restore the morphology and function of the sciatic nerve, effector muscles, and corresponding dorsal root ganglia by activating the PTEN-AKT/mTOR signaling pathway in the dorsal root ganglia. Our findings provide novel therapeutic targets for peripheral nerve injuries.

Abstract 20: Axonal Neuropathy and Inflammatory Response in Peripheral Nerves of a Murine Cerebral Amyloid Angiopathy Model

Introduction: Cerebral amyloid angiopathy (CAA) induces intracerebral hemorrhages, small vessel disease, and cognitive decline in elderly individuals. CAA is also associated with slower walking speed and abnormal gait rhythms compared to healthy controls. Little is known regarding the impact of peripheral nervous system abnormalities on CAA-associated gait disturbance. Furthermore, it is unknown whether peripheral nerves pose extracerebral targets of amyloid-related endoneurial inflammation. Hypothesis: Gait disturbance in a CAA model is associated with peripheral neuropathy through endoneurial inflammation related to amyloid accumulation. Methods: Aged (19-24 months) Tg-SwDI mice (CAA mice) of both sexes harboring mutations of human amyloid precursor protein (APP) were used as a CAA model. Age-matched C57BL/6 wild-type (WT) mice were used as controls (n=6-11/grp). Gait disturbance and sensorimotor function were assessed via DigiGait and grip strength testing. Flow cytometry was used to analyze immune cells in the sciatic nerve. Tibial nerve morphometry was performed to assess for neuropathy. Results: CAA mice had weaker grip strength ( CAA: 97.7 ± 17.6 g, WT 111.5 ± 8.1 g, p=0.039 ) and evidence of neuropathic gait disturbances, reflected by increased paw angles ( CAA: 21.1 ± 4.8°, WT 11.7 ± 3.4°, p=0.0002 ) and reduced paw areas ( CAA: 0.4 ± 0.05 cm 2 , WT 0.5 ± 0.06 cm 2 , p=0.013 ) impacting the ground when walking compared to WT mice. Tibial nerve morphometry showed a reduced number of myelinated nerve fibers ( CAA: 1023 ± 230.1, WT 1318 ± 45.8, p=0.0047 ) suggesting potential axonal degeneration in CAA mice. Flow cytometry showed an increase in the count of macrophage (both M1 and M2 subtypes) lineage cells ( M1 CAA: 102.3 ± 29.2, WT 57.9 ± 36.3, p=0.009 ) as well as M1 macrophage associated pro-inflammatory cytokine TNF-α ( CAA: 99.7 ± 28.3, WT 53.8 ± 12.2, p=0.009 ) in sciatic nerves of CAA mice compared to WT mice. Conclusions: CAA mice display an enhanced inflammatory response within the endoneurium which may contribute to observed axonal degeneration, ultimately impairing sensorimotor function and gait. Further studies are needed to unravel the mechanistic interplay between amyloid pathology, endoneurial inflammation, and axonal neuropathy in this CAA model.

Chitosan nerve conduit filled with ZIF-8-functionalized guide microfibres enhances nerve regeneration and sensory function recovery in sciatic nerve defects

Nerve conduits have shown promise as alternatives to autologous nerves, but their repair effects need to be improved. The topographical guidance and functionalization of scaffolds are crucial in nerve repair. In this work, a chitosan-based nerve graft filled with guiding fibres modified by ZIF-8 nanoparticles (CS@ZIF-8) was fabricated for defective nerve repair. An in vitro study demonstrated that CS@ZIF-8 exhibited excellent cytocompatibility and could significantly promote Schwann cell proliferation. In vivo, nerve conduits filled with CS@ZIF-8 were observed to guide stronger axonal longitudinal elongation. Rats bridged with the conduit filled with CS@ZIF-8 showed significant morphological and functional improvements in terms of regenerated nerve density, the number of myelinated nerve fibres, the number of myelin layers, the thickness of myelin sheath, target muscle recovery and sensory function compared to those transplanted with the hollow conduit and the conduit filled with pure chitosan fibres. The repair effects achieved by using the conduit filled with CS@ZIF-8 were similar to those of autografts. Altogether, the data here show that nerve conduits filled with ZIF-8-loaded guide fibres provide a promising approach for repairing nerve defects.

Acupuncture on “Huantiao” (GB30) and "Yanglingquan" (GB34) acupoints promotes nerve regeneration in mice model of peripheral nerve injury

ObjectiveTo investigate the effects of acupuncture on promoting nerve regeneration in mice with sciatic nerve crushed injury, an animal model of peripheral nerve injury (PNI). MethodsAcupuncture was performed on the "Huantiao" (GB30) and "Yanglingquan" (GB34) acupoints in PNI mice model for 2 weeks. Gait analysis, toe spreading test, electrophysiological test, toluidine blue staining and immunostaining of myelin basic protein (MBP), neurofilament-200 (NF200), p75 neurotrophin receptor (p75NTR), and growth associated protein-43 (GAP43) were respectively performed to investigate the effects of acupuncture on crushed sciatic nerve. ResultsAcupuncture stimulation of “Huantiao” (GB30) and "Yanglingquan" (GB34) acupoints promoted the recovery of motor function and electrophysiological function in PNI mice model, which was indicated by a better gait level, toe spreading level and CMAP value in acupuncture group. The number of myelinated nerve fibers and the fluorescence intensity of MBP, NF200, p75NTR and GAP43 staining demonstrated that the acupuncture stimulation promoted the regeneration of injured nerves in PNI mice model. ConclusionAcupuncture significantly promoted the functional and morphological recovery of crushed sciatic nerve via promoting the expression of p75NTR in Schwann cells.

(001) How many Nerve Fibers Innervate the Human Clitoris? A Histomorphometric Evaluation of the Dorsal Nerve of the Clitoris

Abstract Introduction It is frequently quoted in mainstream media that the clitoris has “8000 nerve endings”. However, no study has yet quantified the number of nerve fibers (axons) innervating the human clitoris. The dorsal nerve of the clitoris (DNC) is the primary source of somatic clitoral innervation. Reporting the number of axons in the DNC is an important step in our understanding of clitoral innervation and sexual response with implications for many fields of medical practice. Reconstruction following iatrogenic injuries to the dorsal clitoral nerve and restoration following cases of genital mutilation will benefit from a better understanding of the DNC. This knowledge will also be an important factor contributing to the optimization of nerve selection and sensory outcomes in gender-affirming genital surgery. Objective The purpose of this study is to quantify the number of nerve fibers in the human dorsal nerve of the clitoris (DNC) and report the approximate number of nerve fibers that innervate the human clitoris. Methods Following institutional approval and informed consent, dorsal clitoral nerve samples were obtained from 7 transmasculine patients undergoing gender-affirming phalloplasty surgery. In phalloplasty one of the two dorsal clitoral nerves is used to coapt to a sensory nerve in the phallus in order to provide for erogenous phallic sensation. At the time of nerve coaptation, a small excess of dorsal clitoral nerve (5 mm) was collected for analysis at the proximal level of the clitoral body, just after appearance of the dorsal clitoral nerve from underneath the pubic symphysis. The samples were placed into 3% glutaraldehyde fixative, post-fixed in 1% osmium tetroxide and serially dehydrate in ethanol and toluene. They were then embedded in araldite, sectioned on ultramicrotome into 1 μm cross sections and counter-stained with 1% toluidine blue. Histomorphometric evaluation was performed at 1000x magnification using a Leitz Laborlux S microscope and image analysis software (Clemex Vision Professional, Longueuil, Quebec) in order to obtain a nerve fiber count from each dorsal clitoral nerve specimen. Descriptive statistics were performed to yield a mean and range of the number of nerve fibers in the DNC. Assuming anatomic symmetry between bilateral DNC, the total number of somatic nerve fibers innervating the human clitoris was obtained by doubling the mean count of the DNC. Results 7 samples of the DNC were collected. The mean number of nerve fibers in the human dorsal clitoral nerve was 5140 with a range of 4926 to 5543. The mean number of myelinated nerve fibers innervating the human clitoris was 10281 (range 9852 to 11086). Conclusions This study is the first to report the number of myelinated nerve fibers in the human dorsal clitoral nerve and approximate the number of nerve fibers innervating the human clitoris. Findings demonstrate high and consistent myelinated axon counts and density. When taking into account the presence of uncounted unmyelinated axons, it is clear that far more than 8000 fibers innervate the human clitoris. Disclosure No

How many nerve fibers innervate the human glans clitoris: a histomorphometric evaluation of the dorsal nerve of the clitoris.

It is frequently quoted in mainstream media that the clitoris has "8000 nerve endings." However, no study has yet quantified the number of nerve fibers (axons) innervating the human clitoris. The dorsal nerves of the clitoris (DNCs) are the primary source of sensation and somatic clitoral innervation. Therefore, reporting the number of axons in the DNCs is an important step in our understanding of clitoral innervation and sexual response with implications for many fields of medical practice. The purpose of this study is to quantify the mean number of axons in the human DNCs and to report the approximate mean number of nerve fibers that innervate the human glans clitoris. DNC samples were obtained from 7 transmasculine patients undergoing gender-affirming phalloplasty surgery. At the time of nerve coaptation, a small excess of the DNC (5 mm) was collected for analysis at the proximal level of the clitoral body, just distal of the emergence of the DNCs from underneath the pubic symphysis. Samples were placed into 3% glutaraldehyde fixative, postfixed in 1% osmium tetroxide, and serially dehydrated in ethanol and toluene. Samples were then embedded in araldite, sectioned on an ultramicrotome into 1-μm cross sections, and counterstained with 1% toluidine blue. Histomorphometric evaluation was performed at 1000x magnification with a Leitz Laborlux S microscope and image analysis software (Clemex Vision Professional) to obtain an axon counts. Descriptive statistics were performed to yield a mean and standard deviation of the number of axons in the DNCs. Assuming anatomic symmetry between bilateral DNCs, mean total number of somatic nerve fibers innervating the human glans clitoris was obtained by doubling the mean count of the DNCs. Seven sample DNCs were collected. Of those, 5 were analyzed as 2 did not have sufficient nerve tissue present. The mean number of nerve fibers in the human DNCs was 5140 (SD = 218.4). The mean number of myelinated nerve fibers innervating the human clitoris was 10,281 (SD = 436.8). This study is the first to report the number of axons in the human DNC, at a mean 5140. Given the bilateral nature of clitoral innervation and symmetry of anatomic structures, the approximate mean number of myelinated axons that innervate the human glans clitoris is 10,280. When the uncaptured unmyelinated fibers and contributions from the cavernosal innervation are accounted for, it is clear that far Moree than 8000 axons innervate the human clitoris.

Comparative analysis of intracardiac neural structures in the aged rats with essential hypertension.

Persistent arterial hypertension initiates cardiac autonomic imbalance and alters cardiac tissues. Previous studies have shown that neural component contributes to arterial hypertension etiology, maintenance, and progression and leads to brain damage, peripheral neuropathy, and remodeling of intrinsic cardiac neural plexus. Recently, significant structural changes of the intracardiac neural plexus were demonstrated in young prehypertensive and adult hypertensive spontaneously hypertensive rats (SHR), yet structural alterations of intracardiac neural plexus that occur in the aged SHR remain undetermined. Thus, we analyzed the impact of uncontrolled arterial hypertension in old (48-52 weeks) SHR and the age-matched Wistar-Kyoto rats (WKY). Intrinsic cardiac neural plexus was examined using a combination of immunofluorescence confocal microscopy and transmission electron microscopy in cardiac sections and whole-mount preparations. Our findings demonstrate that structural changes of intrinsic cardiac neural plexus caused by arterial hypertension are heterogeneous and may support recent physiological implications about cardiac denervation occurring together with the hyperinnervation of the SHR heart. We conclude that arterial hypertension leads to (i) the decrease of the neuronal body area, the thickness of atrial nerves, the number of myelinated nerve fibers, unmyelinated axon area and cumulative axon area in the nerve, and the density of myocardial nerve fibers, and (ii) the increase in myelinated nerve fiber area and density of neuronal bodies within epicardiac ganglia. Despite neuropathic alterations of myelinated fibers were exposed within intracardiac nerves of both groups, SHR and WKY, we consider that the determined significant changes in structure of intrinsic cardiac neural plexus were predisposed by arterial hypertension.

INTRATRUNK STRUCTURE AND MYELOARCHITECTONICS OF THE FACIAL NERVE AT THE LEVEL OF THE STYLOMASTOID FORAMEN IN ADULTS

The aim of the presented study was to study the intratrunk structure of the facial nerve at the exit from the stylomastoid foramen. Material and methods. Fragments of the nerve were taken to study the intratrunk structure of the facial nerve at the exit from the stylomastoid foramen of the facial nerve. During microscopic examination, special attention was paid to the study of the features of the internal structure of the facial nerve - the shape, number, size and topography of nerve fibers. The quantitative indicators obtained during the study were carried out in the IBM Statistics SPSS-26 program using the variational and dispersion methods. To describe the variation series in the analysis of indicators, the following were calculated: mean (M), standard error (±m), 95% confidence interval (95% CI) and the average structure - Me (median), the smallest and largest (min, max) indicators. The results of the study showed that the myelinated fibers of the stem part of the facial nerve, emerging from the stylomastoid foramen, consist of conductive elements that have undergone myelination and differentiation in the nerve. As part of the facial nerve, small nerve bundles were identified, consisting of only a few myelinated nerve fibers, usually occupying the peripheral parts of the nerve trunk. It should be noted that, in general, the number of myelinated nerve fibers in the facial nerve does not change significantly in adulthood. Conclusion. In adulthood, the myeloarchitectonics of the facial nerve is characterized by distinct polymorphism, the presence of all types of myelin fibers in each nerve bundle. There are different, individual and age-related variability of the main indicators of myelinated nerve fibers, which is associated with certain individual dynamics and age-related restructuring of the connective tissue sheath.

Construction and effect evaluation of different sciatic nerve injury models in rats.

BackgroundThe most commonly used experimental model for preclinical studies on peripheral nerve regeneration is the sciatic nerve injury model. However, no experimental study has been conducted to evaluate acute injury modes at the same time.ObjectiveWe conducted sciatic nerve transverse injury, clamp injury, keep epineurium and axon cutting injury, and chemical damage injury in rats to evaluate the degree of damage of the four different injury modes and the degree of self-repair after injury.MethodsThe sciatic nerve transverse injury model, clamp injury model, keep epineurium injury model, and chemical damage injury model were constructed. Then, the sciatic nerve function was assessed using clinical evaluation methods and electrophysiological examinations, as well as immunofluorescence and axonal counting assessments of the reconstructed nerve pathways.ResultsThe evaluations showed that the transverse group had the lowest muscle action potential, sciatic functional index, nociceptive threshold, mechanical threshold, rate of wet gastrocnemius muscle weight, area of muscle fiber, and numbers of myelinated nerve fibers. The chemical group had the highest, while the clamp group and the keep epineurium group had medium.ConclusionTransverse injury models have the most stable effect among all damage models; chemical injury models self-recover quickly and damage incompletely with poor stability of effect; and clamp injury models and keep epineurium injury models have no significant differences in many ways with medium stability.

Interleukin 37's role in promoting nerve repair and attenuating immune rejection of peripheral nerve xenografts in mice

BackgroundThe aim of the study was to explore the potential role of IL-37 in nerve repair and immune regulation in peripheral nerve xenograft hosts.MethodsRat nerve xenografts were transplanted into mouse recipients. Transplanted mice received an intraperitoneal injection of IL-37 on the day before transplantation, whereas control mice remained untreated. At postoperative 2, 4, 8, and 12 weeks, the effects of IL-37 were examined on motor function, tissue morphology, and regenerative ability of xenograft nerves. Levels of IL-17 and IL-22 in serum and spleen were measured at 3, 7, 14, and 28 days after nerve transplantation.ResultsAt 12 postoperative weeks, grafted nerves grew well in IL-37 treatment group, as documented by the recovery in function of sciatic nerves compared to untreated controls. In particular, IL-37-treated mice showed more complete neuromorphology, thicker myelin sheath, compact structure, and the increased number of myelinated nerve fibers in histological examination. The number of T helper (Th)17 (CD3 + CD4 + IL-17+) and Th22 (CD3 + CD4 + IL-22+) cells in the spleen was reduced in the IL-37-treated group, as well as serum IL-17 and IL-22 were decreased after IL-37 treatment compared with the untreated group.ConclusionsIL-37 attenuates immunomodulatory responses induced by xenografts, contributing to the recovery of nerve function and the prevention of muscle atrophy caused by nerve grafts.

Morphological basis of radial nerve dysfunction in newborns differs from that of no radial nerve dysfunction in adults in C5–C6–C7 injuries to the brachial plexus: a cadaveric study

Objective Injuries to the upper and middle trunks of brachial plexus result in dysfunction of radial nerves in newborns but do not in adults. We hypothesized that the radial nerve had a lower proportion of myelinated nerve fibers (MNFs) from the lower trunk in newborns than in adults, and in newborns those MNFs were less developed than MNFs in the radial nerve from the middle and upper trunks. Methods We dissected bilateral brachial plexus of six newborn and six adult cadavers. The radial nerve and its fascicles were separated proximally to posterior divisions of the upper, middle and lower trunks, and fascicles of the radial nerve were harvested from three trunks to calculate respective percentage of MNFs accounting for the total number of MNFs in the radial nerve. We determined diameters of axons and g-ratios of MNFs in the radial nerve from three trunks. Results Compared with adults, the percentage of MNFs in the radial nerve from the lower trunk was lower (p < 0.05), from the middle trunk higher (p < 0.05) and from the upper trunk similar (p > 0.05) in newborns, though MNF counts from three trunks were higher in newborns, respectively (p < 0.01, all). In newborns, MNFs in the radial nerve from the lower trunk had smaller axonal diameters and higher g-ratios than those from the middle and upper trunks (p < 0.017, all), while in adults there were no such differences. Conclusions Lower proportion of MNFs in the radial nerve from the lower trunk in newborns than in adults, and in newborns immaturity of MNFs from the lower trunk relative to MNFs from the middle and upper trunks may be the major morphological basis of difference in clinical appearances of radial nerve palsy caused by injuries to C5–C6–C7 between newborns and adults.

Effects of Theranekron and alpha-lipoic acid combined treatment on GAP-43 and Krox-20 gene expressions and inflammation markers in peripheral nerve injury

ABSTRACT Peripheral nerve injury (PNI) is a major health problem that results in loss of motor and sensory functions. In treatment of PNI, various methods such as anastomosis, nerve grafts, nonneural tissue grafts, and nerve conduits are applied. In the present study, it was aimed to investigate the effects of Theranekron and Alpha-lipoic acid (ALA) combined treatment on nerve healing in experimental PNI by using histomorphometric, electron microscopic, immunohistochemical and molecular biological methods. Sixty-two Wistar rats were divided into six groups; the normal control group, sham operation group, experimental control group having a crush type injury with no treatment, Theranekron treatment group, ALA treatment group and Theranekron+ALA combined treatment group. Sciatic nerve tissue samples were obtained on days 1, 7 and 14 following injury in all groups. GAP-43 expression was upregulated in all PNI received groups compared to the control group. Krox-20 expression was downregulated in all groups that received PNI compared to the control group. While intensely positive TNF-α and IL-6 expressions were observed up to the 1st to the 14th day for the experimental control group, these expressions were seen as “weakly positive” in the treatment groups from the 1st day to the 14th day. The number of myelinated fibers was higher in the control and sham operation groups. Additionally, the number of myelinated nerve fibers increased in the combined treatment group. In conclusion, these findings suggest that combined therapy of Theranekron and ALA promotes structural recovery and it should be considered as an effective treatment protocol following PNI.

Honokiol exerts protective effects on neural myelin sheaths after compressed spinal cord injury by inhibiting oligodendrocyte apoptosis through regulation of ER-mitochondrial interactions

Objective To investigate the effect of honokiol on demyelination after compressed spinal cord injury (CSCI) and it's possible mechanism. Design Animal experiment study. Setting Institute of Neuroscience of Chongqing Medical University. Interventions Total of 69 Sprague–Dawley (SD) rats were randomly divided into 3 groups: sham group (n=15), honokiol group (n=27) and vehicle group (n=27). After established CSCI model by a custom-made compressor successfully, the rats of sham group were subjected to the limited laminectomy without compression; the rats of honokiol group were subjected to CSCI surgery and intraperitoneal injection of 20 mg/kg honokiol; the rats of vehicle group were subjected to CSCI surgery and intraperitoneal injection of an equivalent volume of saline. Outcome measures: The locomotor function of each group was assessed using the Basso, Beattie and Bresnahan (BBB) rating scale. The pathological changes of myelinated nerve fibers of spinal cord in 3 groups were detected by osmic acid staining and transmission electron microcopy (TME). Immunofluorescence and Western blot were used to research the experessions of active caspase-3, caspase-12, cytochrome C and myelin basic protein (MBP) respectively. Results In the vehicle group, the rats became paralyzed and spastic after injury, and the myelin sheath became swollen and broken down along with decreased number of myelinated nerve fibers. Western blot analysis manifested that active caspase-3, caspase-12 and cytochrome C began to increase 1 d after injury while the expression of MBP decreased gradually. After intervened with honokiol for 6 days, compared with the vehicle group, the locomotor function and the pathomorphological changes of myelin sheath of the CSCD rats were improved with obviously decreased expression of active caspase-3, caspase-12 and cytochrome C. Conclusions Honokiol may improve locomotor function and protect neural myelin sheat from demyelination via prevention oligodendrocytes (OLs) apoptosis through mediate endoplasmic reticulum (ER)-mitochondria pathway after CSCI.

Green Tea Polyphenols Promote Functional Recovery from Peripheral Nerve Injury in Rats.

BackgroundPeripheral nerve injury (PNI) is a common and progressive disorder with sensory and motor deficits in the peripheral nervous system (PNS). Treatment is difficult, with unfavorable prognosis. Green tea polyphenols (GTPs) exert neuroprotective effects on regeneration of the central nervous system (CNS). However, the effects of GTPs on functional recovery of the PNS have not been fully characterized. Consequently, the present study investigated the effects of GTPs on nerve regeneration of rats with PNI.Material/MethodsThe model of PNI was established in rats by sciatic nerve injury (SNI). Adult male Wistar rats with SNI were randomly divided into a vehicle group and a GTPs group. The compound muscle action potential (CMAP) of rat sciatic nerves (SN) was measured using the CM6240 physiological signal acquisition and processing system. The wet weight of the triceps muscle was determined using an analytical balance. The number of myelinated nerve fibers was counted under an optical microscope. Ultrastructure of the regenerated nerves in SN was observed by transmission electron microscopy. The mRNA and protein expression of nerve growth factor (NGF), growth-associated protein-43 (GAP-43), neurofilament 200 (NF200), and myelin-associated glycoprotein (MAG) in SN stumps were measured by real-time quantification PCR (RT-qPCR) and Western blot, respectively.ResultsIn rats with SNI, GTPs relieved the adhesion between nerve anastomosis and surrounding tissues, and significantly increased nerve conduction velocity, wet weight of the triceps muscle, and development and axonal regeneration of myelinated nerve fibers. Moreover, GTPs promoted the mRNA and protein expressions of NGF, GAP-43, NF200, and MAG in SN stumps.ConclusionsGTPs promotes nerve regeneration in rats with SNI.

Grafts of human adipose-derived stem cells into a biodegradable poly (acid lactic) conduit enhances sciatic nerve regeneration

Despite the regenerative potential of the Peripheral Nervous System (PNS), injuries with loss of a nerve segment make the functional recovery a challenge. This work aimed to investigate the effects of the association of biodegradable conduits of poly (lactic acid) (PLA) with human adipose-derived stem cells (hADSCs) on the regeneration of the sciatic nerve. C57BL / 6 male mice were submitted to sciatic nerve transection followed by tubulization with PLA conduit. Animals were allocated in two groups: the first received an injection of DMEM inside the conduit (DMEM) and the second received hADSCs inside it (hADSC). Sensory and motor functions were assessed by the pinprick test and electroneuromiography, respectively. To assess neuronal survival the retrograde tracer fluorogold was injected into the sciatic nerve distally to the lesion site. One week after that, animals were sacrificed, tissues harvested and processed for morphological evaluation. After eight weeks, all animals showed sensory recovery in the pinprick test and there was no significant difference between the two groups. The amplitude of the compound muscle action potential was higher in the hADSCs group. The number of myelinated nerve fibers, muscle cells and motor plates was higher in the hADSC group. There was also greater survival of sensory and motor neurons in the hADSC animals. These results suggest that the association of PLA conduit and cell therapy with hADSCs leads to a better functional and morphological recovery after sciatic nerve transection.

Investigation of adult-onset multiple acyl-CoA dehydrogenase deficiency associated with peripheral neuropathy.

Multiple Acyl-CoA dehydrogenase deficiency (MADD), one of the most common lipid storage myopathies (LSMs), is a heterogeneous inherited muscular disorder that is pathologically characterized by numerous lipid droplets in muscle fibers due to lipid metabolism disturbance. MADD exhibits a wide range of clinical features, including skeletal muscle weakness and multisystem dysfunctions. However, MADD, as well as other types of LSM, associated with peripheral neuropathy has rarely been reported during the past four decades. Here, we present four Chinese patients affected by MADD with peripheral neuropathy in our neuromuscular center. Clinically, these four patients showed skeletal muscle weakness and prominent paresthesia. Muscle biopsy detected characteristic myopathological patterns of LSM, such as obvious lipid droplets in muscle fibers. Sural nerve biopsy revealed a severe reduction in number of myelinated nerve fibers, which is a typical neuropathological pattern of peripheral neuropathy. Causative ETFDH mutations were found in all four cases. The skeletal muscle weakness was rapidly improved after some treatments while paresthesia showed unsatisfactory improvement. The features of previously reported patients of this specific type are also summarized in this paper. We propose that MADD with peripheral neuropathy may be a new phenotypic subtype because the pathology and reaction to riboflavin treatment are different from those of traditional MADD, although further research on the precise pathogenesis and mechanisms is needed.

Transfer of the Distal Anterior Interosseous Nerve for Thumb Motion Reconstruction in Radial Nerve Paralysis

With nerve or tendon surgery, the results of thumb reconstruction to treat radial nerve paralysis are suboptimal. The goals of this study were to describe the anatomy of the deep branch of the posterior interosseous nerve (PIN) to the thumb extensor muscles (DBPIN), and to report the clinical results of transferring the distal anterior interosseous nerve (DAIN) to the DBPIN. The PIN was dissected in 12 fresh upper limbs. Myelinated nerve fibers in the DBPIN and DAIN were counted. Five patients with radial nerve paralysis underwent transfer of the motor branch to the flexor carpi radialis to the PIN and a motor branch of the pronator teres to the extensor carpi radialis brevis. In addition, these patients had selective reconstruction of thumb motion by transferring the DAIN to the DBPIN, through either a combined volar and dorsal approach (n= 2) or a single dorsal approach (n= 3) with division of the interosseous membrane. At the origin of the abductor pollicis longus, the DBPIN divided into a lateral branch that innervated the abductor pollicis longus and extensor pollicis brevis, and a medial branch that innervated the extensor pollicis longus and extensor index proprius. The number of myelinated nerve fibers in the DAIN corresponded to 65% of that of the DBPIN. In each of the 5 patients, full thumb motion at the trapeziometacarpal joint was restored with no, or minimal, extension lag at the metacarpophalangeal (MCP) joint. The anatomy of the DBPIN is predictable. Transferring the DAIN to the DBPIN is feasible through a single dorsal approach, allowing full recovery of thumb motion. Therapeutic V.

Experimental study on the effect of green tea polyphenols combined with Mecobalamin on the repair of peripheral nerve injury

Objective To investigate the effect of green tea polyphenols combined with Mecobalamin on nerve regeneration after sciatic nerve injury and repair. Methods Sixty adult Wistar rats were randomly divided into two groups, the experimental group and the control group, 30 rats in each group. Another 6 Wistar rats were taken as the blank control group. The experimental group was given green tea polyphenols 50 mg/(kg·d) and Mecobalamin 50 μ g/(kg·d) by gavage, while the control group was given Mecobalamin 50 μ g/(kg·d) by gavage for 2 weeks. Then the general condition, electrophysiological recovery, wet weight recovery rate of triceps surae muscle, the number of myelinated nerve fibers and the difference of histopathology were observed. Results The average nerve conduction velocity and myelinated nerve fiber count in the experimental group were significantly higher than those in the control group at the 2nd, 4th and 6th week after operation (P 0.05), and there was no significant difference between the experimental group, the control group and the blank control group at the 12th week after operation (P>0.05). The recovery rate of wet weight of triceps surae muscle in experimental group was significantly higher than that in control group (P<0.05). In the experimental group, the regenerated myelinated nerve fibers were evenly distributed, arranged relatively orderly, with high density and less hyperplasia of connective tissue. Conclusion The green tea polyphenols may play an important role in promoting peripheral nerve regeneration. Key words: Peripheral nerve; Nerve regeneration; Green tea polyphenols; Mecobalamin

Intraoperative single administration of neutrophil peptide 1 accelerates the early functional recovery of peripheral nerves after crush injury.

Neutrophil peptide 1 belongs to a family of peptides involved in innate immunity. Continuous intramuscular injection of neutrophil peptide 1 can promote the regeneration of peripheral nerves, but clinical application in this manner is not convenient. To this end, the effects of a single intraoperative administration of neutrophil peptide 1 on peripheral nerve regeneration were experimentally observed. A rat model of sciatic nerve crush injury was established using the clamp method. After model establishment, a normal saline group and a neutrophil peptide 1 group were injected with a single dose of normal saline or 10 μg/mL neutrophil peptide 1, respectively. A sham group, without sciatic nerve crush was also prepared as a control. Sciatic nerve function tests, neuroelectrophysiological tests, and hematoxylin-eosin staining showed that the nerve conduction velocity, sciatic functional index, and tibialis anterior muscle fiber cross-sectional area were better in the neutrophil peptide 1 group than in the normal saline group at 4 weeks after surgery. At 4 and 8 weeks after surgery, there were no differences in the wet weight of the tibialis anterior muscle between the neutrophil peptide 1 and saline groups. Histological staining of the sciatic nerve showed no significant differences in the number of myelinated nerve fibers or the axon cross-sectional area between the neutrophil peptide 1 and normal saline groups. The above data confirmed that a single dose of neutrophil peptide 1 during surgery can promote the recovery of neurological function 4 weeks after sciatic nerve injury. All the experiments were approved by the Medical Ethics Committee of Peking University People's Hospital, China (approval No. 2015-50) on December 9, 2015.

Comparative study of pronator teres branch transfer and brachialis motor branch transfer to the anterior interosseous nerve to treat lower brachial plexus injury in rats

Distal nerve transfer is used to treat lower brachial plexus palsy, but outcome series on these transfer procedures following lower plexus injuries are sparse. The objective of this study is to compare treatment outcomes after nerve transfer using the brachialis motor branch (BMB) versus that using the pronator teres motor branch (PTMB). One hundred twenty adult rats with C8T1 nerve root avulsion were randomly divided into three groups (40 each): A: BMB transfer to the anterior interosseous nerve (AIN), B: PTMB transfer to the AIN, and C: no repair. Electrophysiological examination result, muscle tension test result, muscle weight and muscle fiber cross-sectional area of the flexor digitorum profundus and flexor pollicis longus, and number of myelinated nerve fibers in the AIN were compared among the groups to evaluate the treatment outcome. Nerve regeneration and muscle recovery in group B was better than those in group A at 4 and 8 weeks postoperatively (P<0.05). There was no significant difference in the myelinated nerve fibers in groups A and B at 12 and 16 weeks postoperatively. The rats in group B showed greater and more significant improvement in other measured values than those in group A (P<0.05). In conclusion, the PTMB seems a better donor nerve than the BMB for distal nerve transfer to treat lower brachial plexus injury according to the electrophysiological and histological examination in this rat study.