A study on peripheral nerve regeneration via biomimetic conduits loadedwith Schwann cells and nerve growth factor

Guided tissue regeneration is a new approach in the reconstructive surgery of pe-ripheral nerves. Biomimetic conducts were construct from the expanded vein onwhose inner surface composited with amnion filaments( cf.Fig1 ) .F ig.1　 The Scheme of biomim etic conduit1 .Proximal nerve2 . Nerve growth factor ( NGF)3.Schwann cell( SC)4 . Amnion filaments with 1 mm in width and 1 5mm in length5.The expanded vein( V) with1 8mm in length6. Distal nerve　　 Conduit made from( 1 ) the expanded vei…     

The effect of collagen-binding NGF-β on the promotion of sciatic nerve regeneration in a rat sciatic nerve crush injury model

Nerve growth factor plays a critical role in peripheral nerve regeneration. However, the lack of efficient NGF delivery approach limits its clinical application. It has demonstrated in our previous work that the native human NGF-β (NAT-NGF) fused with a collagen-binding domain (CBD) could bind to collagen specifically. Since collagen is the major component of nerve extracellular matrix, we speculated that the collagen-binding NGF would target to nerve cells and improve their regeneration. In this report, we found that the fusion protein could specifically bind to endogenous collagen of the rat sciatic nerves and maintain NGF activity both in vitro and in vivo. In the rat sciatic nerve crush injury model, we found that collagen-binding NGF could be retained and concentrated at the nerve injured site to promote nerve repair and enhance function recovery following nerve damage. Thus, the collagen-binding NGF could improve the repair of peripheral nerve injury.     

Neuromediators in inflammation—a macrophage/nerve connection

Macrophages are key players not only during initiation of inflammation but also during its resolution. This is achieved by their high functional plasticity and the demand to recognize an enormous repertoire of danger signals and cytokines/chemokines derived from adaptive immune cells. Studies predominantly conducted over the last two decades implicate that macrophage responses are also modulated by neuronal mediators such as neurotransmitters or neurotrophic factors. Here we summarize the current understanding of neuromediator-dependent interplay between macrophages and the nervous system.     

Is the cranial accessory nerve really a portion of the accessory nerve? Anatomy of the cranial nerves in the jugular foramen

The accessory nerve is traditionally described as having both spinal and cranial roots, with the spinal root originating from the upper cervical segments of the spinal cord and the cranial root originating from the dorsolateral surface of the medulla oblongata. The spinal rootlets and cranial rootlets converge either before entering the jugular foramen or within it. In a recent report, this conventional view has been challenged by finding no cranial contribution to the accessory nerve. The present study was undertaken to re-examine the accessory and vagus nerves within the cranium and jugular foramen, with particular emphasis on the components of the accessory nerve. These nerves were traced from their rootlets attaching to the spinal cord and the medulla and then through the jugular foramen. The jugular foramen was exposed by removing the dural covering and surrounding bone. A surgical dissecting microscope was used to trace the roots of the glossopharyngeal nerve (CN IX), vagus nerve (CN X) and accessory nerve (CN XI) before they entered the jugular foramen and during their travel through it. The present study demonstrates that the accessory nerve exists in two forms within the cranial cavity. In the majority of cases (11 of 12), CN XI originated from the spinal cord with no distinct contribution from the medulla. However, in one of 12 cases, a small but distinct connection was seen between the vagus and the spinal accessory nerves within the jugular foramen.     

Does the conduction velocity distribution change along the nerve?

Nerve conduction velocity distribution (CVD) is a very useful tool to examine the state and function of nerves. Only one record of compound action potential (CAP) may be sufficient to determine the CVD if the shape functions of the single fiber action potentials (SFAP) of fibers are known. Otherwise, CAP recordings from different locations are necessary to determine CVD. In this case, we confront the problem of whether the shape of the CVD changes along the nerve, because many methods that attempt to determine the CVD are based on the assumption that the CVD is invariant along the nerve. There is not a complete solution to this problem, but there are many suggestions allied with the recording conditions to minimise this effect. The other effect that may influence both shapes of CAP and CVD along the nerve is the volume conductor effect. If a suitable model could isolate and eliminate the volume conductor effect, then the spatial variation of CVD may be attributed to the natural conditions of the nerve. In this study, we followed a procedure to eliminate volume conductor effect and then applied our previously published model to examine the spatial variations in CVD. The results show that CVDs estimated at discrete points along the nerve trunk have significantly different patterns. Consequently, it may be concluded that CVD is not uniform along an isolated nerve trunk contrary to the assumptions of the most CVD estimation methods.     

αN-catenin expression in the normal and regenerating chick sciatic nerve

Summary The Ca²⁺-dependent intercellular adhesion molecule cadherin is known to be linked to the cytoskeleton by the protein catenin, an association of which appears to be important for the cell-adhesion function of cadherin. Catenin consists of three subtypes-, , and . In our previous study, N-cadherin was shown to be localized on the plasmalemma of normal and regenerating chick peripheral nerve. Thus, as N-catenin is a subtype of -catenin (which is specifically associated with N-cadherin), we investigated the immunolocalization of N-catenin in normal and regenerating chick sciatic nerve. In normal nerve, unmyelinated axons exhibited either intense or weak N-catenin immunoreactivity throughout the axoplasm, whereas myelinated axons were completely immunonegative. Regenerating axons, including those derived from parent myelinated axons, showed N-catenin immunoreactivity of variable intensities in growth cones and axon shafts. Schwann cells were invariably devoid of immunoreactivity. Thus N-catenin is not necessarily bound to the surface plasmalemma, but is distributed throughout the cytoplasm, suggesting that most N-catenin molecules are dissociated from N-cadherin.     

Problem in diagnostic imaging: Have you got the nerve?

This article poses a diagnostic problem commonly encountered in neuroradiology and otolaryngology. The solution and ensuing discussion focus on the anatomy of the posterior cranial fossa (with emphasis on the cerebellopontine angle) and the relevant pathology. Current methods of imaging the posterior cranial fossa are explained and their relative merits discussed. Clin. Anat. 10:345–348, 1997. © 1997 Wiley-Liss, Inc.     

Hematopoietic colony-stimulating factors: new players in tumor–nerve interactions

A variety of cancers are accompanied by debilitating pain, which constitutes the primary reason for poor quality of life in cancer patients. There is an urgent demand for the development of specific mechanism-based therapies against cancer pain. Recently, important advances have been made in mechanisms contributing to cancer pain. A notable finding was that the tumor-derived hematopoietic growth factors, granulocyte- and granulocyte-macrophage-colony-stimulating factors (G-CSF/GM-CSF), subserve important functions in the generation of pain hypersensitivity in tumor-affected regions. In this context, their receptors were unexpectedly found on pain-sensing nerves and were observed to be functionally linked to nociceptive sensitization and tumor-induced pain. Here, we review evidence supporting a role for G-/GM-CSF in sensitization of pain-sensing nerves, the underlying signaling pathways and the cross-talk with other pronociceptive cytokines, peptides and modulators derived from immune cells, osteoclasts and tumor cells. These findings hold implications in the therapy of pain in disease states, such as cancer and rheumatoid arthritis.     

The complement system in the peripheral nerve: friend or foe?

The complement (C) system plays a central role in innate immunity and bridges innate and adaptive immune responses. A fine balance of C activation and regulation mediates the elimination of invading pathogens and the protection of the host from excessive C deposition on healthy tissues. If this delicate balance is disrupted, the C system may cause injury and contribute to the pathogenesis of various diseases, including neuropathies. Here we review evidence indicating that C factors and regulators are locally synthesized in the peripheral nerve and we discuss the evidence supporting the protective or detrimental role of C activation in health, injury and disease of the peripheral nerve.     

Acute peripheral facial palsy: Is there a trigeminal nerve involvement?

The aim of this study was to investigate trigeminal nerve involvement in patients with peripheral facial palsy. In total, 25 patients with facial nerve palsy and 19 controls were tested by electrophysiological methods regarding their facial and trigeminal nerve functions within 1 month after disease onset. The presence of an abnormal blink reflex was determined in patients with peripheral facial palsy by comparing paralytic and non-paralytic sides (12.3 ± 1.1 and 10.8 ± 1.3, respectively; p = 0.001). However, the average masseter inhibitory reflex difference between the paretic and non-paralytic sides of patients compared with the corresponding side-to-side comparison for controls was not statistically significant. The masseter inhibitory reflex response was abnormal in some cases. These findings suggest that the masseter inhibitory reflex, a trigemino–trigeminal reflex, was normal in most of our patients with peripheral facial palsy, but may be abnormal in individual cases. Our study showed that subclinical disorders affecting the trigeminal pathways occur in individual patients with idiopathic facial palsy, while the majority of patients have no trigeminal nerve involvement.     

Anodal block: can this occur during routine nerve conduction studies?

The median nerves of five normal subjects were electrically excited at the wrist with fine-tipped stimulating electrodes in a bipolar fashion. Compound sensory nerve action potentials (CSNAPs) were recorded from the index finger and compound muscle action potentials (CMAPs) from the thenar muscles. Both the cathode and the anode were positioned over the length of the nerve. Recordings were performed with different cathode-to-anode distances of 5, 10, 20, and in some cases, 30 mm. Just supramaximal CSNAPs and CMAPs were obtained initially with the cathode situated distal to the anode and then with the stimulus polarity reversed. There were no significant differences in the amplitude, duration, and morphology of the CSNAPs or CMAPs that were recorded by using different stimulus polarities. There was a consistent increase in the onset latency of the responses when the stimulus polarity was reversed (cathode located proximal to anode). This increase in latency was proportionate to the increase in distance from the cathode to the recording electrode. The effect of anodal block could not be observed from the above experiment.     

A case of Sjögren's syndrome presenting as trigeminal nerve palsy

We herein report the case of a female with Sjogren's syndrome (SS) complicated with trigeminal nerve palsy. Although her sicca symptoms had been unnoticed, head magnetic resonance imaging (MRI) for detecting brain abnormalities revealed parotid gland changes associated with SS. SS should be considerd as a possible cause of trigeminal nerve disturbances. In addition, parotid gland changes related to SS should be aware in examination of cranial nerve disturbances with MRI.     

Median nerve compression at the wrist: is it ever unilateral?

OBJECTIVE: Carpal Tunnel Syndrome (CTS) is commonly bilateral, but symptoms and EMG/NCS abnormalities may be seen unilaterally. This study was designed to determine whether there are any subclinical nerve conduction abnormalities on the "uninvolved" side. DESIGN: Statistical analysis of electrodiagnostic data. SETTING: Outpatient academic electrodiagnostic laboratory. PATIENTS: Twenty-two successive patients referred for bilateral upper extremity NCS/EMG with no symptoms or physical signs of CTS and totally normal results, and ten successive patients with an EMG/NCS diagnosis of CTS on one side, and completely normal EMG/NCS on the contralateral side. RESULTS: The median motor and sensory latencies at the wrist were significantly longer in the contralateral "uninvolved" limb than normals (median motor latency 3.75 vs. 3.30 msecs, p = 0.0005, median sensory latency 3.40 vs 3.00 msecs, p = 0.0002). Median sensory amplitude was smaller in the contralateral limb (30.5 uV vs. 41.5 uV, p = 0.0062). The (median-radial) D1 sensory latency difference was greater in the contralateral wrist (0.2 vs. 0.0 msecs, p = 0.0217). The (median-ulnar) sensory latency difference was not significantly increased (0.15 vs. 0.10 msecs, p = 0.2020). CONCLUSIONS: The contralateral limbs of patients with unilateral CTS show significant differences from normals in 4 out of 5 nerve conduction parameters. There is evidence of frequent subclinical median nerve compression in this group.     

Are there one million nerve fibres in the human medullary pyramid?

It has been the accepted opinion that there are one million nerve fibres in the human medullary pyramid. This seemed to be confirmed in several old reports. But we cannot agree with this opinion. We made nitrocellulose-embedded sections from three normal male brains, and stained them by our modification of Masson-Goldner method. With this method, myelinated axons appeared in blue, whereas the glial processes were coloured in red, which allowed easy discrimination between the two. After morphometric evaluation of the pyramidal axons under the microscope, it appeared without the slightest doubt, that the number of axons does not exceed one-tenth of one million.     

Selective stimulation of smaller nerve fibers by single electrode using Biphasic Rectangular Pulses

INTRODUCTION　　Selectivestimulationofsmallernervefibersinacompoundnervetrunkisanim-portantprobleminFunctionalElectricalStimulation(FES)ofthemotorsysteminpatientshavinguppermotorneuroninjures.Undernormalphysiologicalconditions,theneverfibersinacompoundner…     

Early manifestations of pancreatic cancer: The effect of cancer–nerve interaction

Clinical manifestation is important for the diagnosis of pancreatic cancer (PanCa). No typical symptoms have been identified that clearly indicate the early stage of PanCa, although most patients with PanCa have symptoms before the cancer is diagnosed. These symptoms are often regarded as common gastrointestinal symptoms and are ignored. The pancreas is richly supplied with nerves, and neuro-cancer interactions begin prior to PanCa cell migration. We hypothesise that the cancer–nerve interaction does generate typical symptoms such as pseudomorphous satiety and mild pain in early PanCa. Constant satiety leads to weight loss. This biological behaviour allows the cancer to progress without attention from the cancer-bearing host. Cancer cells also target the endocrine pancreas, generating a hyperglycaemic state that results in increased energy for cancer cells. The combination of the so-called common gastrointestinal symptoms and diabetes may represent early typical symptoms of PanCa that can be used to improve early diagnosis.     

Quercetin ameliorates peripheral nerve ischemia–reperfusion injury through the NF-kappa B pathway

This study aimed to investigate the protective effect of quercetin against ischemia–reperfusion (IR) injury induced in the sciatic nerve of the rat. Quercetin (20 mg/kg) was given during ischemia just before reperfusion. Four groups of rats (Q+IR3, Q+IR7, Q+IR14, and Q+IR28) received 3, 7, 14, and 28 days of reperfusion, respectively, after the intraperitoneal injection of quercetin. After reperfusion, a behavioral test was performed and the sciatic functional index was calculated. Each sciatic nerve was stained to check for edema and ischemic fiber degeneration. Immunohistochemical staining was performed to detect TNF-alpha and NF-kappa B, and TUNEL staining was carried out to detect apoptosis. The Q+IR3, Q+IR7, and Q+IR14 groups showed significantly increased behavioral scores and ameliorated sciatic functional index values compared to IR-injured rats that received vehicle alone during ischemia and then the same period of reperfusion. The Q+IR3, Q+IR7, Q+IR14, and Q+IR28 groups presented significant ischemic fiber degeneration (IFD), TNF-alpha expression, and apoptosis as compared with the IR-injured and perfused rats that did not receive quercetin. The Q+IR3, Q+IR7, and Q+IR28 groups also exhibited significantly decreased NF-kappa B expression (p < 0.001, p = 0.001, p = 0.026) as compared with the IR-injured rats that were perfused but did not receive quercetin. These results imply that quercetin may be beneficial in the treatment of sciatic IR injury because of its antiapoptotic and antiinflammatory effects and its ability to decrease the expression of NF-kappa B.     

Segmental nerve damage during a McBurney’s incision: a cadaveric study

Injury to the ilioinguinal and iliohypogastric nerves after a McBurneys incision have been reported to cause paralysis of the conjoint tendon that may lead to the development of an indirect inguinal hernia. This study reports on the incidence of ilioinguinal and iliohypogastric nerve sectioning after the performance of a classic McBurneys incision as well as the distance and relationship of the ilioinguinal and iliohypogastric nerves to the anterior superior iliac spine and a classic McBurneys incision. The right iliac fossa and lumbar region of 33 cadavers were dissected for the uncovering of the ilioinguinal and iliohypogastric nerves after a correct McBurneys incision was made. Injury to the ilioinguinal and iliohypogastric nerves was recorded. The mean distance between the ilioinguinal nerve and the incision line was 41.89 mm and 34.63 mm between the iliohypogastric nerve and the incision line. The ilioinguinal and iliohypogastric nerves were found to be 6.69 mm and 12.08 mm from the anterior superior iliac spine, respectively. No ilioinguinal or iliohypogastric nerve was injured during all 33 McBurneys incisions.