Intact Nerve Research Articles

Sustained Decrease in Blood Pressure and Reduced Anatomical and Functional Reinnervation of Renal Nerves in Hypertensive Sheep 30 Months After Catheter-Based Renal Denervation.

We examined whether renal denervation (RDN) reduced blood pressure (BP), improved glomerular filtration rate, albuminuria, and left ventricular mass in sheep with hypertensive chronic kidney disease (CKD). To examine whether renal nerve function returned in the long term, we examined vascular contraction to nerve stimulation in renal arteries and determined nerve regrowth by assessing renal TH (tyrosine hydroxylase), CGRP (calcitonin gene-related peptide), and norepinephrine levels in kidneys at 30 months after RDN. RDN normalized BP in hypertensive CKD sheep such that BP was similar to that of the normotensive sheep with intact nerves. Glomerular filtration rate decreased by ≈22% in CKD sheep with intact nerves but increased ≈26% in hypertensive CKD-RDN sheep by 30 months. At 30 months, urinary albumin was ≈127% and left ventricular mass was ≈41% greater in CKD sheep with intact nerves than control. However, urinary albumin was ≈60% less and left ventricular mass was ≈40% less in the CKD sheep that underwent RDN compared with intact counterpart. At 30 months in CKD-RDN sheep, neurovascular contraction (≈56%), renal proportion of TH (≈50%), CGRP (≈67%), and norepinephrine content (≈49%) were all less than CKD-intact; all these variables were similar between normotensive-intact and normotensive-RDN groups. RDN caused a sustained reduction in BP and improvements in renal function. Regrowth of renal nerves and return of function were observed in hypertensive CKD-RDN sheep, but levels were only partially restored to levels of intact. These suggest that RDN lowers BP in the long term and is renoprotective and cardioprotective as a result of lesser nerve regrowth in CKD.

Auditory Brainstem Implantation: An Overview

An auditory brainstem implant (ABI) is a surgically implanted central neural auditory prosthesis for the treatment of profound sensorineural hearing loss in children and adults who are not cochlear implant candidates due to a lack of anatomically intact cochlear nerves or implantable cochleae. The device consists of a multielectrode surface array which is placed within the lateral recess of the fourth ventricle along the brainstem and directly stimulates the cochlear nucleus, thereby bypassing the peripheral auditory system. In the United States, candidacy criteria for ABI include deaf patients with neurofibromatosis type 2 (NF2) who are 12 years or older undergoing first- or second-side vestibular schwannoma resection. In recent years, several non-NF2 indications for ABI have been explored, including bilateral cochlear nerve avulsion from trauma, complete ossification of the cochlea due to meningitis, or a severe cochlear malformation not amenable to cochlear implantation. In addition, growing experience with ABI in infants and children has been documented with encouraging outcomes. While cochlear implantation generally remains the first-line option for hearing rehabilitation in NF2 patients with stable tumors or post hearing preservation surgery where hearing is lost but a cochlear nerve remains accessible for stimulation, an ABI is the next alternative in cases where the cochlear nerve is absent and/or if the cochlea cannot be implanted. Herein, we review ABI device design, clinical evaluation, indications, operative technique, and outcomes as it relates to lateral skull base pathology.

The vagus nerve role in antidepressants action: Efferent vagal pathways participate in peripheral anti-inflammatory effect of fluoxetine

The mechanisms responsible for the anti-inflammatory effects of antidepressants are only partially understood. Published data indicate that the vagal anti-inflammatory pathway could be involved in mediating this effect. Therefore, we investigated the influence of subdiaphragmatic vagotomy on the anti-inflammatory effect of fluoxetine in rats injected with lipopolysaccharide (LPS) to induce an inflammatory response. The extent of this response was determined by measurement of TNF-α, IL-1β, and IL-6 plasma levels, along with gene expression of TNF-α, IL-1β, and IL-6 in the spleen and selected structures of the brain. To evaluate possible central mechanisms, c-fos mRNA levels were determined in the nucleus of the solitary tract, dorsal motor nucleus of the vagus, paraventricular hypothalamic nucleus, basolateral amygdala, central nucleus of the amygdala, hippocampus, and frontal cortex. We found that pretreatment with fluoxetine substantially prevented LPS-induced increases of pro-inflammatory cytokines in plasma and gene expression in the spleen and brain in animals with an intact vagus nerve. However, in vagotomized animals, fluoxetine pretreatment only partially attenuated the LPS-induced increase in these markers of peripheral inflammation. Our data has shown that fluoxetine exerts potent anti-inflammatory effects in both the periphery and brain. Moreover, we found that the peripheral anti-inflammatory action of fluoxetine is mediated, at least partially, by activation of a vagal anti-inflammatory pathway. The role of the vagus nerve in mediating the anti-inflammatory effects of antidepressants has been marginally explored and our findings highlight its potential contribution to this mechanism of action of antidepressants.

Impact of Uncomplicated Total Thyroidectomy on Voice and Swallowing Symptoms: a Prospective Clinical Trial

Voice and swallowing alterations are frequently reported after thyroidectomy, even in absence of nerve injury. The symptoms impair the quality of life. Aim of the study was to evaluate prospectively vocal function and swallowing symptom changes after total thyroidectomy in the early and late postoperative period. Prospective observational study. All consecutive patients scheduled for total thyroidectomy were included. Subjective voice evaluation using the Greek version of Voice Handicap Index (VHI) was performed preoperatively and at 2nd postoperative day, 1 month, 12 months postoperatively to assess the functional outcome. Laryngoscopy was performed at the same timing. Subjective swallowing evaluation using the Swallowing Impairment score (SIS) evaluated the swallowing symptoms. The study population included 125 patients. Total VHI score differed significantly between preoperative values and at 48 h and 1 year postoperatively (p = 0.000). Significant changes were observed for the functional and emotional domain of VHI between preoperative and 48 h postoperatively (p = 0.001, 0.003, respectively). There were statistically significant changes for physical domain of VHI between preoperative values and values at 48 h and 1 year (p = 0.000, 0.001, respectively). Regarding the swallowing symptoms, the mean postoperative score at 1 month did not differ significantly from the mean preoperative score (p = 0.103). Swallowing alterations showed a tendency to increase 48 h postoperatively and decreased thereafter. Swallowing score at 1 year postoperatively was statistical significant lower compared to preoperative values. Even with intact laryngeal nerves, transient voice and swallowing alterations may occur after total thyroidectomy. Patients should be informed about these mild changes to lower anxiety following the operation.

Regenerative Failure Following Rat Neonatal Chorda Tympani Transection is Associated with Geniculate Ganglion Cell Loss and Terminal Field Plasticity in the Nucleus of the Solitary Tract

Neural insult during development results in recovery outcomes that vary dependent upon the system under investigation. Nerve regeneration does not occur if the rat gustatory chorda tympani nerve is sectioned (CTX) during neonatal (≤P10) development. It is unclear how chorda tympani soma and terminal fields are affected after neonatal CTX. The current study determined the impact of neonatal CTX on chorda tympani neurons and brainstem gustatory terminal fields. To assess terminal field volume in the nucleus of the solitary tract (NTS), rats received CTX at P5 or P10 followed by chorda tympani label, or glossopharyngeal (GL) and greater superficial petrosal (GSP) label as adults. In another group of animals, terminal field volumes and numbers of chorda tympani neurons in the geniculate ganglion (GG) were determined by labeling the chorda tympani with DiI at the time of CTX in neonatal (P5) and adult (P50) rats. There was a greater loss of chorda tympani neurons following P5 CTX compared to adult denervation. Chorda tympani terminal field volume was dramatically reduced 50 days after P5 or P10 CTX. Lack of nerve regeneration after neonatal CTX is not caused by ganglion cell death alone, as approximately 30% of chorda tympani neurons survived into adulthood. Although the total field volume of intact gustatory nerves was not altered, the GSP volume and GSP-GL overlap increased in the dorsal NTS after CTX at P5, but not P10, demonstrating age-dependent plasticity. Our findings indicate that the developing gustatory system is highly plastic and simultaneously vulnerable to injury.

Sympathetic afferents in the hypogastric nerve facilitate nociceptive bladder activity in cats.

This study in α-chloralose-anesthetized cats revealed a role of hypogastric nerve afferent axons in nociceptive bladder activity induced by bladder irritation using 0.25% acetic acid (AA). In cats with intact hypogastric and pelvic nerves, AA irritation significantly ( P < 0.05) reduced bladder capacity to 45.0 ± 5.7% of the control capacity measured during a saline cystometrogram (CMG). In cats with the hypogastric nerves transected bilaterally, AA irritation also significantly ( P < 0.05) reduced bladder capacity, but the change was significantly smaller (capacity reduced to 71.5 ± 10.6% of saline control, P < 0.05) than that in cats with an intact hypogastric nerve. However, application of hypogastric nerve stimulation (HGNS: 20 Hz, 0.2 ms pulse width) to the central end of the transected nerves at an intensity (16 V) strong enough to activate C-fiber afferent axons facilitated the effect of AA irritation and further ( P < 0.05) reduced bladder capacity to 48.4 ± 7.4% of the saline control. This facilitation by HGNS was effective only at selected frequencies (1, 20, and 30 Hz) when the stimulation intensity was above the threshold for activating C-fibers. Tramadol (an analgesic agent) at 3 mg/kg iv completely blocked the nociceptive bladder activity and eliminated the facilitation by HGNS. HGNS did not alter non-nociceptive bladder activity induced by saline distention of the bladder. These results indicate that sympathetic afferents in the hypogastric nerve play an important role in the facilitation of the nociceptive bladder activity induced by bladder irritation that activates the silent C-fibers in the pelvic nerve.

Possibility of reinnervation and prevention of distal target organ atrophy following side to side neurorrhaphy to the intact nerve after end to end repair of proximal transected peripheral nerves

The aim of the study is to investigate the possibility of reinnervation and prevention of muscle atrophy following side to side neurorrhaphy to the intact nerve after end to end repair of proximal transected peripheral nerves in order to prevent distal target organ atrophy. For this, four groups each containing five Sprague–Dawley female rats were used. In group I, no surgical procedure was performed as a control group. In group II, side to side distal neurorrhaphy performed to the tibial and peroneal nerves after end to end repair of transected proximal tibial nerve. In group III. distally side to side epineural neurorrhaphy performed to the tibial and peroneal nerves. In group IV, end to end epineural repair was performed after proximal tibial nerve transection. The rats were followed up for 3 months for nerve regeneration. Subsequently group II, III and IV were evaluated histopathologically. In all group, tibial and fibular bony weights, foot weights, anterior and posterior crural muscle weights and EMG parameters were evaluated. Comparison between the groups revealed no significant differences regarding EMG and muscle weights between groups 2 and 4 also axonal degeneration was observed in 3 group after neurorrhaphy. As result of experimental study, we think that side to side repair of intact distal nerves as an adjunct to end to end repair of proximal nerve transections has no additional benefit to prevent distal organ atrophy but rather may be caused harm on the intact nerve. In addition, it has been observed that this technique affects the intact nerve rather than the transected nerve.

Plasticity of Unmyelinated Fibers in a Side-to-end Tubulization Model.

Background:Histomorphometric studies of unmyelinated fibers of the rat fibular nerves are uncommon, and side-to-end neurorrhaphy studies using the fibular nerve investigate primarily motor fibers. We investigated side-to-end tubulization (SET) technique, in which occurs collateral sprouting from the intact donor nerve fibers to the distal stump of receptor nerve, with muscle reinnervation and functional rehabilitation, to assess whether there is a successful growth of unmyelinated fibers in this model.Methods:Adult Wistar rats fibular nerves were sectioned to create a 5-mm gap. A 6-mm silicone tube was attached between a side of the intact tibial nerve and the sectioned fibular nerve distal stump (SET group), with the left fibular nerve as normal (sham group). Seventy days postsurgery, unmyelinated fibers from the distal segment of the fibular nerve were quantified using light and transmission electron microscopy and their diameters were measured.Results:The number of unmyelinated fibers was similar between sham (1,882 ± 270.9) and SET (2,012 ± 1,060.8), but axons density was significantly greater in the SET (18,733.3 ± 5,668.6) than sham (13,935.0 ± 1,875.8). Additionally, the axonal diameters differed significantly between groups with mean measures in sham (0.968 ± 0.10) > SET (0.648 ± 0.08).Conclusions:Unmyelinated fiber growth occurred even with a 5-mm distance between the donor and receptor nerves, reaching similar axonal number to the normal nerve, demonstrating that the SET is a reliable technique that can promote a remarkable plasticity of unmyelinated axons.

Toward a phenomic analysis of chronic postsurgical pain following cardiac surgery

ABSTRACT Background Despite the same surgical approach, up to 40% of patients develop chronic postsurgical pain (CPSP) following cardiac surgery, whereas the rest are chronic pain free. This variability suggests that CPSP is controlled partially through genetics, but the genes for CPSP are largely unknown. Aims The aim of this study was to identify potential CPSP phenotypes by comparing patients who developed CPSP following cardiac surgery vs. those who did not. Methods A research ethics board–approved, cross-sectional study of post–cardiac surgery pain was conducted at Toronto General Hospital from 2011 to 2015. Patients were recruited to complete a short survey of chronic pain scores and the Short-Form McGill Pain Questionnaire–2. A subset of patients completed a longer survey of eight validated pain phenotyping questionnaires and/or four psychophysical assessments. All surveys and psychophysical testing were conducted after surgery. Patients were stratified by presence of chronic pain and groups were compared using descriptive statistics. Results Six hundred forty-three patients completed the short form survey. The mean postsurgery assessment time was 41.5 (SD = ±25.1) months. Over a quarter (27.8%) reported CPSP at the chest as a consequence of their surgery. Of patients reporting CPSP, 46.6% reported mild pain (0–3), 35.8% reported moderate pain (4–7), and 17.6% reported severe pain (7–10) in accordance with the numerical rating scale. Patients with moderate and/or severe CPSP were younger, had a greater body mass index, and had higher anxiety sensitivity, pain catastrophizing, and somatization scores. Conclusions Chronic pain levels after cardiac surgery are associated with anxiety, catastrophizing, and sensory abnormalities in body parts outside the field innervated by injured nerves, indicating the presence of widespread central sensitization to incoming sensory inputs from intact nerves.

Epithelial myoepithelial carcinoma arising in a pleomrophic adenoma

Epithelial–myoepithelial carcinoma (EMC) is a rare and low-grade malignant tumor of the salivary gland. We present a case of a 37-year-old male with good general condition with swelling in the right preauricular region for the past 3 years measuring 3 cm × 2 cm with intact facial nerve. This patient had a history of preauricular sinus excision surgery 15 years ago. EMC mostly occurs in elderly females. Rarity of our case is in the fact that it has occurred in a middle-aged male with histologic evidence of preexisting pleomorphic adenoma.

An iatropathic tibial nerve injury in a patient following total ankle replacement

Ankle arthroplasty is an infrequent procedure, and there is a risk of injury to nearby neurovascular structures from direct injury and from traction. The risk of nerve injury is difficult to quantify due to low-procedure numbers, non-mandatory nerve injury reporting to the National Joint Registry in the UK and delayed recognition of nerve injury despite the British Orthopaedic Association Standards for Trauma 5 guidelines on the management of peripheral nerve injury. Neuropathic pain following a major joint procedure with disordered sensation, motor paralysis and alterations in autonomic function in the distal skin are suggestive of nerve injury. A Tinel's sign at the site of suspected injury is diagnostic and the nerve should be promptly explored by a surgeon familiar with the operative assessment and reconstruction options for nerve injury. Processed nerve allograft is a useful adjunct in the reconstruction algorithm in cases of non-critical nerve disruption and central sensitisation to avoid the harvest of an intact sensory autologous nerve and risking further exacerbation of neuropathic pain at another site. The case presented discusses an iatropathic tibial nerve injury in a 48-year-old man who underwent reconstruction using nerve allograft.

Increased brain responsivity to galvanic vestibular stimulation in bilateral vestibular failure.

In this event-related functional magnetic resonance imaging (fMRI) study we investigated how the brain of patients with bilateral vestibular failure (BVF) responds to vestibular stimuli. We used imperceptible noisy galvanic vestibular stimulation (GVS) and perceptible bi-mastoidal GVS intensities and related the corresponding brain activity to the evoked motion perception. In contrast to caloric irrigation, GVS stimulates the vestibular organ at its potentially intact afferent nerve site.Motion perception thresholds and cortical responses were compared between 26 BVF patients to 27 age-matched healthy control participants. To identify the specificity of vestibular cortical responses we used a parametric design with different stimulus intensities (noisy imperceptible, low perceptible, high perceptible) allowing region-specific stimulus response functions. In a 2 × 3 flexible factorial design all GVS-related brain activities were contrasted with a sham condition that did not evoke perceived motion.Patients had a higher motion perception threshold and rated the vestibular stimuli higher than the healthy participants. There was a stimulus intensity related and region-specific increase of activity with steep stimulus response functions in parietal operculum (e.g. OP2), insula, superior temporal gyrus, early visual cortices (V3) and cerebellum while activity in the hippocampus and intraparietal sulcus did not correlate with vestibular stimulus intensity. Using whole brain analysis, group comparisons revealed increased brain activity in early visual cortices (V3) and superior temporal gyrus of patients but there was no significant interaction, i.e. stimulus-response function in these regions were still similar in both groups. Brain activity in these regions during (high)GVS increased with higher dizziness-related handicap scores but was not related to the degree of vestibular impairment or disease duration. nGVS did not evoke cortical responses in any group.Our data indicate that perceptible GVS-related cortical responsivity is not diminished but increased in multisensory (visual-vestibular) cortical regions despite bilateral failure of the peripheral vestibular organ. The increased activity in early visual cortices (V3) and superior temporal gyrus of BVF patients has several potential implications: (i) their cortical reciprocal inhibitory visuo-vestibular interaction is dysfunctional, (ii) it may contribute to the visual dependency of BVF patients, and (iii) it needs to be considered when BVF patients receive peripheral vestibular stimulation devices, e.g. vestibular implants or portable GVS devices. Imperceptible nGVS did not elicit cortical brain responses making it unlikely that the reported balance improvement of BVF by nGVS is mediated by cortical mechanisms.

Diffusion tensor imaging reveals changes in microstructural integrity along compressed nerve roots that correlate with chronic pain symptoms and motor deficiencies in elderly stenosis patients.

Age-related degenerative changes in the lumbar spine frequently result in nerve root compression causing severe pain and disability. Given the increasing incidence of lumbar spinal disorders in the aging population and the discrepancies between the use of current diagnostic imaging tools and clinical symptoms, novel methods of nerve root assessment are needed. We investigated elderly patients with stenosis at L4-L5 or L5-S1 levels. Diffusion tensor imaging (DTI) was used to quantify microstructure in compressed L5 nerve roots and investigate relationships to clinical symptoms and motor neurophysiology. DTI metrics (i.e. FA, MD, AD and RD) were measured at proximal, mid and distal segments along compressed (i.e. L5) and intact (i.e. L4 or S1) nerve roots. FA was significantly reduced in compressed nerve roots and MD, AD and RD were significantly elevated in the most proximal segment of the nerve root studied. FA was significantly correlated with electrophysiological measures of root function: minimum F-wave latency and peripheral motor conduction time (PMCT). In addition, FA along the compressed root also correlated with leg pain and depression score. There was also a relationship between RD and anxiety, leg pain and disability score and AD correlated with depression score. Taken together, these data show that DTI metrics are sensitive to nerve root compression in patients with stenosis as a result of age-related lumbar degeneration. Critically, they show that the changes in microstructural integrity along compressed L5 nerve roots are closely related to a number of clinical symptoms associated with the development of chronic pain as well as neurophysiological assessments of motor function. These inherent relationships between nerve root damage and phenotype suggest that the use DTI is a promising method as a way to stratify treatment selection and predict outcomes.

Adolf stoffel and the development of peripheral neurosurgical reconstruction for the management of paralysis: One hundred years of nerve transfer surgery

The concept of nerve transfer as an alternative solution for paralysis through rewiring a denervated motor nerve using an intact and expendable nerve branch or fascicle in proximity to the injured nerve became widely adopted as a strategy for nerve root avulsion in brachial plexus injuries. The success of the technique has encouraged clinicians to extend the indications for other complex nerve injuries, and the technique may be considered as an adjunct or replacement to nerve grafting for some proximal, high-energy, and late-presenting peripheral nerve injuries. The technique is not new. Many of the current “advances” in peripheral nerve transfer were described contemporaneously by Adolf Stoffel in 1911. He was an orthopedic surgeon working in Germany in the early 1900s. He had an interest in nerve injury reconstruction, described the functional fascicular anatomy of the peripheral nerves, developed an intraoperative nerve stimulator, and pioneered many of the techniques used today. His work was never translated from the German language and did not, therefore, receive wide acknowledgment. The aim of this study is to correct the perceived timeline of nerve transfer surgery and include the pioneering work of Adolf Stoffel.

Innervation of the Nose and Nasal Region of the Rat: Implications for Initiating the Mammalian Diving Response.

Most terrestrial animals demonstrate an autonomic reflex that facilitates survival during prolonged submersion under water. This diving response is characterized by bradycardia, apnea and selective increases in peripheral vascular resistance. Stimulation of the nose and nasal passages is thought to be primarily responsible for providing the sensory afferent signals initiating this protective reflex. Consequently, the primary objective of this research was to determine the central terminal projections of nerves innervating the external nose, nasal vestibule and nasal passages of rats. We injected wheat germ agglutinin (WGA) into specific external nasal locations, into the internal nasal passages of rats both with and without intact anterior ethmoidal nerves (AENs), and directly into trigeminal nerves innervating the nose and nasal region. The central terminations of these projections within the medulla were then precisely mapped. Results indicate that the internal nasal branch of the AEN and the nasopalatine nerve, but not the infraorbital nerve (ION), provide primary innervation of the internal nasal passages. The results also suggest afferent fibers from the internal nasal passages, but not external nasal region, project to the medullary dorsal horn (MDH) in an appropriate anatomical way to cause the activation of secondary neurons within the ventral MDH that express Fos protein during diving. We conclude that innervation of the anterior nasal passages by the AEN and nasopalatine nerve is likely to provide the afferent information responsible for the activation of secondary neurons within MDH during voluntary diving in rats.

Parotidectomy

When a patient presents with a mass at the angle of the mandible, a neoplasm within the parotid gland is a strong consideration. The parotid is the largest of the salivary glands. Terminal branches of the facial nerve are found within the gland. Their functional preservation is an important goal of parotid surgery. Risks of facial nerve injury rise in reoperative procedures and resection of cancers. Surgical principles apply in parotidectomy. In addition to facial nerve injury, a numb earlobe, contour deficit, salivary fistula, and gustatory sweating should be discussed with the patient before an operation. Most lesions can be removed after identification of the main trunk of the facial nerve, but a retrograde approach after finding a peripheral branch may be required. No randomized trials support a benefit from nerve monitoring. An intact facial nerve will usually begin to function, but months of recovery time may be needed. Permanent paralysis is rare. Salivary fistulae are usually self-limited. Many methods to ameliorate the cosmetic changes after parotidectomy have been described. None has gained ascendency. This review contains 6 figures and 61 references. Key words: facial nerve, facial paralysis, Frey syndrome, gustatory sweating, nerve monitoring, parotid gland, parotid neoplasm, parotidectomy, salivary fistula

Non-invasive transcutaneous auricular vagus nerve stimulation prevents postoperative ileus and endotoxemia in mice.

The cholinergic anti-inflammatory pathway comprises the perception of peripheral inflammation by afferent sensory neurons and reflex activation of efferent vagus nerve activity to regulate inflammation. Activation of this pathway was shown to reduce the inflammatory response and improve outcome of postoperative ileus (POI) and sepsis in rodents. Herein, we tested if a non-invasive auricular electrical transcutaneous vagus nerve stimulation (tVNS) affects inflammation in models of POI or endotoxemia. Mice underwent tVNS or sham stimulation before and after induction of either POI by intestinal manipulation (IM) or endotoxemia by lipopolysaccharide administration. Some animals underwent a preoperative right cervical vagotomy. Neuronal activation of the solitary tract nucleus (NTS) and the dorsal motor nucleus of the vagus nerve (DMV) were analyzed by immunohistological detection of c-fos+ cells. Gene and protein expression of IL-6, MCP-1, IL-1β as well as leukocyte infiltration and gastrointestinal transit were analyzed at different time points after IM. IL-6, TNFα, and IL-1β serum levels were analyzed 3hours after lipopolysaccharide administration. tVNS activated the NTS and DMV and reduced intestinal cytokine expression, reduced leukocyte recruitment to the manipulated intestine segment, and improved gastrointestinal transit after IM. Endotoxemia-induced IL-6 and TNF-α release was also reduced by tVNS. The protective effects of tVNS on POI and endotoxemia were abrogated by vagotomy. tVNS prevents intestinal and systemic inflammation. Activation of the DMV indicates an afferent to efferent central circuitry of the tVNS stimulation and the beneficial effects of tVNS depend on an intact vagus nerve. tVNS may become a non-invasive approach for treatment of POI.

Surgical Algorithm for Neuroma Management: A Changing Treatment Paradigm.

Successful treatment of the painful neuroma is a particular challenge to the nerve surgeon. Historically, symptomatic neuromas have primarily been treated with excision and implantation techniques, which are inherently passive and do not address the terminal end of the nerve. Over the past decade, the surgical management of neuromas has undergone a paradigm shift synchronous with the development of contemporary techniques aiming to satisfy the nerve end. In this article, we describe the important features of surgical treatment, including the approach to diagnosis with consideration of neuroma type and the decision of partial versus complete neuroma excision. A comprehensive list of the available surgical techniques for management following neuroma excision is presented, the choice of which is often predicated upon the availability of the terminal nerve end for reconstruction. Techniques for neuroma reconstruction in the presence of an intact terminal nerve end include hollow tube reconstruction and auto- or allograft nerve reconstruction. Techniques for neuroma management in the absence of an intact or identifiable terminal nerve end include submuscular or interosseous implantation, centro-central neurorrhaphy, relocation nerve grafting, nerve cap placement, use of regenerative peripheral nerve interface, “end-to-side” neurorrhaphy, and targeted muscle reinnervation. These techniques can be further categorized into passive/ablative and active/reconstructive modalities. The nerve surgeon must be aware of available treatment options and should carefully choose the most appropriate intervention for each patient. Comparative studies are lacking and will be necessary in the future to determine the relative effectiveness of each technique.

Alterations in Gastric Mucosal Expression of Calcitonin Gene-Related Peptides, Vanilloid Receptors, and Heme Oxygenase-1 Mediate Gastroprotective Action of Carbon Monoxide against Ethanol-Induced Gastric Mucosal Lesions.

Carbon monoxide (CO) has been reported to contribute to the maintenance of gastric mucosal integrity, gastroprotection, and ulcer healing. However, involvement of transient receptor potential vanilloid receptor type 1 (TRPV1) located on afferent sensory fibers endings and sensory neuropeptide calcitonin gene-related peptide (CGRP) in CO-mediated gastroprotection against ethanol-induced gastric damage has not been explored. Male Wistar rats with and without denervation of afferent sensory neurons induced by capsaicin (total dose 125 mg/kg within 3 days) were pretreated with vehicle, CO donor tricarbonyldichlororuthenium (II) dimer (CORM-2, 5 mg/kg i.g.), administered alone or with CGRP-α (10 μg/kg i.p.) or TRPV1 antagonist capsazepine (5 mg/kg i.g.), followed 30 min later by intragastric (i.g.) administration of 75% ethanol. The area of gastric damage and gastric blood flow (GBF) were assessed planimetrically and by laser flowmetry, respectively. Microscopic evaluation of ethanol-induced gastric lesions was performed after haematoxylin/eosin (H&E) or alcian blue/periodic acid-Schiff/alcian blue (AB/PAS) staining. Gastric mucosal mRNA fold change for heme oxygenase (HMOX)-1, HMOX-2, CGRP-α, CGRP-β, inducible nitric oxide synthase (iNOS), endothelial (e)NOS, neuronal (n)NOS, cyclooxygenase (COX)-1, COX-2, and protein expression for HMOX-1 and TRPV1 was determined by real-time PCR or Western blot, respectively. Pretreatment with CORM-2 combined or not with CGRP reduced ethanol-induced gastric lesions and elevated GBF. Capsaicin-denervation or co-treatment with capsazepine or CGRP and CORM-2 in capsaicin-denervated animals failed to affect these beneficial effects of CO donor. In rats with intact sensory nerves, CORM-2 increased gastric mRNA level for HMOX-1 and CGRP-α. In capsaicin-denervated rats, CORM-2 increased eNOS mRNA fold change and TRPV1 protein expression while capsaicin denervation itself decreased HMOX-1 protein expression and eNOS mRNA level. We conclude that CO prevents gastric mucosa from ethanol-induced lesions due to activation of TRPV1/CGRP-α system and accompanying increase in gastric microcirculation but independently on afferent sensory nerve activity despite the stimulation of TRPV1 protein and CGRP-α mRNA expression.

113 Ultrasound of the Optic Nerve Sheath as an Indicator of Mild Traumatic Brain Injury: Animal Model Provides Anatomical Basis

With no definitive method for diagnosis, many cases of mild traumatic brain injury (mTBI) receive suboptimal clinical management. Since emergency physicians and emergency medical services personnel are on the front lines with regard to mTBI, a tool for more accurate and timely indication of mTBI could improve diagnosis and management of mTBI in acute settings. Clinically, we have begun to validate that ultrasound measurements of optic nerve sheath dilation can be used to indicate mTBI. The objective of this study was to investigate the anatomical mechanism behind what has been observed clinically. More specifically, we evaluated the effect of increased intracranial pressure (ICP) on the fiber bundles connecting the optic nerve to the optic sheath in a swine model. Four experimental, 2 sham, and 4 normal swine were used in this study. In the experimental swine models, increased ICP was induced by passing a Foley catheter through a drilled opening into the epidural space and inflating a balloon. ICP was monitored continuously. For all animals, a section of optic nerve sheath with the intact nerve was removed after euthanasia and enucleation. The tissue was fixed overnight in paraformaldehyde and glutaraldehyde in a sodium cacodylate buffer, postfixed in osmium tetroxide in a sodium cacodylate buffer, dehydrated with a graded ethanol series, and critical point dried with carbon dioxide. The dried control and experimental model sections were mounted and imaged using a scanning electron microscope (SEM). Images of the trabecular meshwork were taken radially around the optic nerve at several magnifications. The images were segmented and analyzed using the ImageJ plug-in DiameterJ. Segmentation quality was confirmed using image subtraction of the original image from the segmented image and vice versa. All images had false positive and false negative total percentages of less than 5% of all pixels. Image overlays of the segmented and original images confirmed this qualitatively. This is an ongoing study. Image processing and analysis is still in progress. For a normal and an experimental animal, mean and median fiber bundle diameters were recorded for a total of 61 images. Thirty (49.1%) of the images analyzed were from the control sample and 31 (50.9%) were from the experimental sample. An analysis of variance found that both the mean (.52 μm) and median (.62 μm) fibrous bundle diameters were significantly different (ie, smaller) for the experimental model as compared to the mean (.73 μm) and median (.85 μm) fibrous bundle diameters for the control (p<.0001). The relationship between mean and median fibrous bundle diameters and sample (control or experimental) was not significantly correlated to radial location (relative to the optic nerve) or magnification of the image based on analyses of covariance. Thus far, this research demonstrates that in a swine model the fibrous bundles of the optic sheath’s connections to the optic nerve are statistically different (smaller) after exposure to increased ICP. We anticipate similar results from the other samples. Future research will evaluate if the thinning of fibrous bundles between optic sheath and optic nerve is caused by increased ICP. This will be accomplished by increasing the sample size and using other methods to induce increased ICP.