Altered Nerve Research Articles

Proceedings From the Clinical and Scientific Innovations in Oral and Maxillofacial Surgery Conference 2019

Proceedings From the Clinical and Scientific Innovations in Oral and Maxillofacial Surgery Conference 2019

Transoral Sialolitectomy Combined With Sialoendoscopy Versus Open Submaxilectomy for the Management of Hilar Lithiasis of the Submandibular Gland

IntroductionThe treatment of salivary obstructive pathology by minimally invasive techniques has been an object of assessment by different studies for decades. Lithiasis at the level of the salivary duct will be the most frequent cause of obstruction, representing more than 50% of the pathology of the major salivary glands and almost 80% of these affecting the Wharton duct. Material and methodsA Prospective study comparing the results of combined transoral sialolitectomy and open submaxillectomy techniques by cervicotomy in 2 groups of patients treated by lithiasis at the level of the hilum of the submaxillary gland. Results22 patients were included in the study 16 (72.7%) were men and 6 (27.3%) were women, the average age was 54.41 years ± 12.75 (Min: 30/Max: 77). Regarding the variables associated with the disease: average lithiasis, size of the stone, hospital stay, lingual nerve alteration or complications for both techniques, differences were not found between both groups. There were only statistically significant differences in the average stay in favor of the STA (P = .001). ConclusionThe minimally invasive approaches to the salivary ductal system, associated or not with sialoendoscopy, can be efficacy and can be associated with lower number of complications. The natural tendency should be aimed to gradually replacing open sialoadenectomy techniques, reserving its indication for the treatment of tumor pathology.

Oxidative and histopathological effects of the application of electrosurgical devices to the penile tissue of rats

This study was performed to evaluate the oxidative and histopathological changes that occur following the application of electrosurgical devices (monopolar or bipolar cautery) to penile tissue. Eighteen Wistar albino male rats were randomly distributed into three groups. In the control group (CG, n=6), all penile tissues were sampled without any additional process following the administration of anesthesia. In the monopolar cautery group (MPG, n=6), a 15-W cauterization process lasting 5s was performed on an approximately 2mm2 area of the ventral side of the penile shaft, 0.5cm proximal to the edge of the glans in the midline. Bipolar cautery was practiced in the third group (BPG, n=6) using the same techniques outlined in the previous statement. Penile tissues consisted of the cautery application area, the edge of the glans, and dorsal side of the penis and were sampled after 90min; then, histopathological evaluation and biochemical examination involving malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) measurements were performed. Histopathologically, the MPG and BPG demonstrated increased inflammation, fibrosis, and epithelial loss in the urethra in the areas to which cautery was applied as compared to the CG (P<0.05). The vascular structures of the corpus cavernosa were significantly decreased in the cautery application area of both the MPG and the BPG as compared to the CG (P<0.05). In the Masson's trichrome stained samples, significant collagen deposition was observed in the cautery application area both in the MPG and the BPG as compared to the CG (P<0.05). However, S-100 staining was decreased in these groups as compared to the CG (P<0.05). S-100 staining was also decreased in the MPG as compared to the BPG on the edge of the glans (P<0.05). Biochemically, MDA values were significantly increased in the MPG as compared to the CG and the BPG (P<0.05). Monopolar and bipolar cautery both did cause oxidative changes and triggered inflammatory, vascular, and peripheral nerve alterations in the cautery application area while bipolar cautery did not cause any distant effects.

Incidence of epilepsy and brain toxoplasmosis in hospital Mario Rivas, Honduras

The presence of neurological alterations is a frequent manifestation in patients with HIV, especially focal onset epilepsy. The cerebral toxoplasmosis represents the main cause of occupational injury in an immunological patient for HIV related to a CD4 T lymphocyte count less than 100/uL. A descriptive, cross-sectional study was carried out in which the clinical characteristics associated with cerebral toxoplasmosis were determined, as well as the alterations in the main encephalographic alterations and the findings in neuroimaging studies (cranial tomography or cerebral magnetic resonance). All patients underwent a complete medical history including history of neurological diseases. A total of 26 patients with a diagnosis of HIV-AIDS infection and cerebral toxoplasmosis were evaluated, of which 15 (57.7%) were women. The age of the patients ranged between 23 and 65 years (standard deviation 11,081). The manifestation by which the patients were admitted (main symptom) were altered state of consciousness (2, 7.7%), acute psychotic outbreak (4, 15.3%), headache (1, 3.8%), seizures (10, 38.5 %), focal motor deficit (5, 19.2%), vertigo (1, 3.8%), diarrhea (1, 3.8%), fever (1, 3.8%) and alteration of cranial nerves (1, 3.8%). Differents findings was found in patients: slow-wave, spike-slow wave complex, polymorphic slow wave. Toxoplasmosis is a frequent opportunistic infection in patients with HIV, with epilepsy being one of the main manifestations of this. Neuroimaging studies (brain CT or brain MRI) allow diagnosis. The encephalogram study is frequently associated with alterations in patients with toxoplasmosis. Timely diagnosis is associated with a good prognosis in our patients.

Neurological complications and quality of life after submandibular gland resection. A Prospective, non-randomized, single-centre study.

There are different complications related to the submandibular gland resection, like damage to the mandibular branch of the facial nerve, lingual or hypoglossal nerve. Moreover, subjective complaints like dry mouth, altered sensation around the scar and taste alterations were described. A prospective, non-randomized study was performed including 20 patients treated with submandibular gland resection. The most common etiology was sialolithiasis affecting 9 (45%) patients. One (5%) patient presented a lingual nerve paresis, 2 (10%) patients presented a transient marginal mandibular branch paresis and no hypoglossal nerve alteration was observed. Factors like the size of the lithiasis (P = 0.293), size of the tumor (P = 0.445) or type of pathology (P = 0.694) were not related with neurological complications. Altered sensation in the skin around a scar was the most severely weighted problem (55% and 33.3%), and xerostomia was the second one (33% and 27.3%) at one month and at six months after surgery, respectively. The submandibular gland resection remains to be a safe technique with a low rate of surgical and neurological complications. However, patients should be informed about sequelae like xerostomia, altered sensation in the skin or pain around the scar, which may be discomforting. The cosmetic result can be satisfactory, but a surgical scar can be avoided with another approach. Although rare, the risk of MBFN, lingual and hypoglossal nerve damage should always be included in the preoperative information on surgical risks.

Implementation of a functional endpoint to the zebrafish embryotoxicity test to evaluate craniofacial abnormalities

The inclusion of a read-out to detect functional consequences of craniofacial alterations in the zebrafish embryotoxicity test will allow to evaluate these alterations which are difficult to assess morphologically, and to detect alterations in cranial nerves functions leading to impairment of jaw movements. In this study we have established an ingestion test in zebrafish larvae younger than 120 hpf. To overcome the challenge of evaluating larvae which still do not present independent feeding behaviour, we have tested the ability of 72, 96 or 102 hpf larvae to ingest food mixed with fluorescent microspheres under several conditions (dark/light, with/without shaking) to find the best experimental set-up for the test. We have included the investigation of two substances as potential positive controls: ketoconazole and tricaine. Ketoconazole 10 μM exposure during development produced significant embryotoxic effects including a characteristic craniofacial alteration pattern consisting in impaired development of brain, nasal cavity, mouth opening and jaw, as well as a significant decrease in food intake. Tricaine exposure at 380 μM during the food availability period significantly decreased the food intake. The method proposed will be a useful alternative tool to animal testing to detect compounds inducing adverse effects on craniofacial development.

Assessment of optic nerve and optic tract alterations in patients with orbital space-occupying lesions using probabilistic diffusion tractography.

To investigate the diffusion changes in both the optic nerve and optic tract in orbital space-occupying lesion patients with decreased visual acuity, and its clinical significance using probabilistic diffusion tractography (PDT). Twenty patients with orbital space-occupying lesions and 25 age- and gender-matched healthy persons were included. All patients and controls underwent routine orbital magnetic resonance imaging and diffusion tensor imaging (DTI), using a 3.0T magnetic resonance scanner (Trio Tim Siemens). After the image data were preprocessed, each DTI parameters of the optic nerve and optic tract was obtained by PDT, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). The asymmetry index (AI) of each parameter was calculated. Compared the parameters of the affected side optic nerve and ipsilateral optic tract with the contralateral side by paired sample t-test; compared AI of parameters of optic nerve and optic tract between the patient group and the control group by independent sample t-test. Patients were divided into three subgroups according to the low vision grade standard of WHO, compared the FA and AI of FA between the three subgroups by single factor variance analysis. The affected side optic nerve presented significantly decreased FA, increased MD, AD, and RD values compared to the unaffected side (P<0.05). The AI of FA, MD, AD, and RD of optic nerve in the patients was significantly higher than that of the controls (P<0.05). The comparison results of the optic tract showed that there was no significant difference between the patient group and control group in terms of the bilateral optic tracts in patients (P>0.05). The AIs of the FA value of the optic nerve in the eyesight <0.1 subgroup was significantly higher than that in the other groups (P<0.05). FA, MD, AD, and RD of the affected side optic nerve of the orbital space-occupying lesions have significantly changed, the FA value is the most sensitive. The PDT could be a useful tool to provide valid quantitative markers of optic nerve injuries and evaluate the severity of orbital diseases, which other examinations cannot be acquired.

Sciatic Nerve Structural and Functional Recovery with Extract of Phyllanthus amarus and Esculetin in STZ-Induced Hyperglycemic Rats.

Background: Diabetes-instigated nerve damage is a chronic complication including impaired peripheral nerve function with lowered nerve conduction velocity (NCV), demyelination of nerve fibres and alterations in the behaviour. Many clinical and experimental studies have proved that Phyllanthus amarus and esculetin have potential effects against various diseases.Purpose: The aim of this study is to assess the neuroprotective role of hydro-ethanolic extract of Phyllanthus amaras (PAE) and esculetin (ESC) on NCV, metabolism, behavioural and structural changes in diabetic rats.Methods: The extent of protection using PAE and ESC in diabetic rats was determined by checking the HbA1c, NO, myeloperoxidase (MPO), total calcium, protein content, Na+-K+ ATPase activity, acetylcholine content and behavioural alterations using rotarod and maze learning tests on 7, 14 and 21 days. NCV was measured on the 21st day.Results: The diabetic rats showed increased HbA1c, nitrite, MPO, calcium and decreased protein, Na+-K+ ATPase activity, NCV, acetylcholine, behavioural alterations and morphological changes of sciatic nerve so that diabetic peripheral neuropathy (DPN) is manifested. Continuous treatment for three weeks with Phyllanthus amarus and esculetin significantly minimized the damage to axons and myelin sheath and enhanced the sciatic NCV by reversing all the mentioned parameters.Conclusion: Phyllanthus amarus and esculetin showed the anti-diabetic as well as anti-inflammatory characteristics by prevention of initiation of adverse processes of the sciatic nerve morphology, internal cell functions leading to improved coordination, behavioural and physiological functions in STZ-induced diabetic rats. PAE has shown similar effects with the ESC. However, further studies are essential to confirm their detailed therapeutic effects.

Degeneration of Corneal Sensation and Innervation in Patients with Facial Paralysis: A Cross-Sectional Study Using in Vivo Confocal Microscopy

ABSTRACTPurpose: Facial paralysis (FP) leads to diverse periocular complications which threats visual acuity and affects corneal nerve functionally and morphologically. This study aims to summarize the clinical ophthalmic outcomes, corneal sensation, and morphological alterations of subbasal nerve and dendritic cells (DCs) in patients with facial paralysis.Methods: We performed a cross-sectional study of 48 consecutive patients with facial paralysis at one tertiary hospital. Forty-eight healthy participants were enrolled as controls. The images of corneal nerves and epithelial DCs were detected by in vivo confocal microscopy (IVCM). Each patient received thorough ophthalmic examination, tear film function tests, corneal fluorescence staining and Cochet-Bonnet esthesiometry test. Clinical and morphologic data were compared with controls.Results: Forty patients (83.3%) showed corneal injuries from punctate epithelial defects to corneal ulcers and scars. Visual impairment and eyelid malposition were observed. Corneal sensitivity remarkably decreased (25.1 ± 23.8 mm) in the affected eyes and was correlated to diminished subbasal nerve density (P = .019, r = 0.387). Numbers of corneal main nerve trunks and branches were significantly reduced (P < .0001) while DCs were increased (P < .0001) in patients with FP when compared with controls. Nerve fiber density showed inverse association with DC density (P = .019, r = −0.389).Conclusions: Ocular complications including corneal erosions, loss of corneal sensation, visual impairment and eyelid malposition have largely affected patients with facial paralysis. Morphological changes of diminished corneal subbasal nerve and increased DCs were detected by IVCM. Corneal epithelial defect, corneal opacity, corneal sensation, dendritic cell density are factors associated with corneal subbasal nerve density. Patients with FP are suggested to have complete ophthalmic evaluation and early instruction on ocular prevention.

Sensory Adaptation to Silicone Hydrogel Contact Lens Wear Is Not Associated With Alterations in the Corneal Subbasal Nerve Plexus.

To evaluate corneal subbasal nerve alterations in contact lens (CL)-naive silicone hydrogel CL wearers and to investigate the relationship between structural subbasal nerve changes with corneal sensitivity. Twenty eyes of 20 neophyte daily silicone hydrogel CL wearers and 20 eyes of age-matched control subjects were recruited for this prospective longitudinal study. Corneal subbasal nerve densities were evaluated using in vivo confocal microscopy. Central corneal tactile sensitivity was measured using Cochet-Bonnet esthesiometers. In vivo confocal microscopy and Cochet-Bonnet esthesiometry were performed before and at the 6-month time point after the initiation of CL wear. Two-way repeated measures analysis of variance, χ, and Wilcoxon signed-rank tests were used for statistical analyses. The mean ages of CL users and control subjects were 21.8 ± 1.8 years (range = 19-24 years) and 21.5 ± 2.3 years (range = 20-24 years), respectively (P = 0.579). Compared with their baseline values, there were no significant changes at the 6-month follow-up period in the mean total subbasal nerve fiber length (2266.6 ± 414.6 vs. 2277.9 ± 405.0 μm/frame; P = 0.432), mean total subbasal nerve branch density (10.4 ± 1.5 vs. 10.5 ± 1.3 nerves/frame; P = 0.655), or the mean long nerve fiber density (4.7 ± 0.7 vs. 4.8 ± 0.7 nerves/frame; P = 0.564) of CL users. Mechanical corneal sensitivity remained unaltered during the 6-month period in CL users (11.2 ± 0.5 vs. 11.2 ± 0.5; P = 1.000). No significant changes were observed in the subbasal nerve plexus or corneal tactile sensitivity of the control subjects during the study interval. Sensory adaptation to CL wear is not mediated through attenuation of the subbasal nerve or reduction of corneal tactile sensitivity in CL-naive users.

Ultrastructural changes of the human enteric nervous system and interstitial cells of Cajal in diverticular disease.

In spite of numerous advances in understanding diverticular disease, its pathogenesis remains one of the main problems to be solved. We aimed to investigate the ultrastructural changes of the enteric nervous system in unaffected individuals, in asymptomatic patients with diverticulosis and in patients with diverticular disease. Transmission electron microscopy was used to analyse samples of the myenteric, outer submucosal and inner submucosal plexuses from patients without diverticula (n=9), asymptomatic patients with diverticulosis (n=7) and in patients with complicated diverticular disease (n=9). We described the structure of ganglia, interstitial cells of Cajal and enteric nerves, as well as their relationship with each other. The distribution and size of nerve processes were analysed quantitatively. In complicated diverticular disease, neurons exhibited larger lipofuscin-like inclusions, their membranous organelles had larger cisterns and the nucleus showed deeper indentations. Nerve remodeling occurred in every plexus, characterised by an increased percentage of swollen and fine neurites. Interstitial cells of Cajal had looser contacts with the surrounding cells and showed cytoplasmic depletion and proliferation of the rough endoplasmic reticulum. In asymptomatic patients with diverticulosis, alterations of enteric nerves and ICC were less pronounced. In conclusion, the present findings suggest that most ultrastructural changes of the enteric nervous system occur in complicated diverticular disease. The changes are compatible with damage to the enteric nervous system and reactive remodeling of enteric ganglia, nerves and interstitial cells of Cajal. Disrupted architecture of enteric plexuses might explain clinical and pathophysiological changes associated with diverticular disease.

Diffusion tensor imaging of microstructural alterations in the trigeminal nerve due to neurovascular contact/compression.

Several recent studies have focused on microstructural changes in the trigeminal nerve in trigeminal neuralgia using diffusion tensor imaging (DTI). However, alterations after microvascular decompression (MVD) have rarely been investigated. Furthermore, the trigeminal nerve of asymptomatic individuals also presenting with neurovascular contact/compression (NVC) has not yet been studied. Thirty-four patients suffering from trigeminal neuralgia and 34 healthy age-matched controls, who were identified as having unilateral NVC signs, underwent both DTI and high-resolution magnetic resonance imaging (MRI) for comparison. All trigeminal neuralgia patients underwent a post-surgical MRI scan after 7days and a follow-up MRI scan within 6-8months after surgery. The apparent diffusion coefficients (ADCs) and fractional anisotropy (FA) values were measured from coronal images in which the nerves from the root exit point to the distal segment were clearly shown. In 34 trigeminal neuralgia patients, the absolute FA value was significantly lower on the affected side (mean FA, 0.34 ± 0.03) than on the unaffected side (mean FA, 0.37 ± 0.05, p < 0.001). The FA ratio was also significantly different between the trigeminal neuralgia group (RsFA, 0.92 ± 0.06) and the control group (RsFA, 0.99 ± 0.09) (p = 0.001). The absolute ADC value between the two sides in patients and the ratios of ADC between the trigeminal neuralgia and control groups did not show any significant differences (p = 0.21 and 0.29, respectively). However, in 34 healthy subjects presenting with signs of NVC, neither the FA value nor the ADC showed a difference between sides (p > 0.05). The FA ratio of patients showed a significant increase on two follow-up MRI scans compared to the preoperative FA (p = 0.02 and 0.002, respectively), while the ADC ratio showed a significant decrease at 6months after MVD (p = 0.004). This study of trigeminal neuralgia due to NVC found that DTI indexes could reflect alterations in the affected trigeminal nerve. Furthermore, a reversible change after MVD surgery could be potentially valuable for monitoring the change in white matter of the trigeminal nerve.

Corneal subbasal nerve plexus changes in patients with episodic migraine: an in vivo confocal microscopy study.

Background and purpose: It has been generally thought that activation and sensitization of the trigeminovascular system may contribute to the pathogenesis of migraine. Nevertheless, there is little evidence on abnormalities in peripheral trigeminal afferent nerves from humans in vivo. Alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve may support the notion that trigeminal afferent nerves are involved in migraine pathophysiology. The aim of the present study was to investigate the structural changes in corneal subbasal nerve plexus in patients with episodic migraine (EM) with in vivo confocal microscope (IVCM).Methods: In this cross-sectional observational study, 10 EM patients and 10 age- and sex-matched healthy controls were included. Analysis of IVCM images with Image J software was performed to quantify the changes in the corneal subbasal nerve plexus.Results: EM patients showed an increase in nerve fiber length (25.0±2.65 vs 22.3±2.41 mm/mm2, p=0.047) and nerve fiber density (36.3±7.29 vs 30.5±6.19 fibers/mm2, p=0.104) as compared with normal controls, but this difference was not statistically significant. Nerve branching and tortuosity were significantly increased in the EM subjects compared to the normal subjects (91.3±13.8 vs 75.0±14.2 branches/mm2, p=0.030 and 2.30±0.46 versus 1.63±0.52, p=0.011, respectively). In addition, nerve sprouts and increased number of Langerhans cells were observed in the EM patients.Conclusion: The morphologic changes of corneal subbasal nerve plexus and Langerhans cell aggregation suggest the presence of nerve regeneration and inflammation in EM. Furthermore, the alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve offer support for the hypothesis that the peripheral trigeminal system may be involved in the pathogenesis of migraine.

Clinical aspects of the anatomical correlation between mandibular canal, inferior third molar and sensitive alterations of the inferior alveolar nerve

Clinical aspects of the anatomical correlation between mandibular canal, inferior third molar and sensitive alterations of the inferior alveolar nerve

Anti-Neurofascin-155 IgG4 antibodies prevent paranodal complex formation in vivo.

Neurofascin-155 (Nfasc155) is an essential glial cell adhesion molecule expressed in paranodal septate-like junctions of peripheral and central myelinated axons. The genetic deletion of Nfasc155 results in the loss of septate-like junctions and in conduction slowing. In humans, IgG4 antibodies against Nfasc155 are implicated in the pathogenesis of chronic inflammatory demyelinating polyneuropathy (CIDP). These antibodies are associated with an aggressive onset, a refractoriness to intravenous immunoglobulin, and tremor of possible cerebellar origin. Here, we examined the pathogenic effects of patient-derived anti-Nfasc155 IgG4. These antibodies did not inhibit the ability of Nfasc155 to complex with its axonal partners contactin-1/CASPR1 or induce target internalization. Passive transfer experiments revealed that IgG4 antibodies target Nfasc155 on Schwann cell surface, and diminished Nfasc155 protein levels and prevented paranodal complex formation in neonatal animals. In adult animals, chronic intrathecal infusions of antibodies also induced the loss of Nfasc155 and of paranodal specialization and resulted in conduction alterations in motor nerves. These results indicate that anti-Nfasc155 IgG4 perturb conduction in absence of demyelination, validating the existence of paranodopathy. These results also shed light on the mechanisms regulating protein insertion at paranodes.

Sympathetic Neurotransmission in Resistance Mesenteric Arteries in Obesity‐Related Hypertension

Hyperactivity of sympathetic nerves has an important role in the pathogenesis of obesity‐related hypertension. The mechanisms linking obesity to hypertension are unclear. Small mesenteric arteries (MA, &lt;300 mm dia.) are resistance blood vessels that are densely innervated by sympathetic nerves. Nerve varicosities release norepinephrine (NE) and ATP which cause arterial constriction. Impaired control of NE and/or ATP release and clearance would cause hypertension. Alterations in sympathetic nerves supplying MAs contribute to hypertension in several animal models. This study examined whether alterations of sympathetic neurotransmission in the resistance MAs contribute to high blood pressure in high fat‐fed (HF) Dahl salt‐sensitive rats. Sympathetic nerves supplying MAs maintained in vitro were stimulated focally. Electrically‐evoked NE and ATP release were detected by using amperometry with carbon fiber electrodes, and intracellular recording of excitatory junction potentials (EJPs) from arterial smooth muscle cells, respectively. Data were obtained from male and female rats at 10, 17, and 24 weeks of control and HF diet. Peak amplitudes of NE oxidation current and EJPs were assessed. NE oxidation current from all groups were blocked by a Na+ channel blocker, tetrodotoxin (TTX, 300 nM), suggesting that NE release in neurogenic. EJPs from all groups were abolished by TTX, and PPADS (10 μM), a P2X receptor antagonist, indicating that EJPs were neurogenic and purinergic. Frequency (1–30 Hz, 50 pulses) response curves using amperometric measurement of NE release showed similar responses in MAs from control and HF fed male and female rats. EJP frequency (0.5–10Hz, 5 pulses) response curves were also similar in MA from control and HF fed male and female rats. We investigated prejunctional α2‐adrenergic receptor function using the α2 receptor agonist (UK14,304) and antagonist (yohimbine). UK14,304 (0.0001–10 μM) inhibited NE and ATP release equally well and in a concentration‐dependent manner in MAs from control and HF rats. In the presence of 1 μM yohimbine, NE and ATP release was increased equally in MA from all rats. We conclude that adrenergic and purinergic neurotransmission by periarterial sympathetic nerves are not affected in HF Dahl salt sensitive rats. Elevated blood pressure in this animal model is not dependent on altered sympathetic neurotransmission to the mesenteric vasculature.Support or Funding InformationNIH 2P01HL070687 (For JJG), and Post‐doctoral training scholarship, Faculty of Medicine, Thammasat University, Thailand (For SS).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Catfish (Arius bilineatus, Val.) skin protein preparation ameliorates neurobehavioral and axonal and neuronal histopathological alterations in a sciatic nerve crush injury rat model: a novel approach

Preliminary investigations showed that soluble protein fraction‐Fraction C (SPF‐FC) from catfish skin preparations (CSP) from the Arabian Gulf catfish (Arius bilineatus, Val.) exhibit potent anti‐inflammatory and healing properties as shown in our previous clinical trials for the healing of non‐healing diabetic foot ulcers, chronic back pain, and some other neurological disorders. The present study was designed to investigate the neuroprotective and neuroregenerative properties of SPF‐FC derived from CSP on the spinal neurons, regeneration of sciatic nerve fibers, and recovery of sensory‐motor functions in the sciatic nerve crush injury model. Male Wistar rats (weight 250–300 g) were randomly assigned to four groups: (I) SHAM, (II) CRUSH, (III) CRUSH+SPF treated intraperitoneally (IP) and (IV) CRUSH+SPF treated subcutaneously (SC) groups. Rats in CRUSH groups underwent surgery, where the sciatic nerve was crushed, followed by treatment with saline (II) or with 3–12 mg/Kg SPF IP (III) or SC (IV) daily for 14 days. All animals were tested for the neurobehavioral parameters throughout the 6 weeks of the study. Sciatic nerve and spinal cord tissues were processed for light and electron histological examinations, stereological analysis, immunohistochemical and biochemical examinations at Week 4 and Week 6 post‐injury. Administration of SPF IP or SC significantly (p&lt;0.05–0.0001) enhanced the sensory and motor performance on different neurobehavioral functional tests of the nerve‐injured rats. The stereological evaluation revealed significant (p&lt;0.000) histomorphological evidence of neuroregeneration in the sciatic nerve of the CRUSH+ SPF groups compared to controls at week 4 and 6. SPF‐FC treatment significantly prevented the decrease in the number of the NeuN‐immunoreactive spinal neurons ipsilateral to the crush injury, decreased the GFAP immunoreactive astrocytes and increased the GAP‐43 immunoreactivity. The data analysis supports our hypothesis that SPF‐FC immunoreactivity treatment lessens neurobehavioral deficits, enhances axonal regeneration and ameliorate histomorphological nerve alterations following nerve injury. Further, SPF‐FC protects spinal neurons and enhances subcellular recovery by decreasing the astrocytic activity and GAP‐43, thus improves nerve regeneration and functional recovery.Support or Funding InformationThis work was supported by Kuwait University Research Administration (KU Grants No. SL03/14 and SL04/09 and RCF/OMICSRU project SRUL02/13) and Kuwait Foundation for the Advancement of Sciences (Grant No. KFAS 2013‐1207‐01A‐D).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Perineural invasion in pancreatic cancer: proteomic analysis and invitro modelling.

Perineural invasion (PNI) is a common and characteristic feature of pancreatic ductal adenocarcinoma (PDAC) that is associated with poor prognosis, tumor recurrence, and generation of pain. However, the molecular alterations in cancer cells and nerves within PNI have not previously been comprehensively analyzed. Here, we describe our proteomic analysis of the molecular changes underlying neuro‐epithelial interactions in PNI using liquid chromatography–mass spectrometry (LC‐MS/MS) in microdissected PNI and non‐PNI cancer, as well as in invaded and noninvaded nerves from formalin‐fixed, paraffin‐embedded PDAC tissues. In addition, an in vitro model of PNI was developed using a co‐culture system comprising PDAC cell lines and PC12 cells as the neuronal element. The overall proteomic profiles of PNI and non‐PNI cancer appeared largely similar. In contrast, upon invasion by cancer cells, nerves demonstrated widespread plasticity with a pattern consistent with neuronal injury. The up‐regulation of SCG2 (secretogranin II) and neurosecretory protein VGF (nonacronymic) in invaded nerves in PDAC tissues was further validated using immunohistochemistry. The tested PDAC cell lines were found to be able to induce neuronal plasticity in PC12 cells in our in vitro established co‐culture model. Changes in expression levels of VGF, as well as of two additional proteins previously reported to be overexpressed in PNI, Nestin and Neuromodulin (GAP43), closely recapitulated our proteomic findings in PDAC tissues. Furthermore, induction of VGF, while not necessary for PC12 survival, mediated neurite extension induced by PDAC cell lines. In summary, here we report the proteomic alterations underlying PNI in PDAC and confirm that PDAC cells are able to induce neuronal plasticity. In addition, we describe a novel, simple, and easily adaptable co‐culture model for in vitro study of neuro‐epithelial interactions.

Association between Chagas disease and changes in the optic nerve and retinal nerve fiber layer.

To test the hypothesis that Chagas disease predisposes to optic nerve and retinal nerve fiber layer alterations. We conducted a cross-sectional study including 41 patients diagnosed with Chagas disease and 41 controls, paired by sex and age. The patients underwent ophthalmologic examinations, including intraocular pressure measurements, optic nerve and retinal nerve fiber layer screening with retinography, optical coherence tomography, and standard automated perimetry. All of the patients with Chagas disease had a recent cardiologic study; 15 (36.6%) had heart failure, 14 (34.1%) had cardiac form without left ventricular dysfunction, and 12 (29.3%) had indeterminate form. Optic nerve/retinal nerve fiber layer alterations were observed in 24 patients (58.5%) in the Chagas disease group and 7 controls (17.1%) (p£0.01). Among these, optic nerve pallor, optic nerve alterations suggestive of glaucoma, notch, peripapillary hemorrhage, and localized retinal nerve fiber layer defect were detected. Alterations were more prominent in patients with Chagas disease and heart failure (11 patients), although they also occurred in those with Chagas disease without left ventricular dysfunction (7 patients) and those with indeterminate form (6 patients). Optical coherence tomography showed that themean of the average retinal nerve fiber layer thickness measured 89 ± 9.7 mm, and the mean of retinal nerve fiber layer superior and inferior thickness measured 109 ± 17.5 and 113 ± 16.8 mm, respectively were lower in patients with Chagas disease. In controls, these values were 94 ± 10.6 (p=0.02); 117 ± 18.1 (p=0.04), and 122 ± 18.4 mm (p=0.03). Changes in optic nerve/ retinal nerve fiber layer were more prevalent in patients with Chagas disease.

Sialolitectomía transoral combinada con sialoendoscopia versus submaxilectomía abierta para el manejo de litiasis hiliares de la glándula submaxilar

IntroductionThe treatment of salivary obstructive pathology by minimally invasive techniques has been an object of assessment by different studies for decades. Lithiasis at the level of the salivary duct will be the most frequent cause of obstruction, representing more than 50% of the pathology of the major salivary glands and almost 80% of these affecting the Wharton duct. Material and methodsA prospective study comparing the results of combined transoral sialolitectomy (CTS) and open submaxillectomy techniques by cervicotomy in 2 groups of patients treated by lithiasis at the level of the hilum of the submaxillary gland. Results22 patients were included in the study 16 (72.7%) were men and 6 (27.3%) were women, the average age was 54.41 years ± 12.75 (Min: 30/Max: 77). Regarding the variables associated with the disease: average lithiasis, size of the stone, hospital stay, lingual nerve alteration or complications for both techniques, differences were not found between both groups. There were only statistically significant differences in the average stay in favor of the CTS (P=.001). ConclusionThe minimally invasive approaches to the salivary ductal system, associated or not with sialoendoscopy, can be efficacy and can be associated with lower number of complications. The natural tendency should be aimed to gradually replacing open sialoadenectomy techniques, reserving its indication for the treatment of tumor pathology.