Sample records for ganglion block sgb

  1. Effectiveness of Stellate Ganglion Block Under Fuoroscopy or Ultrasound Guidance in Upper Extremity CRPS.

    PubMed

    Imani, Farnad; Hemati, Karim; Rahimzadeh, Poupak; Kazemi, Mohamad Reza; Hejazian, Kokab

    2016-01-01

    Stellate Ganglion Block (SGB) is an effective technique which may be used to manage upper extremities pain due to Chronic Regional Pain Syndrome (CRPS), in this study we tried to evaluate the effectiveness of this procedure under two different guidance for management of this syndrome. The purpose of this study was to evaluate the effectiveness of ultrsound guide SGB by comparing it with the furoscopy guided SGB in upper extermities CRPS patients in reducing pain & dysfuction of the affected link. Fourteen patients with sympathetic CRPS in upper extremities in a randomized method with block randomization divided in two equal groups (with ultrasound or fluoroscopic guidance). First group was blocked under fluoroscopic guidance and second group blocked under ultrasound guidance. After correct positioning of the needle, a mixture of 5 ml bupivacaine 0.25% and 1 mL of triamcinolone was injected. These data represent no meaningful statistical difference between the two groups in terms of the number of pain attacks before the blocks, a borderline correlation between two groups one week and one month after the block and a significant statistical correlation between two groups three month after the block. These data represent no meaningful statistical difference between the patients of any group in terms of the pain intensity (from one week to six months after block), p-value = 0.61. These data represent a meaningful statistical difference among patients of any group and between the two groups in terms of the pain intensity (before the block until six months after block), p-values were 0.001, 0.031 respectively. According the above mentioned data, in comparison with fluoroscopic guidance, stellate ganglion block under ultrasound guidance is a safe and effective method with lower complication and better improvement in patient's disability indexes.

  2. Photoacoustic microscopy of complex regional pain syndrome type I (CRPS-1) after stellate ganglion blocks in vivo

    NASA Astrophysics Data System (ADS)

    Zhou, Yong; Yi, Xiaobin; Xing, Wenxin; Hu, Song; Maslov, Konstantin I.; Wang, Lihong V.

    2015-03-01

    We used photoacoustic microscopy (PAM) to assist diagnoses and monitor the progress and treatment outcome of complex regional pain syndrome type 1 (CRPS-1). Blood vasculature and oxygen saturation (sO2) were imaged by PAM in eight adult patients with CRPS-1. Patients' hands and cuticles were imaged both before and after stellate ganglion block (SGB) for comparison. For all patients, both the vascular structure and sO2 could be assessed by PAM. In addition, more vessels and stronger signals were observed after SGB.

  3. Acute effects of unilateral temporary stellate ganglion block on human atrial electrophysiological properties and atrial fibrillation inducibility.

    PubMed

    Leftheriotis, Dionyssios; Flevari, Panayota; Kossyvakis, Charalampos; Katsaras, Dimitrios; Batistaki, Chrysanthi; Arvaniti, Chrysa; Giannopoulos, Georgios; Deftereos, Spyridon; Kostopanagiotou, Georgia; Lekakis, John

    2016-11-01

    In experimental models, stellate ganglion block (SGB) reduces the induction of atrial fibrillation (AF), while data in humans are limited. The aim of this study was to assess the effect of unilateral SGB on atrial electrophysiological properties and AF induction in patients with paroxysmal AF. Thirty-six patients with paroxysmal AF were randomized in a 2:1 order to temporary, transcutaneous, pharmaceutical SGB with lidocaine or placebo before pulmonary vein isolation. Lidocaine was 1:1 randomly infused to the right or left ganglion. Before and after randomization, atrial effective refractory period (ERP) of each atrium, difference between right and left atrial ERP, intra- and interatrial conduction time, AF inducibility, and AF duration were assessed. After SGB, right atrial ERP was prolonged from a median (1st-3rd quartile) of 240 (220-268) ms to 260 (240-300) ms (P < .01) and left atrial ERP from 235 (220-260) ms to 245 (240-280) ms (P < .01). AF was induced by atrial pacing in all 24 patients before SGB, but only in 13 patients (54%) after the intervention (P < .01). AF duration was shorter after SGB: 1.5 (0.0-5.8) minutes from 5.5 (3.0-12.0) minutes (P < .01). Intra- and interatrial conduction time was not significantly prolonged. No significant differences were observed between right and left SGB. No changes were observed in the placebo group. Unilateral temporary SGB prolonged atrial ERP, reduced AF inducibility, and decreased AF duration. An equivalent effect of right and left SGB on both atria was observed. These findings may have a clinical implication in the prevention of drug refractory and postsurgery AF and deserve further clinical investigation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Neurocognitive Performance is Not Degraded After Stellate Ganglion Block Treatment for Post-Traumatic Stress Disorder: A Case Series.

    PubMed

    Mulvaney, Sean W; Lynch, James H; de Leeuw, Jason; Schroeder, Matthew; Kane, Shawn

    2015-05-01

    To measure key neurocognitive performance effects following stellate ganglion block (SGB) administered to treat post-traumatic stress disorder (PTSD) symptoms. Eleven patients diagnosed, screened, and scheduled for SGB to treat their PTSD symptoms were administered a panel of eight cognitive measures before and 1 to 3 weeks after undergoing this procedure. PTSD symptoms were evaluated using the Posttraumatic Stress Disorder Checklist-Military. One to three weeks post-SGB, none of the patients showed any statistically significant decline in neurocognitive performance. Rather, there was a clear trend in improvement, with four out of eight measures reaching statistical significance following SGB. All patients improved in PTSD symptoms with a mean improvement on Posttraumatic Stress Disorder Checklist-Military of 29. In this case series of 11 patients, SGB effectively treated PTSD symptoms and did not impair reaction time, memory, or concentration. Therefore, SGB should be considered as a viable treatment option for personnel with PTSD symptoms who will be placed in demanding conditions such as combat. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

  5. Effect of Stellate Ganglion Block on Specific Symptom Clusters for Treatment of Post-Traumatic Stress Disorder.

    PubMed

    Lynch, James H; Mulvaney, Sean W; Kim, Eugene H; de Leeuw, Jason B; Schroeder, Matthew J; Kane, Shawn F

    2016-09-01

    This study assessed which symptoms are most impacted following stellate ganglion block (SGB) used to treat post-traumatic stress disorder (PTSD) symptoms. 30 active military service members with combat-related PTSD self-referred to their physician and psychologist. Patients were offered a SGB as part of their treatment program. Primary outcome was the magnitude of change for the 17 items on the PTSD Checklist-Military (PCL-M), which was administered the week before SGB, 1 week after SGB, and 2 to 4 months later. Mean PCL-M score decreased from 49 at baseline to 32, 1 week after the procedure (p < 0.001). 2 to 4 months after SGB, patients maintained an average PCL-M of 32. Patients reported greatest improvement in the first week after SGB for the following symptoms: irritability or angry outbursts, difficulty concentrating, and sleep disturbance. 2 to 4 months later, patients reported greatest improvement in the following: feeling distant or cut off, feeling emotionally numb, irritability or angry outbursts, and difficulty concentrating. SGB is a safe procedure that may provide extended relief for all clusters of PTSD symptoms. As a result of the significant reduction in hyperarousal and avoidance symptoms observed, this study supports incorporation of SGB into PTSD treatment plans. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

  6. Stellate ganglion block promotes recovery of Bell's palsy in patients with diabetes mellitus.

    PubMed

    Liu, Guo-Dong; He, Chun-Jing

    2014-06-01

    Stellate ganglion block (SGB) is effective for treatment of Bell's palsy in patients with diabetes mellitus. Corticosteroids are widely used for treatment of Bell's palsy in patients with diabetes mellitus but may induce complications like hyperglycemia, which calls for an alternative therapy. This study aimed to ascertain the effect of SGB on Bell's palsy in patients with diabetes mellitus. This randomized and single-blinded clinical trial involved 96 diabetic patients with Bell's palsy that were randomly divided into a control group (n = 48) and a treatment group (SGB group, n = 48). The House-Brackmann scale and facial disability index (FDI, including FDIP and FDIS) were observed before treatment and at 1 and 3 months after treatment for assessment of the outcome. No statistically significant difference was found between the two groups before treatment as regards the House-Brackmann scale and FDI. There was a statistically significant difference in FDIP score in the two groups after treatment in comparison with before treatment. The FDIS score showed a statistical difference between the two groups after treatment.

  7. Effects of stellate ganglion block on sedation as assessed by bispectral index in normal healthy volunteers.

    PubMed

    Yeo, Jinseok; Jeon, Younghoon

    2015-01-01

    The sympathetic nervous system plays an important role in the arousal response. Recently, the stellate ganglion block (SGB) was found to effectively treat anxiety and night awakening in humans and decrease electroencephalogram (EEG) indices of arousal responses in rat. But, the role of the sympathetic block in human arousal responses has not yet been studied. We performed this prospective, double-blinded, controlled volunteer study to investigate the sedative effects and bispectral index (BIS) changes of SGB. A randomized, double-blind trial. Single academic medical center. This study was approved by the Ethics Committee of Kyungpook National University Hospital (ref: KNUH-10-1081) and registered with CRiS (Clinical Research Information Service, http://cris.cdc.go.kr, ref: KCT0000036, 2010. 9.24). Twenty healthy volunteers were enrolled in this study. The volunteers were randomly assigned to one of 2 groups: the SGB group (n = 10) and the sham group (n =10). Volunteers in SGB group received SGB and volunteers in the sham group received a sham procedure. BIS value, heart rate, and blood pressure were measured before and 5, 10, 20, and 30 minutes after the procedure. Observer's Assessment of Alertness/Sedation (OAA/S) scores were assessed before and 10 and 30 minutes after the intervention. In the SGB group, BIS values and OAA/S scores significantly decreased after the intervention as compared to baseline (P < 0.05). The values were also significantly decreased in the SGB group when compared to the values in sham group after the intervention (P < 0.05). There was a significant change of mean blood pressure 10 to 30 minutes after SGB (P < 0.05). There were no differences in heart rate during study period between groups. This study is limited by a relatively small sample size. This study showed that SGB has a sedative effect in normal healthy volunteers, as evidenced by decreased OAA/S scores and BIS values.

  8. Ultrasound-guided stellate ganglion blocks combined with pharmacological and occupational therapy in Complex Regional Pain Syndrome (CRPS): a pilot case series ad interim.

    PubMed

    Wei, Karin; Feldmann, Robert E; Brascher, Anne-Kathrin; Benrath, Justus

    2014-12-01

    This preliminary and retrospective pilot case series examines a treatment concept consisting of ultrasound-guided stellate ganglion blocks (SGBs) combined with pharmacological and occupational therapy in patients with complex regional pain syndrome (CRPS) of the hand. Efficacy of combined treatment concepts and safety of ultrasound-guided SGB have not been sufficiently investigated yet. A total number of 156 blocks were evaluated in 16 patients with CRPS in a retrospective analysis. All patients received pharmacotherapy and a standard regimen of occupational therapy offered simultaneously to the SGBs. Changes in both spontaneous and evoked pain levels were assessed by numerical pain rating score before and after the last blockade of a series. Side effects were documented. The overall mean pain reduction was 63.2% regarding spontaneous and 45.3% regarding evoked pain. Mild complications, such as hoarseness or dysphagia, occurred in 13.5% of the blocks (21 SGBs). Serious complications, such as plexus paresis or accidental puncture of vessels or other structures, did not occur. Time between symptom onset and start of treatment did not affect the extent of pain reduction. The combination of ultrasound-guided SGB and simultaneous pharmacological and occupational therapy showed encouraging treatment results under conditions of this pilot case series. Assessment of efficacy of this combined treatment concept and safety of ultrasound-guided SGB require further prospective clinical studies with larger number of participants. Wiley Periodicals, Inc.

  9. Effectiveness and Patient Acceptability of Stellate Ganglion Block (SGB) for Treatment of Posttraumatic Stress Disorder (PTSD) Symptoms among Active Duty Military Members

    DTIC Science & Technology

    PTSD) symptoms. We will conduct two parallel studies: a randomized, controlled trial (RCT) to evaluate the effectiveness of SGB for treating PTSD, and a...study, individuals enrolled in the RCT will be asked to participate either in a focus group or an interview with their spouse. In addition, we will...conduct focus groups and key informant interviews with providers: those who refer individuals to the study, and those who provide SGB to service members.

  10. Stellate ganglion block used to treat symptoms associated with combat-related post-traumatic stress disorder: a case series of 166 patients.

    PubMed

    Mulvaney, Sean W; Lynch, James H; Hickey, Matthew J; Rahman-Rawlins, Tabassum; Schroeder, Matthew; Kane, Shawn; Lipov, Eugene

    2014-10-01

    Report the successful use of stellate ganglion blocks (SGBs) in 166 active duty service members with multiple combat deployments experiencing anxiety symptoms associated with post-traumatic stress disorder (PTSD). Successful treatment of PTSD symptoms with SGB has been reported previously. This is the largest published case series evaluating SGB with a minimum of 3 months follow-up. Following clinical interview including administration of the PTSD Checklist (PCL), 166 service members with symptoms of PTSD elected to receive a SGB. All patients received a SGB on the right side at the level of the sixth cervical vertebrae (C6). The PCL was administered the day before treatment to establish a baseline, repeated 1 week later, and then monthly out to 3 months. A positive response was considered to be an improvement in the PCL score by 10 or greater points. Follow-up PCL scores from 3 to 6 months were obtained and analyzed for 166 patients. In a military population with multiple combat deployments, over 70% of the patients treated had a clinically significant improvement in their PCL score which persisted beyond 3 to 6 months postprocedure. Selective blockade of the right cervical sympathetic chain at the C6 level is a safe and minimally invasive procedure that may provide durable relief from anxiety symptoms associated with PTSD. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

  11. Effectiveness and Patient Acceptability of Stellate Ganglion Block (SGB) for Treatment of Posttraumatic Stress Disorder (PTSD) Symptoms among Active Duty Military Members

    DTIC Science & Technology

    2017-03-01

    ORGANIZATION: Research Triangle Institute Research Triangle Park, NC 27709-0155 REPORT DATE: March 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S...ganglion block, Posttraumatic Stress Disorder, randomized controlled trial, qualitative research 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...Posttraumatic Stress Disorder, randomized controlled trial,  qualitative   research     3.  Accomplishments    The major goals of this project for year two

  12. Sonoanatomical Change of Phrenic Nerve According to Posture During Ultrasound-Guided Stellate Ganglion Block

    PubMed Central

    Joeng, Eui Soo; Jeong, Young Cheol; Park, Bum Jun; Kang, Seok; Yang, Seung Nam

    2016-01-01

    Objective To evaluate the risk of phrenic nerve injury during ultrasound-guided stellate ganglion block (US-SGB) according to sonoanatomy of the phrenic nerve, and determine a safer posture for needle insertion by assessing its relationship with surrounding structure according to positional change. Methods Twenty-nine healthy volunteers were recruited and underwent ultrasound in two postures, i.e., supine position with the neck extension and head rotation, and lateral decubitus position. The transducer was placed at the anterior tubercle of the C6 level to identify phrenic nerve. The cross-sectional area (CSA), depth from skin, distance between phrenic nerve and anterior tubercle of C6 transverse process, and the angle formed by anterior tubercle, posterior tubercle and phrenic nerve were measured. Results The phrenic nerve was clearly identified in the intermuscular fascia layer between the anterior scalene and sternocleidomastoid muscles. The distance between the phrenic nerve and anterior tubercle was 10.33±3.20 mm with the supine position and 9.20±3.31 mm with the lateral decubitus position, respectively. The mean CSA and skin depth of phrenic nerve were not statistically different between the two positions. The angle with the supine position was 48.37°±27.43°, and 58.89°±30.02° with the lateral decubitus position. The difference of angle between the two positions was statistically significant. Conclusion Ultrasound is a useful tool for assessing the phrenic nerve and its anatomical relation with other cervical structures. In addition, lateral decubitus position seems to be safer by providing wider angle for needle insertion than the supine position in US-SGB. PMID:27152274

  13. Sonoanatomical Change of Phrenic Nerve According to Posture During Ultrasound-Guided Stellate Ganglion Block.

    PubMed

    Joeng, Eui Soo; Jeong, Young Cheol; Park, Bum Jun; Kang, Seok; Yang, Seung Nam; Yoon, Joon Shik

    2016-04-01

    To evaluate the risk of phrenic nerve injury during ultrasound-guided stellate ganglion block (US-SGB) according to sonoanatomy of the phrenic nerve, and determine a safer posture for needle insertion by assessing its relationship with surrounding structure according to positional change. Twenty-nine healthy volunteers were recruited and underwent ultrasound in two postures, i.e., supine position with the neck extension and head rotation, and lateral decubitus position. The transducer was placed at the anterior tubercle of the C6 level to identify phrenic nerve. The cross-sectional area (CSA), depth from skin, distance between phrenic nerve and anterior tubercle of C6 transverse process, and the angle formed by anterior tubercle, posterior tubercle and phrenic nerve were measured. The phrenic nerve was clearly identified in the intermuscular fascia layer between the anterior scalene and sternocleidomastoid muscles. The distance between the phrenic nerve and anterior tubercle was 10.33±3.20 mm with the supine position and 9.20±3.31 mm with the lateral decubitus position, respectively. The mean CSA and skin depth of phrenic nerve were not statistically different between the two positions. The angle with the supine position was 48.37°±27.43°, and 58.89°±30.02° with the lateral decubitus position. The difference of angle between the two positions was statistically significant. Ultrasound is a useful tool for assessing the phrenic nerve and its anatomical relation with other cervical structures. In addition, lateral decubitus position seems to be safer by providing wider angle for needle insertion than the supine position in US-SGB.

  14. Sphenopalatine ganglion: block, radiofrequency ablation and neurostimulation - a systematic review.

    PubMed

    Ho, Kwo Wei David; Przkora, Rene; Kumar, Sanjeev

    2017-12-28

    Sphenopalatine ganglion is the largest collection of neurons in the calvarium outside of the brain. Over the past century, it has been a target for interventional treatment of head and facial pain due to its ease of access. Block, radiofrequency ablation, and neurostimulation have all been applied to treat a myriad of painful syndromes. Despite the routine use of these interventions, the literature supporting their use has not been systematically summarized. This systematic review aims to collect and summarize the level of evidence supporting the use of sphenopalatine ganglion block, radiofrequency ablation and neurostimulation. Medline, Google Scholar, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were reviewed for studies on sphenopalatine ganglion block, radiofrequency ablation and neurostimulation. Studies included in this review were compiled and analyzed for their treated medical conditions, study design, outcomes and procedural details. Studies were graded using Oxford Center for Evidence-Based Medicine for level of evidence. Based on the level of evidence, grades of recommendations are provided for each intervention and its associated medical conditions. Eighty-three publications were included in this review, of which 60 were studies on sphenopalatine ganglion block, 15 were on radiofrequency ablation, and 8 were on neurostimulation. Of all the studies, 23 have evidence level above case series. Of the 23 studies, 19 were on sphenopalatine ganglion block, 1 study on radiofrequency ablation, and 3 studies on neurostimulation. The rest of the available literature was case reports and case series. The strongest evidence lies in using sphenopalatine ganglion block, radiofrequency ablation and neurostimulation for cluster headache. Sphenopalatine ganglion block also has evidence in treating trigeminal neuralgia, migraines, reducing the needs of analgesics after endoscopic sinus surgery and reducing pain associated with nasal packing

  15. Ganglion blocks as a treatment of pain: current perspectives

    PubMed Central

    Gunduz, Osman Hakan; Kenis-Coskun, Ozge

    2017-01-01

    The inputs from sympathetic ganglia have been known to be involved in the pathophysiology of various painful conditions such as complex regional pain syndrome, cancer pain of different origin, and coccygodynia. Sympathetic ganglia blocks are used to relieve patients who suffer from these conditions for over a century. Many numbers of local anesthetics such as bupivacaine or neurolytic agents such as alcohol can be chosen for a successful block. The agent is selected according to its duration of effect and the purpose of the injection. Most commonly used sympathetic blocks are stellate ganglion block, lumbar sympathetic block, celiac plexus block, superior hypogastric block, and ganglion Impar block. In this review, indications, methods, effectiveness, and complications of these blocks are discussed based on the data from the current literature. PMID:29276402

  16. Strychnine blocks transient but not sustained inhibition in mudpuppy retinal ganglion cells.

    PubMed Central

    Belgum, J H; Dvorak, D R; McReynolds, J S

    1984-01-01

    Transient and sustained inhibitory synaptic inputs to on-centre, off-centre, and on-off ganglion cells in the mudpuppy retina were studied using intracellular recording in the superfused eye-cup preparation. When chemical transmission was blocked with 4 mM-Co2+, application of either glycine or gamma-aminobutyric acid (GABA) caused a hyperpolarization and conductance increase in all ganglion cells. For both amino acids, the responses were dose dependent in the range 0.05-10 mM, with a half-maximal response at about 0.7 mM. Glycine and GABA sensitivities were very similar in all three types of ganglion cells. The response to applied glycine was selectively antagonized by 10(-5) M-strychnine and the response to applied GABA was selectively antagonized by 10(-5) M-picrotoxin. In all ganglion cells, 10(-5) M-strychnine eliminated the transient inhibitory events which occur at the onset and termination of a light stimulus. The block of transient inhibition was associated with a relative depolarization of membrane potential and decrease in conductance at these times. Strychnine had no effect on membrane potential or conductance in darkness or during sustained inhibitory responses to light. Picrotoxin (10(-5) M) did not block transient inhibitory events in any ganglion cells, but did affect other components of their responses. The results suggest that in all three classes of ganglion cells transient inhibition, but not sustained inhibition, may be mediated by glycine or a closely related substance. PMID:6481635

  17. Thalamic pain alleviated by stellate ganglion block: A case report.

    PubMed

    Liao, Chenlong; Yang, Min; Liu, Pengfei; Zhong, Wenxiang; Zhang, Wenchuan

    2017-02-01

    Thalamic pain is a distressing and treatment-resistant type of central post-stroke pain. Although stellate ganglion block is an established intervention used in pain management, its use in the treatment of thalamic pain has never been reported. A 66-year-old woman presented with a 3-year history of severe intermittent lancinating pain on the right side of the face and the right hand. The pain started from the ulnar side of the right forearm after a mild ischemic stroke in bilateral basal ganglia and left thalamus. Weeks later, the pain extended to the dorsum of the finger tips and the whole palmar surface, becoming more severe. Meanwhile, there was also pain with similar characteristics emerging on her right face, resembling atypical trigeminal neuralgia. Thalamic pain was diagnosed. After refusing the further invasive treatment, she was suggested to try stellate ganglion block. After a 3-day period of pain free (numerical rating scale: 0) postoperatively, she reported moderate to good pain relief with a numerical rating scale of about 3 to 4 lasting 1 month after the first injection. Pain as well as the quality of life was markedly improved with less dose of analgesic agents. Stellate ganglion block may be an optional treatment for thalamic pain.

  18. Stellate ganglion blockade and verbal memory in midlife women: Evidence from a randomized trial.

    PubMed

    Maki, Pauline M; Rubin, Leah H; Savarese, Antonia; Drogos, Lauren; Shulman, Lee P; Banuvar, Suzanne; Walega, David R

    2016-10-01

    In a pilot randomized clinical trial of active stellate ganglion blockade (SGB) versus sham control, SGB significantly reduced the frequency of reported moderate to severe vasomotor symptoms (VMS) and the frequency of physiologic VMS measured using ambulatory skin conductance monitors. Here we examine secondary effects of SGB on verbal learning and memory. In a randomized, sham-controlled study, 36 women met eligibility criteria for cognitive assessments, of whom 17 were randomized to receive fluoroscopy-guided SGB and 19 to sham control. At baseline and three months post-treatment, women completed tests of verbal learning and memory (primary outcome) and other cognitive measures and also wore an ambulatory monitor for 24h to measure physiologic VMS and VMS reported in real time. Verbal learning improved following active SGB (p<0.05) but not sham treatment; however, the interaction between group and time was not significant (p values 0.13-0.20). Two secondary cognitive measures improved only in the sham group. Improvements in physiologic VMS correlated significantly with improvements in verbal learning (r=0.51, p<0.05). SGB might confer benefits to memory in relation to the magnitude of improvement in physiologic VMS. Broadly these findings suggest a possible link between physiologic VMS and memory problems in midlife women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. [Ropivacaine use in transnasal sphenopalatine ganglion block for post dural puncture headache in obstetric patients - case series].

    PubMed

    Furtado, Inês; Lima, Isabel Flor de; Pedro, Sérgio

    2018-02-02

    Sphenopalatine ganglion block is widely accepted in chronic pain; however it has been underestimated in post dural puncture headache treatment. The ganglion block does not restore normal cerebrospinal fluid dynamics but effectively reduces symptoms associated with resultant hypotension. When correctly applied it may avoid performance of epidural blood patch. The transnasal approach is a simple and minimally invasive technique. In the cases presented, we attempted to perform and report the ganglion block effectiveness and duration, using ropivacaine. We present four obstetrics patients with post dural puncture headache, after epidural or combined techniques, with Tuohy needle 18G that underwent a safe and successful Sphenopalatine ganglion block. We performed the block 24-48h after dural puncture, with 4mL of ropivacaine 0.75% in each nostril. In three cases pain recurred within 12-48h, although less intense. In one patient a second block was performed with complete relief and without further recurrence. In the other two patients a blood patch was performed without success. All patients were asymptomatic within 7 days. The average duration of analgesic effect of the block remains poorly defined. In the cases reported, blocking with ropivacaine was a simple, safe and effective technique, with immediate and sustained pain relief for at least 12-24h. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  20. Efficacy of Noninvasive Stellate Ganglion Blockade Performed Using Physical Agent Modalities in Patients with Sympathetic Hyperactivity-Associated Disorders: A Systematic Review and Meta-Analysis.

    PubMed

    Liao, Chun-De; Tsauo, Jau-Yih; Liou, Tsan-Hon; Chen, Hung-Chou; Rau, Chi-Lun

    2016-01-01

    Stellate ganglion blockade (SGB) is mainly used to relieve symptoms of neuropathic pain in conditions such as complex regional pain syndrome and has several potential complications. Noninvasive SGB performed using physical agent modalities (PAMs), such as light irradiation and electrical stimulation, can be clinically used as an alternative to conventional invasive SGB. However, its application protocols vary and its clinical efficacy remains controversial. This study investigated the use of noninvasive SGB for managing neuropathic pain or other disorders associated with sympathetic hyperactivity. We performed a comprehensive search of the following online databases: Medline, PubMed, Excerpta Medica Database, Cochrane Library Database, Ovid MEDLINE, Europe PubMed Central, EBSCOhost Research Databases, CINAHL, ProQuest Research Library, Physiotherapy Evidence Database, WorldWideScience, BIOSIS, and Google Scholar. We identified and included quasi-randomized or randomized controlled trials reporting the efficacy of SGB performed using therapeutic ultrasound, transcutaneous electrical nerve stimulation, light irradiation using low-level laser therapy, or xenon light or linearly polarized near-infrared light irradiation near or over the stellate ganglion region in treating complex regional pain syndrome or disorders requiring sympatholytic management. The included articles were subjected to a meta-analysis and risk of bias assessment. Nine randomized and four quasi-randomized controlled trials were included. Eleven trials had good methodological quality with a Physiotherapy Evidence Database (PEDro) score of ≥6, whereas the remaining two trials had a PEDro score of <6. The meta-analysis results revealed that the efficacy of noninvasive SGB on 100-mm visual analog pain score is higher than that of a placebo or active control (weighted mean difference, -21.59 mm; 95% CI, -34.25, -8.94; p = 0.0008). Noninvasive SGB performed using PAMs effectively relieves pain of

  1. Efficacy of stellate ganglion blockade for the management of type 1 complex regional pain syndrome.

    PubMed

    Ackerman, William E; Zhang, Jun-Ming

    2006-10-01

    The purpose of this study was to examine the efficacy of stellate ganglion blockade (SGB) in patients with complex regional pain syndromes (CRPS I) of their hands. After IRB approval and patient informed consent, 25 subjects, with a clinical diagnosis of CRPS I of one hand as defined by the International Association for the Study of Pain (IASP) criteria, had three SGB's performed at weekly intervals. Laser Doppler fluxmetric hand perfusion studies were performed on the normal and CRPS I hands pre- and post-SGB therapy. No patient was included in this study if they used tobacco products or any medication or substance that could affect sympathetic function. The appropriate parametric and nonparametric data analyses were performed and a p value <0.05 was used to reject the null hypothesis. Symptom onset of CRPS I until the initiation of SGB therapy ranged between 3 to 34 weeks. Following the SGB series, patient pain relief was as follows: group I, 10/25 (40%) had complete symptom relief; group II, 9/25 (36%) had partial relief and group III, 6/25 (24%) had no relief. The duration of symptoms until SGB therapy was: group I, 4.6 +/- 1.8 weeks, group II, 11.9 +/- 1.6 weeks and group III, 35.8 +/- 27 weeks. Compared with the normal control hand, the skin perfusion in the CRPS I affected hand was greater in group I and decreased in groups II and III. The results of our study demonstrate that an inverse relationship exists between hand perfusion and the duration of symptoms of CRPS I. On the other hand, a positive correlation exists between SGB efficacy and how soon SGB therapy is initiated. A duration of symptoms greater than 16 weeks before the initial SGB and/or a decrease in skin perfusion of 22% between the normal and affected hands adversely affects the efficacy of SGB therapy.

  2. Gasserian Ganglion and Retrobulbar Nerve Block in the Treatment of Ophthalmic Postherpetic Neuralgia: A Case Report.

    PubMed

    Huang, Jie; Ni, Zhongge; Finch, Philip

    2017-09-01

    Varicella zoster virus reactivation can cause permanent histological changes in the central and peripheral nervous system. Neural inflammatory changes or damage to the dorsal root ganglia sensory nerve fibers during reactivation can lead to postherpetic neuralgia (PHN). For PHN of the first division of the fifth cranial nerve (ophthalmic division of the trigeminal ganglion), there is evidence of inflammatory change in the ganglion and adjacent ocular neural structures. First division trigeminal nerve PHN can prove to be difficult and sometimes even impossible to manage despite the use of a wide range of conservative measures, including anticonvulsant and antidepressant medication. Steroids have been shown to play an important role by suppressing neural inflammatory processes. We therefore chose the trigeminal ganglion as an interventional target for an 88-year-old woman with severe ophthalmic division PHN after she failed to respond to conservative treatment. Under fluoroscopic guidance, a trigeminal ganglion nerve block was performed with lidocaine combined with dexamethasone. A retrobulbar block with lidocaine and triamcinolone settled residual oculodynia. At 1-year follow-up, the patient remained pain free and did not require analgesic medication. To our knowledge, this is the first reported case of ophthalmic division PHN successfully treated with a combination of trigeminal ganglion and retrobulbar nerve block using a local anesthetic agent and steroid for central and peripheral neural inflammatory processes. © 2016 World Institute of Pain.

  3. Efficacy of Noninvasive Stellate Ganglion Blockade Performed Using Physical Agent Modalities in Patients with Sympathetic Hyperactivity-Associated Disorders: A Systematic Review and Meta-Analysis

    PubMed Central

    Liao, Chun-De; Tsauo, Jau-Yih; Liou, Tsan-Hon

    2016-01-01

    Background Stellate ganglion blockade (SGB) is mainly used to relieve symptoms of neuropathic pain in conditions such as complex regional pain syndrome and has several potential complications. Noninvasive SGB performed using physical agent modalities (PAMs), such as light irradiation and electrical stimulation, can be clinically used as an alternative to conventional invasive SGB. However, its application protocols vary and its clinical efficacy remains controversial. This study investigated the use of noninvasive SGB for managing neuropathic pain or other disorders associated with sympathetic hyperactivity. Materials and Methods We performed a comprehensive search of the following online databases: Medline, PubMed, Excerpta Medica Database, Cochrane Library Database, Ovid MEDLINE, Europe PubMed Central, EBSCOhost Research Databases, CINAHL, ProQuest Research Library, Physiotherapy Evidence Database, WorldWideScience, BIOSIS, and Google Scholar. We identified and included quasi-randomized or randomized controlled trials reporting the efficacy of SGB performed using therapeutic ultrasound, transcutaneous electrical nerve stimulation, light irradiation using low-level laser therapy, or xenon light or linearly polarized near-infrared light irradiation near or over the stellate ganglion region in treating complex regional pain syndrome or disorders requiring sympatholytic management. The included articles were subjected to a meta-analysis and risk of bias assessment. Results Nine randomized and four quasi-randomized controlled trials were included. Eleven trials had good methodological quality with a Physiotherapy Evidence Database (PEDro) score of ≥6, whereas the remaining two trials had a PEDro score of <6. The meta-analysis results revealed that the efficacy of noninvasive SGB on 100-mm visual analog pain score is higher than that of a placebo or active control (weighted mean difference, −21.59 mm; 95% CI, −34.25, −8.94; p = 0.0008). Conclusions Noninvasive

  4. Therapeutic potential of stellate ganglion block in orofacial pain: a mini review.

    PubMed

    Jeon, Younghoon

    2016-09-01

    Orofacial pain is a common complaint of patients that causes distress and compromises the quality of life. It has many etiologies including trauma, interventional procedures, nerve injury, varicella-zoster (shingles), tumor, and vascular and idiopathic factors. It has been demonstrated that the sympathetic nervous system is usually involved in various orofacial pain disorders such as postherpetic neuralgia, complex regional pain syndromes, and atypical facial pain. The stellate sympathetic ganglion innervates the head, neck, and upper extremity. In this review article, the effect of stellate ganglion block and its mechanism of action in orofacial pain disorders are discussed.

  5. Safety and Patient Acceptability of Stellate Ganglion Blockade as a Treatment Adjunct for Combat-Related Post-Traumatic Stress Disorder: A Quality Assurance Initiative.

    PubMed

    McLean, Brian

    2015-09-10

     To perform a quality assurance and performance improvement project through review of our single center data on the safety and patient acceptability of the stellate ganglion blockade (SGB) procedure for the relief of symptoms related to chronic post-traumatic stress disorder.  Our interventional pain management service has been offering trials of SGB therapy to assist with the management of the sympathetically mediated anxiety and hyperarousal symptoms of severe and treatment-refractory combat-related PTSD. There have been multiple case series in the literature describing the potential impact of this procedure for PTSD symptom management as well as the safety of image-guided procedures. We wished to ensure that we were performing this procedure safely and that patients were tolerating and accepting of this adjunctive treatment option.  We conducted a review of our quality assurance and performance improvement data over the past 18 months during which we performed 250 stellate ganglion blocks for the management of PTSD symptoms to detect any potential complications or unanticipated side effects.  We also analyzed responses from an anonymous patient de-identified survey collected regarding the comfort and satisfaction associated with the procedure.  We did not identify any immediate post-procedural complications or delayed complications from any of the 250 procedures performed from November 2013 to April 2015. Of the 110 surveys that were returned and tabulated, 100% of the patients surveyed were overall satisfied with our process and with the procedure, 100% said they would recommend the procedure to a friend, and 95% stated that they would be willing to undergo as many repeat procedures as necessary based on little discomfort and tolerable side effects.  Our quality assurance assessment suggests that in our center the SGB procedure for PTSD is a safe, well-tolerated, and acceptable treatment adjunct in the management of

  6. [The neurotrophic effect of endogenous NT-3 from adult cat spared dorsal root ganglion on ganglionic neurons].

    PubMed

    Zhang, Wei; Zhou, Xue; Wang, Ting-hua; Wang, Te-wei; Liu, Su; Chen, Si-xiu; Ou, Ke-qun

    2004-01-01

    To investigate the neurotrophic effect of endogenous NT-3 from adult cat dorsal root ganglion (DRG) on ganglionic neurons. Rhizotomy of bilateral L1, L3, L5 and L7 dorsal roots of cats was performed, leaving L2, L4 and L6 DRG as spared DRGs. The separate neurons of normal (control) DRG, spared DRG and anti-NT-3 antibody blocking DRG were cultured in vitro respectively. The number of survival neurons and the length of neurites were measured and used for comparison in the control, spared DRG, and block groups. There were survival neurons and cell clusters in every group. The number of survival neurons and cell clusters of spared DRG group were much larger than those of the control and block groups. The neurite length of neurons, the neurite number and the length of cell clusters of spared DRG group were much greater than those of control and block groups. Endogenous NT-3 from spared DRG may act on ganglionic neurons to maintain survival of neuron and stimulate growth of neurite.

  7. Effects of nifedipine and captopril on vascular capacitance of ganglion-blocked anesthetized dogs.

    PubMed

    Ogilvie, R I; Zborowska-Sluis, D

    1990-03-01

    The hemodynamic effects of nifedipine and captopril at doses producing similar reductions in arterial pressure were studied in pentobarbital-anesthetized ventilated dogs after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline circulating blood volumes and after increases of 5 and 10 mL/kg. Central blood volumes (pulmonary artery to aortic root) were determined from transit times, and separately determined cardiac outputs (right atrium to pulmonary artery) were estimated by thermodilution. Nifedipine (n = 5) increased Pmcf at all circulating blood volumes and reduced total vascular capacitance without a change in total vascular compliance. Central blood volume, right atrial pressure, and cardiac output were increased with induced increases in circulating blood volume. In contrast, captopril (n = 5) did not alter total vascular capacitance, central blood volume, right atrial pressure, or cardiac output at baseline or with increased circulating volume. Thus, at doses producing similar reductions in arterial pressure, nifedipine but not captopril increased venous return and cardiac output in ganglion-blocked dogs.

  8. Evaluation of the treatment modalities for neurosensory disturbances of the inferior alveolar nerve following retromolar bone harvesting for bone augmentation.

    PubMed

    Nogami, Shinnosuke; Yamauchi, Kensuke; Shiiba, Shunji; Kataoka, Yoshihiro; Hirayama, Bunichi; Takahashi, Tetsu

    2015-03-01

    The purpose of this study was to evaluate the treatment modalities for neurosensory disturbances (NSDs) of the inferior alveolar nerve occurring after retromolar bone harvesting for bone augmentation procedures before implant placement. One hundred four patients, of which 49 and 55 exhibited vertical or horizontal alveolar ridge defects in the mandible and maxilla, respectively, were enrolled. Nineteen patients underwent block bone grafting, 38 underwent guided bone generation or autogenous bone grafting combined with titanium mesh reconstruction, and 47 underwent sinus floor augmentation. Using a visual analog scale, we examined subjective symptoms and discomfort related to sensory alteration within the area of the NSDs in these patients. NSDs were clinically investigated using a two-point discrimination test with blunt-tipped calipers. In addition, neurometry was used for evaluation of trigeminal nerve injury. We tested three treatment modalities for NSDs: follow-up observation (no treatment), medication, and stellate ganglion block (SGB). A week after surgery, 26 patients (25.0%) experienced NSDs. Five patients received no treatment, 10 patients received medication, and 11 patients received SGB. Three months after surgery, patients in the medication and SGB group achieved complete recovery. Current perception threshold values recovered to near-baseline values at 3 months: recovery was much earlier in this group than in the other two groups. SGB can accelerate recovery from NSDs. Our results justify SGB as a reasonable treatment modality for NSDs occurring after the harvesting of retromolar bone grafts. Wiley Periodicals, Inc.

  9. Non-steroidal Anti-inflammatory Drugs Attenuate Hyperalgesia and Block Upregulation of Trigeminal Ganglionic Sodium Channel 1.7 after Induction of Temporomandibular Joint Inflammation in Rats.

    PubMed

    Bi, Rui Yun; Ding, Yun; Gan, Ye Hua

    2016-03-01

    To investigate the association between the analgesic effect of non-steroidal antiinflammatory drugs (NSAIDs) and sodium channel 1.7 (Nav1.7) expression in the trigeminal ganglion (TG). Temporomandibular joint (TMJ) inflammation was induced by complete Freund's adjuvant (CFA) in female rats. Ibuprofen, diclofenac sodium and meloxicam were given intragastrically before induction of TMJ inflammation. Histopathological evaluation and scoring of TMJ inflammation was used to evaluate the level of inflammation. The head withdrawal threshold and food intake were measured to evaluate TMJ nociceptive responses. The mRNA and protein expression of trigeminal ganglionic Nav1.7 was examined using real-time polymerase chain reaction and western blot. Twenty-four hours after the injection of CFA into the TMJs, NSAIDs attenuated hyperalgesia of inflamed TMJ and simultaneously blocked inflammation-induced upregulation of Nav1.7 mRNA and protein expression in the TG. However, ibuprofen and diclofenac sodium slightly attenuated TMJ inflammation and meloxicam did not affect TMJ inflammation. Attenuation of hyperalgesia of inflamed TMJ by NSAIDs might be associated with their role in blocking upregulation of trigeminal ganglionic Nav1.7.

  10. [Geriatric rehabilitation from the perspective of Book 9 of the German social code, SGB IX].

    PubMed

    Fuchs, H

    2007-10-01

    The legal foundations for provision and realization of geriatric rehabilitation benefits are contained in particular in Book 9 of the German social code, SGB IX (covering rehabilitation and participation of people with disabilities). This paper discusses claims foundations and benefit prerequisites of geriatric rehabilitation taking into consideration the relations between Book 5 (on health insurance) and Book 9 of the social code. The article includes a definition of "geriatric rehabilitation" in light of the SGB IX, describes the benefit carriers' obligations as well as the procedure in place for determining geriatric rehab need, in this context appraising the designation as "geriatric patient" in terms of its appropriateness as an identifying criterion in determining need. Provision of geriatric rehab benefits is contingent on a potential for attaining rehab goals as specified by SGB IX as well as on fulfillment of the benefit prerequisites. Responsibility for the content, extent and quality of geriatric rehabilitation lies with the benefit carriers, as is the case for the obligation to secure availability of the required numbers and quality of rehabilitation facilities and services. The article specifies the legal foundations of the various benefit types (ambulatory, mobile rehab, under a Personal Budget, integrated benefit provision, or early rehab), and discusses geriatric rehabilitation in the framework of an insurance-based medical care system as well as of activating care.

  11. Block of the superior cervical ganglion, description of a novel ultrasound-guided technique in human cadavers.

    PubMed

    Siegenthaler, Andreas; Haug, Matthias; Eichenberger, Urs; Suter, Marc Rene; Moriggl, Bernhard

    2013-05-01

    Injection of opioids to the superior cervical ganglion (SCG) has been reported to provide pain relief in patients suffering from different kinds of neuropathic facial pain conditions, such as trigeminal neuralgia, postherpetic neuralgia, and atypical facial pain. The classic approach to the SCG is a transoral technique using a so-called "stopper" to prevent accidental carotid artery puncture. The main disadvantage of this technique is that the needle tip is positioned distant from the actual target, possibly impeding successful block of the SCG. A further limitation is that injection of local anesthetics due to potential carotid artery puncture is contraindicated. We hypothesized that the SCG can be identified and blocked using ultrasound imaging, potentially increasing precision of this technique. In this pilot study, 20 US-guided simulated blocks of the SCG were performed in 10 human cadavers in order to determine the accuracy of this novel block technique. After injection of 0.1 mL of dye, the cadavers were dissected to evaluate the needle position and coloring of the SCG. Nineteen of the 20 needle tips were located in or next to the SCG. This corresponded to a simulated block success rate of 95% (95% confidence interval 85-100%). In 17 cases, the SCG was completely colored, and in two cases, the caudal half of the SCG was colored with dye. The anatomical dissections confirmed that our ultrasound-guided approach to the SCG is accurate. Ultrasound could become an attractive alternative to the "blind" transoral technique of SCG blocks. Wiley Periodicals, Inc.

  12. Pharmacological properties of pempidine (1:2:2:6:6-pentamethylpiperidine), a new ganglion-blocking compound

    PubMed Central

    Corne, S. J.; Edge, N. D.

    1958-01-01

    Pempidine (1:2:2:6:6-pentamethylpiperidine) is a long-acting ganglion-blocking compound which is effective by mouth. By intravenous injection it has a similar potency to hexamethonium on the preganglionically stimulated nictitating membrane of the cat. The compound blocks the effects of intravenous nicotine and of peripheral vagal stimulation on the blood pressure; it also causes dilatation of the pupil after removal of the sympathetic innervation. On the guinea-pig ileum, the predominant effect of the compound is to inhibit nicotine contractions. Pempidine is well absorbed from the gastro-intestinal tract as judged by (a) the low ratio (6.9) of oral to intravenous toxicities, (b) the rapid development of mydriasis in mice after oral administration of small doses, and (c) the rapid onset of hypotension when the compound is injected directly into the duodenum of anaesthetized cats. Other actions include neuromuscular paralysis of curare-like type when large doses of the compound are injected intravenously and central effects such as tremors which occur with near toxic doses. In cats with a low blood pressure, large intravenous doses have a slight pressor action. PMID:13584741

  13. Paracoccygeal corkscrew approach to ganglion impar injections for tailbone pain.

    PubMed

    Foye, Patrick M; Patel, Shounuck I

    2009-01-01

    A new technique for performing nerve blocks of the ganglion impar (ganglion Walther) is presented. These injections have been reported to relieve coccydynia (tailbone pain), as well as other malignant and nonmalignant pelvic pain syndromes. A variety of techniques have been previously described for blocking this sympathetic nerve ganglion, which is located in the retrorectal space just anterior to the upper coccygeal segments. Prior techniques have included approaches through the anococcygeal ligament, through the sacrococcygeal joint, and through intracoccygeal joint spaces. This article presents a new, paracoccygeal approach whereby the needle is inserted alongside the coccyx and the needle is guided through three discrete steps with a rotating or corkscrew trajectory. Compared with some of the previously published techniques, this paracoccygeal corkscrew approach has multiple potential benefits, including ease of fluoroscopic guidance using the lateral view, ability to easily use a stylet for the spinal needle, and use of a shorter, thinner needle. While no single technique works best for all patients and each technique has potential advantages and disadvantages, this new technique adds to the available options.

  14. Ganglion Cysts

    MedlinePlus

    ... Ganglion Cysts Find a hand surgeon near you. Videos Ganglion Cysts Close Popup Figures Figure 1 - Ganglion ... or "in." Also, avoid using media types like "video," "article," and "picture." Tip 4: Your results can ...

  15. Adenovector GAD65 gene delivery into the rat trigeminal ganglion produces orofacial analgesia

    PubMed Central

    Vit, Jean-Philippe; Ohara, Peter T; Sundberg, Christopher; Rubi, Blanca; Maechler, Pierre; Liu, Chunyan; Puntel, Mariana; Lowenstein, Pedro; Castro, Maria; Jasmin, Luc

    2009-01-01

    Background Our goal is to use gene therapy to alleviate pain by targeting glial cells. In an animal model of facial pain we tested the effect of transfecting the glutamic acid decarboxylase (GAD) gene into satellite glial cells (SGCs) of the trigeminal ganglion by using a serotype 5 adenovector with high tropisms for glial cells. We postulated that GABA produced from the expression of GAD would reduce pain behavior by acting on GABA receptors on neurons within the ganglion. Results Injection of adenoviral vectors (AdGAD65) directly into the trigeminal ganglion leads to sustained expression of the GAD65 isoform over the 4 weeks observation period. Immunohistochemical analysis showed that adenovirus-mediated GAD65 expression and GABA synthesis were mainly in SGCs. GABAA and GABAB receptors were both seen in sensory neurons, yet only GABAA receptors decorated the neuronal surface. GABA receptors were not found on SGCs. Six days after injection of AdGAD65 into the trigeminal ganglion, there was a statistically significant decrease of pain behavior in the orofacial formalin test, a model of inflammatory pain. Rats injected with control virus (AdGFP or AdLacZ) had no reduction in their pain behavior. AdGAD65-dependent analgesia was blocked by bicuculline, a selective GABAA receptor antagonist, but not by CGP46381, a selective GABAB receptor antagonist. Conclusion Transfection of glial cells in the trigeminal ganglion with the GAD gene blocks pain behavior by acting on GABAA receptors on neuronal perikarya. PMID:19656360

  16. Adenovector GAD65 gene delivery into the rat trigeminal ganglion produces orofacial analgesia.

    PubMed

    Vit, Jean-Philippe; Ohara, Peter T; Sundberg, Christopher; Rubi, Blanca; Maechler, Pierre; Liu, Chunyan; Puntel, Mariana; Lowenstein, Pedro; Castro, Maria; Jasmin, Luc

    2009-08-05

    Our goal is to use gene therapy to alleviate pain by targeting glial cells. In an animal model of facial pain we tested the effect of transfecting the glutamic acid decarboxylase (GAD) gene into satellite glial cells (SGCs) of the trigeminal ganglion by using a serotype 5 adenovector with high tropisms for glial cells. We postulated that GABA produced from the expression of GAD would reduce pain behavior by acting on GABA receptors on neurons within the ganglion. Injection of adenoviral vectors (AdGAD65) directly into the trigeminal ganglion leads to sustained expression of the GAD65 isoform over the 4 weeks observation period. Immunohistochemical analysis showed that adenovirus-mediated GAD65 expression and GABA synthesis were mainly in SGCs. GABAA and GABAB receptors were both seen in sensory neurons, yet only GABAA receptors decorated the neuronal surface. GABA receptors were not found on SGCs. Six days after injection of AdGAD65 into the trigeminal ganglion, there was a statistically significant decrease of pain behavior in the orofacial formalin test, a model of inflammatory pain. Rats injected with control virus (AdGFP or AdLacZ) had no reduction in their pain behavior. AdGAD65-dependent analgesia was blocked by bicuculline, a selective GABAA receptor antagonist, but not by CGP46381, a selective GABAB receptor antagonist. Transfection of glial cells in the trigeminal ganglion with the GAD gene blocks pain behavior by acting on GABAA receptors on neuronal perikarya.

  17. Management of complex regional pain syndrome type I in upper extremity-evaluation of continuous stellate ganglion block and continuous infraclavicular brachial plexus block: a pilot study.

    PubMed

    Toshniwal, Gokul; Sunder, Rani; Thomas, Ronald; Dureja, G P

    2012-01-01

    Interventional pain management techniques play an important role in the multidisciplinary approach to management of complex regional pain syndrome (CRPS). In this preliminary study we compared the efficacy of continuous stellate ganglion (CSG) block with that of continuous infraclavicular brachial plexus (CIBP) block in management of CRPS type I of upper extremity. Thirty-three patients with CRPS type I of upper extremity were randomly assigned to either CSG or CIBP group. Patients were treated for 1 week with continuous infusion of 0.125% bupivacaine at 2and 5mL/h, respectively. Catheter was removed at 1 week and patients were followed up for 4 weeks. The outcome was evaluated in terms of neuropathic pain scale score (NPSS), edema scores (Grades 0-2), and range of motion (ROM) of all upper extremity joints (Grades 0-2). CIBP group showed statistically significant improvement in NPSS compared with CSG group during the first 12 hours after the procedures (P value <0.05). After 12 hours, the NPSS was comparable between the groups. At 4 weeks, both groups showed clinically significant improvement in edema score and ROM of all upper extremity joints when compared with the baseline. This preliminary study suggests that CIBP block and CSG block may be feasible and effective interventional techniques for the management of CRPS type I of upper extremities. Hence, we recommend a larger well-randomized, well-controlled, clinical trial to confirm our findings and determine if any significant difference exists between the groups in terms of long-term pain relief and functional restoration. Wiley Periodicals, Inc.

  18. Bilateral sphenopalatine ganglion block reduces blood pressure in never treated patients with essential hypertension. A randomized controlled single-blinded study.

    PubMed

    Triantafyllidi, Helen; Arvaniti, Chrysa; Schoinas, Antonios; Benas, Dimitris; Vlachos, Stefanos; Palaiodimos, Leonidas; Pavlidis, George; Ikonomidis, Ignatios; Batistaki, Chrysanthi; Voumvourakis, Costas; Lekakis, John

    2018-01-01

    Sympathetic fibers connect sphenopalatine ganglion (SPG) with the central nervous system. We aimed to study the effect of SPG block in blood pressure (BP) in never treated patients with stage I-II essential hypertension. We performed bilateral SPG block with lidocaine 2% in 33 hypertensive patients (mean age 48±12years, 24 men) and a sham operation with water for injection in 11 patients who served as the control group (mean age 51±12years, 8 men). All patients have been subjected to 24h ambulatory blood pressure monitoring prior and a month after the SBG block in order to estimate any differences in blood pressure parameters. We defined as responders to SBG block those patients with a 24h SBP decrease ≥5mmHg. We found that 24h and daytime DBP (p=0.02) as well as daytime DBP load (p=0.03) were decreased in the study group a month after SPG block. In addition, a significant response was noted in 12/33 responders (36%) regarding: a. SBP and DBP during overall 24h and daytime (p<0.001) and night-time periods, b. pre-awake and early morning SBP and c. SBP (daytime and night-time) and DBP (daytime) load. No differences regarding BP were found in the sham operation group. SPG block is a promising, minimally invasive option of BP decrease in hypertensives, probably through SNS modulation. Additionally, due to its anesthetic effect, SPG block might act as a method of selection for those hypertensive patients with an activated SNS before any other invasive antihypertensive procedure. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Tibial periosteal ganglion cyst: The ganglion in disguise.

    PubMed

    Reghunath, Anjuna; Mittal, Mahesh K; Khanna, Geetika; Anil, V

    2017-01-01

    Soft tissue ganglions are commonly encountered cystic lesions around the wrist presumed to arise from myxomatous degeneration of periarticular connective tissue. Lesions with similar pathology in subchondral location close to joints, and often simulating a geode, is the less common entity called intraosseous ganglion. Rarer still is a lesion produced by mucoid degeneration and cyst formation of the periostium of long bones, rightly called the periosteal ganglion. They are mostly found in the lower extremities at the region of pes anserinus, typically limited to the periosteum and outer cortex without any intramedullary component. We report the case of a 62 year-old male who presented with a tender swelling on the mid shaft of the left tibia, which radiologically suggested a juxtacortical lesion extending to the soft tissue or a soft tissue neoplasm eroding the bony cortex of tibia. It was later diagnosed definitively as a periosteal ganglion in an atypical location, on further radiologic work-up and histopathological correlation.

  20. Tibial periosteal ganglion cyst: The ganglion in disguise

    PubMed Central

    Reghunath, Anjuna; Mittal, Mahesh K; Khanna, Geetika; Anil, V

    2017-01-01

    Soft tissue ganglions are commonly encountered cystic lesions around the wrist presumed to arise from myxomatous degeneration of periarticular connective tissue. Lesions with similar pathology in subchondral location close to joints, and often simulating a geode, is the less common entity called intraosseous ganglion. Rarer still is a lesion produced by mucoid degeneration and cyst formation of the periostium of long bones, rightly called the periosteal ganglion. They are mostly found in the lower extremities at the region of pes anserinus, typically limited to the periosteum and outer cortex without any intramedullary component. We report the case of a 62 year-old male who presented with a tender swelling on the mid shaft of the left tibia, which radiologically suggested a juxtacortical lesion extending to the soft tissue or a soft tissue neoplasm eroding the bony cortex of tibia. It was later diagnosed definitively as a periosteal ganglion in an atypical location, on further radiologic work-up and histopathological correlation. PMID:28515597

  1. [Botulinum toxin type A does not affect spontaneous discharge but blocks sympathetic-sensory coupling in chronically compressed rat dorsal root ganglion neurons].

    PubMed

    Yang, Hong-jun; Peng, Kai-run; Hu, San-jue; Duan, Jian-hong

    2007-11-01

    To study the effect of botulinum toxin type A (BTXA) on spontaneous discharge and sympathetic- sensory coupling in chronically compressed dorsal root ganglion (DRG) neurons in rats. In chronically compressed rat DRG, spontaneous activities of the single fibers from DRG neurons were recorded and their changes observed after BTAX application on the damaged DGR. Sympathetic modulation of the spontaneous discharge from the compressed DRG neurons was observed by electric stimulation of the lumbar sympathetic trunk, and the changes in this effect were evaluated after intravenous BTXA injection in the rats. Active spontaneous discharges were recorded in the injured DRG neurons, and 47 injured DRG neurons responded to Ca2+-free artificial cerebrospinal fluid but not to BTXA treatment. Sixty-four percent of the neurons in the injured DRG responded to sympathetic stimulation, and this response was blocked by intravenously injection of BTXA. BTXA does not affect spontaneous activities of injured DRG neurons, but blocks sympathetic-sensory coupling in these neurons.

  2. Synaptic potentials recorded by the sucrosegap method from the rabbit superior cervical ganglion

    PubMed Central

    Kosterlitz, H. W.; Lees, G. M.; Wallis, D. I.

    1970-01-01

    1. Compound ganglionic potentials evoked by stimulation of the preganglionic nerves to the superior cervical ganglion of the rabbit were recorded by the sucrose-gap method. 2. When the distal part of the ganglion was bathed in flowing isotonic sucrose solution or sodium-deficient solutions, ganglionic action potentials were no longer evoked, only large synaptic potentials. 3. The compound synaptic potential, which remained unaltered for more than 1 h, originated in a population of cells at the interface between the Krebs and sucrose solutions. Hexamethonium reduced the size but did not alter the time course of the synaptic potential. 4. It is suggested that a higher concentration of sodium ions is required for the generation of ganglionic action potentials than for either conduction in the postganglionic axons or production of synaptic potentials. 5. When lithium replaced sodium in the solution bathing the distal part of the ganglion, the synaptic potential was greatly reduced in amplitude. Impulse propagation in the postganglionic axons was only slightly impaired when lithium replaced sodium in the solution bathing the axons. 6. A quantitative assessment of the potency of the ganglion-blocking drugs nicotine, pentolinium, hexamethonium and pempidine was made by measuring the depression of the synaptic potentials produced by bathing the distal part of the ganglion in flowing isotonic sucrose solution. The concentrations which produced a 50% depression were 8·1 μM nicotine, 26·5 μM pentolinium, 111 μM hexamethonium and 22·2 μM pempidine. PMID:5492898

  3. Neuromuscular blocking properties of some bistropinium esters

    PubMed Central

    Haining, C. G.; Johnston, R. G.

    1962-01-01

    The neuromuscular blocking, anti-acetylcholine and ganglion blocking properties of two series of bistropinium esters were examined. The neuromuscular blocking activities of the mandelic acid esters of NN'-polymethylenebis(tropinium halides) were found to depend upon the number of carbon atoms (n) in the linking chain. Potency was enhanced more than 50 times as n was increased from 2 to 7. Compounds in which n equalled 7, 8, 9, 10 and 12 differed little in activity, but were generally more potent than tubocurarine in cats and rabbits. A peak of ganglion blocking action was obtained at the pentamethylene member. Esterification enhanced the feeble neuromuscular blocking properties of NN'-decamethylenebis(tropinium halide), the mandelic acid ester being more effective than the tropic, benzoic or phenylacetic acid esters in cats and rabbits. When two benzoic or mandelic acid esters of tropine were linked through their nitrogen atoms by a phenylenedimethyl grouping (-CH2.C6H4.CH2-), meta substitution was more effective than was ortho or para in producing neuromuscular block. The effectiveness of esterifying acids in m-phenylenedimethyl derivatives decreased in the following order, phenylacetic> tropic or mandelic>benzoic>acetic and diphenylacetic. PMID:13903721

  4. Epibatidine, an alkaloid from the poison frog Epipedobates tricolor, is a powerful ganglionic depolarizing agent.

    PubMed

    Fisher, M; Huangfu, D; Shen, T Y; Guyenet, P G

    1994-08-01

    Epibatidine, a newly discovered alkaloid from the skin of Dendrobatidae frogs, has structural similarities to nicotine. We examined the effects of epibatidine on cardiorespiratory function and ganglionic synaptic transmission. Superior cervical or splanchnic sympathetic nerve discharge (sSND) and phrenic nerve discharge (PND) were recorded along with arterial pressure (AP) in urethane-anesthetized, paralyzed and artificially ventilated rats. Epibatidine administered i.v. at low doses (0.5-2 micrograms/kg) produced a transient increase in AP and sSND, followed by a decrease and return to baseline; this low dose of epibatidine also produced a dose-dependent increase in PND. At high doses (cumulative dose of 8-16 micrograms/kg), epibatidine produced bradycardia, a profound depression in sSND and a transient elimination of PND. After i.v. administration of the ganglionic blocker chlorisondamine (5 mg/kg), AP was still increased by 1 microgram/kg epibatidine (+39 +/- 11 mm Hg). This pressor effect was not altered by pretreatment with the alpha-1 adrenergic antagonist phentolamine (+40 +/- 10 mm Hg); however, it was blocked by additional pretreatment with the vasopressin antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropiony1, O-ET-Tyr2,Val4,Arg8]vasopressin (50 micrograms/kg i.v.; +2 +/- 0.4 mm Hg). Low doses of epibatidine (0.5-2 micrograms/kg) produced firing of postganglionic neurons in a decentralized ganglion preparation and potentiated synaptic transmission; at high doses (cumulative dose of 8-16 micrograms/kg), the alkaloid blocked ganglionic synaptic transmission. These results suggest that epibatidine is a potent agonist of ganglionic nicotinic receptors and that the alkaloid elicits cardiorespiratory effects similar to those of nicotine.

  5. Denervation does not alter the number of neuronal bungarotoxin binding sites on autonomic neurons in the frog cardiac ganglion.

    PubMed

    Sargent, P B; Bryan, G K; Streichert, L C; Garrett, E N

    1991-11-01

    The binding of neuronal bungarotoxin (n-BuTX; also known as bungarotoxin 3.1, kappa-bungarotoxin, and toxin F) was analyzed in normal and denervated parasympathetic cardiac ganglia of the frog Rana pipiens, n-BuTX blocks both EPSPs and ACh potentials at 5-20 nM, as determined by intracellular recording techniques. Scatchard analysis on homogenates indicates that cardiac ganglia have two classes of binding sites for 125I-n-BuTX: a high-affinity site with an apparent dissociation constant (Kd,app) of 1.7 nM and a Bmax (number of binding sites) of 3.8 fmol/ganglion and a low-affinity site with a Kd,app of 12 microM and a Bmax of 14 pmol/ganglion. alpha-Bungarotoxin does not appear to interfere with the binding of 125I-n-BuTX to either site. The high-affinity binding site is likely to be the functional nicotinic ACh receptor (AChR), given the similarity between its affinity for 125I-n-BuTX and the concentration of n-BuTX required to block AChR function. Light microscopic autoradiographic analysis of 125I-n-BuTX binding to the ganglion cell surface reveals that toxin binding is concentrated at synaptic sites, which were identified using a synaptic vesicle-specific antibody. Scatchard analysis of autoradiographic data reveals that 125I-n-BuTX binding to the neuronal surface is saturable and has a Kd,app similar to that of the high-affinity binding site characterized in homogenates. Surface binding of 125I-n-BuTX is blocked by nicotine, carbachol, and d-tubocurarine (IC50 less than 20 microM), but not by atropine (IC50 greater than 10 mM). Denervation of the heart increases the ACh sensitivity of cardiac ganglion cells but has no effect upon the number of high-affinity binding sites for 125I-n-BuTX in tissue homogenates. Moreover, autoradiographic analysis indicates that denervation does not alter the number of 125I-n-BuTX binding sites on the ganglion cell surface. n-BuTX is as effective in reducing ganglion cell responses to ACh in denervated ganglia as it is in

  6. Evaluation of the percentage of ganglion cells in the ganglion cell layer of the rodent retina

    PubMed Central

    Schlamp, Cassandra L.; Montgomery, Angela D.; Mac Nair, Caitlin E.; Schuart, Claudia; Willmer, Daniel J.

    2013-01-01

    Purpose Retinal ganglion cells comprise a percentage of the neurons actually residing in the ganglion cell layer (GCL) of the rodent retina. This estimate is useful to extrapolate ganglion cell loss in models of optic nerve disease, but the values reported in the literature are highly variable depending on the methods used to obtain them. Methods We tested three retrograde labeling methods and two immunostaining methods to calculate ganglion cell number in the mouse retina (C57BL/6). Additionally, a double-stain retrograde staining method was used to label rats (Long-Evans). The number of total neurons was estimated using a nuclear stain and selecting for nuclei that met specific criteria. Cholinergic amacrine cells were identified using transgenic mice expressing Tomato fluorescent protein. Total neurons and total ganglion cell numbers were measured in microscopic fields of 104 µm2 to determine the percentage of neurons comprising ganglion cells in each field. Results Historical estimates of the percentage of ganglion cells in the mouse GCL range from 36.1% to 67.5% depending on the method used. Experimentally, retrograde labeling methods yielded a combined estimate of 50.3% in mice. A retrograde method also yielded a value of 50.21% for rat retinas. Immunolabeling estimates were higher at 64.8%. Immunolabeling may introduce overestimates, however, with non-specific labeling effects, or ectopic expression of antigens in neurons other than ganglion cells. Conclusions Since immunolabeling methods may overestimate ganglion cell numbers, we conclude that 50%, which is consistently derived from retrograde labeling methods, is a reliable estimate of the ganglion cells in the neuronal population of the GCL. PMID:23825918

  7. Enkephalin-like immunoreactive principal ganglion cells and nerve fibres in the inferior mesenteric ganglion of the cat.

    PubMed

    Balayadi, M; Jule, Y; Cupo, A

    1988-10-05

    The occurrence and distribution of methionine-enkephalin (ME), leucine-enkephalin (LE) and methionine-enkephalin-Arg6-Gly7-Leu8 (MERGL)-like (LI) immunoreactive material in the inferior mesenteric ganglion (IMG) of the cat were studied by immunohistochemical techniques using the peroxidase-antiperoxidase method. Numerous ME-Li, LE-Li and MERGL-Li immunoreactive fibres with the same distribution pattern were observed. They were varicose and often surrounded closely neighbouring unlabelled ganglion cell bodies. Sometimes they ran in strands between ganglion cells. ME-Li immunoreactive material was detected in a number of cell bodies, the diameter of which was similar to that of unlabelled principal ganglion cell bodies, and which were probably Enk-Li-containing principal ganglion cells. These immunoreactive cells were often surrounded by ME-Li immunoreactive fibres. No LE-Li or MERGL-Li immunoreactive ganglion cell bodies were observed. The presence of ME-Li immunoreactive principal ganglion cells raises the possibility that the Enk-Li immunoreactive fibres present in the IMG may have a prevertebral ganglionic source. The possibility that the Enk-Li material present in nerve fibres might be derived from preproenkephalin-A was suggested by the occurrence of MERGL-Li immunoreactivity.

  8. Thresholds for activation of rabbit retinal ganglion cells with an ultrafine, extracellular microelectrode.

    PubMed

    Jensen, Ralph J; Rizzo, Joseph F; Ziv, Ofer R; Grumet, Andrew; Wyatt, John

    2003-08-01

    To determine electrical thresholds required for extracellular activation of retinal ganglion cells as part of a project to develop an epiretinal prosthesis. Retinal ganglion cells were recorded extracellularly in retinas isolated from adult New Zealand White rabbits. Electrical current pulses of 100- micro s duration were delivered to the inner surface of the retina from a 5- micro m long electrode. In about half of the cells, the point of lowest threshold was found by searching with anodal current pulses; in the other cells, cathodal current pulses were used. Threshold measurements were obtained near the cell bodies of 20 ganglion cells and near the axons of 19 ganglion cells. Both cathodal and anodal stimuli evoked a neural response in the ganglion cells that consisted of a single action potential of near-constant latency that persisted when retinal synaptic transmission was blocked with cadmium chloride. For cell bodies, but not axons, thresholds for both cathodal and anodal stimulation were dependent on the search method used to find the point of lowest threshold. With search and stimulation of matching polarity, cathodal stimuli evoked a ganglion cell response at lower currents (approximately one seventh to one tenth axonal threshold) than did anodal stimuli for both cell bodies and axons. With cathodal search and stimulation, cell body median thresholds were somewhat lower (approximately one half) than the axonal median thresholds. With anodal search and stimulation, cell body median thresholds were approximately the same as axonal median thresholds. The results suggest that cathodal stimulation should produce lower thresholds, more localized stimulation, and somewhat better selectivity for cell bodies over axons than would anodal stimulation.

  9. Synaptic transmission in the superior cervical ganglion of the cat after reinnervation by vagus fibres

    PubMed Central

    Ceccarelli, B.; Clementi, F.; Mantegazza, P.

    1971-01-01

    1. A vagus-sympathetic anastomosis was performed in the cat by connecting end to end the cranial trunk of the vagus to the cranial end of the cervical sympathetic trunk, both severed under the ganglia. 2. Forty to sixty days after the anastomosis, the ocular signs of sympathetic paralysis (such as myosis and prolapse of the nictitating membrane) which had developed shortly after the operation, had completely disappeared, thus suggesting the recovery of synaptic transmission in the ganglion. In case of plain preganglionic denervation after the same period the ocular signs of cervical sympathetic paralysis were still present. 3. Contraction of the nictitating membrane could be induced by electrical stimulation of both the vagus preanastomotic and the sympathetic postanastomotic—preganglionic trunks. Ganglionic blocking agents induced the blockade of the `new' ganglionic synaptic function, while nicotine and pilocarpine provoked a marked contraction of the nictitating membrane. 4. Electron microscopy showed that the preganglionic regeneration of vagus fibers resulted in the formation of new synapses, mainly of axodendritic type, identical to normal ganglionic synapses. Moreover, after cutting the preanastomotic trunk of the vagus, these new ganglionic presynaptic profiles degenerated, thus proving their vagal origin. 5. During restoration of the synaptic contacts readjustment of dendritic tips occurred. ImagesText-fig. 2Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 16Fig. 17Fig. 14Fig. 15Fig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 7Fig. 8 PMID:4326851

  10. [Long-term effects of pulsed radiofrequency on the dorsal root ganglion and segmental nerve roots for lumbosacral radicular pain: a prospective controlled randomized trial with nerve root block].

    PubMed

    Fujii, Hiromi; Kosogabe, Yoshinori; Kajiki, Hideki

    2012-08-01

    Although pulsed radiofrequency (PRF) method for lumbosacral radicular pain (LSRP) is reportedly effective, there are no prospective controlled trials. We assessed the long-term efficacy of PRF of the dorsal root ganglion and nerve roots for LSRP as compared with nerve root block (RB). The study included 27 patients suffering from LSRP. The design of this study was randomized with a RB control. In the PRF group, the PRF current was applied for 120 seconds after RB. In the RB group, the patients received RB only. Visual analogue scale (VAS) was assessed immediately before, and immediately, 2 hours, 1 day, 1 week, 1 month, 3 months, 6 months, and 1 year after the procedure. P<0.05 was regarded as denoting statistical significance. In both groups, the VAS not only of short-term but also of long-term (6 months and 1 year after procedure) significantly decreased as compared with that before treatment (P<0.05). There were no significant differences of VAS between the two groups at the same time points. This study indicates that PRF adjacent to the dorsal root ganglion and nerve roots for LSRP has long-term effects. There were no significant differences of long-term effects between the two groups.

  11. Ganglion Cyst

    MedlinePlus

    ... with aspiration and injection therapy, there are nevertheless cases in which the ganglion cyst returns. Find an ACFAS Physician Search Search Tools Find an ACFAS Physician: Search by Mail Address ...

  12. Molecular biology of retinal ganglion cells.

    PubMed Central

    Xiang, M; Zhou, H; Nathans, J

    1996-01-01

    Retinal ganglion cells are the output neurons that encode and transmit information from the eye to the brain. Their diverse physiologic and anatomic properties have been intensively studied and appear to account well for a number of psychophysical phenomena such as lateral inhibition and chromatic opponency. In this paper, we summarize our current view of retinal ganglion cell properties and pose a number of questions regarding underlying molecular mechanisms. As an example of one approach to understanding molecular mechanisms, we describe recent work on several POU domain transcription factors that are expressed in subsets of retinal ganglion cells and that appear to be involved in ganglion cell development. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:8570601

  13. A novel revision to the classical transnasal topical sphenopalatine ganglion block for the treatment of headache and facial pain.

    PubMed

    Candido, Kenneth D; Massey, Scott T; Sauer, Ruben; Darabad, Raheleh Rahimi; Knezevic, Nebojsa Nick

    2013-01-01

    The sphenopalatine ganglion (SPG) is located with some degree of variability near the tail or posterior aspect of the middle nasal turbinate. The SPG has been implicated as a strategic target in the treatment of various headache and facial pain conditions, some of which are featured in this manuscript. Interventions for blocking the SPG range from minimally to highly invasive procedures often associated with great cost and unfavorable risk profiles. The purpose of this pilot study was to present a novel, FDA-cleared medication delivery device, the Tx360® nasal applicator, incorporating a transnasal needleless topical approach for SPG blocks. This study features the technical aspects of this new device and presents some limited clinical experience observed in a small series of head and face pain cases. Case series. Pain management center, part of teaching-community hospital, major metropolitan city, United States. After Institutional Review Board (IRB) approval, the technical aspects of this technique were examined on 3 patients presenting with various head and face pain conditions including trigeminal neuralgia (TN), chronic migraine headache (CM), and post-herpetic neuralgia (PHN). The subsequent response to treatment and quality of life was quantified using the following tools: the 11-point Numeric Rating Scale (NRS), Modified Brief Pain Inventory - short form (MBPI-sf), Patient Global Impression of Change (PGIC), and patient satisfaction surveys. The Tx360® nasal applicator was used to deliver 0.5 mL of ropivacaine 0.5% and 2 mg of dexamethasone for SPG block. Post-procedural assessments were repeated at 15 and 30 minutes, and on days one, 7, 14, and 21 with a final assessment at 28 days post-treatment. All patients were followed for one year. Individual patients received up to 10 SPG blocks, as clinically indicated, after the initial 28 days. Three women, ages 43, 18, and 15, presented with a variety of headache and face pain disorders including TN, CM, and

  14. Cortical-basal ganglionic degeneration.

    PubMed

    Riley, D E; Lang, A E; Lewis, A; Resch, L; Ashby, P; Hornykiewicz, O; Black, S

    1990-08-01

    We report our experience with 15 patients believed to have cortical-basal ganglionic degeneration. The clinical picture is distinctive, comprising features referable to both cortical and basal ganglionic dysfunction. Characteristic manifestations include cortical sensory loss, focal reflex myoclonus, "alien limb" phenomena, apraxia, rigidity and akinesia, a postural-action tremor, limb dystonia, hyperreflexia, and postural instability. The asymmetry of symptoms and signs is often striking. Brain imaging may demonstrate greater abnormalities contralateral to the more affected side. Postmortem studies in 2 patients revealed the characteristic pathologic features of swollen, poorly staining (achromatic) neurons and degeneration of cerebral cortex and substantia nigra. Biochemical analysis of 1 brain showed a severe, diffuse loss of dopamine in the striatum. This condition is more frequent than previously believed, and the diagnosis can be predicted during life on the basis of clinical findings. However, as with other "degenerative" diseases of the nervous system, a definitive diagnosis of cortical-basal ganglionic degeneration requires confirmation by autopsy.

  15. Modulation of release of [3H]acetylcholine in the major pelvic ganglion of the rat.

    PubMed

    Somogyi, G T; de Groat, W C

    1993-06-01

    Cholinergic modulation of [3H]acetylcholine release evoked by electrical stimulation was studied in the rat major pelvic ganglion, which was prelabeled with [3H]choline. Acetylcholine (ACh) release was independent of the frequency of stimulation; 0.3 Hz produced the same volley output as 10 Hz. Tetrodotoxin (1 microM) or omission of Ca2+ from the medium abolished ACh release. The M1 receptor agonist (4-hydroxy-2-butynyl)-1-trimethylammonium m-chlorocarbanilate chloride (McN-A 343, 50 microM) increased release (by 136%), whereas the M2 muscarinic agonist oxotremorine (1 microM) decreased ACh release (by 22%). The muscarinic antagonists, atropine (1 microM) or pirenzepine (M1 selective, 1 microM), did not change ACh release. However, pirenzepine (1 microM) blocked the facilitatory effect of McN-A 343, and atropine (1 microM) blocked the inhibitory effect of oxotremorine. The cholinesterase inhibitor physostigmine (1-5 microM), the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP, 10 microM), and the nicotinic antagonist D-tubocurarine (50 microM) did not change ACh release. 4-Aminopyridine, a K+ channel blocker, significantly increased the release (by 146%). Seven days after decentralization of the major pelvic ganglion, the evoked release of ACh was abolished. It is concluded that release of ACh occurs from the preganglionic nerve terminals rather than from the cholinergic cell bodies and is not modulated by actions of endogenous ACh on either muscarinic or nicotinic autoreceptors. These data confirm and extend previous electrophysiological findings indicating that synapses in the major pelvic ganglion have primarily a relay function.

  16. Simultaneous cell death in the trigeminal ganglion and in ganglion neurons present in the oculomotor nerve of the bovine fetus.

    PubMed Central

    Bortolami, R; Lucchi, M L; Callegari, E; Barazzoni, A M; Costerbosa, G L; Scapolo, P A

    1990-01-01

    A well-developed ganglion and scattered ganglion cells are present in the intracranial portion of the oculomotor nerve during the first half of fetal life in the ox. In the second half of fetal life a dramatic reduction of the ganglion cells associated with the oculomotor nerve occurs because of spontaneous cell death. Concomitantly, the same phenomenon of cell death is found in the trigeminal ganglion, especially in its rostromedial portion. Free degenerating perikarya can be found in the cavernous sinus. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 PMID:2384329

  17. Vascular Leiomyoma and Geniculate Ganglion

    PubMed Central

    Magliulo, Giuseppe; Iannella, Giannicola; Valente, Michele; Greco, Antonio; Appiani, Mario Ciniglio

    2013-01-01

    Objectives Discussion of a rare case of angioleiomyoma involving the geniculate ganglion and the intratemporal facial nerve segment and its surgical treatment. Design Case report. Setting Presence of an expansive lesion englobing the geniculate ganglion without any lesion to the cerebellopontine angle. Participants A 45-year-old man with a grade III facial paralysis according to the House-Brackmann scale of evaluation. Main Outcomes Measure Surgical pathology, radiologic appearance, histological features, and postoperative facial function. Results Removal of the entire lesion was achieved, preserving the anatomic integrity of the nerve; no nerve graft was necessary. Postoperative histology and immunohistochemical studies revealed features indicative of solid vascular leiomyoma. Conclusion Angioleiomyoma should be considered in the differential diagnosis of geniculate ganglion lesions. Optimal postoperative facial function is possible only by preserving the anatomical and functional integrity of the facial nerve. PMID:23943721

  18. Acetylcholine release from the rabbit isolated superior cervical ganglion preparation.

    PubMed

    Dawes, P M; Vizi, E S

    1973-06-01

    1. The rabbit isolated superior cervical ganglion preparation has been used to measure the release of acetylcholine from the tissue at rest and during preganglionic nerve stimulation.2. In the presence of physostigmine, the resting release of acetylcholine was 0.13 +/- 0.01 (nmol/g)/min (10 experiments) and that during stimulation with 300 shocks at 10 Hz was 3.1 +/- 0.4 (pmol/g)/volley in 4 experiments (means +/- S.E.M.). The volley output was independent of the frequency of stimulation over the range 1 to 10 Hz but was higher at 0.3 Hz.3. Tetrodotoxin, 0.8 muM, had no effect on the resting release of acetylcholine but reduced the stimulated release below detectable levels (2 pmol). Lowering the temperature of the bathing fluid to 5 degrees C reduced to below detectable levels both the resting release and that produced by nerve stimulation.4. The resting release of acetylcholine was increased by a potassium-rich (49.4 mM K(+)) bathing solution and by replacing the sodium chloride in the solution with lithium chloride (113 mM Li(+)).5. (-)-Noradrenaline bitartrate, 3 muM, and (+/-)-adrenaline bitartrate, 1.5 muM, reduced by 70% the output of acetylcholine induced by stimulation at 0.3 Hz, but failed to reduce the resting release or that evoked by stimulation at 10 Hz. The inhibition was reversed by phentolamine.6. It is concluded that the rabbit superior cervical ganglion in vitro is a suitable preparation for studying transmitter release and that the ganglion blocking effect of catecholamines is due to a reduction in transmitter release.

  19. Conventional Radiofrequency Thermocoagulation vs Pulsed Radiofrequency Neuromodulation of Ganglion Impar in Chronic Perineal Pain of Nononcological Origin.

    PubMed

    Usmani, Hammad; Dureja, G P; Andleeb, Roshan; Tauheed, Nazia; Asif, Naiyer

    2018-01-10

    Chronic nononcological perineal pain has been effectively managed by ganglion Impar block. Chemical neurolysis, cryoablation, and radiofrequency ablation have been the accepted methods of blockade. Recently, pulsed radiofrequency, a novel variant of conventional radiofrequency, has been used for this purpose. This was a prospective, randomized, double-blind study. Two different interventional pain management centers in India. To compare the efficacy of conventional radiofrequency and pulsed radiofrequency for gangliom Impar block. The patients were randomly allocated to one of two groups. In the conventional radiofrequency (CRF) group (N = 34), conventional radiofrequency ablation was done, and in the PRF pulsed radiofrequency (PRF) group (N = 31), pulsed radiofrequency ablation was done. After informed and written consent, fluoroscopy-guided ganglion Impar block was performed through the first intracoccygeal approach. The extent of pain relief was assessed by visual analog scale (VAS) at 24 hours, and at the first, third, and sixth weeks following the intervention. A questionnaire to evaluate subjective patient satisfaction was also used at each follow-up visit. In the CRF group, the mean VAS score decreased significantly from the baseline value at each follow-up visit. But in the PRF group, this decrease was insignificant except at 24-hour follow-up. Intergroup comparison also showed significantly better pain relief in the CRF group as compared with the PRF group. At the end of follow-up, 28 patients (82%) in the CRF group and four patients (13%) in the PRF group had excellent results, as assessed by the subjective patient satisfaction questionnaire. There was no complication in any patient of either study group, except for short-lived infection at the site of skin puncture in a few. Ganglion Impar block by conventional radiofrequency provided a significantly better quality of pain relief with no major side effects in patients with chronic

  20. Short-wavelength cone-opponent retinal ganglion cells in mammals.

    PubMed

    Marshak, David W; Mills, Stephen L

    2014-03-01

    In all of the mammalian species studied to date, the short-wavelength-sensitive (S) cones and the S-cone bipolar cells that receive their input are very similar, but the retinal ganglion cells that receive synapses from the S-cone bipolar cells appear to be quite different. Here, we review the literature on mammalian retinal ganglion cells that respond selectively to stimulation of S-cones and respond with opposite polarity to longer wavelength stimuli. There are at least three basic mechanisms to generate these color-opponent responses, including: (1) opponency is generated in the outer plexiform layer by horizontal cells and is conveyed to the ganglion cells via S-cone bipolar cells, (2) inputs from bipolar cells with different cone inputs and opposite response polarity converge directly on the ganglion cells, and (3) inputs from S-cone bipolar cells are inverted by S-cone amacrine cells. These are not mutually exclusive; some mammalian ganglion cells that respond selectively to S-cone stimulation seem to utilize at least two of them. Based on these findings, we suggest that the small bistratified ganglion cells described in primates are not the ancestral type, as proposed previously. Instead, the known types of ganglion cells in this pathway evolved from monostratified ancestral types and became bistratified in some mammalian lineages.

  1. Reactive oxygen species alters the electrophysiological properties and raises [Ca2+]i in intracardiac ganglion neurons

    PubMed Central

    Dyavanapalli, Jhansi; Rimmer, Katrina

    2010-01-01

    We have investigated the effects of the reactive oxygen species (ROS) donors hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BHP) on the intrinsic electrophysiological characteristics: ganglionic transmission and resting [Ca2+]i in neonate and adult rat intracardiac ganglion (ICG) neurons. Intracellular recordings were made using sharp microelectrodes filled with either 0.5 M KCl or Oregon Green 488 BAPTA-1, allowing recording of electrical properties and measurement of [Ca2+]i. H2O2 and t-BHP both hyperpolarized the resting membrane potential and reduced membrane resistance. In adult ICG neurons, the hyperpolarizing action of H2O2 was reversed fully by Ba2+ and partially by tetraethylammonium, muscarine, and linopirdine. H2O2 and t-BHP reduced the action potential afterhyperpolarization (AHP) amplitude but had no impact on either overshoot or AHP duration. ROS donors evoked an increase in discharge adaptation to long depolarizing current pulses. H2O2 blocked ganglionic transmission in most ICG neurons but did not alter nicotine-evoked depolarizations. By contrast, t-BHP had no significant action on ganglionic transmission. H2O2 and t-BHP increased resting intracellular Ca2+ levels to 1.6 ( ± 0.6, n = 11, P < 0.01) and 1.6 ( ± 0.3, n = 8, P < 0.001), respectively, of control value (1.0, ∼60 nM). The ROS scavenger catalase prevented the actions of H2O2, and this protection extended beyond the period of application. Superoxide dismutase partially shielded against the action of H2O2, but this was limited to the period of application. These data demonstrate that ROS decreases the excitability and ganglionic transmission of ICG neurons, attenuating parasympathetic control of the heart. PMID:20445155

  2. Piriformis ganglion: An uncommon cause of sciatica.

    PubMed

    Park, J H; Jeong, H J; Shin, H K; Park, S J; Lee, J H; Kim, E

    2016-04-01

    Sciatica can occur due to a spinal lesion, intrapelvic tumor, diabetic neuropathy, and rarely piriformis syndrome. The causes of piriformis syndrome vary by a space-occupying lesion. A ganglionic cyst can occur in various lesions in the body but seldom around the hip joint. In addition, sciatica due to a ganglionic cyst around the hip joint has been reported in one patient in Korea who underwent surgical treatment. We experienced two cases of sciatica from a piriformis ganglionic cyst and we report the clinical characterics and progress after non-operative treatment by ultrasonography-guided aspiration. The two cases were diagnosed by magnetic resonance imaging and were treated by ultrasonography-guided aspiration. We followed the patients for more than 6months. The symptoms of piriformis syndrome from the ganglion improved following aspiration and this conservative treatment is a treatment method that can be used without extensive incision or cyst excision. Level IV historical case. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Incomplete segregation of endorgan-specific vestibular ganglion cells in mice and rats

    NASA Technical Reports Server (NTRS)

    Maklad, A.; Fritzsch, B.

    1999-01-01

    The endorgan-specific distribution of vestibular ganglion cells was studied in neonatal and postnatal rats and mice using indocarbocyanine dye (DiI) and dextran amines for retrograde and anterograde labeling. Retrograde DiI tracing from the anterior vertical canal labeled neurons scattered throughout the whole superior vestibular ganglion, with denser labeling at the dorsal and central regions. Horizontal canal neurons were scattered along the dorsoventral axis with more clustering toward the dorsal and ventral poles of this axis. Utricular ganglion cells occupied predominantly the central region of the superior vestibular ganglion. This utricular population overlapped with both the anterior vertical and horizontal canals' ganglion cells. Posterior vertical canal neurons were clustered in the posterior part of the inferior vestibular ganglion. The saccular neurons were distributed in the two parts of the vestibular ganglion, the superior and inferior ganglia. Within the inferior ganglion, the saccular neurons were clustered in the anterior part. In the superior ganglion, the saccular neurons were widely scattered throughout the whole ganglion with more numerous neurons at the posterior half. Small and large neurons were labeled from all endorgans. Examination of the fiber trajectory within the superior division of the vestibular nerve showed no clear lamination of the fibers innervating the different endorgans. These results demonstrate an overlapping pattern between the different populations within the superior ganglion, while in the inferior ganglion, the posterior canal and saccular neurons show tighter clustering but incomplete segregation. This distribution implies that the ganglion cells are assigned for their target during development in a stochastic rather than topographical fashion.

  4. Calcium channels in solitary retinal ganglion cells from post-natal rat.

    PubMed Central

    Karschin, A; Lipton, S A

    1989-01-01

    -Conotoxin fraction GVIA (omega-CgTX VIA), a peptide from the venom of the snail Conus geographus, produces a readily reversible blockade of all components of the calcium current in these central mammalian neurones. This finding is in contrast to that of other preparations in which this toxin is responsible for an ephemeral block of T-current but a long-lasting block of other components of calcium current. 5. In summary, at least two components of calcium current with discrete underlying unitary events are present in post-natal retinal ganglion cells from rat. One component closely resembles the T or transient current observed in other cell types.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2559971

  5. Acetylcholine release from the rabbit isolated superior cervical ganglion preparation

    PubMed Central

    Dawes, P. M.; Vizi, E. S.

    1973-01-01

    1. The rabbit isolated superior cervical ganglion preparation has been used to measure the release of acetylcholine from the tissue at rest and during preganglionic nerve stimulation. 2. In the presence of physostigmine, the resting release of acetylcholine was 0·13 ± 0·01 (nmol/g)/min (10 experiments) and that during stimulation with 300 shocks at 10 Hz was 3·1 ± 0·4 (pmol/g)/volley in 4 experiments (means ± S.E.M.). The volley output was independent of the frequency of stimulation over the range 1 to 10 Hz but was higher at 0·3 Hz. 3. Tetrodotoxin, 0·8 μM, had no effect on the resting release of acetylcholine but reduced the stimulated release below detectable levels (2 pmol). Lowering the temperature of the bathing fluid to 5° C reduced to below detectable levels both the resting release and that produced by nerve stimulation. 4. The resting release of acetylcholine was increased by a potassium-rich (49·4 mM K+) bathing solution and by replacing the sodium chloride in the solution with lithium chloride (113 mM Li+). 5. (-)-Noradrenaline bitartrate, 3 μM, and (±)-adrenaline bitartrate, 1·5 μM, reduced by 70% the output of acetylcholine induced by stimulation at 0·3 Hz, but failed to reduce the resting release or that evoked by stimulation at 10 Hz. The inhibition was reversed by phentolamine. 6. It is concluded that the rabbit superior cervical ganglion in vitro is a suitable preparation for studying transmitter release and that the ganglion blocking effect of catecholamines is due to a reduction in transmitter release. PMID:4733726

  6. PDC-SGB: Prediction of effective drug combinations using a stochastic gradient boosting algorithm.

    PubMed

    Xu, Qian; Xiong, Yi; Dai, Hao; Kumari, Kotni Meena; Xu, Qin; Ou, Hong-Yu; Wei, Dong-Qing

    2017-03-21

    Combinatorial therapy is a promising strategy for combating complex diseases by improving the efficacy and reducing the side effects. To facilitate the identification of drug combinations in pharmacology, we proposed a new computational model, termed PDC-SGB, to predict effective drug combinations by integrating biological, chemical and pharmacological information based on a stochastic gradient boosting algorithm. To begin with, a set of 352 golden positive samples were collected from the public drug combination database. Then, a set of 732 dimensional feature vector involving biological, chemical and pharmaceutical information was constructed for each drug combination to describe its properties. To avoid overfitting, the maximum relevance & minimum redundancy (mRMR) method was performed to extract useful ones by removing redundant subsets. Based on the selected features, the three different type of classification algorithms were employed to build the drug combination prediction models. Our results demonstrated that the model based on the stochastic gradient boosting algorithm yield out the best performance. Furthermore, it is indicated that the feature patterns of therapy had powerful ability to discriminate effective drug combinations from non-effective ones. By analyzing various features, it is shown that the enriched features occurred frequently in golden positive samples can help predict novel drug combinations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Light-evoked currents in retinal ganglion cells from dystrophic RCS rats.

    PubMed

    Liu, Kang; Wang, Yi; Yin, Zhengqin; Weng, Chuanhuang

    2013-01-01

    To study the electrophysiological properties of the light-evoked currents in ganglion cells in situations of retinal degeneration. We investigated light-evoked currents in ganglion cells by performing whole-cell patch-clamp recordings from ganglion cells using a retina-stretched preparation from Royal College of Surgeons (RCS) rats, a model of retinal degeneration and congenic controls at different ages. Pharmacological inhibitors of the AMPA receptor (NBQX), GABA receptor (BMI), and sodium channels (TTX) were used to identify the components of the light-evoked currents in ON, OFF and ON-OFF retinal ganglion cells. We found that the light-evoked currents in ganglion cells from control rats were inhibited by NBQX, BMI and TTX, suggesting that AMPA receptors, GABA receptors and sodium channels contribute to these currents in ganglion cells. However, only AMPA receptor-mediated currents were recorded in RCS rats. Light-evoked inward currents were absent in the majority of ganglion cells from RCS rats, particularly at the later stages of retinal degeneration. At earlier stages of retinal degeneration, we found that both the timing and amplitude of light-evoked currents are significantly different in ganglion cells from RCS and control rats. Our study furthers the understanding of the electrophysiological characteristics of retinal ganglion cells during retinal degeneration, and provides insight into the optimal timing for the treatment of retinal degeneration. Copyright © 2013 S. Karger AG, Basel.

  8. Morphological relationship between the superior cervical ganglion and cervical nerves in Japanese cadaver donors.

    PubMed

    Mitsuoka, Kazuyuki; Kikutani, Takeshi; Sato, Iwao

    2017-02-01

    There are various communications between the superior cervical ganglion (SCG) and the vagus and glossopharyngeal nerves. However, little information exists concerning the origin of these sympathetic ganglion branches at the superior, middle, and inferior regions of the human SCG. The aim of this study was to describe the human SCG in a morphometric manner with the communication with cranial and cervical nerves and supply. This study characterized 72 SCG samples from 54 elderly Japanese human cadavers (30 males, 24 females; 65-100 years old). The SCG size (length, width, and thickness) and location were measured from the jugular foramen. We also defined the communication branches of the SCG to the vagus, glossopharyngeal, cervical, and accessory nerves at three regions (superior, middle, and inferior regions) of the SCG. Finally, we examined the arrangement and origin of the branch communications in detail and confirmed our observations, using histological sections of the SCG. The SCG in all cadaver donors was detected at the C2 and C3 vertebra levels. The number of SCG branches supplied the communicating branches, such as the carotid branch, communicating branch of the vagus nerve, and glossopharyngeal nerve, were frequently detected in the superior region of the SCG (χ 2  = 587.72, df = 26, p  <   .001). The number of ganglion cells with a large number of neurons per unit area (1 mm 2 ) was most often found in the middle region with shrunken neurons of the SCG compared with other regions. The communication branches of the SCG are mainly connected to the vagus and glossopharyngeal nerves. Characterizing these branches can provide useful data for head and neck ganglion block and surgical treatments.

  9. The effects of ropivacaine hydrochloride on the expression of CaMK II mRNA in the dorsal root ganglion neurons.

    PubMed

    Wen, Xianjie; Lai, Xiaohong; Li, Xiaohong; Zhang, Tao; Liang, Hua

    2016-12-01

    In this study, we identified the subtype of Calcium/calmodulin-dependent protein kinase II (CaMK II) mRNA in dorsal root ganglion neurons and observed the effects of ropivacaine hydrochloride in different concentration and different exposure time on the mRNA expression. Dorsal root ganglion neurons were isolated from the SD rats and cultured in vitro. The mRNA of the CaMK II subtype in dorsal root ganglion neurons were detected by real-time PCR. As well as, the dorsal root ganglion neurons were treated with ropivacaine hydrochloride in different concentration (1mM,2mM, 3mM and 4mM) for the same exposure time of 4h, or different exposure time (0h,2h,3h,4h and 6h) at the same concentration(3mM). The changes of the mRNA expression of the CaMK II subtype were observed with real-time PCR. All subtype mRNA of the CaMK II, CaMK II α , CaMK II β , CaMK II δ , CaMK II γ , can be detected in dorsal root ganglion neurons. With the increased of the concentration and exposure time of the ropivacaine hydrochloride, all the subtype mRNA expression increased. Ropivacaine hydrochloride up-regulate the CaMK II β , CaMK II δ , CaMK II g mRNA expression with the concentration and exposure time increasing. The nerve blocking or the neurotoxicity of the ropivacaine hydrochloride maybe involved with CaMK II. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

    PubMed Central

    Sunada, Katsuhisa; Shigeno, Keiji; Nakada, Akira; Honda, Michitaka; Nakamura, Tatsuo

    2017-01-01

    This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB) in a canine model. This study involved two experiments—in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN) repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes) after nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow. PMID:29220373

  11. Morphological patterns in children with ganglion related enteric neuronal abnormalities.

    PubMed

    Henna, Nausheen; Nagi, Abdul H; Sheikh, Muhammad A; Shaukat, Mahmood

    2011-01-01

    Hirschsprung's Disease (HD) is a developmental disorder of enteric nervous system characterised by the absence of ganglion cells in submucosal (Meissner's) and myenteric (Aurbach's) plexuses of distal bowel. The purpose of the present study was to observe and report the morphological patterns of ganglion related enteric neuronal abnormalities in children presented with clinical features of (HD) in a Pakistani population. A total of 92 patients with clinical presentation of HD were enrolled between March 2009 and October 2009. Among them, 8 were excluded according to the exclusion criteria. After detailed history and physical examination, paraffin embedded H and E stained sections were prepared from the serial open biopsies from colorectum. The data was analysed using SPSS-17. Frequencies and percentages are given for qualitative variables. Non-parametric Binomial Chi-Square test was applied to observe within group associations and p<0.05 was considered statistically significant. Among 84 patients, 13 (15.5%) proved to be normally ganglionic whereas 71 (84.5%) showed ganglion related enteric neuronal abnormalities namely isolated hypoganglionosis 9 (12.7%), immaturity of ganglion cells 9 (12.7%), isolated hyperganglionosis (IND Type B) 2 (2.8%) and Hirschsprung's disease 51 (71.8%). Among HD group, 34 (66.7%) belonged to isolated form and 17 (33.3%) showed combined ganglion related abnormalities. Hirschsprung's disease is common in Pakistani population, followed by hypoganglionosis, immaturity of ganglion cells and IND type B. The presence of hypertrophic nerve fibres was significant in HD, hyperganglionosis and hypoganglionosis, whereas, no hypertrophic nerve fibres were appreciated in immaturity of ganglion cell group.

  12. Comparative anatomy of the accessory ciliary ganglion in mammals.

    PubMed

    Kuchiiwa, S; Kuchiiwa, T; Suzuki, T

    1989-01-01

    The orbits of 13 mammalian species (pig, sika deer, domestic sheep, horse, cat, fox, racoon dog, marten, rat, rabbit, crab-eating macaque, japanese macaque and man) were stained with silver nitrate and dissected under a dissecting microscope with special attention to the presence and location of the accessory ciliary ganglion. Some preparations were stained with thionin and examined as whole-mounts in a transmission microscope. The accessory ciliary ganglion was present in all 13 species, although the number and degree of development varied greatly from species to species. The accessory ciliary ganglion could be readily differentiated from the main ciliary ganglion in the following respects: it was located on the short ciliary nerve, and it had no root derived directly from the inferior trunk of the oculomotor nerve and it never attaches to this nerve. In many species, ganglion cells were also scattered in the short ciliary nerves in the stained whole preparations. In a few species, there were one or more small ganglia on the nerve to the inferior oblique muscle.

  13. Depicting the pterygopalatine ganglion on 3 Tesla magnetic resonance images.

    PubMed

    Bratbak, Daniel Fossum; Folvik, Mari; Nordgård, Ståle; Stovner, Lars Jacob; Dodick, David W; Matharu, Manjit; Tronvik, Erling

    2018-06-01

    The pterygopalatine ganglion has yet not been identified on medical images in living humans. The primary aim of this study was to evaluate whether the pterygopalatine ganglion could be identified on 3 T MR imaging. This study was performed on medical images of 20 Caucasian subjects on both sides (n = 40 ganglia) with an exploratory design. 3 T MR images were assessed by two physicians for the presence and size of the pterygopalatine ganglion. The distance from the pterygopalatine ganglion to four bony landmarks was registered from fused MR and CT images. In an equivalence analysis, the distances were compared to those obtained in an anatomical cadaveric study serving as historical controls (n = 50). A structure assumed to be the pterygopalatine ganglion was identified on MR images in all patients on both sides by both physicians. The mean size was depth 2.1 ± 0.5 mm, width 4.2 ± 1.1 mm and height 5.1 ± 1.4 mm, which is in accordance with formerly published data. Equivalence of the measurements on MR images and the historical controls was established, suggesting that the structure identified on the MR images is the pterygopalatine ganglion. Our findings suggest that the pterygopalatine ganglion can be detected on 3 T MR images. Identification of the pterygopalatine ganglion may be important for image-guided interventions targeting the pterygopalatine ganglion, and has the potential to increase the efficacy, safety and reliability for these treatments.

  14. Arthroscopic excision of ganglion cysts.

    PubMed

    Bontempo, Nicholas A; Weiss, Arnold-Peter C

    2014-02-01

    Arthroscopy is an advancing field in orthopedics, the applications of which have been expanding over time. Traditionally, excision of ganglion cysts has been done in an open fashion. However, more recently, studies show outcomes following arthroscopic excision to be as good as open excision. Cosmetically, the incisions are smaller and heal faster following arthroscopy. In addition, there is the suggested benefit that patients will regain function and return to work faster following arthroscopic excision. More prospective studies comparing open and arthroscopic excision of ganglion cysts need to be done in order to delineate if there is a true functional benefit. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Wasp venom blocks central cholinergic synapses to induce transient paralysis in cockroach prey.

    PubMed

    Haspel, G; Libersat, F

    2003-03-01

    The parasitoid wasp Ampulex compressa induces a set of unique behavioral effects upon stinging its prey, the cockroach. It stings into the first thoracic segment inducing 2 to 3 min of transient flaccid paralysis of the front legs. This facilitates a second sting in the cockroach's head that induces 30 min of excessive grooming followed by a 2 to 5-week long lethargic state. In the present study, we examine the immediate effect of the first sting, which is a transient paralysis of the front legs. Using radiolabeled wasps, we demonstrate that the wasp injects its venom directly into the cockroach's first thoracic ganglion. The artificial injection of milked venom into a thoracic ganglion abolishes spontaneous and evoked responses of the motoneurons associated with leg movements. To investigate the physiological mechanism of action of the venom, we injected venom into the last abdominal ganglion of the cockroach, which houses a well-characterized cholinergic synapse. Injected venom abolishes both sensory-evoked and agonist-evoked postsynaptic potentials recorded in the postsynaptic neuron for 2 to 3 min without affecting action potential propagation. Thus, the venom blocking effect has a postsynaptic component that follows the same time course as the transient paralysis induced by the thoracic sting. Finally, injection of a nicotinic antagonist in the front thoracic ganglion induces paralysis of the front legs. We conclude that the transient paralytic effect of the thoracic sting can be mainly accounted for by the presence of a venom active component that induces a postsynaptic block of central cholinergic synaptic transmission. Copyright 2003 Wiley Periodicals, Inc. J Neurobiol 54: 628-637, 2003

  16. Inhibition of mTOR by Rapamycin Results in Auditory Hair Cell Damage and Decreased Spiral Ganglion Neuron Outgrowth and Neurite Formation In Vitro

    PubMed Central

    Leitmeyer, Katharina; Glutz, Andrea; Radojevic, Vesna; Setz, Cristian; Huerzeler, Nathan; Bumann, Helen; Bodmer, Daniel; Brand, Yves

    2015-01-01

    Rapamycin is an antifungal agent with immunosuppressive properties. Rapamycin inhibits the mammalian target of rapamycin (mTOR) by blocking the mTOR complex 1 (mTORC1). mTOR is an atypical serine/threonine protein kinase, which controls cell growth, cell proliferation, and cell metabolism. However, less is known about the mTOR pathway in the inner ear. First, we evaluated whether or not the two mTOR complexes (mTORC1 and mTORC2, resp.) are present in the mammalian cochlea. Next, tissue explants of 5-day-old rats were treated with increasing concentrations of rapamycin to explore the effects of rapamycin on auditory hair cells and spiral ganglion neurons. Auditory hair cell survival, spiral ganglion neuron number, length of neurites, and neuronal survival were analyzed in vitro. Our data indicates that both mTOR complexes are expressed in the mammalian cochlea. We observed that inhibition of mTOR by rapamycin results in a dose dependent damage of auditory hair cells. Moreover, spiral ganglion neurite number and length of neurites were significantly decreased in all concentrations used compared to control in a dose dependent manner. Our data indicate that the mTOR may play a role in the survival of hair cells and modulates spiral ganglion neuronal outgrowth and neurite formation. PMID:25918725

  17. Inhibition of mTOR by Rapamycin Results in Auditory Hair Cell Damage and Decreased Spiral Ganglion Neuron Outgrowth and Neurite Formation In Vitro.

    PubMed

    Leitmeyer, Katharina; Glutz, Andrea; Radojevic, Vesna; Setz, Cristian; Huerzeler, Nathan; Bumann, Helen; Bodmer, Daniel; Brand, Yves

    2015-01-01

    Rapamycin is an antifungal agent with immunosuppressive properties. Rapamycin inhibits the mammalian target of rapamycin (mTOR) by blocking the mTOR complex 1 (mTORC1). mTOR is an atypical serine/threonine protein kinase, which controls cell growth, cell proliferation, and cell metabolism. However, less is known about the mTOR pathway in the inner ear. First, we evaluated whether or not the two mTOR complexes (mTORC1 and mTORC2, resp.) are present in the mammalian cochlea. Next, tissue explants of 5-day-old rats were treated with increasing concentrations of rapamycin to explore the effects of rapamycin on auditory hair cells and spiral ganglion neurons. Auditory hair cell survival, spiral ganglion neuron number, length of neurites, and neuronal survival were analyzed in vitro. Our data indicates that both mTOR complexes are expressed in the mammalian cochlea. We observed that inhibition of mTOR by rapamycin results in a dose dependent damage of auditory hair cells. Moreover, spiral ganglion neurite number and length of neurites were significantly decreased in all concentrations used compared to control in a dose dependent manner. Our data indicate that the mTOR may play a role in the survival of hair cells and modulates spiral ganglion neuronal outgrowth and neurite formation.

  18. Effectiveness and Patient Acceptability of Stellate Ganglion Block (SGB) for Treatment of Posttraumatic Stress Disorder (PTSD) Symptoms Among Active Duty Military Members

    DTIC Science & Technology

    2016-03-01

    ut It Pa rt O f M y Jo b N ot S ur e D oe sn ’t A pp ly 1. Natural disaster (for example, flood, hurricane, tornado , earthquake...of my job (2) Not Sure (1) Doesn’t Apply (0) 1. Natural disaster (for example, flood, hurricane, tornado , earthquake) (LEC_1) 2

  19. Diversity in spatial scope of contrast adaptation among mouse retinal ganglion cells.

    PubMed

    Khani, Mohammad Hossein; Gollisch, Tim

    2017-12-01

    Retinal ganglion cells adapt to changes in visual contrast by adjusting their response kinetics and sensitivity. While much work has focused on the time scales of these adaptation processes, less is known about the spatial scale of contrast adaptation. For example, do small, localized contrast changes affect a cell's signal processing across its entire receptive field? Previous investigations have provided conflicting evidence, suggesting that contrast adaptation occurs either locally within subregions of a ganglion cell's receptive field or globally over the receptive field in its entirety. Here, we investigated the spatial extent of contrast adaptation in ganglion cells of the isolated mouse retina through multielectrode-array recordings. We applied visual stimuli so that ganglion cell receptive fields contained regions where the average contrast level changed periodically as well as regions with constant average contrast level. This allowed us to analyze temporal stimulus integration and sensitivity separately for stimulus regions with and without contrast changes. We found that the spatial scope of contrast adaptation depends strongly on cell identity, with some ganglion cells displaying clear local adaptation, whereas others, in particular large transient ganglion cells, adapted globally to contrast changes. Thus, the spatial scope of contrast adaptation in mouse retinal ganglion cells appears to be cell-type specific. This could reflect differences in mechanisms of contrast adaptation and may contribute to the functional diversity of different ganglion cell types. NEW & NOTEWORTHY Understanding whether adaptation of a neuron in a sensory system can occur locally inside the receptive field or whether it always globally affects the entire receptive field is important for understanding how the neuron processes complex sensory stimuli. For mouse retinal ganglion cells, we here show that both local and global contrast adaptation exist and that this diversity in

  20. Diversity in spatial scope of contrast adaptation among mouse retinal ganglion cells

    PubMed Central

    Khani, Mohammad Hossein

    2017-01-01

    Retinal ganglion cells adapt to changes in visual contrast by adjusting their response kinetics and sensitivity. While much work has focused on the time scales of these adaptation processes, less is known about the spatial scale of contrast adaptation. For example, do small, localized contrast changes affect a cell’s signal processing across its entire receptive field? Previous investigations have provided conflicting evidence, suggesting that contrast adaptation occurs either locally within subregions of a ganglion cell’s receptive field or globally over the receptive field in its entirety. Here, we investigated the spatial extent of contrast adaptation in ganglion cells of the isolated mouse retina through multielectrode-array recordings. We applied visual stimuli so that ganglion cell receptive fields contained regions where the average contrast level changed periodically as well as regions with constant average contrast level. This allowed us to analyze temporal stimulus integration and sensitivity separately for stimulus regions with and without contrast changes. We found that the spatial scope of contrast adaptation depends strongly on cell identity, with some ganglion cells displaying clear local adaptation, whereas others, in particular large transient ganglion cells, adapted globally to contrast changes. Thus, the spatial scope of contrast adaptation in mouse retinal ganglion cells appears to be cell-type specific. This could reflect differences in mechanisms of contrast adaptation and may contribute to the functional diversity of different ganglion cell types. NEW & NOTEWORTHY Understanding whether adaptation of a neuron in a sensory system can occur locally inside the receptive field or whether it always globally affects the entire receptive field is important for understanding how the neuron processes complex sensory stimuli. For mouse retinal ganglion cells, we here show that both local and global contrast adaptation exist and that this diversity

  1. Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line

    PubMed Central

    Hong, Samin; Lee, Jong Eun; Kim, Chan Yun; Seong, Gong Je

    2007-01-01

    Background Agmatine is an endogenous polyamine formed by the decarboxylation of L-arginine. We investigated the protective effects of agmatine against hypoxia-induced apoptosis of immortalized rat retinal ganglion cells (RGC-5). RGC-5 cells were cultured in a closed hypoxic chamber (5% O2) with or without agmatine. Cell viability was determined by lactate dehydrogenase (LDH) assay and apoptosis was examined by annexin V and caspase-3 assays. Expression and phosphorylation of mitogen-activated protein kinases (MAPKs; JNK, ERK p44/42, and p38) and nuclear factor-kappa B (NF-κB) were investigated by Western immunoblot analysis. The effects of agmatine were compared to those of brain-derived neurotrophic factor (BDNF), a well-known protective neurotrophin for retinal ganglion cells. Results After 48 hours of hypoxic culture, the LDH assay showed 52.3% cell loss, which was reduced to 25.6% and 30.1% when agmatine and BDNF were administered, respectively. This observed cell loss was due to apoptotic cell death, as established by annexin V and caspase-3 assays. Although total expression of MAPKs and NF-κB was not influenced by hypoxic injury, phosphorylation of these two proteins was increased. Agmatine reduced phosphorylation of JNK and NF-κB, while BDNF suppressed phosphorylation of ERK and p38. Conclusion Our results show that agmatine has neuroprotective effects against hypoxia-induced retinal ganglion cell damage in RGC-5 cells and that its effects may act through the JNK and NF-κB signaling pathways. Our data suggest that agmatine may lead to a novel therapeutic strategy to reduce retinal ganglion cell injury related to hypoxia. PMID:17908330

  2. Spiral Ganglion Stem Cells Can Be Propagated and Differentiated Into Neurons and Glia

    PubMed Central

    Zecha, Veronika; Wagenblast, Jens; Arnhold, Stefan; Edge, Albert S. B.; Stöver, Timo

    2014-01-01

    Abstract The spiral ganglion is an essential functional component of the peripheral auditory system. Most types of hearing loss are associated with spiral ganglion cell degeneration which is irreversible due to the inner ear's lack of regenerative capacity. Recent studies revealed the existence of stem cells in the postnatal spiral ganglion, which gives rise to the hope that these cells might be useful for regenerative inner ear therapies. Here, we provide an in-depth analysis of sphere-forming stem cells isolated from the spiral ganglion of postnatal mice. We show that spiral ganglion spheres have characteristics similar to neurospheres isolated from the brain. Importantly, spiral ganglion sphere cells maintain their major stem cell characteristics after repeated propagation, which enables the culture of spheres for an extended period of time. In this work, we also demonstrate that differentiated sphere-derived cell populations not only adopt the immunophenotype of mature spiral ganglion cells but also develop distinct ultrastructural features of neurons and glial cells. Thus, our work provides further evidence that self-renewing spiral ganglion stem cells might serve as a promising source for the regeneration of lost auditory neurons. PMID:24940560

  3. Two distinct classes of functional α7-containing nicotinic receptor on rat superior cervical ganglion neurons

    PubMed Central

    Cuevas, Javier; Roth, Adelheid L; Berg, Darwin K

    2000-01-01

    Nicotinic acetylcholine receptors (nAChRs) that bind α-bungarotoxin (αBgt) were studied on isolated rat superior cervical ganglion (SCG) neurons using whole-cell patch clamp recording techniques.Rapid application of ACh onto the soma of voltage clamped neurons evoked a slowly desensitizing current that was reversibly blocked by αBgt (50 nm). The toxin-sensitive current constituted on average about half of the peak whole-cell response evoked by ACh.Nanomolar concentrations of methyllycaconitine blocked the αBgt-sensitive component of the ACh-evoked current as did intracellular dialysis with an anti-α7 monoclonal antibody. The results indicate that the slowly reversible toxin-sensitive response elicited by ACh arises from activation of an unusual class of α7-containing receptor (α7-nAChR) similar to that reported previously for rat intracardiac ganglion neurons.A second class of functional α7-nAChR was identified on some SCG neurons by using rapid application of choline to elicit responses. In these cases a biphasic response was obtained, which included a rapidly desensitizing component that was blocked by αBgt in a pseudo-irreversible manner. The pharmacology and kinetics of the responses resembled those previously attributed to α7-nAChRs in a number of other neuronal cell types.Experiments measuring the dissociation rate of 125I-labelled αBgt from SCG neurons revealed two classes of toxin-binding site. The times for toxin dissociation were consistent with those required to reverse blockade of the two kinds of αBgt-sensitive response.These results indicate that rat SCG neurons express two types of functional α7-nAChR, differing in pharmacology, desensitization and reversibility of αBgt blockade. PMID:10856125

  4. The sympathetic postganglionic fibre and the block by bretylium; the block prevented by hexamethonium and imitated by mecamylamine

    PubMed Central

    Burn, J. H.; Gibbons, W. R.

    1964-01-01

    Acetylcholine, in the presence of atropine, has an action like that of sympathetic stimulation. When injected into the splenic artery it causes contraction of the spleen, but this action is blocked by hexamethonium; stimulation of the splenic nerves, however, is still effective. Thus hexamethonium distinguishes between sympathetic nerve stimulation and the action of acetylcholine. If bretylium is used instead of hexamethonium, there is no such distinction, for bretylium blocks the response to nerve stimulation as well as that to acetylcholine. It appeared that hexamethonium might block the action of acetylcholine by preventing its entry into the sympathetic fibre. Acetylcholine has some structural similarity to bretylium, since acetylcholine is a derivative of trimethylammonium and bretylium is a derivative of dimethylethylammonium. It has been found that hexamethonium, pentolinium and hemicholinium (HC-3), which are all bis-quaternary compounds, block the action of bretylium, presumably by preventing its entry into the fibre. Consistent with the view that ability to enter the fibre is important is the observation that mecamylamine and pempidine, which are ganglion-blocking agents, but not either mono- or bis-quaternary compounds, often abolish the response to stimulation of the sympathetic postganglionic fibre. PMID:14211685

  5. The anti-nociceptive agent ralfinamide inhibits tetrodotoxin-resistant and tetrodotoxin-sensitive Na+ currents in dorsal root ganglion neurons.

    PubMed

    Stummann, Tina C; Salvati, Patricia; Fariello, Ruggero G; Faravelli, Laura

    2005-03-14

    Tetrodotoxin-resistant and tetrodotoxin-sensitive Na+ channels contribute to the abnormal spontaneous firing in dorsal root ganglion neurons associated with neuropathic pain. Effects of the anti-nociceptive agent ralfinamide on tetrodotoxin-resistant and tetrodotoxin-sensitive currents in rat dorsal root ganglion neurons were therefore investigated by patch clamp experiments. Ralfinamide inhibition was voltage-dependent showing highest potency towards inactivated channels. IC50 values for tonic block of half-maximal inactivated tetrodotoxin-resistant and tetrodotoxin-sensitive currents were 10 microM and 22 microM. Carbamazepine, an anticonvulsant used in the treatment of pain, showed significantly lower potency. Ralfinamide produced a hyperpolarising shift in the steady-state inactivation curves of both currents confirming the preferential interaction with inactivated channels. Additionally, ralfinamide use and frequency dependently inhibited both currents and significantly delayed repriming from inactivation. All effects were more pronounced for tetrodotoxin-resistant than tetrodotoxin-sensitive currents. The potency and mechanisms of actions of ralfinamide provide a hypothesis for the anti-nociceptive properties found in animal models.

  6. Characterization of Ganglionic Acetylcholine Receptor Autoantibodies

    PubMed Central

    Vernino, Steven; Lindstrom, Jon; Hopkins, Steve; Wang, Zhengbei; Low, Phillip A.

    2008-01-01

    In myasthenia gravis (MG), autoantibodies bind to the α1 subunit and other subunits of the muscle nicotinic acetylcholine receptor (AChR). Autoimmune autonomic ganglionopathy (AAG) is an antibody-mediated neurological disorder caused by antibodies against neuronal AChRs in autonomic ganglia. Subunits of muscle and neuronal AChR are homologous. We examined the specificity of AChR antibodies in patients with MG and AAG. Ganglionic AChR autoantibodies found in AAG patients are specific for AChRs containing the α3 subunit. Muscle and ganglionic AChR antibody specificities are distinct. Antibody crossreactivity between AChRs with different α subunits is uncommon but can occur. PMID:18485491

  7. Ganglionic adrenergic action modulates ovarian steroids and nitric oxide in prepubertal rat.

    PubMed

    Delgado, Silvia Marcela; Casais, Marilina; Sosa, Zulema; Rastrilla, Ana María

    2006-08-01

    Both peripheral innervation and nitric oxide (NO) participate in ovarian steroidogenesis. The purpose of this work was to analyse the ganglionic adrenergic influence on the ovarian release of steroids and NO and the possible steroids/NO relationship. The experiments were carried out in the ex vivo coeliac ganglion-superior ovarian nerve (SON)-ovary system of prepubertal rats. The coeliac ganglion-SON-ovary system was incubated in Krebs Ringer-bicarbonate buffer in presence of adrenergic agents in the ganglionic compartment. The accumulation of progesterone, androstenedione, oestradiol and NO in the ovarian incubation liquid was measured. Norepinephrine in coeliac ganglion inhibited the liberation of progesterone and increased androstenedione, oestradiol and NO in ovary. The addition of alpha and beta adrenergic antagonists also showed different responses in the liberation of the substances mentioned before, which, from a physiological point of view, reveals the presence of adrenergic receptors in coeliac ganglion. In relation to propranolol, it does not revert the effect of noradrenaline on the liberation of progesterone, which leads us to think that it might also have a "per se" effect on the ganglion, responsible for the ovarian response observed for progesterone. Finally, we can conclude that the ganglionic adrenergic action via SON participates on the regulation of the prepubertal ovary in one of two ways: either increasing the NO, a gaseous neurotransmitter with cytostatic characteristics, to favour the immature follicles to remain dormant or increasing the liberation of androstenedione and oestradiol, the steroids necessary for the beginning of the near first estral cycle.

  8. Evidence that ganglion cells react to retinal detachment.

    PubMed

    Coblentz, Francie E; Radeke, Monte J; Lewis, Geoffrey P; Fisher, Steven K

    2003-03-01

    Growth associated protein 43 (GAP 43) is involved in synapse formation and it is expressed in the retina in a very specific pattern. Although GAP 43 is downregulated at the time of synapse formation, it can be re-expressed following injury such as axotomy or ischemia. Because of this we sought to characterize the expression of GAP 43 after retinal detachment (RD). Immunoblot, immunocytochemical and quantitative polymerase chain reaction (QPCR) techniques were used to assess the level of GAP 43 expression after experimental RD. GAP 43 was localized to three sublaminae of the inner plexiform layer of the normal retina. GAP 43 became upregulated in a subset of retinal ganglion cells following at least 7 days of RD. By immunoblot GAP 43 could be detected by 3 days. QPCR shows the upregulation of GAP 43 message by 6hr of detachment. To further characterize changes in ganglion cells, we used an antibody to neurofilament 70 and 200kDa (NF) proteins. Anti-NF labels horizontal cells, ganglion cell dendrites in the inner plexiform layer, and ganglion cell axons (fasicles) in the normal retina. Following detachment it is upregulated in horizontal cells and ganglion cells. When detached retina was double labelled with anti-GAP 43 and anti-NF, some cells were labelled with both markers, while others labelled with only one. We have previously shown that second order neurons respond to detachment; here we show that third order neurons are responding as well. Cellular remodelling of this type in response to detachment may explain the slow recovery of vision that often occurs after reattachment, or those changes that are often assumed to be permanent.

  9. Retinal ganglion cell topography and spatial resolving power in penguins.

    PubMed

    Coimbra, João Paulo; Nolan, Paul M; Collin, Shaun P; Hart, Nathan S

    2012-01-01

    Penguins are a group of flightless seabirds that exhibit numerous morphological, behavioral and ecological adaptations to their amphibious lifestyle, but little is known about the topographic organization of neurons in their retinas. In this study, we used retinal wholemounts and stereological methods to estimate the total number and topographic distribution of retinal ganglion cells in addition to an anatomical estimate of spatial resolving power in two species of penguins: the little penguin, Eudyptula minor, and the king penguin, Aptenodytes patagonicus. The total number of ganglion cells per retina was approximately 1,200,000 in the little penguin and 1,110,000 in the king penguin. The topographic distribution of retinal ganglion cells in both species revealed the presence of a prominent horizontal visual streak with steeper gradients in the little penguin. The little penguin retinas showed ganglion cell density peaks of 21,867 cells/mm², affording spatial resolution in water of 17.07-17.46 cycles/degree (12.81-13.09 cycles/degree in air). In contrast, the king penguin showed a relatively lower peak density of ganglion cells of 14,222 cells/mm², but--due to its larger eye--slightly higher spatial resolution in water of 20.40 cycles/degree (15.30 cycles/degree in air). In addition, we mapped the distribution of giant ganglion cells in both penguin species using Nissl-stained wholemounts. In both species, topographic mapping of this cell type revealed the presence of an area gigantocellularis with a concentric organization of isodensity contours showing a peak in the far temporal retina of approximately 70 cells/mm² in the little penguin and 39 cells/mm² in the king penguin. Giant ganglion cell densities gradually fall towards the outermost isodensity contours revealing the presence of a vertically organized streak. In the little penguin, we confirmed our cytological characterization of giant ganglion cells using immunohistochemistry for microtubule

  10. Structural basis of orientation sensitivity of cat retinal ganglion cells.

    PubMed

    Leventhal, A G; Schall, J D

    1983-11-10

    We investigated the structural basis of the physiological orientation sensitivity of retinal ganglion cells (Levick and Thibos, '82). The dendritic fields of 840 retinal ganglion cells labeled by injections of horseradish peroxidase into the dorsal lateral geniculate nucleus (LGNd) or optic tracts of normal cats. Siamese cats, and cat deprived of patterned visual experience from birth by monocular lid-suture (MD) were studied. Mathematical techniques designed to analyze direction were used to find the dendritic field orientation of each cell. Statistical techniques designed for angular data were used to determine the relationship between dendritic field orientation and angular position on the retina (polar angle). Our results indicate that 88% of retinal ganglion cells have oriented dendritic fields and that dendritic field orientation is related systematically to retinal position. In all regions of retina more that 0.5 mm from the area centralis the dendritic fields of retinal ganglion cells are oriented radially, i.e., like the spokes of a wheel having the area centralis at its hub. This relationship was present in all animals and cell types studied and was strongest for cells located close to the horizontal meridian (visual streak) of the retina. Retinal ganglion cells appear to be sensitive to stimulus orientation because they have oriented dendritic fields.

  11. Morphology of retinal ganglion cells in the ferret (Mustela putorius furo).

    PubMed

    Isayama, Tomoki; O'Brien, Brendan J; Ugalde, Irma; Muller, Jay F; Frenz, Aaron; Aurora, Vikas; Tsiaras, William; Berson, David M

    2009-12-01

    The ferret is the premiere mammalian model of retinal and visual system development, but the spectrum and properties of its retinal ganglion cells are less well understood than in another member of the Carnivora, the domestic cat. Here, we have extensively surveyed the dendritic architecture of ferret ganglion cells and report that the classification scheme previously developed for cat ganglion cells can be applied with few modifications to the ferret retina. We confirm the presence of alpha and beta cells in ferret retina, which are very similar to those in cat retina. Both cell types exhibited an increase in dendritic field size with distance from the area centralis (eccentricity) and with distance from the visual streak. Both alpha and beta cell populations existed as two subtypes whose dendrites stratified mainly in sublamina a or b of the inner plexiform layer. Six additional morphological types of ganglion cells were identified: four monostratified cell types (delta, epsilon, zeta, and eta) and two bistratified types (theta and iota). These types closely resembled their counterparts in the cat in terms of form, relative field size, and stratification. Our data indicate that, among carnivore species, the retinal ganglion cells resemble one another closely and that the ferret is a useful model for studies of the ontogenetic differentiation of ganglion cell types.

  12. Ganglion cyst of the temporomandibular joint.

    PubMed

    Heng-Kun, W; Yan-Ling, G; Wen-Feng, Z; Zhe, S; Ren-Xin, W; Xiao-Tao, Z

    2014-02-01

    Ganglion cyst of the temporomandibular joint is a rare disease, which may arise from myxoid degeneration of the collagenous tissue of the temporomandibular joint capsule, without epithelial or endothelial lining. We report a case of cystic lesion in a 40-year-old female patient. The patient had a left pre-auricular oval-shaped swelling without any articular symptoms. The pathological analysis after surgical removal allowed diagnosing the lesion as a ganglion cyst of the left temporomandibular joint. We made a literature review and noted that this condition was predominant in female patients. We recommend using MRI for diagnostic purposes and surgery as the best therapeutic alternative. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  13. Effects of nitroglycerin and nitroprusside on vascular capacitance of anesthetized ganglion-blocked dogs.

    PubMed

    Ogilvie, R I; Zborowska-Sluis, D

    1991-10-01

    To determine whether changes in vascular capacitance induced by nitroglycerin (NTG) and nitroprusside were due to changes in compliance or unstressed vascular volume, doses producing similar reductions in arterial pressure (Psa) were studied on separate days in six dogs anesthetized and ventilated with pentobarbital after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline blood volumes and after increases of 5 and 10 ml/kg. Central blood volumes (CBVs, pulmonary artery to aortic root) were determined from transit times, and separately measured cardiac output (CO) was estimated by thermodilution (right atrium to pulmonary artery). NTG and nitroprusside produced similar reductions in Psa and Pmcf without significantly altering right atrial pressure (Pra), pressure gradient for venous return, or CO. Total vascular compliance was not altered, but total vascular capacitance was increased on an average of 4.0 +/- 1.4 ml/kg after NTG and 3.0 +/- 1.3 ml/kg after nitroprusside by increases in unstressed volume. Both drugs caused a variable reduction in CBV, averaging 2 ml/kg. Thus, both drugs produced a large increase in peripheral venous capacitance by increasing unstressed vascular volume without altering total vascular compliance.

  14. An anatomic and morphometric study of C2 nerve root ganglion and its corresponding foramen.

    PubMed

    Bilge, Okan

    2004-03-01

    Exposing and measuring the dorsal root ganglion of the second cervical spinal nerve (C2 ganglion) and the second intervertebral space, which is present between posterior arch of atlas (APA) and lamina of axis (LA). This study aims to investigate the shape, size, and relation of the C2 ganglion with the adjacent structures that limits the corresponding intervertebral space and the alterations of relation between C2 ganglion and APA and between C2 ganglion and LA with the movements of the head bilaterally. In previous studies, the position and the heights of the C2 ganglion have been described. But the shape of the C2 ganglion and its relation to APA and LA by the movement of the head had not been considered previously. Upper cervical spines of 20 cadavers were dissected posteriorly. The muscles attaching to the atlas and axis were resected to ease the head movements. The heights of the C2 ganglion and space were measured in anatomic position and in hyperextension with opposite rotation position of the head. Originally in this study, plastic dough casts were used to obtain reliable outcomes. The shape of the ganglions was defined in three types: 70% were oval, 20% were spindle-like, and 10% were spherical. The height of the C2 ganglion was 4.97 +/- 0.92 mm on the right side and 4.6 +/- 0.84 mm on the left side. The height of the intervertebral space in anatomic position and in hyperextension with rotation to the opposite position of the head were, respectively, 9.74 +/- 1.77 mm and 7.48 +/- 1.44 mm on the right side and 9.64 +/- 1.47 mm and 7.12 +/- 0.96 mm on the left side. There was no bone contact or impact to the ganglion in each position of the head. The C2 ganglions are confident in their place between APA and LA. No bone contact to the C2 ganglion was detected in either normal limited or in forced head motions.

  15. Changes in morphology of retinal ganglion cells with eccentricity in retinal degeneration.

    PubMed

    Anderson, E E; Greferath, U; Fletcher, E L

    2016-05-01

    Ganglion cells are the output neurons of the retina and are known to remodel during the subtle plasticity changes that occur following the death of photoreceptors in inherited retinal degeneration. We examine the influence of retinal eccentricity on anatomical remodelling and ganglion cell morphology well after photoreceptor loss. Rd1 mice that have a mutation in the β subunit of phosphodiesterase 6 were used as a model of retinal degeneration and gross remodelling events were examined by processing serial sections for immunocytochemistry. Retinal wholemounts from rd1-Thy1 and control Thy1 mice that contained a fluorescent protein labelling a subset of ganglion cells were processed for immunohistochemistry at 11 months of age. Ganglion cells were classified based on their soma size, dendritic field size and dendritic branching pattern and their dendritic fields were analysed for their length, area and quantity of branching points. Overall, more remodelling was found in the central compared with the peripheral retina. In addition, the size and complexity of A2, B1, C1 and D type ganglion cells located in the central region of the retina decreased. We propose that the changes in ganglion cell morphology are correlated with remodelling events in these regions and impact the function of retinal circuitry in the degenerated retina.

  16. A Case Report of an Acromioclavicular Joint Ganglion Associated with a Rotator Cuff Tear.

    PubMed

    Tanaka, Suguru; Gotoh, Masafumi; Mitsui, Yasuhiro; Shirachi, Isao; Okawa, Takahiro; Higuchi, Fujio; Shiba, Naoto

    2017-04-13

    We report a case of subcutaneous ganglion adjacent to the acromioclavicular joint with massive rotator cuff tear [1-7]. An 81-year-old woman presented with a ganglion adjacent to the acromioclavicular joint that had first been identified 9 months earlier. The ganglion had recurred after having been aspirated by her local physician, so she was referred to our hospital. The puncture fluid was yellowish, clear and viscous. Magnetic resonance imaging identified a massive rotator cuff tear with multi- lobular cystic lesions continuous to the acromioclavicular joint, presenting the "geyser sign". During arthroscopy, distal clavicular resection and excision of the ganglion were performed together with joint debridement. At present, the ganglion has not recurred and the patient has returned to normal daily activity. In this case, the ganglion may have developed subsequent to the concomitant massive cuff tear, due to subcutaneous fluid flow through the damaged acromioclavicular joint.

  17. Regenerating reptile retinas: a comparative approach to restoring retinal ganglion cell function.

    PubMed

    Williams, D L

    2017-02-01

    Transection or damage to the mammalian optic nerve generally results in loss of retinal ganglion cells by apoptosis. This cell death is seen less in fish or amphibians where retinal ganglion cell survival and axon regeneration leads to recovery of sight. Reptiles lie somewhere in the middle of this spectrum of nerve regeneration, and different species have been reported to have a significant variation in their retinal ganglion cell regenerative capacity. The ornate dragon lizard Ctenophoris ornatus exhibits a profound capacity for regeneration, whereas the Tenerife wall lizard Gallotia galloti has a more variable response to optic nerve damage. Some individuals regain visual activity such as the pupillomotor responses, whereas in others axons fail to regenerate sufficiently. Even in Ctenophoris, although the retinal ganglion cell axons regenerate adequately enough to synapse in the tectum, they do not make long-term topographic connections allowing recovery of complex visually motivated behaviour. The question then centres on where these intraspecies differences originate. Is it variation in the innate ability of retinal ganglion cells from different species to regenerate with functional validity? Or is it variances between different species in the substrate within which the nerves regenerate, the extracellular environment of the damaged nerve or the supporting cells surrounding the regenerating axons? Investigations of retinal ganglion cell regeneration between different species of lower vertebrates in vivo may shed light on these questions. Or perhaps more interesting are in vitro studies comparing axon regeneration of retinal ganglion cells from various species placed on differing substrates.

  18. Dorsal raphe nucleus projecting retinal ganglion cells: Why Y cells?

    PubMed Central

    Pickard, Gary E.; So, Kwok-Fai; Pu, Mingliang

    2015-01-01

    Retinal ganglion Y (alpha) cells are found in retinas ranging from frogs to mice to primates. The highly conserved nature of the large, fast conducting retinal Y cell is a testament to its fundamental task, although precisely what this task is remained ill-defined. The recent discovery that Y-alpha retinal ganglion cells send axon collaterals to the serotonergic dorsal raphe nucleus (DRN) in addition to the lateral geniculate nucleus (LGN), medial interlaminar nucleus (MIN), pretectum and the superior colliculus (SC) has offered new insights into the important survival tasks performed by these cells with highly branched axons. We propose that in addition to its role in visual perception, the Y-alpha retinal ganglion cell provides concurrent signals via axon collaterals to the DRN, the major source of serotonergic afferents to the forebrain, to dramatically inhibit 5-HT activity during orientation or alerting/escape responses, which dis-facilitates ongoing tonic motor activity while dis-inhibiting sensory information processing throughout the visual system. The new data provide a fresh view of these evolutionarily old retinal ganglion cells. PMID:26363667

  19. [Ganglions of the wrist: proposals for topographical systematization and natural history].

    PubMed

    Kuhlmann, J-N; Luboinski, J; Baux, S; Mimoun, M

    2003-06-01

    We looked for the anatomic origin and mechanism of constitution of the so-called "ganglions" of the wrist. Fifty-nine formations considered to be synovial ganglions were dissected and removed according to the same protocol by the same surgeon. Eleven were re-examined by a pathologist. All ganglions were extra-articular but had intra- and extra-capsular components. The extra-capsular part was the clinically palpable main cyst. The intra-capsular part was composed of the cystic stalk and its base of implantation. An intra-capsular stalk was present in 58 cases. The stalk was situated between the joint synovium and the capsula which it perforated at a weak point between two ligaments, forming a collar before expanding outwardly. Based on our findings, we propose a topographical systematization and natural history of ganglions of the wrist. The stalk's implantation base was always located on bone and found in the intermediate area of Colomniati and Soubbotine, which lies outside the articular cartilage between the synovium and the ligamentous capsula. This area is exposed to mechanical stress initiating histological degenerative lesions, particularly mucoid degeneration. At the radiocarpal joint, the stalk's base of implantation was located at the distal end of the lateral dorsal or volar edge of the lunate bone or at the corresponding part of the scaphoid. The collar of the proximal ganglions was situated between the dorsal radiocarpal and transverse scaphotriquetral ligament. The collar of distal dorsal ganglions was situated between the transverse scaphotriquetral and the trapezotriquetral ligament. The collar of the lateral ganglions was situated between the lateral collateral and the transverse ligament. The collar of the volar ganglions was situated between the stylocarpal ligament and the radiolunotriquetral ligament, or between the different stylocarpal ligaments. At the level of the scaphotrapezal joint, the stalk's base of implantation was located near the

  20. Calcium Channel Block by Cadmium in Chicken Sensory Neurons

    NASA Astrophysics Data System (ADS)

    Swandulla, D.; Armstrong, C. M.

    1989-03-01

    Cadmium block of calcium channels was studied in chicken dorsal root ganglion cells by a whole-cell patch clamp that provides high time resolution. Barium ion was the current carrier, and the channel type studied had a high threshold of activation and fast deactivation (type FD). Block of these channels by 20 μ M external Cd2+ is voltage dependent. Cd2+ ions can be cleared from blocked channels by stepping the membrane voltage (Vm) to a negative value. Clearing the channels is progressively faster and more complete as Vm is made more negative. Once cleared of Cd2+, the channels conduct transiently on reopening but reequilibrate with Cd2+ and become blocked within a few milliseconds. Cd2+ equilibrates much more slowly with closed channels, but at a holding potential of -80 mV virtually all channels are blocked at equilibrium. Cd2+ does not slow closing of the channels, as would be expected if it were necessary for Cd2+ to leave the channels before closing occurred. Instead, the data show unambiguously that the channel gate can close when the channel is Cd2+ occupied.

  1. Bilirubin Modulates Acetylcholine Receptors In Rat Superior Cervical Ganglionic Neurons In a Bidirectional Manner

    PubMed Central

    Zhang, Chengmi; Wang, Zhenmeng; Dong, Jing; Pan, Ruirui; Qiu, Haibo; Zhang, Jinmin; Zhang, Peng; Zheng, Jijian; Yu, Weifeng

    2014-01-01

    Autonomic dysfunction as a partial contributing factor to cardiovascular instability in jaundiced patients is often associated with increased serum bilirubin levels. Whether increased serum bilirubin levels could directly inhibit sympathetic ganglion transmission by blocking neuronal nicotinic acetylcholine receptors (nAChRs) remains to be elucidated. Conventional patch-clamp recordings were used to study the effect of bilirubin on nAChRs currents from enzymatically dissociated rat superior cervical ganglia (SCG) neurons. The results showed that low concnetrations (0.5 and 2 μM) of bilirubin enhanced the peak ACh-evoked currents, while high concentrations (3 to 5.5 µM) of bilirubin suppressed the currents with an IC50 of 4 ± 0.5 μM. In addition, bilirubin decreased the extent of desensitization of nAChRs in a concentration-dependent manner. This inhibitory effect of bilirubin on nAChRs channel currents was non-competitive and voltage independent. Bilirubin partly improved the inhibitory effect of forskolin on ACh-induced currents without affecting the action of H-89. These data suggest that the dual effects of enhancement and suppression of bilirubin on nAChR function may be ascribed to the action mechanism of positive allosteric modulation and direct blockade. Thus, suppression of sympathetic ganglionic transmission through postganglionic nAChRs inhibition may partially contribute to the adverse cardiovascular effects in jaundiced patients. PMID:25503810

  2. The Sigma Receptor Ligand (+)-Pentazocine Prevents Apoptotic Retinal Ganglion Cell Death induced in vitro by Homocysteine and Glutamate

    PubMed Central

    Martin, Pamela Moore; Ola, Mohammad S.; Agarwal, Neeraj; Ganapathy, Vadivel; Smith, Sylvia B.

    2013-01-01

    Recent studies demonstrated that the excitotoxic amino acid homocysteine induces apoptotic death of retinal ganglion cells in vivo. In the present study, an in vitro rat retinal ganglion cell (RGC-5) culture system was used to analyze the toxicity of acute exposure to high levels of homocysteine, the mechanism of homocysteine-induced toxicity and the usefulness of σR1 ligands as neuroprotectants. When cultured RGC-5 cells were subjected to treatment with 1 mM D, L- homocysteine, a significant increase in cell death was detected by TUNEL analysis and analysis of activated caspase. When cells were treated with homocysteine- or glutamate in the presence of MK-801, an antagonist of the NMDA receptor, the cell death was inhibited significantly. In contrast, NBQX, an antagonist of the AMPA/Kainate receptor, and nifedipine, a calcium channel blocker, did not prevent the homocysteine- or glutamate-induced cell death. Semi-quantitative RT-PCR and immunocytochemical analysis demonstrated that RGC-5 cells exposed to homocysteine or glutamate express type 1 sigma receptor at levels similar to control cells. Treatment of RGC-5 cells with 3 µM or 10 µM concentrations of the σR1-specific ligand (+)-pentazocine inhibited significantly the apoptotic cell death induced by homocysteine or glutamate. The results suggest that homocysteine is toxic to ganglion cells in vitro, that the toxicity is mediated via NMDA receptor activation, and that the σR1-specific ligand (+)-pentazocine can block the RGC-5 cell death induced by homocysteine and glutamate. PMID:15046867

  3. Quantifying Spiral Ganglion Neurite and Schwann Behavior on Micropatterned Polymer Substrates.

    PubMed

    Cheng, Elise L; Leigh, Braden; Guymon, C Allan; Hansen, Marlan R

    2016-01-01

    The first successful in vitro experiments on the cochlea were conducted in 1928 by Honor Fell (Fell, Arch Exp Zellforsch 7(1):69-81, 1928). Since then, techniques for culture of this tissue have been refined, and dissociated primary culture of the spiral ganglion has become a widely accepted in vitro model for studying nerve damage and regeneration in the cochlea. Additionally, patterned substrates have been developed that facilitate and direct neural outgrowth. A number of automated and semi-automated methods for quantifying this neurite outgrowth have been utilized in recent years (Zhang et al., J Neurosci Methods 160(1):149-162, 2007; Tapias et al., Neurobiol Dis 54:158-168, 2013). Here, we describe a method to study the effect of topographical cues on spiral ganglion neurite and Schwann cell alignment. We discuss our microfabrication process, characterization of pattern features, cell culture techniques for both spiral ganglion neurons and spiral ganglion Schwann cells. In addition, we describe protocols for reducing fibroblast count, immunocytochemistry, and methods for quantifying neurite and Schwann cell alignment.

  4. Characterization of peripheral and central sensitization after dorsal root ganglion intervention in patients with unilateral lumbosacral radicular pain: a prospective pilot study.

    PubMed

    Mehta, V; Snidvongs, S; Ghai, B; Langford, R; Wodehouse, T

    2017-06-01

    Quantitative sensory testing (QST) has been used to predict the outcome of epidural steroid injections in lumbosacral radicular pain and has the potential to be an important tool in the selection of appropriate treatment (such as epidural steroid injections vs surgery) for patients with chronic radicular pain. In addition, QST assists in identification of the pain pathways of peripheral and central sensitization in selected groups of patients. Twenty-three patients were given dorsal root ganglion (DRG) infiltration with local anaesthesia and steroid ('DRG block'), and those who demonstrated at least 50% pain relief were offered pulsed radiofrequency (PRF) to the DRG. Questionnaires and QST scores were measured before the DRG blocks and at 1 week and 3 months after their procedure. Those who received PRF also answered questionnaires and underwent QST measurements at 1 week and 3 months after their procedure. There was a significant increase in pressure pain threshold scores after DRG blocks. A reduced conditioned pain modulation response was seen before DRG, which increased after the procedure. Ten out of 23 patients underwent PRF to the DRG, and an increase in pressure pain threshold scores after PRF was observed. The conditioned pain modulation response was maintained in this group and increased after PRF. The study demonstrates that patients with unilateral radicular low back pain who receive dorsal root ganglion interventions show changes in pressure pain thresholds and conditioned pain modulation that are consistent with a 'normalization' of peripheral and central sensitization. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  5. A high-threshold heat-activated channel in cultured rat dorsal root ganglion neurons resembles TRPV2 and is blocked by gadolinium.

    PubMed

    Leffler, Andreas; Linte, Ramona Madalina; Nau, Carla; Reeh, Peter; Babes, Alexandru

    2007-07-01

    Heat-activated ion channels from the vanilloid-type TRP group (TRPV1-4) seem to be central for heat-sensitivity of nociceptive sensory neurons. Displaying a high-threshold (> 52 degrees C) for activation, TRPV2 was proposed to act as a sensor for intense noxious heat in mammalian sensory neurons. However, although TRPV2 is expressed in a distinct population of thinly myelinated primary afferents, a widespread expression in a variety of neuronal and non-neuronal tissues suggests a more diverse physiological role of TRPV2. In its role as a heat-sensor, TRPV2 has not been thoroughly characterized in terms of biophysical and pharmacological properties. In the present study, we demonstrate that the features of heterologously expressed rat TRPV2 closely resemble those of high-threshold heat-evoked currents in medium- and large-sized capsaicin-insensitive rat dorsal root ganglion (DRG) neurons. Both in TRPV2-expressing human embryonic kidney (HEK)293t cells and in DRGs, high-threshold heat-currents were sensitized by repeated activation and by the TRPV1-3 agonist, 2-aminoethoxydiphenyl borate (2-APB). In addition to a previously described block by ruthenium red, we identified the trivalent cations, lanthanum (La(3+)) and gadolinium (Gd(3+)) as potent blockers of TRPV2. Thus, we present a new pharmacological tool to distinguish between heat responses of TRPV2 and the closely related capsaicin-receptor, TRPV1, which is strongly sensitized by trivalent cations. We demonstrate that self-sensitization of heat-evoked currents through TRPV2 does not require extracellular calcium and that TRPV2 can be activated in cell-free membrane patches in the outside-out configuration. Taken together our results provide new evidence for a role of TRPV2 in mediating high-threshold heat responses in a subpopulation of mammalian sensory neurons.

  6. The nervus terminalis ganglion in Anguilla rostrata: an immunocytochemical and HRP histochemical analysis.

    PubMed

    Grober, M S; Bass, A H; Burd, G; Marchaterre, M A; Segil, N; Scholz, K; Hodgson, T

    1987-12-08

    Immunocytochemistry and retrograde horseradish peroxidase (HRP) transport were used to study the ganglion of the nervus terminalis in the American eel, Anguilla rostrata. Luteinizing hormone releasing hormone (LHRH) like immunoreactivity was found in large, ganglion-like cells located ventromedially at the junction of the telencephalon and olfactory bulb and in fibers within the retina and olfactory epithelium. HRP transport from the retina demonstrated direct connections with both the ipsi- and contralateral populations of these ganglion-like cells. Given the well-documented role of both olfaction and vision during migratory and reproductive phases of the life cycle of eels, the robust nature of a nervus terminalis system in these fish may present a unique opportunity to study the behavioral correlates of structure-function organization in a discrete population of ganglion-like cells.

  7. Protecting retinal ganglion cells.

    PubMed

    Khatib, T Z; Martin, K R

    2017-02-01

    Retinal ganglion cell degeneration underlies several conditions which give rise to significant visual compromise, including glaucoma, hereditary optic neuropathies, ischaemic optic neuropathies, and demyelinating disease. In this review, we discuss the emerging strategies for neuroprotection specifically in the context of glaucoma, including pharmacological neuroprotection, mesenchymal stem cells, and gene therapy approaches. We highlight potential pitfalls that need to be considered when developing these strategies and outline future directions, including the prospects for clinical trials.

  8. Parasitoid wasp sting: a cocktail of GABA, taurine, and beta-alanine opens chloride channels for central synaptic block and transient paralysis of a cockroach host.

    PubMed

    Moore, Eugene L; Haspel, Gal; Libersat, Frederic; Adams, Michael E

    2006-07-01

    The wasp Ampulex compressa injects venom directly into the prothoracic ganglion of its cockroach host to induce a transient paralysis of the front legs. To identify the biochemical basis for this paralysis, we separated venom components according to molecular size and tested fractions for inhibition of synaptic transmission at the cockroach cercal-giant synapse. Only fractions in the low molecular weight range (<2 kDa) caused synaptic block. Dabsylation of venom components and analysis by HPLC and MALDI-TOF-MS revealed high levels of GABA (25 mM), and its receptor agonists beta-alanine (18 mM), and taurine (9 mM) in the active fractions. Each component produces transient block of synaptic transmission at the cercal-giant synapse and block of efferent motor output from the prothoracic ganglion, which mimics effects produced by injection of whole venom. Whole venom evokes picrotoxin-sensitive chloride currents in cockroach central neurons, consistent with a GABAergic action. Together these data demonstrate that Ampulex utilizes GABAergic chloride channel activation as a strategy for central synaptic block to induce transient and focal leg paralysis in its host. Copyright 2006 Wiley Periodicals, Inc.

  9. Clustering is a feature of the spiral ganglion in the basal turn.

    PubMed

    Gacek, Richard R

    2012-01-01

    To demonstrate the organization of the spiral ganglion in the mammalian species. Temporal bone (TB) specimens from man (n = 2), monkey (n = 2), lion (n = 2) and cat (n = 20) were stained, decalcified and dissected according to the Sudan black B method of Rasmussen. These TB specimens were examined under a Zeiss operating microscope and photographed with a Canon 100 camera interfaced with the microscope. Spiral ganglion cells occurred in clusters within Rosenthal's canal in all four species. The location of the clusters was marked by the interface between axon and dendritic bundles as well as groups of ganglion cells. In monkey and man the clusters were more separated than in lion and cat. These observations indicate that the spiral ganglion forms clusters of neurons within Rosenthal's canal at the basal cochlear turn in the mammals investigated here. The formation of clusters may be related to the principles of neurogenesis. Copyright © 2011 S. Karger AG, Basel.

  10. Berberine exerts antioxidant effects via protection of spiral ganglion cells against cytomegalovirus-induced apoptosis.

    PubMed

    Zhuang, Wei; Li, Ting; Wang, Caiji; Shi, Xi; Li, Yalan; Zhang, Shili; Zhao, Zeqi; Dong, Hongyan; Qiao, Yuehua

    2018-06-01

    Cytomegalovirus (CMV) is the leading cause of sensorineural hearing loss (SNHL) in children because of its damage to the cochlea and spiral ganglion cells. Therefore, it has become a top priority to devise new methods to effectively protect spiral ganglion cells from damage. Berberine (BBR) has gained attention for its vast beneficial biological effects through immunomodulation, and its anti-inflammatory and anti-apoptosis properties. However, the effect of BBR on spiral ganglion cells and molecular mechanisms are still unclear. This study aims to investigate whether BBR has an anti-apoptosis effect in CMV-induced apoptosis in cultured spiral ganglion cells and explore the possible mechanism. In this study, TUNEL and MTT assays significantly demonstrated that low doses of BBR did not promote cell apoptosis and they also inhibited the CMV-induced cultured spiral ganglion cell apoptosis. Immunofluorescence and Western blot assays indicated that the anti-apoptosis effect of BBR was related to Nox3. Mitochondrial calcium and Western blot assays revealed that NMDAR1 mediated this anti-apoptosis effect. Our results demonstrated that BBR exerted an anti-apoptosis effect against CMV in cultured spiral ganglion cells, and the mechanism is related to NMDAR1/Nox3-mediated mitochondrial reactive oxygen species (ROS) generation. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Retinal ganglion cell distribution and spatial resolving power in elasmobranchs.

    PubMed

    Lisney, Thomas J; Collin, Shaun P

    2008-01-01

    The total number, distribution and peak density of presumed retinal ganglion cells was assessed in 10 species of elasmobranch (nine species of shark and one species of batoid) using counts of Nissl-stained cells in retinal wholemounts. The species sampled include a number of active, predatory benthopelagic and pelagic sharks that are found in a variety of coastal and oceanic habitats and represent elasmobranch groups for which information of this nature is currently lacking. The topographic distribution of cells was heterogeneous in all species. Two benthic species, the shark Chiloscyllium punctatum and the batoid Taeniura lymma, have a dorsal or dorso-central horizontal streak of increased cell density, whereas the majority of the benthopelagic and pelagic sharks examined exhibit a more concentric pattern of increasing cell density, culminating in a central area centralis of higher cell density located close to the optic nerve head. The exception is the shark Alopias superciliosus, which possesses a ventral horizontal streak. Variation in retinal ganglion cell topography appears to be related to the visual demands of different habitats and lifestyles, as well as the positioning of the eyes in the head. The upper limits of spatial resolving power were calculated for all 10 species, using peak ganglion cell densities and estimates of focal length taken from cryo-sectioned eyes in combination with information from the literature. Spatial resolving power ranged from 2.02 to 10.56 cycles deg(-1), which is in accordance with previous studies. Species with a lower spatial resolving power tend to be benthic and/or coastal species that feed on benthic invertebrates and fishes. Active, benthopelagic and pelagic species from more oceanic habitats which feed on larger, more active prey, possess a higher resolving power. Additionally, ganglion cells in a juvenile of C. punctatum, were retrogradely-labeled from the optic nerve with biotinylated dextran amine (BDA). A comparison

  12. [Met]- and [Leu]enkephalin-like immunoreactive cell bodies and nerve fibres in the coeliac ganglion of the cat.

    PubMed

    Julé, Y; Clerc, N; Niel, J P; Condamin, M

    1986-06-01

    The occurrence and distribution of methionine- and leucine-enkephalin-like immunoreactivity were investigated in the cat coeliac ganglion using either the indirect immunoperoxidase method or the peroxidase-antiperoxidase technique. Several antisera raised to methionine- and leucine-enkephalin were used. Their specificity was assessed by incubating sections of the coeliac ganglion with increasing dilutions of antisera and with antisera saturated with their respective antigen. The present study was performed both in untreated and in colchicine-treated cats. Immunoreactive methionine- and leucine-enkephalin-like cell bodies were only visualized in colchicine-treated cats. Two types of labeled cells were observed. The first type had a size similar to that of unlabeled principal ganglion cells. These labeled cells were numerous and scattered throughout the ganglion; they probably represented enkephalin-containing ganglion cells. The second type of immunoreactive cells were of a much smaller size. They were always gathered in small clusters of about 5-15 cells and were not numerous; they presumably represented enkephalin-containing small intensely fluorescent cells. Immunoreactive nerve fibres were mainly observed in untreated cats and accessorily in colchicine-treated cats. In untreated animals dense networks of methionine- and leucine-enkephalin-like immunoreactive fibres were found in the coeliac ganglion. These fibres had numerous varicosities which often closely surrounded unlabeled principal ganglion cells. In colchicine-treated cats some immunoreactive fibres surrounded labeled principal ganglion cell bodies. The present results establish for the first time the presence of enkephalin-like immunoreactive principal ganglion cells in a mammalian sympathetic prevertebral ganglion. The presence of enkephalin-containing principal ganglion cells, small intensely fluorescent cells and nerve terminals, supports an important role of enkephalins in the integrative synaptic

  13. Protecting retinal ganglion cells

    PubMed Central

    Khatib, T Z; Martin, K R

    2017-01-01

    Retinal ganglion cell degeneration underlies several conditions which give rise to significant visual compromise, including glaucoma, hereditary optic neuropathies, ischaemic optic neuropathies, and demyelinating disease. In this review, we discuss the emerging strategies for neuroprotection specifically in the context of glaucoma, including pharmacological neuroprotection, mesenchymal stem cells, and gene therapy approaches. We highlight potential pitfalls that need to be considered when developing these strategies and outline future directions, including the prospects for clinical trials. PMID:28085136

  14. Features and functions of nonlinear spatial integration by retinal ganglion cells.

    PubMed

    Gollisch, Tim

    2013-11-01

    Ganglion cells in the vertebrate retina integrate visual information over their receptive fields. They do so by pooling presynaptic excitatory inputs from typically many bipolar cells, which themselves collect inputs from several photoreceptors. In addition, inhibitory interactions mediated by horizontal cells and amacrine cells modulate the structure of the receptive field. In many models, this spatial integration is assumed to occur in a linear fashion. Yet, it has long been known that spatial integration by retinal ganglion cells also incurs nonlinear phenomena. Moreover, several recent examples have shown that nonlinear spatial integration is tightly connected to specific visual functions performed by different types of retinal ganglion cells. This work discusses these advances in understanding the role of nonlinear spatial integration and reviews recent efforts to quantitatively study the nature and mechanisms underlying spatial nonlinearities. These new insights point towards a critical role of nonlinearities within ganglion cell receptive fields for capturing responses of the cells to natural and behaviorally relevant visual stimuli. In the long run, nonlinear phenomena of spatial integration may also prove important for implementing the actual neural code of retinal neurons when designing visual prostheses for the eye. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Spontaneous Discharge Patterns in Cochlear Spiral Ganglion Cells Prior to the Onset of Hearing in Cats

    PubMed Central

    Jones, Timothy A.; Leake, Patricia A.; Snyder, Russell L.; Stakhovskaya, Olga; Bonham, Ben

    2008-01-01

    Spontaneous neural activity has been recorded in the auditory nerve of cats as early as 2 days postnatal (P2 ), yet individual auditory neurons do not respond to ambient sound levels below 90–100 dB SPL until about P10. Significant refinement of the central projections from the spiral ganglion to the cochlear nucleus occurs during this neonatal period. This refinement may be dependent on peripheral spontaneous discharge activity. We recorded from single spiral ganglion cells in kittens aged P3 to P9. The spiral ganglion was accessed via the round window through the spiral lamina. A total of 112 ganglion cells were isolated for study in 9 animals. Spike rates in neonates were very low, ranging from 0.06 to 56 sp/s with a mean of 3.09 +/− 8.24 sp/s. Ganglion cells in neonatal kittens exhibited remarkable repetitive spontaneous bursting discharge patterns. The unusual patterns were evident in the large mean interval coefficient of variation (CVi = 2.9 +/−1.6) and burst index of 5.2 +/− 3.5 across ganglion cells. Spontaneous bursting patterns in these neonatal mammals were similar to those reported for cochlear ganglion cells of the embryonic chicken suggesting this may be a general phenomenon that is common across animal classes. Rhythmic spontaneous discharge of retinal ganglion cells has been shown to be important in the development of central retinotopic projections and normal binocular vision (Shatz, 1996, Proc Natl Acad Sci 93). Bursting rhythms in cochlear ganglion cells may play a similar role in the auditory system during pre-hearing periods. PMID:17686914

  16. Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons.

    PubMed

    Rejali, Darius; Lee, Valerie A; Abrashkin, Karen A; Humayun, Nousheen; Swiderski, Donald L; Raphael, Yehoash

    2007-06-01

    Spiral ganglion neurons often degenerate in the deaf ear, compromising the function of cochlear implants. Cochlear implant function can be improved by good preservation of the spiral ganglion neurons, which are the target of electrical stimulation by the implant. Brain derived neurotrophic factor (BDNF) has previously been shown to enhance spiral ganglion survival in experimentally deafened ears. Providing enhanced levels of BDNF in human ears may be accomplished by one of several different methods. The goal of these experiments was to test a modified design of the cochlear implant electrode that includes a coating of fibroblast cells transduced by a viral vector with a BDNF gene insert. To accomplish this type of ex vivo gene transfer, we transduced guinea pig fibroblasts with an adenovirus with a BDNF gene cassette insert, and determined that these cells secreted BDNF. We then attached BDNF-secreting cells to the cochlear implant electrode via an agarose gel, and implanted the electrode in the scala tympani. We determined that the BDNF expressing electrodes were able to preserve significantly more spiral ganglion neurons in the basal turns of the cochlea after 48 days of implantation when compared to control electrodes. This protective effect decreased in the higher cochlear turns. The data demonstrate the feasibility of combining cochlear implant therapy with ex vivo gene transfer for enhancing spiral ganglion neuron survival.

  17. Preferential inhibition of Ih in rat trigeminal ganglion neurons by an organic blocker.

    PubMed

    Janigro, D; Martenson, M E; Baumann, T K

    1997-11-15

    The potency and specificity of a novel organic Ih current blocker DK-AH 268 (DK, Boehringer) was studied in cultured rat trigeminal ganglion neurons using whole-cell patch-clamp recording techniques. In neurons current-clamped at the resting potential, the application of 10 microM DK caused a slight hyperpolarization of the membrane potential and a small increase in the threshold for action potential discharge without any major change in the shape of the action potential. In voltage-clamped neurons, DK caused a reduction of a hyperpolarization-activated current. Current subtraction protocols revealed that the time-dependent, hyperpolarization-activated currents blocked by 10 microM DK or external Cs+ (3 mM) had virtually identical activation properties, suggesting that DK and Cs+ caused blockade of the same current, namely Ih. The block of Ih by DK was dose-dependent. At the intermediate and higher concentrations of DK (10 and 100 microM) a decrease in specificity was observed so that time-independent, inwardly rectifying and noninactivating, voltage-gated outward potassium currents were also reduced by DK but to a much lesser extent than the time-dependent, hyperpolarization-activated currents. Blockade of the time-dependent, hyperpolarization-activated currents by DK appeared to be use-dependent since it required hyperpolarization for the effect to take place. Relief of DK block was also aided by membrane hyperpolarization. Since both the time-dependent current blocked by DK and the Cs+-sensitive time-dependent current behaved as Ih, we conclude that 10 microM DK can preferentially reduce Ih without a major effect on other potassium currents. Thus, DK may be a useful agent in the investigation of the function of Ih in neurons.

  18. Intrinsically photosensitive retinal ganglion cells.

    PubMed

    Do, Michael Tri Hoang; Yau, King-Wai

    2010-10-01

    Life on earth is subject to alternating cycles of day and night imposed by the rotation of the earth. Consequently, living things have evolved photodetective systems to synchronize their physiology and behavior with the external light-dark cycle. This form of photodetection is unlike the familiar "image vision," in that the basic information is light or darkness over time, independent of spatial patterns. "Nonimage" vision is probably far more ancient than image vision and is widespread in living species. For mammals, it has long been assumed that the photoreceptors for nonimage vision are also the textbook rods and cones. However, recent years have witnessed the discovery of a small population of retinal ganglion cells in the mammalian eye that express a unique visual pigment called melanopsin. These ganglion cells are intrinsically photosensitive and drive a variety of nonimage visual functions. In addition to being photoreceptors themselves, they also constitute the major conduit for rod and cone signals to the brain for nonimage visual functions such as circadian photoentrainment and the pupillary light reflex. Here we review what is known about these novel mammalian photoreceptors.

  19. TRPC1 is required for survival and proliferation of cochlear spiral ganglion stem/progenitor cells.

    PubMed

    Chen, Hsin-Chien; Wang, Chih-Hung; Shih, Cheng-Ping; Chueh, Sheau-Huei; Liu, Shu-Fan; Chen, Hang-Kang; Lin, Yi-Chun

    2015-12-01

    The present studies were designed to test the hypothesis that canonical transient receptor potential channel 1 (TRPC1) is required for the proliferation of cochlear spiral ganglion stem/progenitor cells (SPCs). TRPC1 were detected and evaluated in postnatal day 1 CBA/CaJ mice pups derived-cochlear spiral ganglion SPCs by reverse transcription-polymerase chain reaction, Western blot, immunocytochemistry, and calcium imaging. The cell viability and proliferation of the spiral ganglion SPCs following si-RNA mediated knockdown of TRPC1 or addition of TRPC channel blocker SKF9635 were compared to controls. In spiral ganglion SPCs, TRPC1 was found to be the most abundantly expressed TRPC subunit and shown to contribute to store-operated calcium entry. Silencing of TRPC1 or addition of TRPC channel blockers significantly decreased the rate of cell proliferation. The results suggest that TRPC1 might serve as an essential molecule in regulating the proliferation of spiral ganglion SPCs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. A decay of gap junctions associated with ganglion cell differentiation during retinal regeneration of the adult newt.

    PubMed

    Oi, Hanako; Chiba, Chikafumi; Saito, Takehiko

    2003-12-01

    Changes in the gap junctional coupling and maturation of voltage-activated Na(+) currents during regeneration of newt retinas were examined by whole-cell patch-clamping in slice preparations. Progenitor cells in regenerating retinas did not exhibit Na(+) currents but showed prominent electrical and tracer couplings. Cells identified by LY-fills were typically slender. Na(+) currents were detected in premature ganglion cells with round somata in the 'intermediate-II' regenerating retina. No electrical and tracer couplings were observed between these cells. Mature ganglion cells did not exhibit electrical coupling, but showed tracer coupling. On average, the maximum Na(+) current amplitude recorded from premature ganglion cells was roughly 2.5-fold smaller than that of mature ganglion cells. In addition, the activation threshold of the Na(+) current was nearly 11 mV more positive than that of mature cells. We provide morphological and physiological evidence showing that loss of gap junctions between progenitor cells is associated with ganglion cell differentiation during retinal regeneration and that new gap junctions are recreated between mature ganglion cells. Also we provide evidence suggesting that the loss of gap junctions correlates with the appearance of voltage-activated Na(+) currents in ganglion cells.

  1. Accelerated retinal ganglion cell death in mice deficient in the Sigma-1 receptor.

    PubMed

    Mavlyutov, Timur A; Nickells, Robert W; Guo, Lian-Wang

    2011-04-26

    The sigma-1 receptor (σR1), a ligand-operated chaperone, has been inferred to be neuroprotective in previous studies using σR1 ligands. The σR1 specificity of the protective function, however, has yet to be firmly established, due to the existence of non-σR1 targets of the ligands. Here, we used the σR1-knockout mouse (Sigmar1(-/-)) to demonstrate unambiguously the role of the σR1 in protecting the retinal ganglion cells against degeneration after acute damage to the optic nerve. Retinal σR binding sites were labeled with radioiodinated σR ligands and analyzed by autoradiography. Localization of the σR1 was performed by indirect immunofluorescence on frozen retinal sections. Retinal ganglion cell death was induced by acute optic nerve crush in wild-type and Sigmar1(-/-) mice. Surviving cells in the ganglion cell layer were counted on Nissl-stained retinal whole mounts 7 days after the crush surgery. Photoaffinity labeling indicated the presence of the σR1 in the retina, in concentrations equivalent to those in liver tissue. Immunolabeling detected this receptor in cells of both the ganglion cell layer and the photoreceptor cell layer in wild-type retinas. Quantification of cells remaining after optic nerve crush showed that 86.8±7.9% cells remained in the wild-type ganglion cell layer, but only 68.3±3.4% survived in the Sigmar1(-/-), demonstrating a significant difference between the wild-type and the Sigmar1(-/-) in crush-induced ganglion cell loss. Our data indicated faster retinal ganglion cell death in Sigmar1(-/-) than in wild-type mice under the stresses caused by optic nerve crush, providing direct evidence for a role of the σR1 in alleviating retinal degeneration. This conclusion is consistent with the previous pharmacological studies using σR1 agonists. Thus, our study supports the idea that the σR1 is a promising therapeutic target for neurodegenerative retinal diseases, such as glaucoma.

  2. Angioarchitecture of the coeliac sympathetic ganglion complex in the common tree shrew (Tupaia glis)

    PubMed Central

    PROMWIKORN, WARAPORN; THONGPILA, SAKPORN; PRADIDARCHEEP, WISUIT; MINGSAKUL, THAWORN; CHUNHABUNDIT, PANJIT; SOMANA, REON

    1998-01-01

    The angioarchitecture of the coeliac sympathetic ganglion complex (CGC) of the common tree shrew (Tupaia glis) was studied by the vascular corrosion cast technique in conjunction with scanning electron microscopy. The CGC of the tree shrew was found to be a highly vascularised organ. It normally received arterial blood supply from branches of the inferior phrenic, superior suprarenal and inferior suprarenal arteries and of the abdominal aorta. In some animals, its blood supply was also derived from branches of the middle suprarenal arteries, coeliac artery, superior mesenteric artery and lumbar arteries. These arteries penetrated the ganglion at variable points and in slightly different patterns. They gave off peripheral branches to form a subcapsular capillary plexus while their main trunks traversed deeply into the inner part before branching into the densely packed intraganglionic capillary networks. The capillaries merged to form venules before draining into collecting veins at the peripheral region of the ganglion complex. Finally, the veins coursed to the dorsal aspect of the ganglion to drain into the renal and inferior phrenic veins and the inferior vena cava. The capillaries on the coeliac ganglion complex do not possess fenestrations. PMID:9877296

  3. Retinal ganglion cell projections to the hamster suprachiasmatic nucleus, intergeniculate leaflet, and visual midbrain: bifurcation and melanopsin immunoreactivity

    NASA Technical Reports Server (NTRS)

    Morin, Lawrence P.; Blanchard, Jane H.; Provencio, Ignacio

    2003-01-01

    The circadian clock in the suprachiasmatic nucleus (SCN) receives direct retinal input via the retinohypothalamic tract (RHT), and the retinal ganglion cells contributing to this projection may be specialized with respect to direct regulation of the circadian clock. However, some ganglion cells forming the RHT bifurcate, sending axon collaterals to the intergeniculate leaflet (IGL) through which light has secondary access to the circadian clock. The present studies provide a more extensive examination of ganglion cell bifurcation and evaluate whether ganglion cells projecting to several subcortical visual nuclei contain melanopsin, a putative ganglion cell photopigment. The results showed that retinal ganglion cells projecting to the SCN send collaterals to the IGL, olivary pretectal nucleus, and superior colliculus, among other places. Melanopsin-immunoreactive (IR) ganglion cells are present in the hamster retina, and some of these cells project to the SCN, IGL, olivary pretectal nucleus, or superior colliculus. Triple-label analysis showed that melanopsin-IR cells bifurcate and project bilaterally to each SCN, but not to the other visual nuclei evaluated. The melanopsin-IR cells have photoreceptive characteristics optimal for circadian rhythm regulation. However, the presence of moderately widespread bifurcation among ganglion cells projecting to the SCN, and projection by melanopsin-IR cells to locations distinct from the SCN and without known rhythm function, suggest that this ganglion cell type is generalized, rather than specialized, with respect to the conveyance of photic information to the brain. Copyright 2003 Wiley-Liss, Inc.

  4. Muscarinic Acetylcholine Receptor Localization and Activation Effects on Ganglion Response Properties

    PubMed Central

    Renna, Jordan M.; Amthor, Franklin R.; Keyser, Kent T.

    2010-01-01

    Purpose. The activation and blockade of muscarinic acetylcholine receptors (mAChRs) affects retinal ganglion cell light responses and firing rates. This study was undertaken to identify the full complement of mAChRs expressed in the rabbit retina and to assess mAChR distribution and the functional effects of mAChR activation and blockade on retinal response properties. Methods. RT-PCR, Western blot analysis, and immunohistochemistry were used to identify the complement and distribution of mAChRs in the rabbit retina. Extracellular electrophysiology was used to determine the effects of the activation or blockade of mAChRs on ganglion cell response properties. Results. RT-PCR of whole neural retina resulted in the amplification of mRNA transcripts for the m1 to m5 mAChR subtypes. Western blot and immunohistochemical analyses confirmed that all five mAChR subtypes were expressed by subpopulations of bipolar, amacrine, and ganglion cells in the rabbit retina, including subsets of cells in cholinergic and glycinergic circuits. Nonspecific muscarinic activation and blockade resulted in the class-specific modulation of maintained ganglion cell firing rates and light responses. Conclusions. The expression of mAChR subtypes on subsets of bipolar, amacrine, and ganglion cells provides a substrate for both enhancement and suppression of retinal responses via activation by cholinergic agents. Thus, the muscarinic cholinergic system in the retina may contribute to the modulation of complex stimuli. Understanding the distribution and function of mAChRs in the retina has the potential to provide important insights into the visual changes that are caused by decreased ACh in the retinas of Alzheimer's patients and the potential visual effects of anticholinergic treatments for ocular diseases. PMID:20042645

  5. Broad Thorny Ganglion Cells: A Candidate for Visual Pursuit Error Signaling in the Primate Retina

    PubMed Central

    Manookin, Michael B.; Neitz, Jay; Rieke, Fred

    2015-01-01

    Functional analyses exist only for a few of the morphologically described primate ganglion cell types, and their correlates in other mammalian species remain elusive. Here, we recorded light responses of broad thorny cells in the whole-mounted macaque retina. They showed ON-OFF-center light responses that were strongly suppressed by stimulation of the receptive field surround. Spike responses were delayed compared with parasol ganglion cells and other ON-OFF cells, including recursive bistratified ganglion cells and A1 amacrine cells. The receptive field structure was shaped by direct excitatory synaptic input and strong presynaptic and postsynaptic inhibition in both ON and OFF pathways. The cells responded strongly to dark or bright stimuli moving either in or out of the receptive field, independent of the direction of motion. However, they did not show a maintained spike response either to a uniform background or to a drifting plaid pattern. These properties could be ideally suited for guiding movements involved in visual pursuit. The functional characteristics reported here permit the first direct cross-species comparison of putative homologous ganglion cell types. Based on morphological similarities, broad thorny ganglion cells have been proposed to be homologs of rabbit local edge detector ganglion cells, but we now show that the two cells have quite distinct physiological properties. Thus, our data argue against broad thorny cells as the homologs of local edge detector cells. PMID:25834063

  6. Diagnostic ability of macular ganglion cell asymmetry for glaucoma.

    PubMed

    Hwang, Young Hoon; Ahn, Sang Il; Ko, Sung Ju

    2015-11-01

    Using spectral-domain optical coherence tomography (OCT), this study aims to investigate the glaucoma diagnostic ability of macular ganglion cell asymmetry analysis. A cross-sectional study was conducted. This study was performed to investigate glaucoma diagnostic ability of macular ganglion cell asymmetry analysis in eyes with various degrees of glaucoma. We enrolled 181 healthy eyes and 265 glaucomatous eyes. Glaucomatous eyes were subdivided into pre-perimetric, early, moderate and advanced-to-severe glaucoma based on visual field test results. For each eye, macular ganglion cell-inner plexiform layer (GCIPL) thickness was measured using OCT. Average GCIPL thickness, GCIPL thicknesses in superior and inferior hemispheres, absolute difference in GCIPL thickness between superior and inferior hemispheres and GCIPL asymmetry index calculated as the absolute value of log10 (inferior hemisphere thickness/superior hemisphere thickness) were analysed. Areas under the receiver operating characteristics curves (AUCs) of GCIPL parameter were calculated and compared. All of the GCIPL parameters showed good glaucoma diagnostic ability (AUCs ≥ 0.817, P < 0.01). AUCs of average, superior and inferior GCIPL thickness increased as the severity of glaucoma increased. GCIPL thickness difference and asymmetry index showed the highest AUCs in early and moderate glaucoma and lower AUCs in pre-perimetric and advanced-to-severe glaucoma. GCIPL thickness difference and asymmetry index showed better glaucoma diagnostic ability than other GCIPL parameters only in early stage of glaucoma (P < 0.05); in other stages, these parameters had similar to or worse glaucoma diagnostic ability than other GCIPL parameters. Macular ganglion cell asymmetry analysis showed good glaucoma diagnostic ability, especially in early-stage glaucoma. However, it has limited usefulness in other stages of glaucoma. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

  7. [Evaluation of external quality assurance in accordance with sect. 137 SGB V at the Carl Gustav Carus university hospital in Dresden].

    PubMed

    Petzold, Thomas; Steinwitz, Adrienne; Schmitt, Jochen; Eberlein-Gonska, Maria

    2013-01-01

    Obligatory external quality assurance is an established method used to ensure the quality of inpatient care in Germany. The comprehensive approach is unique in international comparison. In addition to the statutory requirement, the health insurance funds require this form of external quality control in order to foster quality-based competition between hospitals. Ever since its introduction, healthcare providers have scrutinised the effects of the mandatory use of this survey. The study was based on all patients in the University Hospital Dresden, for whom a quality assurance sheet (n = 45,639) had to be recorded between 2003 and 2011. The documentation of these sheets was carried out by specially trained personnel. For each performance area, the duration of the documentation quality sheets was assessed, and a descriptive analysis of all quality assurance sheets was conducted. In the presence of statistical significance the so-called "Structured Dialogues" were analysed. Over the whole period, 167 statistically noticeable problems occurred. Nine of these have been rated as noticeable problems in medical quality by the specialised working groups of the project office quality assurance (PGSQS) at the Saxon State Medical Association (SLÄK). The remaining 158 statistical anomalies included 25 documentation errors; 96 were classified as statistically significant, and only 37 were marked to indicate that re-observation by the PGSQS was required. The total effort estimate for the documentation of quality assurance sheets was approximately 1,420 working days in the observation period. As far as the quality of patient care is concerned, the results can be considered positive because only a small number of quality indicators indicate noticeable qualitative problems. This statement is based primarily on the comparison of the groups of Saxony and Germany, which are included in the quality report of external quality assurance in accordance with sect. 137 SGB V. The majority of

  8. Accelerated retinal ganglion cell death in mice deficient in the Sigma-1 receptor

    PubMed Central

    Mavlyutov, Timur A.; Nickells, Robert W.

    2011-01-01

    Purpose The sigma-1 receptor (σR1), a ligand-operated chaperone, has been inferred to be neuroprotective in previous studies using σR1 ligands. The σR1 specificity of the protective function, however, has yet to be firmly established, due to the existence of non-σR1 targets of the ligands. Here, we used the σR1-knockout mouse (Sigmar1−/−) to demonstrate unambiguously the role of the σR1 in protecting the retinal ganglion cells against degeneration after acute damage to the optic nerve. Methods Retinal σR binding sites were labeled with radioiodinated σR ligands and analyzed by autoradiography. Localization of the σR1 was performed by indirect immunofluorescence on frozen retinal sections. Retinal ganglion cell death was induced by acute optic nerve crush in wild-type and Sigmar1−/− mice. Surviving cells in the ganglion cell layer were counted on Nissl-stained retinal whole mounts 7 days after the crush surgery. Results Photoaffinity labeling indicated the presence of the σR1 in the retina, in concentrations equivalent to those in liver tissue. Immunolabeling detected this receptor in cells of both the ganglion cell layer and the photoreceptor cell layer in wild-type retinas. Quantification of cells remaining after optic nerve crush showed that 86.8±7.9% cells remained in the wild-type ganglion cell layer, but only 68.3±3.4% survived in the Sigmar1−/−, demonstrating a significant difference between the wild-type and the Sigmar1−/− in crush-induced ganglion cell loss. Conclusions Our data indicated faster retinal ganglion cell death in Sigmar1−/− than in wild-type mice under the stresses caused by optic nerve crush, providing direct evidence for a role of the σR1 in alleviating retinal degeneration. This conclusion is consistent with the previous pharmacological studies using σR1 agonists. Thus, our study supports the idea that the σR1 is a promising therapeutic target for neurodegenerative retinal diseases, such as glaucoma. PMID

  9. Relationship between macular ganglion cell complex thickness and macular outer retinal thickness: a spectral-domain optical coherence tomography study.

    PubMed

    Kita, Yoshiyuki; Kita, Ritsuko; Takeyama, Asuka; Anraku, Ayako; Tomita, Goji; Goldberg, Ivan

    2013-01-01

    To assess the relationship between macular ganglion cell complex and macular outer retinal thicknesses. Case-control study. Forty-two normal eyes and 91 eyes with primary open-angle glaucoma were studied. Spectral-domain optical coherence tomography (RTVue-100) was used to measure the macular ganglion cell complex and macular outer retinal thickness. Ganglion cell complex to outer retinal thickness ratio was also calculated. The relationships between the ganglion cell complex and outer retinal thicknesses and between the ganglion cell complex to outer retinal thickness ratio and outer retinal thickness were evaluated. There was a positive correlation between ganglion cell complex and outer retinal thicknesses in the normal group and the glaucoma group (r = 0.53, P < 0.001 and r = 0.42, P < 0.001, respectively). In that respect, there was no correlation between ganglion cell complex to outer retinal thickness ratio and outer retinal thickness in the both groups (r = -0.07, P = 0.657, and r = 0.04, P = 0.677, respectively). The ganglion cell complex to outer retinal thickness ratio was 55.65% in the normal group, 45.07% in the glaucoma group. This difference was statistically significant. The ganglion cell complex thickness may be affected by outer retinal thickness, and there is individual variation in the outer retinal thickness. Therefore, when determining the ganglion cell complex, it seems necessary to consider the outer retinal thickness as well. We propose the ratio as a suitable parameter to account for individual variations in outer retinal thickness. © 2013 The Authors. Clinical and Experimental Ophthalmology © 2013 Royal Australian and New Zealand College of Ophthalmologists.

  10. Digital Museum of Retinal Ganglion Cells with Dense Anatomy and Physiology.

    PubMed

    Bae, J Alexander; Mu, Shang; Kim, Jinseop S; Turner, Nicholas L; Tartavull, Ignacio; Kemnitz, Nico; Jordan, Chris S; Norton, Alex D; Silversmith, William M; Prentki, Rachel; Sorek, Marissa; David, Celia; Jones, Devon L; Bland, Doug; Sterling, Amy L R; Park, Jungman; Briggman, Kevin L; Seung, H Sebastian

    2018-05-17

    When 3D electron microscopy and calcium imaging are used to investigate the structure and function of neural circuits, the resulting datasets pose new challenges of visualization and interpretation. Here, we present a new kind of digital resource that encompasses almost 400 ganglion cells from a single patch of mouse retina. An online "museum" provides a 3D interactive view of each cell's anatomy, as well as graphs of its visual responses. The resource reveals two aspects of the retina's inner plexiform layer: an arbor segregation principle governing structure along the light axis and a density conservation principle governing structure in the tangential plane. Structure is related to visual function; ganglion cells with arbors near the layer of ganglion cell somas are more sustained in their visual responses on average. Our methods are potentially applicable to dense maps of neuronal anatomy and physiology in other parts of the nervous system. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Visual Field Defects and Retinal Ganglion Cell Losses in Human Glaucoma Patients

    PubMed Central

    Harwerth, Ronald S.; Quigley, Harry A.

    2007-01-01

    Objective The depth of visual field defects are correlated with retinal ganglion cell densities in experimental glaucoma. This study was to determine whether a similar structure-function relationship holds for human glaucoma. Methods The study was based on retinal ganglion cell densities and visual thresholds of patients with documented glaucoma (Kerrigan-Baumrind, et al.) The data were analyzed by a model that predicted ganglion cell densities from standard clinical perimetry, which were then compared to histologic cell counts. Results The model, without free parameters, produced accurate and relatively precise quantification of ganglion cell densities associated with visual field defects. For 437 sets of data, the unity correlation for predicted vs. measured cell densities had a coefficient of determination of 0.39. The mean absolute deviation of the predicted vs. measured values was 2.59 dB, the mean and SD of the distribution of residual errors of prediction was -0.26 ± 3.22 dB. Conclusions Visual field defects by standard clinical perimetry are proportional to neural losses caused by glaucoma. Clinical Relevance The evidence for quantitative structure-function relationships provides a scientific basis of interpreting glaucomatous neuropathy from visual thresholds and supports the application of standard perimetry to establish the stage of the disease. PMID:16769839

  12. Expression of squid iridescence depends on environmental luminance and peripheral ganglion control.

    PubMed

    Gonzalez-Bellido, P T; Wardill, T J; Buresch, K C; Ulmer, K M; Hanlon, R T

    2014-03-15

    Squid display impressive changes in body coloration that are afforded by two types of dynamic skin elements: structural iridophores (which produce iridescence) and pigmented chromatophores. Both color elements are neurally controlled, but nothing is known about the iridescence circuit, or the environmental cues, that elicit iridescence expression. To tackle this knowledge gap, we performed denervation, electrical stimulation and behavioral experiments using the long-fin squid, Doryteuthis pealeii. We show that while the pigmentary and iridescence circuits originate in the brain, they are wired differently in the periphery: (1) the iridescence signals are routed through a peripheral center called the stellate ganglion and (2) the iridescence motor neurons likely originate within this ganglion (as revealed by nerve fluorescence dye fills). Cutting the inputs to the stellate ganglion that descend from the brain shifts highly reflective iridophores into a transparent state. Taken together, these findings suggest that although brain commands are necessary for expression of iridescence, integration with peripheral information in the stellate ganglion could modulate the final output. We also demonstrate that squid change their iridescence brightness in response to environmental luminance; such changes are robust but slow (minutes to hours). The squid's ability to alter its iridescence levels may improve camouflage under different lighting intensities.

  13. Macroanatomical investigation of the aorticorenal ganglion in 1-day-old infant sheep.

    PubMed

    Klećkowska-Nawrot, J; Kaczyńska, K; Jakubowska, W

    2009-06-01

    The aorticorenal gland belongs to the paired splanchnic ganglion, which is the main component of the coeliac plexus. It lies near the renal artery and suprarenal gland. The research was conducted on 13 1-day-old infant sheep - eight males and five females. Based on the conducted studies, it was concluded that the aorticorenal ganglion is characterized by the variable location in relation to the abdominal aorta, renal artery, caudal vena cava and suprarenal gland (holotopy), the thoracic and lumbar segment of the vertebral column (skeletotopy) (between L(1) and L(3)) and also a different shape (elongated, round, triangular, oval) as well as variable length (the aorticorenal ganglion is longer on the left side of the body; 2.72 mm) and distance from the caudal end of the suprarenal gland (longer on the left side of the body; 8.34 mm). With regard to the sex of the animal, the ganglion is the longest on the left side in ewes (3.02 mm), while in rams it is the longest on the right side (2.68 mm). Regarding the division according to sex, the longest segment was observed on the right side in ewes (9.27 mm), and the shortest segment in rams was also on the right side (6.84 mm).

  14. Painful Pathways Induced by Toll-like Receptor Stimulation of Dorsal Root Ganglion Neurons

    PubMed Central

    Qi, Jia; Buzas, Krisztina; Fan, Huiting; Cohen, Jeffrey I.; Wang, Kening; Mont, Erik; Klinman, Dennis; Oppenheim, Joost J.; Howard, O.M. Zack

    2011-01-01

    We hypothesize that innate immune signals from infectious organisms and/or injured tissues may activate peripheral neuronal pain signals. In this study, we demonstrated that toll-like receptors 3/7/9 (TLRs) are expressed by human dorsal root ganglion neurons (DRGNs) and in cultures of primary mouse DRGNs. Stimulation of murine DRGNs with TLR ligands induced expression and production of proinflammatory chemokines and cytokines CCL5 (RANTES), CXCL10 (IP10), interleukin-1alpha, interleukin-1beta, and prostaglandin E2 (PGE2), which have previously been shown to augment pain. Further, TLR ligands up-regulated the expression of a nociceptive receptor transient receptor potential vanilloid type 1 (TRPV1), and enhanced calcium flux by TRPV1 expressing DRGNs. Using a tumor-induced temperature sensitivity model, we showed that in vivo administration of a TLR9 antagonist, known as a suppressive ODN, blocked tumor-induced temperature sensitivity. Taken together, these data indicate that stimulation of peripheral neurons by TLR ligands can induce nerve pain. PMID:21515789

  15. Processing of central and reflex vagal drives by rat cardiac ganglion neurones: an intracellular analysis

    PubMed Central

    McAllen, Robin M; Salo, Lauren M; Paton, Julian F R; Pickering, Anthony E

    2011-01-01

    Abstract Cardiac vagal tone is an important indicator of cardiovascular health, and its loss is an independent risk factor for arrhythmias and mortality. Several studies suggest that this loss of vagal tone can occur at the cardiac ganglion but the factors affecting ganglionic transmissionin vivoare poorly understood. We have employed a novel approach allowing intracellular recordings from functionally connected cardiac vagal ganglion cells in the working heart–brainstem preparation. The atria were stabilisedin situpreserving their central neural connections, and ganglion cells (n = 32) were impaled with sharp microelectrodes. Cardiac ganglion cells with vagal synaptic inputs (spontaneous, n = 10; or electrically evoked from the vagus, n = 3) were identified as principal neurones and showed tonic firing responses to current injected to their somata. Cells lacking vagal inputs (n = 19, presumed interneurones) were quiescent but showed phasic firing responses to depolarising current. In principal cells the ongoing action potentials and EPSPs exhibited respiratory modulation, with peak frequency in post-inspiration. Action potentials arose from unitary EPSPs and autocorrelation of those events showed that each ganglion cell received inputs from a single active preganglionic source. Peripheral chemoreceptor, arterial baroreceptor and diving response activation all evoked high frequency synaptic barrages in these cells, always from the same single preganglionic source. EPSP amplitudes showed frequency dependent depression, leading to more spike failures at shorter inter-event intervals. These findings indicate that rather than integrating convergent inputs, cardiac vagal postganglionic neurones gate preganglionic inputs, so regulating the proportion of central parasympathetic tone that is transmitted on to the heart. PMID:22005679

  16. Recurrent Cubital Tunnel Syndrome Caused by Ganglion: A Report of Nine Cases.

    PubMed

    Komatsu, Masatoshi; Uchiyama, Shigeharu; Kimura, Takumi; Suenaga, Naoki; Hayashi, Masanori; Kato, Hiroyuki

    2018-06-01

    Cubital tunnel syndrome (CuTS) is generally treated successfully by surgery and recurrent cases are rare. This study retrospectively investigated the clinical characteristics of recurrent CuTS caused by ganglion. We evaluated nine patients who were surgically treated for recurrent CuTS caused by ganglion. Age distribution at recurrence ranged from 43 to 79 years. The initial surgery for CuTS had been performed using various methods. The asymptomatic period from initial surgery to recurrence ranged from 22 to 252 months. Clinical, diagnostic imaging, and operative findings during the second surgery were analyzed. All patients were treated by anterior subcutaneous ulnar nerve transposition with ganglion resection and later examined directly within a mean of 71 months after the second surgery. The interval from recurrence to consultation was shorter than two months for eight cases. Chief complaints included numbness with or without pain in the ring and little fingers in all patients and resting pain in the medial elbow in five patients. Elbow osteoarthritis was present in all cases. Although four of 10 ganglia were palpable, ultrasonography and magnetic resonance imaging could identify all ganglia preoperatively. The ulnar nerve typically had become entrapped by the ganglion posteriorly and by fascia, scar tissue, and/or muscle anteriorly. Chief complaints and ulnar nerve function were improved in all patients following revision surgery. The acute onset of numbness with or without intolerable pain in the ring and little fingers after a long-term remission period following initial surgery for CuTS in patients with elbow osteoarthritis appears to be the characteristic clinical profile of recurrent CuTS caused by ganglion. As ganglia are often not palpable, ultrasonography and magnetic resonance imaging are recommended for accurate diagnosis.

  17. Complex distribution patterns of voltage-gated calcium channel α-subunits in the spiral ganglion

    PubMed Central

    Chen, Wei Chun; Xue, Hui Zhong; Hsu, Yun (Lucy); Liu, Qing; Patel, Shail; Davis, Robin L.

    2011-01-01

    As with other elements of the peripheral auditory system, spiral ganglion neurons display specializations that vary as a function of location along the tonotopic axis. Previous work has shown that voltage-gated K+ channels and synaptic proteins show graded changes in their density that confers rapid responsiveness to neurons in the high frequency, basal region of the cochlea and slower, more maintained responsiveness to neurons in the low frequency, apical region of the cochlea. In order to understand how voltage-gated calcium channels (VGCCs) may contribute to these diverse phenotypes, we identified the VGCC α-subunits expressed in the ganglion, investigated aspects of Ca2+-dependent neuronal firing patterns, and mapped the intracellular and intercellular distributions of seven VGCC α-subunits in the spiral ganglion in vitro. Initial experiments with qRT-PCR showed that eight of the ten known VGCC α-subunits were expressed in the ganglion and electrophysiological analysis revealed firing patterns that were consistent with the presence of both LVA and HVA Ca2+ channels. Moreover, we were able to study seven of the α-subunits with immunocytochemistry, and we found that all were present in spiral ganglion neurons, and that three of them were neuron-specific (CaV1.3, CaV2.2, and CaV3.3). Further characterization of neuron-specific α-subunits showed that CaV1.3 and CaV3.3 were tonotopically-distributed, whereas CaV2.2 was uniformly distributed in apical and basal neurons. Multiple VGCC α-subunits were also immunolocalized to Schwann cells, having distinct intracellular localizations, and, significantly, appearing to distinguish putative compact0 (CaV2.3, CaV3.1) from loose (CaV1.2) myelin. Electrophysiological evaluation of spiral ganglion neurons in the presence of TEA revealed Ca2+ plateau potentials with slopes that varied proportionately with the cochlear region from which neurons were isolated. Because afterhyperpolarizations were minimal or absent under

  18. Central Projections of Melanopsin-Expressing Retinal Ganglion Cells in the Mouse

    PubMed Central

    HATTAR, SAMER; KUMAR, MONICA; PARK, ALEXANDER; TONG, PATRICK; TUNG, JONATHAN; YAU, KING-WAI; BERSON, DAVID M.

    2010-01-01

    A rare type of ganglion cell in mammalian retina is directly photosensitive. These novel retinal photoreceptors express the photopigment melanopsin. They send axons directly to the suprachiasmatic nucleus (SCN), intergeniculate leaflet (IGL), and olivary pretectal nucleus (OPN), thereby contributing to photic synchronization of circadian rhythms and the pupillary light reflex. Here, we sought to characterize more fully the projections of these cells to the brain. By targeting tau-lacZ to the melanopsin gene locus in mice, ganglion cells that would normally express melanopsin were induced to express, instead, the marker enzyme β-galactosidase. Their axons were visualized by X-gal histochemistry or anti-β-galactosidase immunofluorescence. Established targets were confirmed, including the SCN, IGL, OPN, ventral division of the lateral geniculate nucleus (LGv), and preoptic area, but the overall projections were more widespread than previously recognized. Targets included the lateral nucleus, peri-supraoptic nucleus, and subparaventricular zone of the hypothalamus, medial amygdala, margin of the lateral habenula, posterior limitans nucleus, superior colliculus, and periaqueductal gray. There were also weak projections to the margins of the dorsal lateral geniculate nucleus. Co-staining with the cholera toxin B subunit to label all retinal afferents showed that melanopsin ganglion cells provide most of the retinal input to the SCN, IGL, and lateral habenula and much of that to the OPN, but that other ganglion cells do contribute at least some retinal input to these targets. Staining patterns after monocular enucleation revealed that the projections of these cells are overwhelmingly crossed except for the projection to the SCN, which is bilaterally symmetrical. PMID:16736474

  19. A Learning Model for L/M Specificity in Ganglion Cells

    NASA Technical Reports Server (NTRS)

    Ahumada, Albert J.

    2016-01-01

    An unsupervised learning model for developing LM specific wiring at the ganglion cell level would support the research indicating LM specific wiring at the ganglion cell level (Reid and Shapley, 2002). Removing the contributions to the surround from cells of the same cone type improves the signal-to-noise ratio of the chromatic signals. The unsupervised learning model used is Hebbian associative learning, which strengthens the surround input connections according to the correlation of the output with the input. Since the surround units of the same cone type as the center are redundant with the center, their weights end up disappearing. This process can be thought of as a general mechanism for eliminating unnecessary cells in the nervous system.

  20. An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival

    PubMed Central

    Tang, Zhongshu; Zhang, Shuihua; Lee, Chunsik; Kumar, Anil; Arjunan, Pachiappan; Li, Yang; Zhang, Fan; Li, Xuri

    2011-01-01

    Injury to the optic nerve can lead to axonal degeneration, followed by a gradual death of retinal ganglion cells (RGCs), which results in irreversible vision loss. Examples of such diseases in human include traumatic optic neuropathy and optic nerve degeneration in glaucoma. It is characterized by typical changes in the optic nerve head, progressive optic nerve degeneration, and loss of retinal ganglion cells, if uncontrolled, leading to vision loss and blindness. The optic nerve crush (ONC) injury mouse model is an important experimental disease model for traumatic optic neuropathy, glaucoma, etc. In this model, the crush injury to the optic nerve leads to gradual retinal ganglion cells apoptosis. This disease model can be used to study the general processes and mechanisms of neuronal death and survival, which is essential for the development of therapeutic measures. In addition, pharmacological and molecular approaches can be used in this model to identify and test potential therapeutic reagents to treat different types of optic neuropathy. Here, we provide a step by step demonstration of (I) Baseline retrograde labeling of retinal ganglion cells (RGCs) at day 1, (II) Optic nerve crush injury at day 4, (III) Harvest the retinae and analyze RGC survival at day 11, and (IV) Representative result. PMID:21540827

  1. Learning LM Specificity for Ganglion Cells

    NASA Technical Reports Server (NTRS)

    Ahumada, Albert J.

    2015-01-01

    Unsupervised learning models have been proposed based on experience (Ahumada and Mulligan, 1990;Wachtler, Doi, Lee and Sejnowski, 2007) that allow the cortex to develop units with LM specific color opponent receptive fields like the blob cells reported by Hubel and Wiesel on the basis of visual experience. These models used ganglion cells with LM indiscriminate wiring as inputs to the learning mechanism, which was presumed to occur at the cortical level.

  2. Protective effects of brain-derived neurotrophic factor on the noise-damaged cochlear spiral ganglion.

    PubMed

    Zhai, S-Q; Guo, W; Hu, Y-Y; Yu, N; Chen, Q; Wang, J-Z; Fan, M; Yang, W-Y

    2011-05-01

    To explore the protective effects of brain-derived neurotrophic factor on the noise-damaged cochlear spiral ganglion. Recombinant adenovirus brain-derived neurotrophic factor vector, recombinant adenovirus LacZ and artificial perilymph were prepared. Guinea pigs with audiometric auditory brainstem response thresholds of more than 75 dB SPL, measured seven days after four hours of noise exposure at 135 dB SPL, were divided into three groups. Adenovirus brain-derived neurotrophic factor vector, adenovirus LacZ and perilymph were infused into the cochleae of the three groups, variously. Eight weeks later, the cochleae were stained immunohistochemically and the spiral ganglion cells counted. The auditory brainstem response threshold recorded before and seven days after noise exposure did not differ significantly between the three groups. However, eight weeks after cochlear perfusion, the group receiving brain-derived neurotrophic factor had a significantly decreased auditory brainstem response threshold and increased spiral ganglion cell count, compared with the adenovirus LacZ and perilymph groups. When administered via cochlear infusion following noise damage, brain-derived neurotrophic factor appears to improve the auditory threshold, and to have a protective effect on the spiral ganglion cells.

  3. Ocular anatomy, ganglion cell distribution and retinal resolution of a killer whale (Orcinus orca).

    PubMed

    Mass, Alla M; Supin, Alexander Y; Abramov, Andrey V; Mukhametov, Lev M; Rozanova, Elena I

    2013-01-01

    Retinal topography, cell density and sizes of ganglion cells in the killer whale (Orcinus orca) were analyzed in retinal whole mounts stained with cresyl violet. A distinctive feature of the killer whale's retina is the large size of ganglion cells and low cell density compared to terrestrial mammals. The ganglion cell diameter ranged from 8 to 100 µm, with the majority of cells within a range of 20-40 µm. The topographic distribution of ganglion cells displayed two spots of high cell density located in the temporal and nasal quadrants, 20 mm from the optic disk. The high-density areas were connected by a horizontal belt-like area passing below the optic disk of the retina. Peak cell densities in these areas were evaluated. Mean peak cell densities were 334 and 288 cells/mm(2) in the temporal and nasal high-density areas, respectively. With a posterior nodal distance of 19.5 mm, these high-density data predict a retinal resolution of 9.6' (3.1 cycles/deg.) and 12.6' (2.4 cycles/deg.) in the temporal and nasal areas, respectively, in water. Copyright © 2012 S. Karger AG, Basel.

  4. Lithium alters the morphology of neurites regenerating from cultured adult spiral ganglion neurons.

    PubMed

    Shah, S M; Patel, C H; Feng, A S; Kollmar, R

    2013-10-01

    The small-molecule drug lithium (as a monovalent ion) promotes neurite regeneration and functional recovery, is easy to administer, and is approved for human use to treat bipolar disorder. Lithium exerts its neuritogenic effect mainly by inhibiting glycogen synthase kinase 3, a constitutively-active serine/threonine kinase that is regulated by neurotrophin and "wingless-related MMTV integration site" (Wnt) signaling. In spiral ganglion neurons of the cochlea, the effects of lithium and the function of glycogen synthase kinase 3 have not been investigated. We, therefore, set out to test whether lithium modulates neuritogenesis from adult spiral ganglion neurons. Primary cultures of dissociated spiral ganglion neurons from adult mice were exposed to lithium at concentrations between 0 and 12.5 mM. The resulting neurite morphology and growth-cone appearance were measured in detail by using immunofluorescence microscopy and image analysis. We found that lithium altered the morphology of regenerating neurites and their growth cones in a differential, concentration-dependent fashion. Low concentrations of 0.5-2.5 mM (around the half-maximal inhibitory concentration for glycogen synthase kinase 3 and the recommended therapeutic serum concentration for bipolar disorder) enhanced neurite sprouting and branching. A high concentration of 12.5 mM, in contrast, slowed elongation. As the lithium concentration rose from low to high, the microtubules became increasingly disarranged and the growth cones more arborized. Our results demonstrate that lithium selectively stimulates phases of neuritogenesis that are driven by microtubule reorganization. In contrast, most other drugs that have previously been tested on spiral ganglion neurons are reported to inhibit neurite outgrowth or affect only elongation. Lithium sensitivity is a necessary, but not sufficient condition for the involvement of glycogen synthase kinase 3. Our results are, therefore, consistent with, but do not prove

  5. Enkephalin modulation of neural transmission in the cat stellate ganglion: pharmacological actions of exogenous opiates.

    PubMed

    Prosdocimi, M; Finesso, M; Gorio, A

    1986-11-01

    Neural ganglionic transmission was studied in vivo in the cat, using closed chest anesthetized preparations. The right stellate ganglion and its branches were exposed retropleurally and prepared for electrical stimulation of pre- and postganglionic nerve fibers. The axillary artery was cannulated allowing direct administration of drugs in the arterial blood supplying the ganglion. Stimulation of postjunctional receptors could thus be obtained by local administration of selective agents. Local administration of nicotinic, muscarinic or histaminergic agents increased heart rate and blood pressure. Opiates were given either i.v. or locally through the axillary artery: we tested the effects of morphine, Leu-enkephalin (Leu-enk), Met-enkephalin (Met-enk), [D-ala2]-Met-enkephalinamide (DAME) and etorphine. When given locally, Leu-enk (from 10 micrograms), Met-enk (from 20 micrograms), DAME (from 5 micrograms) and etorphine (from 0.2 micrograms) inhibited tachycardia induced by preganglionic stimulation and reduced the amplitude of the compound action potential recorded from the postganglionic nerve. Morphine (10-200 micrograms) had no effect. On the other hand, tachycardia induced by postganglionic nerve stimulation was unaffected by opiates in the same experimental conditions. Intravenous administration of similar doses of opiates had no effect on ganglionic transmission. When tachycardia was induced by chemical stimulation of nicotinic (DMPP), muscarinic (McN-A-343-11) or histamine receptors in the stellate ganglia, opiates were still active in reducing the effect of these chemicals. These data provide evidence that exogenous opiates exert a depressing action on postsynaptic responses of sympathetic ganglia tested in vivo, although an additional action on presynaptic terminals is not excluded. As endogenous opiates are normally present in various sympathetic ganglia, including the stellate ganglion of the cat, it is possible that they play some modulatory role on

  6. Neuroprotective Effect of Tauroursodeoxycholic Acid on N-Methyl-D-Aspartate-Induced Retinal Ganglion Cell Degeneration

    PubMed Central

    Fernández-Sánchez, Laura; Rondón, Netxibeth; Esquiva, Gema; Germain, Francisco; de la Villa, Pedro; Cuenca, Nicolás

    2015-01-01

    Retinal ganglion cell degeneration underlies the pathophysiology of diseases affecting the retina and optic nerve. Several studies have previously evidenced the anti-apoptotic properties of the bile constituent, tauroursodeoxycholic acid, in diverse models of photoreceptor degeneration. The aim of this study was to investigate the effects of systemic administration of tauroursodeoxycholic acid on N-methyl-D-aspartate (NMDA)-induced damage in the rat retina using a functional and morphological approach. Tauroursodeoxycholic acid was administered intraperitoneally before and after intravitreal injection of NMDA. Three days after insult, full-field electroretinograms showed reductions in the amplitudes of the positive and negative-scotopic threshold responses, scotopic a- and b-waves and oscillatory potentials. Quantitative morphological evaluation of whole-mount retinas demonstrated a reduction in the density of retinal ganglion cells. Systemic administration of tauroursodeoxycholic acid attenuated the functional impairment induced by NMDA, which correlated with a higher retinal ganglion cell density. Our findings sustain the efficacy of tauroursodeoxycholic acid administration in vivo, suggesting it would be a good candidate for the pharmacological treatment of degenerative diseases coursing with retinal ganglion cell loss. PMID:26379056

  7. Visual pattern recognition based on spatio-temporal patterns of retinal ganglion cells’ activities

    PubMed Central

    Jing, Wei; Liu, Wen-Zhong; Gong, Xin-Wei; Gong, Hai-Qing

    2010-01-01

    Neural information is processed based on integrated activities of relevant neurons. Concerted population activity is one of the important ways for retinal ganglion cells to efficiently organize and process visual information. In the present study, the spike activities of bullfrog retinal ganglion cells in response to three different visual patterns (checker-board, vertical gratings and horizontal gratings) were recorded using multi-electrode arrays. A measurement of subsequence distribution discrepancy (MSDD) was applied to identify the spatio-temporal patterns of retinal ganglion cells’ activities in response to different stimulation patterns. The results show that the population activity patterns were different in response to different stimulation patterns, such difference in activity pattern was consistently detectable even when visual adaptation occurred during repeated experimental trials. Therefore, the stimulus pattern can be reliably discriminated according to the spatio-temporal pattern of the neuronal activities calculated using the MSDD algorithm. PMID:21886670

  8. Ganglion cell distribution and retinal resolution in the Florida manatee, Trichechus manatus latirostris.

    PubMed

    Mass, Alla M; Ketten, Darlene R; Odell, Daniel K; Supin, Alexander Ya

    2012-01-01

    The topographic organization of retinal ganglion cells was examined in the Florida manatee (Trichechus manatus latirostris) to assess ganglion cell size and distribution and to estimate retinal resolution. The ganglion cell layer of the manatee's retina was comprised primarily of large neurons with broad intercellular spaces. Cell sizes varied from 10 to 60 μm in diameter (mean 24.3 μm). The retinal wholemounts from adult animals measured 446-501 mm(2) in area with total ganglion cell counts of 62,000-81,800 (mean 70,200). The cell density changed across the retina, with the maximum in the area below the optic disc and decreasing toward the retinal edges and in the immediate vicinity of the optic disc. The maximum cell density ranged from 235 to 337 cells per millimeter square in the adult retinae. Two wholemounts obtained from juvenile animals were 271 and 282 mm(2) in area with total cell numbers of 70,900 and 68,700, respectively (mean 69,800), that is, nearly equivalent to those of adults, but juvenile retinae consequently had maximum cell densities that were higher than those of adults: 478 and 491 cells per millimeter square. Calculations indicate a retinal resolution of ∼19' (1.6 cycles per degree) in both adult and juvenile retinae. Copyright © 2011 Wiley Periodicals, Inc.

  9. Periosteal ganglion: a report of three new cases including MRI findings and a review of the literature.

    PubMed

    Okada, K; Unoki, E; Kubota, H; Abe, E; Taniwaki, M; Morita, M; Sato, K

    1996-02-01

    To clarify the clinicopathological features of periosteal ganglion. Three patients with periosteal ganglion were studied clinicopathologically. One patient was selected from the files of our institute and two from a consultation file. All three lesions were located over the medial aspect of the tibia. Plain radiographs showed cortical erosions of varying degrees and mild periosteal reaction of the medial side of the tibia. MR images demonstrated well-circumscribed lesions overlying the cortical bone of the tibia, shown as low-intensity areas on T1-weighted images. On T2-weighted images, lesions were homogeneous, lobulated, and showed a characteristic markedly increased signal intensity. These findings are helpful in making a diagnosis of periosteal ganglion. Each patient had an uneventful clinical course after an excision involving the wall of the ganglion, the adjoining periosteum, and the underlying sclerotic cortical bone.

  10. Spatial resolution, contrast sensitivity, and sensitivity to defocus of chicken retinal ganglion cells in vitro.

    PubMed

    Diedrich, Erich; Schaeffel, Frank

    2009-11-01

    The chicken has been extensively studied as an animal model for myopia because its eye growth is tightly controlled by visual experience. It has been found that the retina controls the axial eye growth rates depending on the amount and the sign of defocus imposed in the projected image. Glucagonergic amacrine cells were discovered that appear to encode for the sign of imposed defocus. It is not clear whether the downstream neurons, the retinal ganglion cells, still have access to this information-and whether it ultimately reaches the brain. We have analyzed the spike rates of chicken retinal ganglion cells in vitro using a microelectrode array. For this purpose, we initially defined spatial resolution and contrast sensitivity in vitro. Two classes of chicken retinal ganglions were found, depending on the linearity of their responses with increasing contrast. Responses generally declined with increasing defocus of the visual stimulus. These responses were well predicted by the modulation transfer function for a diffraction-limited defocused optical system, the first Bessel function. Thus, the studied retinal ganglion cells did not distinguish between a loss of contrast at a given spatial frequency due to reduced contrast of the stimulus pattern or because the pattern was presented out of focus. Furthermore, there was no indication that the retinal ganglion cells responded differently to defocus of either sign, at least for the cells that were recorded in this study.

  11. Distribution of TRPV1 and TRPV2 in the human stellate ganglion and spinal cord.

    PubMed

    Kokubun, Souichi; Sato, Tadasu; Ogawa, Chikara; Kudo, Kai; Goto, Koju; Fujii, Yuki; Shimizu, Yoshinaka; Ichikawa, Hiroyuki

    2015-03-17

    Immunohistochemistry for the transient receptor potential cation channel subfamily V member 1 (TRPV1) and 2 (TRPV2) was performed on the stellate ganglion and spinal cord in human cadavers. In the stellate ganglion, 25.3% and 16.2% of sympathetic neurons contained TRPV1- and TRPV2-immunoreactivity, respectively. The cell size analysis also demonstrated that proportion of TRPV1- or TRPV2-immunoreactive (-IR) neurons among large (>600 μm(2)) sympathetic neurons (TRPV1, 30.7%; TRPV2, 27.0%) was higher than among small (<600 μm(2)) sympathetic neurons (TRPV1, 22.0%; TRPV2, 13.6%). The present study also demonstrated that 10.0% of sympathetic neurons in the stellate ganglion had pericellular TRPV2-IR nerve fibers. Fourteen percent of large neurons and 7.8% of small neurons were surrounded by TRPV2-IR nerve fibers. TRPV2-immunoreactivity was also detected in about 40% of neuronal cell bodies with pericellular TRPV2-IR nerve fibers. In the lateral horn of the human thoracic spinal cord, TRPV2-immunoreactivity was expressed by some neurons and many varicose fibers surrounding TRPV2-immunonegative neurons. TRPV2-IR pericellular fibers in the stellate ganglion may originate from the lateral horn of the spinal cord. There appears to be TRPV1- or TRPV2-IR sympathetic pathway in the human stellate ganglion and spinal cord. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Molecular Responses of the Spiral Ganglion to Aminoglycosides

    ERIC Educational Resources Information Center

    Balaban, Carey D.

    2005-01-01

    Aminoglycosides are toxic to both the inner ear hair cells and the ganglion cells that give rise to the eighth cranial nerve. According to recent studies, these cells have a repertoire of molecular responses to aminoglycoside exposure that engages multiple neuroprotective mechanisms. The responses appear to involve regulation of ionic homeostasis,…

  13. Pulsed Infrared Releases Ca2+ from the Endoplasmic Reticulum of Cultured Spiral Ganglion Neurons.

    PubMed

    Barrett, John N; Rincon, Samantha; Singh, Jayanti; Matthewman, Cristina; Pasos, Julio; Barrett, Ellen F; Rajguru, Suhrud M

    2018-04-18

    We investigated the effects of pulsed infrared radiation (IR, 1863 nm) stimulation on cytosolic [Ca 2+ ] in inner ear spiral ganglion neurons cultured from day 4 postnatal mice and loaded with a fluorescent Ca 2+ indicator (fluo-4, -5F or -5N). IR pulse trains (200 µs, 200-250 Hz, 2-5 s) delivered via an optical fiber coupled to IR source produced a rapid, transient temperature increase of 6-11ºC (above a baseline of 24-30 ºC) and evoked transient increases in both nuclear and cytosolic [Ca 2+ ] of 0.20 - 1.4 µM, with a simultaneous reduction of [Ca 2+ ] in regions containing endoplasmic reticulum (ER). IR-induced increases in cytosolic [Ca 2+ ] continued in medium containing no added Ca 2+ ({plus minus} Ca 2+ buffers) and low [Na + ], indicating that the [Ca 2+ ] increase was mediated by release from intracellular stores. Consistent with this hypothesis, the IR-induced [Ca 2+ ] response was prolonged and eventually blocked by inhibition of ER Ca-ATPase with cyclopiazonic acid, and was also inhibited by a high concentration of ryanodine and by inhibitors of IP 3 -mediated Ca 2+ release (xestospongin C and 2-APB). The thermal sensitivity of the response suggested involvement of warm-sensitive transient receptor potential (TRP) receptors. Immunostaining of the spiral ganglion demonstrated the presence of intracellular TRPV4 and TRPM2, and the IR-induced [Ca 2+ ] increase was inhibited by TRPV4 inhibitors (HC067047 and GSK2193874). These results suggest that the temperature-sensitivity of IR-induced [Ca 2+ ] elevations is conferred by TRP channels on ER membranes, which facilitate Ca 2+ efflux into the cytosol and initiate Ca 2+ -induced Ca 2+ -release via IP 3 and ryanodine receptors.

  14. The spiral ganglion: connecting the peripheral and central auditory systems

    PubMed Central

    Nayagam, Bryony A; Muniak, Michael A; Ryugo, David K

    2011-01-01

    In mammals, the initial bridge between the physical world of sound and perception of that sound is established by neurons of the spiral ganglion. The cell bodies of these neurons give rise to peripheral processes that contact acoustic receptors in the organ of Corti, and the central processes collect together to form the auditory nerve that projects into the brain. In order to better understand hearing at this initial stage, we need to know the following about spiral ganglion neurons: (1) their cell biology including cytoplasmic, cytoskeletal, and membrane properties, (2) their peripheral and central connections including synaptic structure; (3) the nature of their neural signaling; and (4) their capacity for plasticity and rehabilitation. In this report, we will update the progress on these topics and indicate important issues still awaiting resolution. PMID:21530629

  15. The retina of the shovel-nosed ray, Rhinobatos batillum (Rhinobatidae): morphology and quantitative analysis of the ganglion, amacrine and bipolar cell populations.

    PubMed

    Collin, S P

    1988-01-01

    A light microscopy study of the retina of the shovel-nosed ray, Rhinobatos batillum (Rhinobatidae) has revealed a duplex retina with a rod to cone ratio between 4:1 and 6:1. The inner nuclear layer consists of three layers of large horizontal cells, tightly packed, stellate bipolar cells, and up to three substrata of amacrine cells. The collaterals of the many supporting Müller cells project from the inner to the outer limiting membrane and divide the retina into many subunits. The cells of the ganglion cell layer are distributed into two layers, although a large proportion of ganglion cells are also displaced into the inner plexiform and inner nuclear layers. Topographic analysis of the cells in the ganglion cell layer, inner plexiform and inner nuclear layers reveals a number of regional specializations or "areae centrales". Ganglion cells were retrogradely-labelled with cobalt-lysine from the optic nerve, and three sub-populations of neurons characterized on their soma size and position. Small (20-50 microns2), large (80-300 microns2) and giant (greater than 300 microns2) sub-populations of ganglion cells each revealed distinct retinal specializations with peak densities of 3 x 10(3), 1.25 x 10(3) and 1.57 x 10(3) cells per mm2, respectively. Topographical comparison between Nissl-stained and retrogradely-labelled ganglion cell populations have established that a maximum of 20% in the "area centralis", and 75% in unspecialized, peripheral regions of the retina are non-ganglion cells. Out of a total of 210,566 cells in the ganglion cell layer, 49% were found to be non-ganglion cells. Iso-density contour maps of amacrine and bipolar cell distributions also reveal some specializations. These cell concentrations lie in corresponding regions to areas of increased density in the large and giant ganglion cell populations, suggesting some functional association.

  16. Effect of duration and severity of migraine on retinal nerve fiber layer, ganglion cell layer, and choroidal thickness.

    PubMed

    Abdellatif, Mona K; Fouad, Mohamed M

    2018-03-01

    To investigate the factors in migraine that have the highest significance on retinal and choroidal layers' thickness. Ninety patients with migraine and 40 age-matched healthy participants were enrolled in this observational, cross-sectional study. After full ophthalmological examination, spectral domain-optical coherence tomography was done for all patients measuring the thickness of ganglion cell layer and retinal nerve fiber layer. Enhanced depth imaging technique was used to measure the choroidal thickness. There was significant thinning in the superior and inferior ganglion cell layers, all retinal nerve fiber layer quadrants, and all choroidal quadrants (except for the central subfield) in migraineurs compared to controls. The duration of migraine was significantly correlated with ganglion cell layer, retinal nerve fiber layer, and all choroidal quadrants, while the severity of migraine was significantly correlated with ganglion cell layer and retinal nerve fiber layer only. Multiregression analysis showed that the duration of migraine is the most important determinant factor of the superior retinal nerve fiber layer quadrant (β = -0.375, p = 0.001) and in all the choroidal quadrants (β = -0.531, -0.692, -0.503, -0.461, -0.564, respectively, p  < 0.001), while severity is the most important determinant factor of inferior, nasal, and temporal retinal nerve fiber layer quadrants (β = -0.256, -0.335, -0.308; p  = 0.036, 0.005, 0.009, respectively) and the inferior ganglion cell layer hemisphere (β = -0.377 and p = 0.001). Ganglion cell layer, retinal nerve fiber layer, and choroidal thickness are significantly thinner in patients with migraine. The severity of migraine has more significant influence in the thinning of ganglion cell layer and retinal nerve fiber layer, while the duration of the disease affected the choroidal thickness more.

  17. Clinical value of a self-designed training model for pinpointing and puncturing trigeminal ganglion.

    PubMed

    He, Yu-Quan; He, Shu; Shen, Yun-Xia; Qian, Cheng

    2014-04-01

    OBJECTIVES. A training model was designed for learners and young physicians to polish their skills in clinical practices of pinpointing and puncturing trigeminal ganglion. METHODS. A head model, on both cheeks of which the deep soft tissue was replaced by stuffed organosilicone and sponge while the superficial soft tissue, skin and the trigeminal ganglion were made of organic silicon rubber for an appearance of real human being, was made from a dried skull specimen and epoxy resin. Two physicians who had experiences in puncturing foramen ovale and trigeminal ganglion were selected to test the model, mainly for its appearance, X-ray permeability, handling of the puncture, and closure of the puncture sites. Four inexperienced physicians were selected afterwards to be trained combining Hartel's anterior facial approach with the new method of real-time observation on foramen ovale studied by us. RESULTS. Both appearance and texture of the model were extremely close to those of a real human. The fact that the skin, superficial soft tissue, deep muscles of the cheeks, and the trigeminal ganglion made of organic silicon rubber all had great elasticity resulted in quick closure and sealing of the puncture sites. The head model made of epoxy resin had similar X-ray permeability to a human skull specimen under fluoroscopy. The soft tissue was made of radiolucent material so that the training can be conducted with X-ray guidance. After repeated training, all the four young physicians were able to smoothly and successfully accomplish the puncture. CONCLUSION. This self-made model can substitute for cadaver specimen in training learners and young physicians on foramen ovale and trigeminal ganglion puncture. It is very helpful for fast learning and mastering this interventional operation skill, and the puncture accuracy can be improved significantly with our new method of real-time observation on foramen ovale.

  18. A morphometric analysis of the superior cervical ganglion and its surrounding structures.

    PubMed

    Fazliogullari, Zeliha; Kilic, Cenk; Karabulut, Ahmet Kagan; Yazar, Fatih

    2016-04-01

    The aim of this cadaveric study was to detect the superior cervical ganglion (SCG) in a topographic manner according to vertebrae and to determine the relationship between the vertebrae, mandibular angle and longus colli muscle through morphometric analysis. The present study was performed on 40 SCG of 20 human cadavers (16 males, 4 females). The level of the SCG was determined based on the vertebrae. Ganglion length, width and thickness were detected. Distance to the adjacent vertebra, the mandibular angle and medial side of the longus colli muscle were measured. The results were evaluated statistically. The SCG existing in all cadavers was detected at the C2 vertebra level in 34 cadavers and at the C3 vertebra level in 6 cadavers. The average length, width and thickness of the SCG were 15.18 ± 1.12, 4.62 ± 0.25, and 1.83 ± 0.10 mm, respectively. No statistically significant difference was detected in terms of the distances between the ganglion and anterior tubercle of transverse processes of the vertebrae as well as the mandibular angle on either side. The distance between the SCG and the medial edge of the longus colli muscle was significantly greater on the left side in both men (p < 0.001) and women (p < 0.01). Recognition of morphometric characteristics of the SCG and detection of its location according to adjacent formations may serve as a guide for nerve blockage studies and help surgeons to preserve the ganglion in both anterior and anterolateral cervical approaches.

  19. Pulsed infrared radiation excites cultured neonatal spiral and vestibular ganglion neurons by modulating mitochondrial calcium cycling

    PubMed Central

    Lumbreras, Vicente; Bas, Esperanza; Gupta, Chhavi

    2014-01-01

    Cochlear implants are currently the most effective solution for profound sensorineural hearing loss, and vestibular prostheses are under development to treat bilateral vestibulopathies. Electrical current spread in these neuroprostheses limits channel independence and, in some cases, may impair their performance. In comparison, optical stimuli that are spatially confined may result in a significant functional improvement. Pulsed infrared radiation (IR) has previously been shown to elicit responses in neurons. This study analyzes the response of neonatal rat spiral and vestibular ganglion neurons in vitro to IR (wavelength = 1,863 nm) using Ca2+ imaging. Both types of neurons responded consistently with robust intracellular Ca2+ ([Ca2+]i) transients that matched the low-frequency IR pulses applied (4 ms, 0.25–1 pps). Radiant exposures of ∼637 mJ/cm2 resulted in continual neuronal activation. Temperature or [Ca2+] variations in the media did not alter the IR-evoked transients, ruling out extracellular Ca2+ involvement or primary mediation by thermal effects on the plasma membrane. While blockage of Na+, K+, and Ca2+ plasma membrane channels did not alter the IR-evoked response, blocking of mitochondrial Ca2+ cycling with CGP-37157 or ruthenium red reversibly inhibited the IR-evoked [Ca2+]i transients. Additionally, the magnitude of the IR-evoked transients was dependent on ryanodine and cyclopiazonic acid-dependent Ca2+ release. These results suggest that IR modulation of intracellular calcium cycling contributes to stimulation of spiral and vestibular ganglion neurons. As a whole, the results suggest selective excitation of neurons in the IR beam path and the potential of IR stimulation in future auditory and vestibular prostheses. PMID:24920028

  20. Pulsed infrared radiation excites cultured neonatal spiral and vestibular ganglion neurons by modulating mitochondrial calcium cycling.

    PubMed

    Lumbreras, Vicente; Bas, Esperanza; Gupta, Chhavi; Rajguru, Suhrud M

    2014-09-15

    Cochlear implants are currently the most effective solution for profound sensorineural hearing loss, and vestibular prostheses are under development to treat bilateral vestibulopathies. Electrical current spread in these neuroprostheses limits channel independence and, in some cases, may impair their performance. In comparison, optical stimuli that are spatially confined may result in a significant functional improvement. Pulsed infrared radiation (IR) has previously been shown to elicit responses in neurons. This study analyzes the response of neonatal rat spiral and vestibular ganglion neurons in vitro to IR (wavelength = 1,863 nm) using Ca(2+) imaging. Both types of neurons responded consistently with robust intracellular Ca(2+) ([Ca(2+)]i) transients that matched the low-frequency IR pulses applied (4 ms, 0.25-1 pps). Radiant exposures of ∼637 mJ/cm(2) resulted in continual neuronal activation. Temperature or [Ca(2+)] variations in the media did not alter the IR-evoked transients, ruling out extracellular Ca(2+) involvement or primary mediation by thermal effects on the plasma membrane. While blockage of Na(+), K(+), and Ca(2+) plasma membrane channels did not alter the IR-evoked response, blocking of mitochondrial Ca(2+) cycling with CGP-37157 or ruthenium red reversibly inhibited the IR-evoked [Ca(2+)]i transients. Additionally, the magnitude of the IR-evoked transients was dependent on ryanodine and cyclopiazonic acid-dependent Ca(2+) release. These results suggest that IR modulation of intracellular calcium cycling contributes to stimulation of spiral and vestibular ganglion neurons. As a whole, the results suggest selective excitation of neurons in the IR beam path and the potential of IR stimulation in future auditory and vestibular prostheses. Copyright © 2014 the American Physiological Society.

  1. Changes in ganglion cell physiology during retinal degeneration influence excitability by prosthetic electrodes

    NASA Astrophysics Data System (ADS)

    Cho, Alice; Ratliff, Charles; Sampath, Alapakkam; Weiland, James

    2016-04-01

    Objective. Here we investigate ganglion cell physiology in healthy and degenerating retina to test its influence on threshold to electrical stimulation. Approach. Age-related Macular Degeneration and Retinitis Pigmentosa cause blindness via outer retinal degeneration. Inner retinal pathways that transmit visual information to the central brain remain intact, so direct electrical stimulation from prosthetic devices offers the possibility for visual restoration. Since inner retinal physiology changes during degeneration, we characterize physiological properties and responses to electrical stimulation in retinal ganglion cells (RGCs) of both wild type mice and the rd10 mouse model of retinal degeneration. Main results. Our aggregate results support previous observations that elevated thresholds characterize diseased retinas. However, a physiology-driven classification scheme reveals distinct sub-populations of ganglion cells with thresholds either normal or strongly elevated compared to wild-type. When these populations are combined, only a weakly elevated threshold with large variance is observed. The cells with normal threshold are more depolarized at rest and exhibit periodic oscillations. Significance. During degeneration, physiological changes in RGCs affect the threshold stimulation currents required to evoke action potentials.

  2. Periosteal ganglion: a cause of cortical bone erosion.

    PubMed

    McCarthy, E F; Matz, S; Steiner, G C; Dorfman, H D

    1983-01-01

    Three cases of periosteal ganglia of long bones are presented. These lesions are produced by mucoid degeneration and cyst formation of the periosteum to produce external cortical erosion and reactive periosteal new bone. They are not associated with a soft tissue ganglion or an intraosseous lesion. They may radiologically mimic other periosteal lesions or soft tissue neoplasms which erode bone.

  3. One-day high-fat diet induces inflammation in the nodose ganglion and hypothalamus of mice.

    PubMed

    Waise, T M Zaved; Toshinai, Koji; Naznin, Farhana; NamKoong, Cherl; Md Moin, Abu Saleh; Sakoda, Hideyuki; Nakazato, Masamitsu

    2015-09-04

    A high-fat diet (HFD) induces inflammation in systemic organs including the hypothalamus, resulting in obesity and diabetes. The vagus nerve connects the visceral organs and central nervous system, and the gastric-derived orexigenic peptide ghrelin transmits its starvation signals to the hypothalamus via the vagal afferent nerve. Here we investigated the inflammatory response in vagal afferent neurons and the hypothalamus in mice following one day of HFD feeding. This treatment increased the number of macrophages/microglia in the nodose ganglion and hypothalamus. Furthermore, one-day HFD induced expression of Toll-like receptor 4 in the goblet cells of the colon and upregulated mRNA expressions of the proinflammatory biomarkers Emr1, Iba1, Il6, and Tnfα in the nodose ganglion and hypothalamus. Both subcutaneous administration of ghrelin and celiac vagotomy reduced HFD-induced inflammation in these tissues. HFD intake triggered inflammatory responses in the gut, nodose ganglion, and subsequently in the hypothalamus within 24 h. These findings suggest that the vagal afferent nerve may transfer gut-derived inflammatory signals to the hypothalamus via the nodose ganglion, and that ghrelin may protect against HFD-induced inflammation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Laminin γ3 plays an important role in retinal lamination, photoreceptor organisation and ganglion cell differentiation.

    PubMed

    Dorgau, Birthe; Felemban, Majed; Sharpe, Alexander; Bauer, Roman; Hallam, Dean; Steel, David H; Lindsay, Susan; Mellough, Carla; Lako, Majlinda

    2018-05-23

    Laminins are heterotrimeric glycoproteins of the extracellular matrix. Eleven different laminin chains have been identified in vertebrates. They are ubiquitously expressed in the human body, with a distinct tissue distribution. Laminin expression in neural retina and their functional role during human retinogenesis is still unknown. This study investigated the laminin expression in human developing and adult retina, showing laminin α1, α5, β1, β2 and γ1 to be predominantly expressed in Bruch's membrane and the inner limiting membrane. Laminin-332 and laminin γ3 expression were mainly observed in the neural retina during retinal histogenesis. These expression patterns were largely conserved in pluripotent stem cell-derived retinal organoids. Blocking of laminin γ3 function in retinal organoids resulted in the disruption of laminar organisation and synapse formation, the loss of photoreceptor organisation and retinal ganglion cells. Our data demonstrate a unique temporal and spatial expression for laminins and reveal a novel role for laminin γ3 during human retinogenesis.

  5. Ganglion Cell and Displaced Amacrine Cell Density Distribution in the Retina of the Howler Monkey (Alouatta caraya)

    PubMed Central

    Muniz, José Augusto Pereira Carneiro; de Athaide, Luana Modesto; Gomes, Bruno Duarte; Finlay, Barbara L.; Silveira, Luiz Carlos de Lima

    2014-01-01

    Unlike all other New World (platyrrine) monkeys, both male and female howler monkeys (Alouatta sp.) are obligatory trichromats. In all other platyrrines, only females can be trichromats, while males are always dichromats, as determined by multiple behavioral, electrophysiological, and genetic studies. In addition to obligatory trichromacy, Alouatta has an unusual fovea, with substantially higher peak cone density in the foveal pit than every other diurnal anthropoid monkey (both platyrrhines and catarrhines) and great ape yet examined, including humans. In addition to documenting the general organization of the retinal ganglion cell layer in Alouatta, the distribution of cones is compared to retinal ganglion cells, to explore possible relationships between their atypical trichromacy and foveal specialization. The number and distribution of retinal ganglion cells and displaced amacrine cells were determined in six flat-mounted retinas from five Alouatta caraya. Ganglion cell density peaked at 0.5 mm between the fovea and optic nerve head, reaching 40,700–45,200 cells/mm2. Displaced amacrine cell density distribution peaked between 0.5–1.75 mm from the fovea, reaching mean values between 2,050–3,100 cells/mm2. The mean number of ganglion cells was 1,133,000±79,000 cells and the mean number of displaced amacrine cells was 537,000±61,800 cells, in retinas of mean area 641±62 mm2. Ganglion cell and displaced amacrine cell density distribution in the Alouatta retina was consistent with that observed among several species of diurnal Anthropoidea, both platyrrhines and catarrhines. The principal alteration in the Alouatta retina appears not to be in the number of any retinal cell class, but rather a marked gradient in cone density within the fovea, which could potentially support high chromatic acuity in a restricted central region. PMID:25546077

  6. Chronic cervical radiculopathic pain is associated with increased excitability and hyperpolarization-activated current ( Ih) in large-diameter dorsal root ganglion neurons.

    PubMed

    Liu, Da-Lu; Wang, Xu; Chu, Wen-Guang; Lu, Na; Han, Wen-Juan; Du, Yi-Kang; Hu, San-Jue; Bai, Zhan-Tao; Wu, Sheng-Xi; Xie, Rou-Gang; Luo, Ceng

    2017-01-01

    Cervical radiculopathic pain is a very common symptom that may occur with cervical spondylosis. Mechanical allodynia is often associated with cervical radiculopathic pain and is inadequately treated with current therapies. However, the precise mechanisms underlying cervical radiculopathic pain-associated mechanical allodynia have remained elusive. Compelling evidence from animal models suggests a role of large-diameter dorsal root ganglion neurons and plasticity of spinal circuitry attached with Aβ fibers in mediating neuropathic pain. Whether cervical radiculopathic pain condition induces plastic changes of large-diameter dorsal root ganglion neurons and what mechanisms underlie these changes are yet to be known. With combination of patch-clamp recording, immunohistochemical staining, as well as behavioral surveys, we demonstrated that upon chronic compression of C7/8 dorsal root ganglions, large-diameter cervical dorsal root ganglion neurons exhibited frequent spontaneous firing together with hyperexcitability. Quantitative analysis of hyperpolarization-activated cation current ( I h ) revealed that I h was greatly upregulated in large dorsal root ganglion neurons from cervical radiculopathic pain rats. This increased I h was supported by the enhanced expression of hyperpolarization-activated, cyclic nucleotide-modulated channels subunit 3 in large dorsal root ganglion neurons. Blockade of I h with selective antagonist, ZD7288 was able to eliminate the mechanical allodynia associated with cervical radiculopathic pain. This study sheds new light on the functional plasticity of a specific subset of large-diameter dorsal root ganglion neurons and reveals a novel mechanism that could underlie the mechanical allodynia associated with cervical radiculopathy.

  7. Enkephalin-containing neurons in the inferior mesenteric ganglion projecting to the distal colon of cat: evidence from combined retrograde tracing by fluorescent microspheres and immunohistochemistry.

    PubMed

    Bagnol, D; Jule, Y; Kirchner, G; Cupo, A; Roman, C

    1993-02-01

    Retrograde tracing with rhodamine fluorescent microspheres combined with fluorescein immunolabelling of methionine-enkephalin showed the presence of enkephalin-like material in neurons of the inferior mesenteric ganglion (sympathetic prevertebral ganglion) projecting to the distal colon in cat. Two weeks after injecting the microspheres into the wall of the distal colon, the inferior mesenteric ganglion was dissected out and incubated for 24 hours in a colchicine-containing culture medium in order to facilitate the detection of enkephalins in the soma of ganglion neurons. It was observed that retrogradely labelled ganglion cells contained enkephalin-like immunoreactive material. These ganglion cells corresponded to enkephalin-like postganglionic neurons, the terminals of which were located inside the wall of the distal colon. These enkephalin-like neurons were numerous and scattered throughout the ganglion. Sometimes enkephalin-like immunoreactive fibers, probably originating from spinal preganglionic neurons, ran close to immunoreactive and non-immunoreactive retrogradely labelled ganglion cells. This suggests that enkephalin-like immunoreactive fibers may make synaptic connections with enkephalin-like and non-enkephalin-like postganglionic neurons projecting to the distal colon. The present study establishes for the first time the existence of an enkephalin-like postganglionic pathway to the digestive tract originating from a sympathetic prevertebral ganglion. This finding indicates that the enkephalinergic innervation of the cat digestive tract may have at least two possible sources: (i) the sympathetic prevertebral ganglia; and (ii) the enteric nervous ganglia.

  8. Functional interdependence of neurons in a single canine intrinsic cardiac ganglionated plexus

    PubMed Central

    Thompson, G W; Collier, K; Ardell, J L; Kember, G; Armour, J A

    2000-01-01

    To determine the activity characteristics displayed by different subpopulations of neurons in a single intrinsic cardiac ganglionated plexus, the behaviour and co-ordination of activity generated by neurons in two loci of the right atrial ganglionated plexus (RAGP) were evaluated in 16 anaesthetized dogs during basal states as well as in response to increasing inputs from ventricular sensory neurites. These sub-populations of right atrial neurons received afferent inputs from sensory neurites in both ventricles that were responsive to local mechanical stimuli and the nitric oxide donor nitroprusside. Neurons in at least one RAGP locus were activated by epicardial application of veratridine, bradykinin, the β1-adrenoceptor agonist prenaterol or glutamate. Epicardial application of angiotensin II, the selective β2-adrenoceptor agonist terbutaline and selective α-adrenoceptor agonists elicited inconsistent neuronal responses. The activity generated by both populations of atrial neurons studied over 5 min periods during basal states displayed periodic coupled behaviour (cross-correlation coefficients of activities that reached, on average, 0·88 ± 0·03; range 0·71–1) for 15–30 s periods of time. These periods of coupled activity occurred every 30–50 s during basal states, as well as when neuronal activity was enhanced by chemical activation of their ventricular sensory inputs. These results indicate that neurons throughout one intrinsic cardiac ganglionated plexus receive inputs from mechano- and chemosensory neurites located in both ventricles. That such neurons respond to multiple chemical stimuli, including those liberated from adjacent adrenergic efferent nerve terminals, indicates the complexity of the integrative processing of information that occurs within the intrinsic cardiac nervous system. It is proposed that the interdependent activity displayed by populations of neurons in different regions of one intrinsic cardiac ganglionated plexus

  9. Influence of needle position on lumbar segmental nerve root block selectivity.

    PubMed

    Wolff, André P; Groen, Gerbrand J; Wilder-Smith, Oliver H

    2006-01-01

    In patients with chronic low back pain radiating to the leg, segmental nerve root blocks (SNRBs) are performed to predict surgical outcome and identify the putative symptomatic spinal nerve. Epidural spread may lead to false interpretation, affecting clinical decision making. Systematic fluoroscopic analysis of epidural local anesthetic spread and its relationship to needle tip location has not been published to date. Study aims include assessment of epidural local anesthetic spread and its relationship to needle position during fluoroscopy-assisted blocks. Patients scheduled for L4, L5, and S1 blocks were included in this prospective observational study. Under fluoroscopy and electrostimulation, they received 0.5 mL of a mixture containing lidocaine 5 mg and iohexol 75 mg. X-rays with needle tip and contrast were scored for no epidural spread (grade 0), local spread epidurally (grade 1), or to adjacent nerve roots (grade 2). Sixty-five patients were analyzed for epidural spread, 62 for needle position. Grade 1 epidural spread occurred in 47% of L4 and 28% of L5 blocks and grade 2 spread in 3 blocks (5%; L5 n = 1, S1 n = 2). For lumbar blocks, the needle was most frequently found in the lateral upper half of the intervertebral foramen. Epidural spread occurred more frequently with medial needle positions (P = .06). The findings suggest (P = .06) that the risk of grade 1 and 2 lumbar epidural spread, which results in decreased SNRB selectivity, is greater with medial needle positions in the intervertebral foramen. The variability in anatomic position of the dorsal root ganglion necessitates electrostimulation to guide SNRB in addition to fluoroscopy.

  10. Protective effect of oestradiol in the coeliac ganglion against ovarian apoptotic mechanism on dioestrus.

    PubMed

    Cynthia, Bronzi; Cristina, Daneri Becerra; Adriana, Vega Orozco; Belén, Delsouc María; María, Rastrilla Ana; Marilina, Casais; Zulema, Sosa

    2013-05-01

    The aims of this work were to investigate if oestradiol 10(-8)M in the incubation media of either the ovary alone (OV) or the ganglion compartment of an ex vivo coeliac ganglion-superior ovarian nerve-ovary system (a) modifies the release of ovarian progesterone (P4) and oestradiol (E2) on dioestrus II, and (b) modifies the ovarian gene expression of 3β-HSD and 20α-HSD enzymes and markers of apoptosis. The concentration of ovarian P4 release was measured in both experimental schemes, and ovarian P4 and E2 in the ex vivo system by RIA at different times. The expression of 3β-hydroxysteroid dehydrogenase, 20α-hydroxysteroid dehydrogenase and antiapoptotic bcl-2 and proapoptotic bax by RT-PCR were determined. E2 added in the coeliac ganglion caused an increase in the ovarian release of the P4, E2 and 3β-HSD, while in the ovary incubation alone it decreased P4 and 3β-HSD but increased and 20α-HSD and bax/bcl-2 ratio. It is concluded that through a direct effect on the ovary, E2 promotes luteal regression in DII rats, but the addition of E2 in the coeliac ganglion does not have the same effect. The peripheral nervous system, through the superior ovarian nerve, has a protective effect against the apoptotic mechanism on DII. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. [Effects on survival of shRNA mediated APE/Ref1 gene silencing in rat spiral ganglion cells in oxidative stress].

    PubMed

    Jiang, Zhendong; Zhong, Cheng; Li, Taijun; Xiang, Zhaolan; Zhang, Xueyuan

    2014-02-01

    To investigate the effects of reducing APE/Ref1 expression in the cultures of rat spiral ganglion cells with oxidative damage induced by H(2)O(2). Primary cultured rat spiral ganglion cells were infected with small interfering RNA to APE/Ref1 (Ape1siRNA) for 72 h, followed by treating with H(2)O(2) (0, 10, 25, 50, 100 and 300 µmol/L) for 1 h , and then cultured in normal medium for 24 h. Western blot were used to detect the level of APE/Ref1 protein and phosphorylation of histone protein H2AX in the infected cells. The caspase3 activation was tested by spectrophotometric method . The cell viability was determined by MTT and the apoptosis of spiral ganglion cells was determined by terminal-deoxynucleotidyl transferase mediated nick and labeling (TUNEL). Western blot showed that infection with Ape1siRNA resulted in APE/Ref1 reduced expression in the spiral ganglion cells. Exposing spiral ganglion cultures with reduced expression of APE/Ref1 to H(2)O(2) (50, 100, 300 µmol/L) for 1 h resulted in increasing in the phosphorylation of histone protein H2AX. The reduction in APE/Ref1 significantly reduced cell viability in cultures 24 h after 1 h expression to 50-300 µmol/L H(2)O(2). The apoptosis of cells and caspase 3 activity was detected significantly improved. The induced of APE/Ref1 results in significantly decrease in spiral ganglion cells viability in oxidative stress. The repairing function of APE/Ref1 is necessary for optimal levels of neuronal rat spiral ganglion cells survival.

  12. Melatonin potentiates glycine currents through a PLC/PKC signalling pathway in rat retinal ganglion cells.

    PubMed

    Zhao, Wen-Jie; Zhang, Min; Miao, Yanying; Yang, Xiong-Li; Wang, Zhongfeng

    2010-07-15

    In vertebrate retina, melatonin regulates various physiological functions. In this work we investigated the mechanisms underlying melatonin-induced potentiation of glycine currents in rat retinal ganglion cells (RGCs). Immunofluorescence double labelling showed that rat RGCs were solely immunoreactive to melatonin MT(2) receptors. Melatonin potentiated glycine currents of RGCs, which was reversed by the MT(2) receptor antagonist 4-P-PDOT. The melatonin effect was blocked by intracellular dialysis of GDP-beta-S. Either preincubation with pertussis toxin or application of the phosphatidylcholine (PC)-specific phospholipase C (PLC) inhibitor D609, but not the phosphatidylinositol (PI)-PLC inhibitor U73122, blocked the melatonin effect. The protein kinase C (PKC) activator PMA potentiated the glycine currents and in the presence of PMA melatonin failed to cause further potentiation of the currents, whereas application of the PKC inhibitor bisindolylmaleimide IV abolished the melatonin-induced potentiation. The melatonin effect persisted when [Ca(2+)](i) was chelated by BAPTA, and melatonin induced no increase in [Ca(2+)](i). Neither cAMP-PKA nor cGMP-PKG signalling pathways seemed to be involved because 8-Br-cAMP or 8-Br-cGMP failed to cause potentiation of the glycine currents and both the PKA inhibitor H-89 and the PKG inhibitor KT5823 did not block the melatonin-induced potentiation. In consequence, a distinct PC-PLC/PKC signalling pathway, following the activation of G(i/o)-coupled MT(2) receptors, is most likely responsible for the melatonin-induced potentiation of glycine currents of rat RGCs. Furthermore, in rat retinal slices melatonin potentiated light-evoked glycine receptor-mediated inhibitory postsynaptic currents in RGCs. These results suggest that melatonin, being at higher levels at night, may help animals to detect positive or negative contrast in night vision by modulating inhibitory signals largely mediated by glycinergic amacrine cells in the inner

  13. Melatonin potentiates glycine currents through a PLC/PKC signalling pathway in rat retinal ganglion cells

    PubMed Central

    Zhao, Wen-Jie; Zhang, Min; Miao, Yanying; Yang, Xiong-Li; Wang, Zhongfeng

    2010-01-01

    In vertebrate retina, melatonin regulates various physiological functions. In this work we investigated the mechanisms underlying melatonin-induced potentiation of glycine currents in rat retinal ganglion cells (RGCs). Immunofluorescence double labelling showed that rat RGCs were solely immunoreactive to melatonin MT2 receptors. Melatonin potentiated glycine currents of RGCs, which was reversed by the MT2 receptor antagonist 4-P-PDOT. The melatonin effect was blocked by intracellular dialysis of GDP-β-S. Either preincubation with pertussis toxin or application of the phosphatidylcholine (PC)-specific phospholipase C (PLC) inhibitor D609, but not the phosphatidylinositol (PI)-PLC inhibitor U73122, blocked the melatonin effect. The protein kinase C (PKC) activator PMA potentiated the glycine currents and in the presence of PMA melatonin failed to cause further potentiation of the currents, whereas application of the PKC inhibitor bisindolylmaleimide IV abolished the melatonin-induced potentiation. The melatonin effect persisted when [Ca2+]i was chelated by BAPTA, and melatonin induced no increase in [Ca2+]i. Neither cAMP-PKA nor cGMP-PKG signalling pathways seemed to be involved because 8-Br-cAMP or 8-Br-cGMP failed to cause potentiation of the glycine currents and both the PKA inhibitor H-89 and the PKG inhibitor KT5823 did not block the melatonin-induced potentiation. In consequence, a distinct PC-PLC/PKC signalling pathway, following the activation of Gi/o-coupled MT2 receptors, is most likely responsible for the melatonin-induced potentiation of glycine currents of rat RGCs. Furthermore, in rat retinal slices melatonin potentiated light-evoked glycine receptor-mediated inhibitory postsynaptic currents in RGCs. These results suggest that melatonin, being at higher levels at night, may help animals to detect positive or negative contrast in night vision by modulating inhibitory signals largely mediated by glycinergic amacrine cells in the inner retina. PMID

  14. Intracochlear electrical stimulation suppresses apoptotic signaling in rat spiral ganglion neurons after deafening in vivo.

    PubMed

    Kopelovich, Jonathan C; Cagaanan, Alain P; Miller, Charles A; Abbas, Paul J; Green, Steven H

    2013-11-01

    To establish the intracellular consequences of electrical stimulation to spiral ganglion neurons after deafferentation. Here we use a rat model to determine the effect of both low and high pulse rate acute electrical stimulation on activation of the proapoptotic transcription factor Jun in deafferented spiral ganglion neurons in vivo. Experimental animal study. Hearing research laboratories of the University of Iowa Departments of Biology and Otolaryngology. A single electrode was implanted through the round window of kanamycin-deafened rats at either postnatal day 32 (P32, n = 24) or P60 (n = 22) for 4 hours of stimulation (monopolar, biphasic pulses, amplitude twice electrically evoked auditory brainstem response [eABR] threshold) at either 100 or 5000 Hz. Jun phosphorylation was assayed by immunofluorescence to quantitatively assess the effect of electrical stimulation on proapoptotic signaling. Jun phosphorylation was reliably suppressed by 100 Hz stimuli in deafened cochleae of P32 but not P60 rats. This effect was not significant in the basal cochlear turns. Stimulation frequency may be consequential: 100 Hz was significantly more effective than was 5 kHz stimulation in suppressing phospho-Jun. Suppression of Jun phosphorylation occurs in deafferented spiral ganglion neurons after only 4 hours of electrical stimulation. This finding is consistent with the hypothesis that electrical stimulation can decrease spiral ganglion neuron death after deafferentation.

  15. Biofunctionalized peptide-based hydrogels provide permissive scaffolds to attract neurite outgrowth from spiral ganglion neurons.

    PubMed

    Frick, Claudia; Müller, Marcus; Wank, Ute; Tropitzsch, Anke; Kramer, Benedikt; Senn, Pascal; Rask-Andersen, Helge; Wiesmüller, Karl-Heinz; Löwenheim, Hubert

    2017-01-01

    Cochlear implants (CI) allow for hearing rehabilitation in patients with sensorineural hearing loss or deafness. Restricted CI performance results from the spatial gap between spiral ganglion neurons and the CI, causing current spread that limits spatially restricted stimulation and impairs frequency resolution. This may be substantially improved by guiding peripheral processes of spiral ganglion neurons towards and onto the CI electrode contacts. An injectable, peptide-based hydrogel was developed which may provide a permissive scaffold to facilitate neurite growth towards the CI. To test hydrogel capacity to attract spiral ganglion neurites, neurite outgrowth was quantified in an in vitro model using a custom-designed hydrogel scaffold and PuraMatrix ® . Neurite attachment to native hydrogels is poor, but significantly improved by incorporation of brain-derived neurotrophic factor (BDNF), covalent coupling of the bioactive laminin epitope IKVAV and the incorporation a full length laminin to hydrogel scaffolds. Incorporation of full length laminin protein into a novel custom-designed biofunctionalized hydrogel (IKVAV-GGG-SIINFEKL) allows for neurite outgrowth into the hydrogel scaffold. The study demonstrates that peptide-based hydrogels can be specifically biofunctionalized to provide a permissive scaffold to attract neurite outgrowth from spiral ganglion neurons. Such biomaterials appear suitable to bridge the spatial gap between neurons and the CI. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. A novel model for rapid induction of apoptosis in spiral ganglions of mice.

    PubMed

    Lee, Ji Eun; Nakagawa, Takayuki; Kim, Tae Soo; Iguchi, Fukuichiro; Endo, Tsuyoshi; Dong, Youyi; Yuki, Kazuo; Naito, Yasushi; Lee, Sang Heun; Ito, Juichi

    2003-06-01

    The survival of the spiral ganglion (SG) is a critical issue in preservation of hearing. Research on topics related to this issue requires a mouse experimental model because such a model has advantages including use of genetic information and knockout or "knockin" mice. Thus, the aim of the study was to establish a mouse model for induction of apoptosis of SG neurons with a definite time course. Laboratory study using experimental animals. C57BL/6 mice were used as experimental animals and were subjected to direct application of cisplatin into the inner ear. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and immunostaining for Neurofilament 200-kD (NF) and peripherin were used for analysis of SG degeneration. In addition, generation of peroxynitrite in affected spiral ganglions was examined by immunostaining for nitrotyrosine. Cellular location of activated caspase-9 and cytochrome-c in dying SG neurons were examined for analysis of cell death pathway. The TUNEL assay and immunohistochemical analysis for NF and peripherin indicated that type I neurons in spiral ganglions were deleted through the apoptotic pathway over time. Spiral ganglion neurons treated with cisplatin exhibited expression of nitrotyrosine, indicating induction of peroxynitrite by cisplatin. In dying SG neurons, expression of activated caspase-9 and translocation of cytochrome-c from mitochondria to cytoplasm were observed, indicating the mitochondrial pathway of apoptosis. The predictable fashion of induction of apoptosis in SG neurons over a well-defined time course in the model in the study will aid studies of the molecular mechanism of cell death and elucidation of a strategy for prevention of SG degeneration.

  17. Immediate Nerve Transfer for Treatment of Peroneal Nerve Palsy Secondary to an Intraneural Ganglion: Case Report and Review.

    PubMed

    Ratanshi, Imran; Clark, Tod A; Giuffre, Jennifer L

    2018-05-01

    Intraneural ganglion cysts, which occur within the common peroneal nerve, are a rare cause of foot drop. The current standard of treatment for intraneural ganglion cysts involving the common peroneal nerve involves (1) cyst decompression and (2) ligation of the articular nerve branch to prevent recurrence. Nerve transfers are a time-dependent strategy for recovering ankle dorsiflexion in cases of high peroneal nerve palsy; however, this modality has not been performed for intraneural ganglion cysts involving the common peroneal nerve. We present a case of common peroneal nerve palsy secondary to an intraneural ganglion cyst occurring in a 74-year-old female. The patient presented with a 5-month history of pain in the right common peroneal nerve distribution and foot drop. The patient underwent simultaneous cyst decompression, articular nerve branch ligation, and nerve transfer of the motor branch to flexor hallucis longus to a motor branch of anterior tibialis muscle. At final follow-up, the patient demonstrated complete (M4+) return of ankle dorsiflexion, no pain, no evidence of recurrence and was able to bear weight without the need for orthotic support. Given the minimal donor site morbidity and recovery of ankle dorsiflexion, this report underscores the importance of considering early nerve transfers in cases of high peroneal neuropathy due to an intraneural ganglion cyst.

  18. Sodium channel diversity in the vestibular ganglion: NaV1.5, NaV1.8, and tetrodotoxin-sensitive currents

    PubMed Central

    2016-01-01

    Firing patterns differ between subpopulations of vestibular primary afferent neurons. The role of sodium (NaV) channels in this diversity has not been investigated because NaV currents in rodent vestibular ganglion neurons (VGNs) were reported to be homogeneous, with the voltage dependence and tetrodotoxin (TTX) sensitivity of most neuronal NaV channels. RT-PCR experiments, however, indicated expression of diverse NaV channel subunits in the vestibular ganglion, motivating a closer look. Whole cell recordings from acutely dissociated postnatal VGNs confirmed that nearly all neurons expressed NaV currents that are TTX-sensitive and have activation midpoints between −30 and −40 mV. In addition, however, many VGNs expressed one of two other NaV currents. Some VGNs had a small current with properties consistent with NaV1.5 channels: low TTX sensitivity, sensitivity to divalent cation block, and a relatively negative voltage range, and some VGNs showed NaV1.5-like immunoreactivity. Other VGNs had a current with the properties of NaV1.8 channels: high TTX resistance, slow time course, and a relatively depolarized voltage range. In two NaV1.8 reporter lines, subsets of VGNs were labeled. VGNs with NaV1.8-like TTX-resistant current also differed from other VGNs in the voltage dependence of their TTX-sensitive currents and in the voltage threshold for spiking and action potential shape. Regulated expression of NaV channels in primary afferent neurons is likely to selectively affect firing properties that contribute to the encoding of vestibular stimuli. PMID:26936982

  19. The morphology and classification of α ganglion cells in the rat retinae: a fractal analysis study.

    PubMed

    Jelinek, Herbert F; Ristanović, Dušan; Milošević, Nebojša T

    2011-09-30

    Rat retinal ganglion cells have been proposed to consist of a varying number of subtypes. Dendritic morphology is an essential aspect of classification and a necessary step toward understanding structure-function relationships of retinal ganglion cells. This study aimed at using a heuristic classification procedure in combination with the box-counting analysis to classify the alpha ganglion cells in the rat retinae based on the dendritic branching pattern and to investigate morphological changes with retinal eccentricity. The cells could be divided into two groups: cells with simple dendritic pattern (box dimension lower than 1.390) and cells with complex dendritic pattern (box dimension higher than 1.390) according to their dendritic branching pattern complexity. Both were further divided into two subtypes due to the stratification within the inner plexiform layer. In the present study we have shown that the alpha rat RCGs can be classified further by their dendritic branching complexity and thus extend those of previous reports that fractal analysis can be successfully used in neuronal classification, particularly that the fractal dimension represents a robust and sensitive tool for the classification of retinal ganglion cells. A hypothesis of possible functional significance of our classification scheme is also discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Effects of nano red elemental selenium on sodium currents in rat dorsal root ganglion neurons.

    PubMed

    Yuan, Huijun; Lin, Jiarui; Lan, Tonghan

    2006-01-01

    Nano red elemental selenium (Nano-Se), was demonstrated to be useful in medical and scientific researches. Here, we investigated the effects of Nano-Se on sodium currents on rat dorsal root ganglion neurons (DRG), using the whole-cell patch clamp method. Nano-Se reversibly decrease the I(Na)(TTX-S) in a concentration-dependent, time-dependent and open-channel block manners without affecting I(Na)(TTX-R). It shifted the steady-state activation and inactivation curves for I(Na) to more negative potentials. In the research of recovery from inactivation, the recovery time constant is longer in the present of Nano-Se. Nano-Se had a weaker inhibitory effect on I(Na), compared with marked decrease caused by selenite which indicated that Nano-Se is less neurotoxic than selenite in short-term/large dose treatments and had similar bio availability to sodium selenite. The results of interaction between the effects of Nano-Se and selenite on sodium currents indicated a negative allosteric interaction between the selenite binding site and the Nano-Se binding site or that they have the same competitive binding site.

  1. Nitrergic nerves derived from the pterygopalatine ganglion innervate arteries irrigating the cerebrum but not the cerebellum and brain stem in monkeys.

    PubMed

    Ayajiki, Kazuhide; Kobuchi, Shuhei; Tawa, Masashi; Okamura, Tomio

    2012-01-01

    The functional roles of the nitrergic nerves innervating the monkey cerebral artery were evaluated in a tension-response study examining isolated arteries in vitro and cerebral angiography in vivo. Nicotine produced relaxation of arteries by stimulation of nerve terminals innervating isolated monkey arteries irrigating the cerebrum, cerebellum and brain stem. Relaxation of arteries induced by nicotine was abolished by treatment with N(G)-nitro-L-arginine, a nitric oxide synthase inhibitor, and was restored by addition of L-arginine. Cerebral angiography showed that electrical stimulation of the unilateral greater petrosal nerve, which connects to the pterygopalatine ganglion via the parasympathetic ganglion synapse, produced vasodilatation of the anterior, middle and posterior cerebral arteries in the stimulated side. However, stimulation failed to produce vasodilatation of the superior and anterior-inferior cerebellar arteries and the basilar artery in anesthetized monkeys. Therefore, nitrergic nerves derived from the pterygopalatine ganglion appear to regulate cerebral vasomotor function. In contrast, circulation in the cerebellum and brain stem might be regulated by nitrergic nerves originating not from the pterygopalatine ganglion, but rather from an unknown ganglion (or ganglia).

  2. Neuroprotection by GH against excitotoxic-induced cell death in retinal ganglion cells.

    PubMed

    Martínez-Moreno, Carlos G; Ávila-Mendoza, José; Wu, Yilun; Arellanes-Licea, Elvira Del Carmen; Louie, Marcela; Luna, Maricela; Arámburo, Carlos; Harvey, Steve

    2016-08-01

    Retinal growth hormone (GH) has been shown to promote cell survival in retinal ganglion cells (RGCs) during developmental waves of apoptosis during chicken embryonic development. The possibility that it might also against excitotoxicity-induced cell death was therefore examined in the present study, which utilized quail-derived QNR/D cells as an in vitro RGC model. QNR/D cell death was induced by glutamate in the presence of BSO (buthionine sulfoxamide) (an enhancer of oxidative stress), but this was significantly reduced (P<0.01) in the presence of exogenous recombinant chicken GH (rcGH). Similarly, QNR/D cells that had been prior transfected with a GH plasmid to overexpress secreted and non-secreted GH. This treatment reduced the number of TUNEL-labeled cells and blocked their release of lactate dehydrogenase (LDH). In a further experiment with dissected neuroretinal explants from ED (embryonic day) 10 embryos, rcGH treatment of the explants also reduced (P<0.01) the number of glutamate-BSO-induced apoptotic cells and blocked the explant release of LDH. This neuroprotective action was likely mediated by increased STAT5 phosphorylation and increased bcl-2 production, as induced by exogenous rcGH treatment and the media from GH-overexpressing QNR/D cells. As rcGH treatment and GH-overexpression cells also increased the content of IGF-1 and IGF-1 mRNA this neuroprotective action of GH is likely to be mediated, at least partially, through an IGF-1 mechanism. This possibility is supported by the fact that the siRNA knockdown of GH or IGF-1 significantly reduced QNR/D cell viability, as did the immunoneutralization of IGF-1. GH is therefore neuroprotective against excitotoxicity-induced RGC cell death by anti-apoptotic actions involving IGF-1 stimulation. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Effects of cholinergic drugs on receptive field properties of rabbit retinal ganglion cells

    PubMed Central

    Ariel, M.; Daw, N. W.

    1982-01-01

    1. Retinal ganglion cells were recorded extracellularly from the rabbit's eye in situ to study the effects of cholinergic drugs on receptive field properties. Physostigmine, an acetylcholinesterase inhibitor, and nicotine increased the spontaneous activity of nearly all retinal ganglion cell types. The effectiveness of physostigmine was roughly correlated with the neurone's inherent level of spontaneous activity. Brisk cells, having high rates of spontaneous firing, showed large increases in their maintained discharge, whereas sluggish cells, with few or no spontaneous spikes, showed small and sometimes transient increases in spontaneous activity during physostigmine. 2. The sensitivity of ganglion cells to spots of optimal size and position did not change substantially during the infusion of physostigmine. However, the responsiveness to light (number of spikes per stimulus above the spontaneous level) increased. This effect occurred with sluggish and more complex cells, rarely with brisk cells. 3. Another effect of physostigmine on sluggish and more complex cells was to make these cells `on—off'. The additional response to the inappropriate change in contrast had a long latency and lacked an initial transient burst. 4. Complex receptive field properties such as orientation sensitivity, radial grating inhibition, speed tuning and size specificity were also examined. These inhibitory properties were still present during infusion of physostigmine and, in most cases, the trigger feature of each cell type remained. 5. These results are consistent with pharmacological results on ACh release from the retina. There appear to be two types of release of ACh, having their most powerful influences on separate classes of cells. One release (transient), occurs at light onset and offset and acts primarily on sluggish and more complex ganglion cells; the other release (tonic) is not light-modulated and acts primarily on brisk cells. A wiring diagram for the ACh cells is

  4. Distinguishing ischaemic optic neuropathy from optic neuritis by ganglion cell analysis.

    PubMed

    Erlich-Malona, Natalie; Mendoza-Santiesteban, Carlos E; Hedges, Thomas R; Patel, Nimesh; Monaco, Caitlin; Cole, Emily

    2016-12-01

    To determine whether a pattern of altitudinal ganglion cell loss, as detected and measured by optical coherence tomography (OCT), can be used to distinguish non-arteritic ischaemic optic neuropathy (NAION) from optic neuritis (ON) during the acute phase, and whether the rate or severity of ganglion cell loss differs between the two diseases. We performed a retrospective, case-control study of 44 patients (50 eyes) with ON or NAION and 44 age-matched controls. Non-arteritic ischaemic optic neuropathy and ON patients had OCT at presentation and four consecutive follow-up visits. Controls had OCT at one point in time. The ganglion cell complex (GCC) was evaluated in the macula, and the retinal nerve fibre layer (RNFL) was evaluated in the peripapillary region. Ganglion cell complex thickness, RNFL thickness and GCC mean superior and inferior hemispheric difference were compared between NAION and ON patients at each time-point using unpaired t-tests and between disease and control subjects at first measurement using paired t-tests. Mean time from onset of symptoms to initial presentation was 10.7 ± 6.6 days in NAION and 11.7 ± 8.6 days in ON (p = 0.67). There was a significantly greater vertical hemispheric difference in GCC thickness in NAION patients than ON patients at all time-points (5.5-10.7 μm versus 3.1-3.6 μm, p = 0.01-0.049). Mean GCC thickness was significantly decreased at less than 2 weeks after onset in NAION compared to age-matched controls (72.1 μm versus 82.1 μm, p < 0.001), as well as in ON compared to age-matched controls (74.3 μm versus 84.5 μm, p < 0.001). Progression and severity of GCC and RNFL loss did not differ significantly between NAION and ON. A quantitative comparison of mean superior and inferior hemispheric GCC thickness with OCT may be used to distinguish NAION from ON. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  5. Ganglion Cell Loss and Age-Related Visual Loss: A Cortical Pooling Analysis

    PubMed Central

    SCHMIDT, LAURA A.; LY-SCHROEDER, EMILY; SWANSON, WILLIAM H.

    2006-01-01

    Purpose To evaluate the ability of the cortical pooling model to predict the effects of random, mild ganglion cell loss, we compared the predictions of the model with the age-related loss and variability in achromatic and chromatic contrast sensitivity. Methods The relative sensitivity to small (0.5°) and large (3.0°) stimuli was compared in older (mean = 67 years, n = 27) and younger (mean = 23 years, n = 32) adults. Contrast sensitivity for modulations along the luminance, equiluminant L-cone, and equiluminant S-cone axes was assessed at the fovea and at four peripheral locations (12°). Results When the stimuli were large, threshold measurements obtained from all participants were reliable and well within the range of modulations along the chromatic axes that could be produced by the phosphors of the CRT. For the large stimuli, neither long- nor short-term variability increased as a function of age. Increasing the size of the stimulus did not decrease the magnitude of the age-related losses when the stimulus was chromatic, and visual losses observed with large chromatic stimuli were not different from those obtained with small achromatic stimuli. Moreover, chromatic contrast sensitivity assessments identified significant visual losses in four individuals who were not identified by achromatic contrast sensitivity assessments and only missed identifying one individual with significant losses in achromatic contrast sensitivity. Conclusions The declines in achromatic and chromatic sensitivity as a function of age (0.4 – 0.7 dB per decade) were similar to those obtained in previous studies of achromatic and chromatic perimetry and are consistent with the loss of retinal ganglion cells reported in histologic studies. The results of this study are consistent with the predictions the cortical pooling model makes for both variability and contrast sensitivity. These findings emphasize that selective visual impairments do not necessarily reflect preferential damage to

  6. Spatial segregation of adaptation and predictive sensitization in retinal ganglion cells

    PubMed Central

    Kastner, David B.; Baccus, Stephen A.

    2014-01-01

    Sensory systems change their sensitivity based upon recent stimuli to adjust their response range to the range of inputs, and to predict future sensory input. Here we report the presence of retinal ganglion cells that have antagonistic plasticity, showing central adaptation and peripheral sensitization. Ganglion cell responses were captured by a spatiotemporal model with independently adapting excitatory and inhibitory subunits, and sensitization requires GABAergic inhibition. Using a simple theory of signal detection we show that the sensitizing surround conforms to an optimal inference model that continually updates the prior signal probability. This indicates that small receptive field regions have dual functionality—to adapt to the local range of signals, but sensitize based upon the probability of the presence of that signal. Within this framework, we show that sensitization predicts the location of a nearby object, revealing prediction as a new functional role for adapting inhibition in the nervous system. PMID:23932000

  7. Four alpha ganglion cell types in mouse retina: Function, structure, and molecular signatures

    PubMed Central

    Sanes, Joshua R.

    2017-01-01

    The retina communicates with the brain using ≥30 parallel channels, each carried by axons of distinct types of retinal ganglion cells. In every mammalian retina one finds so-called "alpha" ganglion cells (αRGCs), identified by their large cell bodies, stout axons, wide and mono-stratified dendritic fields, and high levels of neurofilament protein. In the mouse, three αRGC types have been described based on responses to light steps: On-sustained, Off-sustained, and Off-transient. Here we employed a transgenic mouse line that labels αRGCs in the live retina, allowing systematic targeted recordings. We characterize the three known types and identify a fourth, with On-transient responses. All four αRGC types share basic aspects of visual signaling, including a large receptive field center, a weak antagonistic surround, and absence of any direction selectivity. They also share a distinctive waveform of the action potential, faster than that of other RGC types. Morphologically, they differ in the level of dendritic stratification within the IPL, which accounts for their response properties. Molecularly, each type has a distinct signature. A comparison across mammals suggests a common theme, in which four large-bodied ganglion cell types split the visual signal into four channels arranged symmetrically with respect to polarity and kinetics. PMID:28753612

  8. The role of RIP3 mediated necroptosis in ouabain-induced spiral ganglion neurons injuries.

    PubMed

    Wang, Xi; Wang, Ye; Ding, Zhong-jia; Yue, Bo; Zhang, Peng-zhi; Chen, Xiao-dong; Chen, Xin; Chen, Jun; Chen, Fu-quan; Chen, Yang; Wang, Ren-feng; Mi, Wen-juan; Lin, Ying; Wang, Jie; Qiu, Jian-hua

    2014-08-22

    Spiral ganglion neuron (SGN) injury is a generally accepted precursor of auditory neuropathy. Receptor-interacting protein 3 (RIP3) has been reported as an important necroptosis pathway mediator that can be blocked by necrostatin-1 (Nec-1). In our study, we sought to identify whether necroptosis participated in SGN injury. Ouabain was applied to establish an SGN injury model. We measured the auditory brain-stem response (ABR) threshold shift as an indicator of the auditory conditions. Positive β3-tubulin immunofluorescence staining indicated the surviving SGNs. RIP3 expression was evaluated using immunofluorescence, quantitative real-time polymerase chain reaction and western blot. SGN injury promoted an increase in RIP3 expression that could be suppressed by application of the necroptosis inhibitor Nec-1. A decreased ABR threshold shift and increased SGN density were observed when Nec-1 was administered with apoptosis inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD). These results demonstrated that necroptosis is an indispensable pathway separately from apoptosis leading to SGN death pathway, in which RIP3 plays an important role. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Strychnine, but not PMBA, inhibits neuronal nicotinic acetylcholine receptors expressed by rabbit retinal ganglion cells.

    PubMed

    Renna, J M; Strang, C E; Amthor, F R; Keyser, K T

    2007-01-01

    Strychnine is considered a selective competitive antagonist of glycine gated Cl- channels (Saitoh et al., 1994) and studies have used strychnine at low micromolar concentrations to study the role of glycine in rabbit retina (Linn, 1998; Protti et al., 2005). However, other studies have shown that strychnine, in the concentrations commonly used, is also a potent competitive antagonist of alpha7 nicotinic acetylcholine receptors (nAChRs; Matsubayashi et al., 1998). We tested the effects of low micromolar concentrations of strychnine and 3-[2'-phosphonomethyl[1,1'-biphenyl]-3-yl] alanine (PMBA), a specific glycine receptor blocker (Saitoh et al., 1994; Hosie et al., 1999) on the activation of both alpha7 nAChRs on retinal ganglion cells and on ganglion cell responses to a light flash. Extracellular recordings were obtained from ganglion cells in an isolated retina/choroid preparation and 500 microM choline was used as an alpha7 agonist (Alkondon et al., 1997). We recorded from brisk sustained and brisk transient OFF cells, many of which have been previously shown to have alpha7 receptors (Strang et al., 2005). Further, we tested the effect of strychnine, PMBA and alpha-bungarotoxin on the binding of tetramethylrhodamine alpha-bungarotoxin in the inner plexiform layer. Our data indicates that strychnine, at doses as low as 1.0 microM, can inhibit the alpha7 nAChR-mediated response to choline, but PMBA at concentrations as high as 0.4 microM does not. Binding studies show strychnine and alpha-bungarotoxin inhibit binding of labeled alpha-bungarotoxin in the IPL. Thus, the effects of strychnine application may be to inhibit glycine receptors expressed by ganglion cell or to inhibit amacrine cell alpha7 nAChRs, both of which would result in an increase in the ganglion cell responses. Further research will be required to disentangle the effects of strychnine previously believed to be caused by a single mechanism of glycine receptor inhibition.

  10. Crocin prevents retinal ischaemia/reperfusion injury-induced apoptosis in retinal ganglion cells through the PI3K/AKT signalling pathway.

    PubMed

    Qi, Yun; Chen, Li; Zhang, Lei; Liu, Wen-Bo; Chen, Xiao-Yan; Yang, Xin-Guang

    2013-02-01

    Crocin is a pharmacologically active component of Crocus sativus L. (saffron) and has been reported to be useful in the treatment of neuronal damage. In the present study, we investigated the neuroprotective effect of crocin on retinal ganglion cells (RGCs) after retinal ischaemia/reperfusion (IR) injury, and our results show that crocin acts through the PI3K/AKT signalling pathway. Retinal IR injury was induced by raising the intraocular pressure of Sprague-Dawley rats to 110 mmHg for 60 min. The neuroprotective effect of crocin was determined by quantifying the surviving RGCs and apoptotic RGCs following IR injury by means of retrograde labelling and TUNEL staining, respectively. The phosphorylated AKT protein level was determined by western blot and immunohistochemical analysis. To determine the extent to which the PI3K/AKT pathway contributes to the neuroprotective effect of crocin, experiments were also performed using the PI3K inhibitor LY294002. Compared with the IR + vehicle group, crocin (50 mg/kg) treatment enhanced RGC survival by approximately 36% and decreased RGC apoptosis by 44% after retinal IR injury. Western blot and immunohistochemical analysis demonstrated that the PI3K/AKT pathway was activated by crocin in the ganglion cell layer after retinal IR injury. Intravitreal injection of LY294002 blocked the neuroprotective effect of crocin on IR-induced RGC death. In conclusion, crocin prevents retinal IR-induced apoptosis of RGCs by activating the PI3K/AKT signalling pathway. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Nervus terminalis ganglion of the bonnethead shark (Sphyrna tiburo): evidence for cholinergic and catecholaminergic influence on two cell types distinguished by peptide immunocytochemistry.

    PubMed

    White, J; Meredith, M

    1995-01-16

    The nervus terminalis is a ganglionated vertebrate cranial nerve of unknown function that connects the brain and the peripheral nasal structures. To investigate its function, we have studied nervus terminalis ganglion morphology and physiology in the bonnethead shark (Sphyrna tiburo), where the nerve is particularly prominent. Immunocytochemistry for gonadotropin-releasing hormone (GnRH) and Leu-Pro-Leu-Arg-Phe-NH2 (LPLRFamide) revealed two distinct populations of cells. Both were acetylcholinesterase positive, but LPLR-Famide-immunoreactive cells consistently stained more darkly for acetylcholinesterase activity. Tyrosine hydroxylase immunocytochemistry revealed fibers and terminal-like puncta in the ganglion, primarily in areas containing GnRH-immunoreactive cells. Consistent with the anatomy, in vitro electrophysiological recordings provided evidence for cholinergic and catecholaminergic actions. In extracellular recordings, acetylcholine had a variable effect on baseline ganglion cell activity, whereas norepinephrine consistently reduced activity. Electrical stimulation of the nerve trunks suppressed ganglion activity, as did impulses from the brain in vivo. During electrical suppression, acetylcholine consistently increased activity, and norepinephrine decreased activity. Muscarinic and, to a lesser extent, alpha-adrenergic antagonists both increased activity during the electrical suppression, suggesting involvement of both systems. Intracellular recordings revealed two types of ganglion cells that were distinguishable pharmacologically and physiologically. Some cells were hyperpolarized by cholinergic agonists and unaffected by norepinephrine; these cells did not depolarize with peripheral nerve trunk stimulation. Another group of cells did depolarize with peripheral trunk stimulation; a representative of this group was depolarized by carbachol and hyperpolarized by norepinephrine. These and other data suggest that the bonnethead nervus terminalis ganglion

  12. Effect of Tissue Heterogeneity on the Transmembrane Potential of Type-1 Spiral Ganglion Neurons: A Simulation Study.

    PubMed

    Sriperumbudur, Kiran Kumar; Pau, Hans Wilhelm; van Rienen, Ursula

    2018-03-01

    Electric stimulation of the auditory nerve by cochlear implants has been a successful clinical intervention to treat the sensory neural deafness. In this pathological condition of the cochlea, type-1 spiral ganglion neurons in Rosenthal's canal play a vital role in the action potential initiation. Various morphological studies of the human temporal bones suggest that the spiral ganglion neurons are surrounded by heterogeneous structures formed by a variety of cells and tissues. However, the existing simulation models have not considered the tissue heterogeneity in the Rosenthal's canal while studying the electric field interaction with spiral ganglion neurons. Unlike the existing models, we have implemented the tissue heterogeneity in the Rosenthal's canal using a computationally inexpensive image based method in a two-dimensional finite element model. Our simulation results suggest that the spatial heterogeneity of surrounding tissues influences the electric field distribution in the Rosenthal's canal, and thereby alters the transmembrane potential of the spiral ganglion neurons. In addition to the academic interest, these results are especially useful to understand how the latest tissue regeneration methods such as gene therapy and drug-induced resprouting of peripheral axons, which probably modify the density of the tissues in the Rosenthal's canal, affect the cochlear implant functionality.

  13. The Effect of Transcutaneous Electrical Nerve Stimulation of Sympathetic Ganglions and Acupuncture Points on Distal Blood Flow.

    PubMed

    Kamali, Fahimeh; Mirkhani, Hossein; Nematollahi, Ahmadreza; Heidari, Saeed; Moosavi, Elahesadat; Mohamadi, Marzieh

    2017-04-01

    Transcutaneous electrical nerve stimulation (TENS) is a widely-practiced method to increase blood flow in clinical practice. The best location for stimulation to achieve optimal blood flow has not yet been determined. We compared the effect of TENS application at sympathetic ganglions and acupuncture points on blood flow in the foot of healthy individuals. Seventy-five healthy individuals were randomly assigned to three groups. The first group received cutaneous electrical stimulation at the thoracolumbar sympathetic ganglions. The second group received stimulation at acupuncture points. The third group received stimulation in the mid-calf area as a control group. Blood flow was recorded at time zero as baseline and every 3 minutes after baseline during stimulation, with a laser Doppler flow-meter. Individuals who received sympathetic ganglion stimulation showed significantly greater blood flow than those receiving acupuncture point stimulation or those in the control group (p<0.001). Data analysis revealed that blood flow at different times during stimulation increased significantly from time zero in each group. Therefore, the application of low-frequency TENS at the thoracolumbar sympathetic ganglions was more effective in increasing peripheral blood circulation than stimulation at acupuncture points. Copyright © 2017 Medical Association of Pharmacopuncture Institute. Published by Elsevier B.V. All rights reserved.

  14. Selective block of late Na+ current by local anaesthetics in rat large sensory neurones

    PubMed Central

    Baker, Mark D

    2000-01-01

    The actions of lignocaine and benzocaine on transient and late Na+ current generated by large diameter (⩾50 μm) adult rat dorsal root ganglion neurones, were studied using patch-clamp techniques.Both drugs blocked whole-cell late Na+ current in a concentration-dependent manner. At 200 ms following the onset of a clamp step from −110 to −40 mV, the apparent K for block of late Na+ current by lignocaine was 57.8±15 μM (mean±s.e.mean, n=4). The value for benzocaine was 24.9±3.3 μM, (mean±s.e.mean, n=3).The effect of lignocaine on transient current, in randomly selected neurones, appeared variable (n=8, half-block from ∼50 to 400 μM). Half-block by benzocaine was not attained, but both whole-cell (n=11) and patch data suggested a high apparent K,>250 μM. Transient current always remained after late current was blocked.The voltage-dependence of residual late current steady-state inactivation was not shifted by 20 μM benzocaine (n=3), whereas 200 μM benzocaine shifted the voltage-dependence of transient current steady-state inactivation by −18.7±5.9 mV (mean±s.e.mean, n=4).In current-clamp, benzocaine (250 μM) could block subthreshold, voltage-dependent inward current, increasing the threshold for eliciting action potentials, without preventing their generation (n=2).Block of late Na+ current by systemic local anaesthetic may play a part in preventing ectopic impulse generation in sensory neurones. PMID:10780966

  15. The transcription factor C/EBPβ in the dorsal root ganglion contributes to peripheral nerve trauma–induced nociceptive hypersensitivity

    PubMed Central

    Li, Zhisong; Mao, Yuanyuan; Liang, Lingli; Wu, Shaogen; Yuan, Jingjing; Mo, Kai; Cai, Weihua; Mao, Qingxiang; Cao, Jing; Bekker, Alex; Zhang, Wei; Tao, Yuan-Xiang

    2017-01-01

    Changes in gene transcription in the dorsal root ganglion (DRG) after nerve trauma contribute to the genesis of neuropathic pain. We report that peripheral nerve trauma caused by chronic constriction injury (CCI) increased the abundance of the transcription factor C/EBPβ (CCAAT/enhancer binding protein β) in the DRG. Blocking this increase mitigated the development and maintenance of CCI-induced mechanical, thermal, and cold pain hypersensitivities without affecting basal responses to acute pain and locomotor activity. Conversely, mimicking this increase produced hypersensitivity to mechanical, thermal, or cold pain. In the ipsilateral DRG, C/EBPβ promoted a decrease in the abundance of the voltage-gated potassium channel subunit Kv1.2 and µ opioid receptor (MOR) at the mRNA and protein levels, which would be predicted to increase excitability in the ipsilateral DRG neurons and reduce the efficacy of morphine analgesia. These effects required C/EPBβ-mediated transcriptional activation of Ehmt2 (euchromatic histonelysine N-methyltransferase 2), which encodes G9a, an epigenetic silencer of the genes encoding Kv1.2 and MOR. Blocking the increase in C/EBPβ in the DRG improved morphine analgesia after CCI. These results suggest that C/EBPβ is an endogenous initiator of neuropathic pain and could be a potential target for the prevention and treatment of this disorder. PMID:28698219

  16. Vesicular glutamate transporters, VGluT1 and VGluT2, in the trigeminal ganglion neurons of the rat, with special reference to coexpression.

    PubMed

    Li, Jin-Lian; Xiong, Kang-Hui; Dong, Yu-Lin; Fujiyama, Fumino; Kaneko, Takeshi; Mizuno, Noboru

    2003-08-18

    Vesicular glutamate transporters are responsible for glutamate transport into synaptic vesicles. In the present study, we examined immunohistochemically the expression of vesicular glutamate transporters, VGluT1 and VGluT2, in trigeminal ganglion neurons of the rat. Immunohistochemistry for VGluT1 and VGluT2 indicated that more than 80% of trigeminal ganglion neurons express VGluT1 and/or VGluT2 in their cell bodies. It also indicated that large and small trigeminal ganglion neurons express VGluT2 more frequently than VGluT1. Dual immunofluorescence histochemistry for VGluT1 and VGluT2 indicated that trigeminal ganglion neurons express VGluT2 more frequently than VGluT1 and that more than 80% of VGluT-expressing trigeminal ganglion neurons express VGluT1 and VGluT2. Many axon terminals in the superficial layers of the medullary dorsal horn also showed VGluT1 and VGluT2 immunoreactivities. Some of these axon terminals were confirmed to form the central core of the synaptic glomerulus. These results indicated that VGluT1 and VGluT2 are coexpressed in the cell bodies and axon terminals in most trigeminal ganglion neurons. Copyright 2003 Wiley-Liss, Inc.

  17. Retinal ganglion cells in diabetes

    PubMed Central

    Kern, Timothy S; Barber, Alistair J

    2008-01-01

    Diabetic retinopathy has long been recognized as a vascular disease that develops in most patients, and it was believed that the visual dysfunction that develops in some diabetics was due to the vascular lesions used to characterize the disease. It is becoming increasingly clear that neuronal cells of the retina also are affected by diabetes, resulting in dysfunction and even degeneration of some neuronal cells. Retinal ganglion cells (RGCs) are the best studied of the retinal neurons with respect to the effect of diabetes. Although investigations are providing new information about RGCs in diabetes, including therapies to inhibit the neurodegeneration, critical information about the function, anatomy and response properties of these cells is yet needed to understand the relationship between RGC changes and visual dysfunction in diabetes. PMID:18565995

  18. Progranulin deficiency causes the retinal ganglion cell loss during development.

    PubMed

    Kuse, Yoshiki; Tsuruma, Kazuhiro; Mizoguchi, Takahiro; Shimazawa, Masamitsu; Hara, Hideaki

    2017-05-10

    Astrocytes are glial cells that support and protect neurons in the central nervous systems including the retina. Retinal ganglion cells (RGCs) are in contact with the astrocytes and our earlier findings showed the reduction of the number of cells in the ganglion cell layer in adult progranulin deficient mice. In the present study, we focused on the time of activation of the astrocytes and the alterations in the number of RGCs in the retina and optic nerve in progranulin deficient mice. Our findings showed that the number of Brn3a-positive cells was reduced and the expression of glial fibrillary acidic protein (GFAP) was increased in progranulin deficient mice. The progranulin deficient mice had a high expression of GFAP on postnatal day 9 (P9) but not on postnatal day 1. These mice also had a decrease in the number of the Brn3a-positive cells on P9. Taken together, these findings indicate that the absence of progranulin can affect the survival of RGCs subsequent the activation of astrocytes during retinal development.

  19. Spontaneous cell death in the semilunar ganglion during fetal and postnatal life in the ox, sheep, goat and guinea pig.

    PubMed

    Bortolami, R; Lucchi, M L; Callegari, E; De Pasquale, V; Lalatta Costerbosa, G

    1979-07-15

    A massive cell loss occurs in the semilunar ganglion. It is the result of either a casting-off of the semilunar ganglion cells into the cavernous sinus or a transformation of several cells into polyhedral cells with an epithelial-like organization, a process which immediately precedes their further degeneration.

  20. Eliminating Glutamatergic Input onto Horizontal Cells Changes the Dynamic Range and Receptive Field Organization of Mouse Retinal Ganglion Cells.

    PubMed

    Ströh, Sebastian; Puller, Christian; Swirski, Sebastian; Hölzel, Maj-Britt; van der Linde, Lea I S; Segelken, Jasmin; Schultz, Konrad; Block, Christoph; Monyer, Hannah; Willecke, Klaus; Weiler, Reto; Greschner, Martin; Janssen-Bienhold, Ulrike; Dedek, Karin

    2018-02-21

    In the mammalian retina, horizontal cells receive glutamatergic inputs from many rod and cone photoreceptors and return feedback signals to them, thereby changing photoreceptor glutamate release in a light-dependent manner. Horizontal cells also provide feedforward signals to bipolar cells. It is unclear, however, how horizontal cell signals also affect the temporal, spatial, and contrast tuning in retinal output neurons, the ganglion cells. To study this, we generated a genetically modified mouse line in which we eliminated the light dependency of feedback by deleting glutamate receptors from mouse horizontal cells. This genetic modification allowed us to investigate the impact of horizontal cells on ganglion cell signaling independent of the actual mode of feedback in the outer retina and without pharmacological manipulation of signal transmission. In control and genetically modified mice (both sexes), we recorded the light responses of transient OFF-α retinal ganglion cells in the intact retina. Excitatory postsynaptic currents (EPSCs) were reduced and the cells were tuned to lower temporal frequencies and higher contrasts, presumably because photoreceptor output was attenuated. Moreover, receptive fields of recorded cells showed a significantly altered surround structure. Our data thus suggest that horizontal cells are responsible for adjusting the dynamic range of retinal ganglion cells and, together with amacrine cells, contribute to the center/surround organization of ganglion cell receptive fields in the mouse. SIGNIFICANCE STATEMENT Horizontal cells represent a major neuronal class in the mammalian retina and provide lateral feedback and feedforward signals to photoreceptors and bipolar cells, respectively. The mode of signal transmission remains controversial and, moreover, the contribution of horizontal cells to visual processing is still elusive. To address the question of how horizontal cells affect retinal output signals, we recorded the light

  1. Diagnostic accuracy of ganglion cell complex substructures in different stages of primary open-angle glaucoma.

    PubMed

    Elbendary, Amal M; Abd El-Latef, Mohamed Hafez; Elsorogy, Hisham I; Enaam, Kamal M

    2017-08-01

    To evaluate diagnostic accuracy of substructure of ganglion cell complex versus peripapillary nerve fiber layer (NFL) thickness using spectral domain optical coherence tomography (SD-OCT) in different stages of glaucoma. Thirty eyes were normal, 120 were glaucomatous. Glaucomatous eyes were classified into: early glaucoma (46), moderate glaucoma (48), and severe glaucoma (26). Perimetry and SD-OCT were done. Peripapillary NFL thickness, ganglion cell layer (GCL), macular NFL thickness, combined GCL and macular ganglion cell complex (GCC), were recorded. Area under receiver operating characteristic curves (AUCs) was used to verify performance of different OCT parameters. Peripapillary NFL, GCL, and GCC thickness values were significantly different in all stages of glaucoma. All comparisons were significantly different; normal versus early, early versus moderate and moderate versus severe. The best parameters that distinguished normal from early stage were: peripapillary NFL (AUC: 0.90), GCC (AUC: 0.75), early from moderate stage were: peripapillary NFL thickness (AUC: 0.85), GCL (0.81),GCC (0.81), moderate from severe stage were: GCC (AUC:0.95), macular NFL (AUC:0.91), GCL (AUC:0.89), and peripapillary NFL (AUC:0.88). Peripapllary NFL and GCC thinning showed paradoxical course. The most diagnosed parameter in early glaucoma was peripapillary NFL and in severe glaucoma was GCC. In severe glaucoma, macular NFL showed higher diagnostic power than GCL and peripapillary NFL. Ganglion cell complex mapping may provide good alternative to optic disc imaging in advanced glaucoma with poor fixation. Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  2. Outcomes of Open Dorsal Wrist Ganglion Excision in Active-Duty Military Personnel.

    PubMed

    Balazs, George C; Donohue, Michael A; Drake, Matthew L; Ipsen, Derek; Nanos, George P; Tintle, Scott M

    2015-09-01

    To examine the most common presenting complaints of active-duty service members with isolated dorsal wrist ganglions and to determine the rate of return to unrestricted duty after open excision. Surgical records at 2 military facilities were screened to identify male and female active duty service members undergoing isolated open excision of dorsal wrist ganglions from January 1, 2006 to January 1, 2014. Electronic medical records and service disability databases were searched to identify the most common presenting symptoms and to determine whether patients returned to unrestricted active duty after surgery. Postoperative outcomes examined were pain persisting greater than 4 weeks after surgery, stiffness requiring formal occupational therapy treatment, surgical wound complications, and recurrence. A total of 125 active duty military personnel (Army, 54; Navy, 43; and Marine Corps, 28) met criteria for inclusion. Mean follow-up was 45 months. Fifteen percent (8 of 54) of the Army personnel were given permanent waivers from performing push-ups owing to persistent pain and stiffness. Pain persisting greater than 4 weeks after surgery was an independent predictor of eventual need for a permanent push-up waiver. The overall recurrence incidence was 9%. No demographic or perioperative factors were associated with recurrence. Patients whose occupation or activities require forceful wrist extension should be counseled on the considerable risk of residual pain and functional limitations that may occur after open dorsal wrist ganglion excision. Therapeutic IV. Published by Elsevier Inc.

  3. Functional expression of ionotropic glutamate receptors in the rabbit retinal ganglion cells.

    PubMed

    Chen, Yin-Peng; Chiao, Chuan-Chin

    2012-01-03

    It has been known that retinal ganglion cells (RGCs) with distinct morphologies have different physiological properties. It was hypothesized that different functions of RGCs may in part result from various expressions of N-methyl-d-aspartate (NMDA), α-amino-3-hydroxyl-5-methyl-isoxazole-4-propinoic acid (AMPA), and kainic acid (KA) receptors on their dendrites. In the present study, we aimed to characterize the functional expression of AMPA and NMDA receptors of morphologically identified RGCs in the wholemount rabbit retina. The agmatine (AGB) activation assay was used to reveal functional expression of ionotropic glutamate receptors after the RGCs were targeted by injecting Neurobiotin. To examine the excitability of these glutamate receptors in an agonist specific manner, the lower concentrations of AMPA (2 μM) and NMDA (100 μM) were chosen to examine G7 (ON-OFF direction selective ganglion cells) and G11 (alpha ganglion cells) types of RGCs. We found that less than 40% of G7 type RGCs had salient AGB activation when incubated with 2 μM AMPA or 100 μM NMDA. The G11 type RGCs also showed similar activation frequencies, except that all of the OFF subtype examined had no AGB permeation under the same AMPA concentration. These results suggest that RGCs with large somata (G7 and G11 types) may express various heterogeneous functional ionotropic glutamate receptors, thus in part rendering their functional diversity. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Nanosecond laser pulse stimulation of spiral ganglion neurons and model cells.

    PubMed

    Rettenmaier, Alexander; Lenarz, Thomas; Reuter, Günter

    2014-04-01

    Optical stimulation of the inner ear has recently attracted attention, suggesting a higher frequency resolution compared to electrical cochlear implants due to its high spatial stimulation selectivity. Although the feasibility of the effect is shown in multiple in vivo experiments, the stimulation mechanism remains open to discussion. Here we investigate in single-cell measurements the reaction of spiral ganglion neurons and model cells to irradiation with a nanosecond-pulsed laser beam over a broad wavelength range from 420 nm up to 1950 nm using the patch clamp technique. Cell reactions were wavelength- and pulse-energy-dependent but too small to elicit action potentials in the investigated spiral ganglion neurons. As the applied radiant exposure was much higher than the reported threshold for in vivo experiments in the same laser regime, we conclude that in a stimulation paradigm with nanosecond-pulses, direct neuronal stimulation is not the main cause of optical cochlea stimulation.

  5. Sciatica and claudication caused by ganglion cyst.

    PubMed

    Yang, Guang; Wen, Xiaoyu; Gong, Yubao; Yang, Chen

    2013-12-15

    Case report. We report a rare case that a ganglion cyst compressed the sciatic nerve and caused sciatica and claudication in a 51-year-old male. Sciatica and claudication commonly occurs in spinal stenosis. To our knowledge, only 4 cases have been reported on sciatica resulting from posterior ganglion cyst of hip. A 51-year-old male had a 2-month history of radiating pain on his right leg. He could only walk 20 to 30 m before stopping and standing to rest for 1 to 3 minutes. Interestingly, he was able to walk longer distances (about 200 m) when walking slowly in small steps, without any rest. He had been treated as a case of lumbar disc herniation, but conservative treatment was ineffective. On buttock examination, a round, hard, and fixative mass was palpated at the exit of the sciatic nerve. MR imaging of hip revealed a multilocular cystic mass located on the posterior aspect of the superior gemellus and obturator internus, compressing the sciatic nerve. On operation, we found that the cyst extended to the superior gemellus and the obturator internus, positioned right at the outlet of the sciatic nerve. At 18 months of follow-up, the patient continued to be symptom free. He returned to comprehensive physical activity with no limitations. For an extraspinal source, a direct compression on the sciatic nerve also resulted in sciatica and claudication. A meticulous physical examination is very important for the differential diagnosis of extraspinal sciatica from spinal sciatica.

  6. Drug discovery for hearing loss: Phenotypic screening of chemical compounds on primary cultures of the spiral ganglion.

    PubMed

    Whitlon, Donna S

    2017-06-01

    In the United States there are, at present, no drugs that are specifically FDA approved to treat hearing loss. Although several clinical trials are ongoing, including one testing D-methionine that is supported by the US Army, none of these trials directly address the effect of noise exposure on cochlear spiral ganglion neurons. We recently published the first report of a systematic chemical compound screen using primary, mammalian spiral ganglion cultures in which we were able to detect a compound and others in its class that increased neurite elongation, a critical step in restoring cochlear synapses after noise induced hearing loss. Here we discuss the issues, both pro and con, that influenced the development of our approach. These considerations may be useful for future compound screens that target the same or other attributes of cochlear spiral ganglion neurons. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. [Sphenopalatine ganglion pulsed radiofrequency treatment in patients suffering from chronic face and head pain].

    PubMed

    Akbas, Mert; Gunduz, Emel; Sanli, Suat; Yegin, Arif

    2016-01-01

    There are various facial pain syndromes including trigeminal neuralgia, trigeminal neuropathic pain and atypical facial pain syndromes. Effectiveness of the pulsed radiofrequency in managing various pain syndromes has been clearly demonstrated. There are a limited number of studies on the pulsed radiofrequency treatment for sphenopalatine ganglion in patients suffering from face and head pain. The purpose of this study is to evaluate the satisfaction of pulsed radiofrequency treatment at our patients retrospectively. Infrazygomatic approach was used for the pulsed radiofrequency of the sphenopalatine ganglion under fluoroscopic guidance. After the tip of the needle reached the target point, 0.25-0.5ms pulse width was applied for sensory stimulation at frequencies from 50Hz to 1V. Paraesthesias were exposed at the roof of the nose at 0.5-0.7V. To rule out trigeminal contact that led to rhythmic mandibular contraction, motor stimulation at a frequency of 2Hz was applied. Then, four cycles of pulsed radiofrequency lesioning were performed for 120s at a temperature of 42°C. Pain relief could not be achieved in 23% of the patients (unacceptable), whereas pain was completely relieved in 35% of the patients (excellent) and mild to moderate pain relief could be achieved in 42% of the patients (good) through sphenopalatine ganglion-pulsed radiofrequency treatment. Pulsed radiofrequency of the sphenopalatine ganglion is effective in treating the patients suffering from intractable chronic facial and head pain as shown by our findings. There is a need for prospective, randomized, controlled trials in order to confirm the efficacy and safety of this new treatment modality in chronic head and face pain. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  8. Sphenopalatine ganglion pulsed radiofrequency treatment in patients suffering from chronic face and head pain.

    PubMed

    Akbas, Mert; Gunduz, Emel; Sanli, Suat; Yegin, Arif

    2016-01-01

    There are various facial pain syndromes including trigeminal neuralgia, trigeminal neuropathic pain and atypical facial pain syndromes. Effectiveness of the pulsed radiofrequency in managing various pain syndromes has been clearly demonstrated. There are a limited number of studies on the pulsed radiofrequency treatment for sphenopalatine ganglion in patients suffering from face and head pain. The purpose of this study is to evaluate the satisfaction of pulsed radiofrequency treatment at our patients retrospectively. Infrazygomatic approach was used for the pulsed radiofrequency of the sphenopalatine ganglion under fluoroscopic guidance. After the tip of the needle reached the target point, 0.25-0.5 ms pulse width was applied for sensory stimulation at frequencies from 50 Hz to 1 V. Paraesthesias were exposed at the roof of the nose at 0.5-0.7 V. To rule out trigeminal contact that led to rhythmic mandibular contraction, motor stimulation at a frequency of 2 Hz was applied. Then, four cycles of pulsed radiofrequency lesioning were performed for 120 s at a temperature of 42°C. Pain relief could not be achieved in 23% of the patients (unacceptable), whereas pain was completely relieved in 35% of the patients (excellent) and mild to moderate pain relief could be achieved in 42% of the patients (good) through sphenopalatine ganglion-pulsed radiofrequency treatment. Pulsed radiofrequency of the sphenopalatine ganglion is effective in treating the patients suffering from intractable chronic facial and head pain as shown by our findings. There is a need for prospective, randomized, controlled trials in order to confirm the efficacy and safety of this new treatment modality in chronic head and face pain. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  9. Citrus fruit and fabacea secondary metabolites potently and selectively block TRPM3

    PubMed Central

    Straub, I; Mohr, F; Stab, J; Konrad, M; Philipp, SE; Oberwinkler, J; Schaefer, M

    2013-01-01

    Background and Purpose The melastatin-related transient receptor potential TRPM3 is a calcium-permeable nonselective cation channel that can be activated by the neurosteroid pregnenolone sulphate (PregS) and heat. TRPM3-deficient mice show an impaired perception of noxious heat. Hence, drugs inhibiting TRPM3 possibly get in focus of analgesic therapy. Experimental Approach Fluorometric methods were used to identify novel TRPM3-blocking compounds and to characterize their potency and selectivity to block TRPM3 but not other sensory TRP channels. Biophysical properties of the block were assessed using electrophysiological methods. Single cell calcium measurements confirmed the block of endogenously expressed TRPM3 channels in rat and mouse dorsal root ganglion (DRG) neurones. Key Results By screening a compound library, we identified three natural compounds as potent blockers of TRPM3. Naringenin and hesperetin belong to the citrus fruit flavanones, and ononetin is a deoxybenzoin. Eriodictyol, a metabolite of naringenin and hesperetin, was still biologically active as a TRPM3 blocker. The compounds exhibited a marked specificity for recombinant TRPM3 and blocked PregS-induced [Ca2+]i signals in freshly isolated DRG neurones. Conclusion and Implications The data indicate that citrus fruit flavonoids are potent and selective blockers of TRPM3. Their potencies ranged from upper nanomolar to lower micromolar concentrations. Since physiological functions of TRPM3 channels are still poorly defined, the development and validation of potent and selective blockers is expected to contribute to clarifying the role of TRPM3 in vivo. Considering the involvement of TRPM3 in nociception, TRPM3 blockers may represent a novel concept for analgesic treatment. PMID:23190005

  10. Citrus fruit and fabacea secondary metabolites potently and selectively block TRPM3.

    PubMed

    Straub, I; Mohr, F; Stab, J; Konrad, M; Philipp, S E; Oberwinkler, J; Schaefer, M

    2013-04-01

    The melastatin-related transient receptor potential TRPM3 is a calcium-permeable nonselective cation channel that can be activated by the neurosteroid pregnenolone sulphate (PregS) and heat. TRPM3-deficient mice show an impaired perception of noxious heat. Hence, drugs inhibiting TRPM3 possibly get in focus of analgesic therapy. Fluorometric methods were used to identify novel TRPM3-blocking compounds and to characterize their potency and selectivity to block TRPM3 but not other sensory TRP channels. Biophysical properties of the block were assessed using electrophysiological methods. Single cell calcium measurements confirmed the block of endogenously expressed TRPM3 channels in rat and mouse dorsal root ganglion (DRG) neurones. By screening a compound library, we identified three natural compounds as potent blockers of TRPM3. Naringenin and hesperetin belong to the citrus fruit flavanones, and ononetin is a deoxybenzoin. Eriodictyol, a metabolite of naringenin and hesperetin, was still biologically active as a TRPM3 blocker. The compounds exhibited a marked specificity for recombinant TRPM3 and blocked PregS-induced [Ca(2+)]i signals in freshly isolated DRG neurones. The data indicate that citrus fruit flavonoids are potent and selective blockers of TRPM3. Their potencies ranged from upper nanomolar to lower micromolar concentrations. Since physiological functions of TRPM3 channels are still poorly defined, the development and validation of potent and selective blockers is expected to contribute to clarifying the role of TRPM3 in vivo. Considering the involvement of TRPM3 in nociception, TRPM3 blockers may represent a novel concept for analgesic treatment. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  11. The release of acetylcholine from post-ganglionic cell bodies in response to depolarization.

    PubMed Central

    Johnson, D A; Pilar, G

    1980-01-01

    1. Acetylcholine (Ach) release from parasympathetic ganglia cell somata was investigated in denervated avian ciliary ganglia. Three days after the input to the ganglion (the oculomotor nerve) was sectioned, all presynaptic nerve terminals had degenerated. 2. Denervated ganglia were shown to contain endogenous ACh and to be capable of synthesizing [3H]ACh from [3H]choline added to the incubation medium. 3. In response to depolarization induced by incubation in 50 mM-[K+]o, denervated ganglia released [3H]ACh into bath effluents in amounts approximately 15% of the non-denervated contralateral control. This release was shown to be Ca2+ dependent in both intact and denervated ganglia. 4. Antidromic electrical stimulation of ciliary nerves also elicited [3H]ACh release. Nicotine (1 microgram/microliter.) depolarized denervated ciliary ganglion cells and evoked release of the transmitter and this release was antagonized by curare. 5. It is concluded that the ganglionic cell bodies sysnthesized ACh and released the transmitter in response to K+ depolarization, antidromic stimulation and cholinergic agonists, despite the lack of morphological specializations usually associated with stimulus-induced release of neurotransmitter. The evidence suggests the existence of a mechanism of transmitter release which is Ca2+ dependent, probably from a cytoplasmic pool and therefore distinct from the usual vesicular release at the nerve terminal. Images Plate 1 Plate 2 PMID:6247485

  12. Ouabain-Induced Apoptosis in Cochlear Hair Cells and Spiral Ganglion Neurons In Vitro

    PubMed Central

    Fu, Yong; Ding, Dalian; Jiang, Haiyan; Salvi, Richard

    2013-01-01

    Ouabain is a common tool to explore the pathophysiological changes in adult mammalian cochlea in vivo. In prior studies, locally administering ouabain via round window membrane demonstrated that the ototoxic effects of ouabain in vivo varied among mammalian species. Little is known about the ototoxic effects in vitro. Thus, we prepared cochlear organotypic cultures from postnatal day-3 rats and treated these cultures with ouabain at 50, 500, and 1000 μM for different time to elucidate the ototoxic effects of ouabain in vitro and to provide insights that could explain the comparative ototoxic effects of ouabain in vivo. Degeneration of cochlear hair cells and spiral ganglion neurons was evaluated by hair-cell staining and neurofilament labeling, respectively. Annexin V staining was used to detect apoptotic cells. A quantitative RT-PCR apoptosis-focused gene array determined changes in apoptosis-related genes. The results showed that ouabain-induced damage in vitro was dose and time dependent. 500 μM ouabain and 1000 μM ouabain were destructively traumatic to both spiral ganglion neurons and cochlear hair cells in an apoptotic signal-dependent pathway. The major apoptotic pathways in ouabain-induced spiral ganglion neuron apoptosis culminated in the stimulation of the p53 pathway and triggering of apoptosis by a network of proapoptotic signaling pathways. PMID:24228256

  13. The novel cyclophilin D inhibitor compound 19 protects retinal pigment epithelium cells and retinal ganglion cells from UV radiation.

    PubMed

    Xie, Laiqing; Cheng, Long; Xu, Guoxu; Zhang, Ji; Ji, Xiaoyan; Song, E

    2017-06-10

    Excessive Ultra violet (UV) radiation induces injuries to retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs), causing retinal degeneration. Cyclophilin D (Cyp-D)-dependent mitochondrial permeability transition pore (mPTP) opening mediates UV-induced cell death. In this study, we show that a novel Cyp-D inhibitor compound 19 efficiently protected RPEs and RGCs from UV radiation. Compound 19-mediated cytoprotection requires Cyp-D, as it failed to further protect RPEs/RGCs from UV when Cyp-D was silenced by targeted shRNAs. Compound 19 almost blocked UV-induced p53-Cyp-D mitochondrial association, mPTP opening and subsequent cytochrome C release. Further studies showed that compound 19 inhibited UV-induced reactive oxygen species (ROS) production, lipid peroxidation and DNA damage. Together, compound 19 protects RPEs and RGCs from UV radiation, possibly via silencing Cyp-D-regulated intrinsic mitochondrial death pathway. Compound 19 could a lead compound for treating UV-associated retinal degeneration diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Electrical Interaction of Paired Ganglion Cells in the Leech

    PubMed Central

    Eckert, Roger

    1963-01-01

    The two paired giant ganglion cells (PGC's) found in each ganglion of the leech central nervous system fire synchronously in response to certain sensory input. Polarizing current passed into either of these cells is seen to displace the membrane potentials of both cells, the voltage attenuation between the two somata ranging from 2 to 5 times. This attenuation factor remains unchanged when the direction of the polarizing current is reversed, and remains about the same when the other cell of the pair is directly polarized. When one of the PGC's is partially depolarized with outward current, a repetitive train of impulses is generated. Each spike is followed by a spike in the other cell. Occasionally, a small subspike potential is seen in place of a follower spike. This potential appears to differ in shape and time course from synaptic potentials elicited by afferent input to these cells, and appears rather to be an electrotonic potential derived from the prejunctional impulse in the stimulated PGC. It is proposed that transmission between these cells is electrical, being accomplished by a flow of local circuit current across a non-rectifying junction or connection to the spike-initiating region of the other PGC. PMID:19873553

  15. The trophic effect of ouabain on retinal ganglion cells is mediated by IL-1β and TNF-α

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Salles von-Held-Ventura, Juliana; Mázala-de-Oliveira, Thalita; Cândida da Rocha Oliveira, Amanda

    Ouabain is a steroid hormone that binds to the enzyme Na{sup +}, K{sup +} – ATPase and stimulates different intracellular pathways controlling growth, proliferation and cell survival. IL-1β and TNF-α are pleiotropic molecules, conventionally regarded as pro-inflammatory cytokines with well-known effects in the immune system. In addition, IL-1β and TNF-α also play important roles in the nervous system including neuroprotective effects. Previous data from our group showed that ouabain treatment is able to induce an increase in retinal ganglion cell survival kept in mixed retinal cell cultures. The aim of this work was to investigate if IL-1β and TNF-α couldmore » be mediating the trophic effect of ouabain on retinal ganglion cells. Our results show that the trophic effect of ouabain on retinal ganglion cell was inhibited by either anti-IL-1β or anti-TNF-α antibodies. In agreement, IL-1β or TNF-α increased the retinal ganglion cells survival in a dose-dependent manner. Accordingly, ouabain treatment induces a temporal release of TNF-α and IL-1β from retinal cell cultures. Interestingly, TNF-α and IL-1β regulate each other intracellular levels. Our results suggest that ouabain treatment triggers the activation of TNF-α and IL-1β signaling pathways leading to an increase in retinal ganglion cell survival. - Highlights: • Pro-inflammatory cytokines regulates the ouabain effect on RGC survival. • Ouabain treatment modulates the intracellular levels of TNF-α and IL-1β. • Ouabain induces the release of TNF-α and IL-1β in retinal cell cultures.« less

  16. Satellite glial cells in the trigeminal ganglion as a determinant of orofacial neuropathic pain

    PubMed Central

    VIT, JEAN-PHILIPPE; JASMIN, LUC; BHARGAVA, ADITI; OHARA, PETER T.

    2008-01-01

    Satellite glial cells (SGCs) tightly envelop the perikarya of primary sensory neurons in peripheral ganglion and are identified by their morphology and the presence of proteins not found in ganglion neurons. These SGC-unique proteins include the inwardly rectifying K+ channel Kir4.1, the connexin-43 (Cx43) subunit of gap junctions, the purinergic receptor P2Y4 and soluble guanylate cyclase. We also present evidence that the small-conductance Ca2+-activated K+ channel SK3 is present only in SGCs and that SGCs divide following nerve injury. All the above proteins are involved, either directly or indirectly, in potassium ion (K+) buffering and, thus, can influence the level of neuronal excitability, which, in turn, has been associated with neuropathic pain conditions. We used in vivo RNA interference to reduce the expression of Cx43 (present only in SGCs) in the rat trigeminal ganglion and show that this results in the development of spontaneous pain behavior. The pain behavior is present only when Cx43 is reduced and returns to normal when Cx43 concentrations are restored. This finding shows that perturbation of a single SGC-specific protein is sufficient to induce pain responses and demonstrates the importance of PNS glial cell activity in the pathophysiology of neuropathic pain. PMID:18568096

  17. Localization of laminin B1 mRNA in retinal ganglion cells by in situ hybridization

    PubMed Central

    1990-01-01

    In the nervous system, neuronal migration and axonal growth are dependent on specific interactions with extracellular matrix proteins. During development of the vertebrate retina, ganglion cell axons extend along the internal limiting (basement) membrane and form the optic nerve. Laminin, a major component of basement membranes, is known to be present in the internal limiting membrane, and might be involved in the growth of ganglion cell axons. The identity of the cells that produce retinal laminin, however, has not been established. In the present study, we have used in situ hybridization to localize the sites of laminin B1 mRNA synthesis in the developing mouse retina. Our results show that there are at least two principal sites of laminin B1 mRNA synthesis: (a) the hyaloid vessels and the lens during the period of major axonal outgrowth, and (b) the retinal ganglion cells at later development stages. Muller (glial) cells, the major class of nonneuronal cells in the retina, do not appear to express laminin B1 mRNA either during development or in the adult retina. In Northern blots, we found a single transcript of approximately 6-kb size that encodes the laminin B1 chain in the retina. Moreover, laminin B1 mRNA level was four- to fivefold higher in the postnatal retina compared to that in the adult. Our results show that in addition to nonneuronal cells, retinal ganglion cells also synthesize laminin. The function of laminin in postnatal retinas, however, remains to be elucidated. Nevertheless, our findings raise the possibility that neurons in other parts of the nervous system might also synthesize extracellular matrix proteins. PMID:2351694

  18. Bupivacaine-induced cellular entry of QX-314 and its contribution to differential nerve block

    PubMed Central

    Brenneis, C; Kistner, K; Puopolo, M; Jo, S; Roberson, DP; Sisignano, M; Segal, D; Cobos, EJ; Wainger, BJ; Labocha, S; Ferreirós, N; Hehn, C; Tran, J; Geisslinger, G; Reeh, PW; Bean, BP; Woolf, C J

    2014-01-01

    Background and Purpose: Selective nociceptor fibre block is achieved by introducing the cell membrane impermeant sodium channel blocker lidocaine N-ethyl bromide (QX-314) through transient receptor potential V1 (TRPV1) channels into nociceptors. We screened local anaesthetics for their capacity to activate TRP channels, and characterized the nerve block obtained by combination with QX-314. Experimental Approach: We investigated TRP channel activation in dorsal root ganglion (DRG) neurons by calcium imaging and patch-clamp recordings, and cellular QX-314 uptake by MS. To characterize nerve block, compound action potential (CAP) recordings from isolated nerves and behavioural responses were analysed. Key Results: Of the 12 compounds tested, bupivacaine was the most potent activator of ruthenium red-sensitive calcium entry in DRG neurons and activated heterologously expressed TRPA1 channels. QX-314 permeated through TRPA1 channels and accumulated intracellularly after activation of these channels. Upon sciatic injections, QX-314 markedly prolonged bupivacaine's nociceptive block and also extended (to a lesser degree) its motor block. Bupivacaine's blockade of C-, but not A-fibre, CAPs in sciatic nerves was extended by co-application of QX-314. Surprisingly, however, this action was the same in wild-type, TRPA1-knockout and TRPV1/TRPA1-double knockout mice, suggesting a TRP-channel independent entry pathway. Consistent with this, high doses of bupivacaine promoted a non-selective, cellular uptake of QX-314. Conclusions and Implications: Bupivacaine, combined with QX-314, produced a long-lasting sensory nerve block. This did not require QX-314 permeation through TRPA1, although bupivacaine activated these channels. Regardless of entry pathway, the greatly extended duration of block produced by QX-314 and bupivacaine may be clinically useful. PMID:24117225

  19. Frequency-Dependent Activation of Glucose Utilization in the Superior Cervical Ganglion by Electrical Stimulation of Cervical Sympathetic Trunk

    NASA Astrophysics Data System (ADS)

    Yarowsky, Paul; Kadekaro, Massako; Sokoloff, Louis

    1983-07-01

    Electrical stimulation of the distal stump of the transected cervical sympathetic trunk produces a frequency-dependent activation of glucose utilization, measured by the deoxy[14C]glucose method, in the superior cervical ganglion of the urethane-anesthetized rat. The frequency dependence falls between 0-15 Hz; at 20 Hz the activation of glucose utilization is no greater than at 15 Hz. Deafferentation of the superior cervical ganglion by transection of the cervical sympathetic trunk does not diminish the rate of glucose utilization in the ganglion in the urethane-anesthetized rat. These results indicate that the rate of energy metabolism in an innervated neural structure is, at least in part, regulated by the impulse frequency of the electrical input to the structure, and this regulation may be an essential component of the mechanism of the coupling of metabolic activity to functional activity in the nervous system.

  20. A novel astrovirus associated with encephalitis and ganglionitis in domestic sheep.

    PubMed

    Pfaff, F; Schlottau, K; Scholes, S; Courtenay, A; Hoffmann, B; Höper, D; Beer, M

    2017-06-01

    In June 2013, a 4-year-old Welsh Mountain ewe and in March 2014 a 10-day-old lamb of the same breed and the same flock presented progressive neurological signs including depressed sensorium, tremor, and unusual behaviour. Neuropathological examination of the brain and spinal cord detected non-suppurative polioencephalomyelitis and dorsal root ganglionitis, characteristic of a neurotropic viral agent in both sheep. Metagenomic analysis of different tissue samples from both animals identified a novel Ovine Astrovirus (OvAstV). The presence of viral genome in the central nervous system was confirmed by RT-qPCR. Although the cases presented nine months apart, the identified OvAstV shared nearly identical sequences, differing in only three nucleotide positions across the complete genome. Phylogenetic analysis revealed a close relation of OvAstV to neurotropic bovine astroviruses and an enteric OvAstV. In conclusion, these are the first reported cases of astrovirus infection in domestic sheep that were associated with encephalitis and ganglionitis. © 2017 Blackwell Verlag GmbH.

  1. Sphenopalatine (nasal) ganglion: remote effects including "psychosomatic" symptoms, rage reaction, pain, and spasm.

    PubMed

    Ruskin, A P

    1979-08-01

    Many articles implicate the nasal ganglion in the production of remote symptoms and discuss treatment. Symptoms are primarily spastic, involving both visceral and voluntary muscles including muscle spasm in the neck, shoulder, and low back; asthma, hypertension, intestinal spasm; diarrhea, angina pectoris, uterine spasm; intractable hiccup, and many others. All these symptoms appear to have 2 common denominators. They are mediated by the autonomic nervous system and at least in some instances can be "psychosomatic." The sphenopalatine ganglion (SPG) is a major autonomic ganglion located superficially in the pterygopalatine fossa, with major afferent distribution to the entire nasopharynx and important connections with the trigeminal nerve, facial nerve, internal carotid artery plexus of the sympathetic nervous system and, as shown in the rat, direct connection with the anterior pituitary gland. This paper presents arguments supporting the following hypotheses: 1. The SPG probably has a crucial role in lower animals in declenching the reflex responses known collectively as the rage reaction. 2. The SPG is a major point of entry to the autonomic system exposed to pathologic influences and readily accessible for therapeutic influences and readily accessible for therapeutic intervention. 3. A wide variety of symptoms are produced or maintained by alteration in autonomic system tonus and some of these may be affected by intervention on the SPG. 4. The possible relationship of some symptoms and "psychosomatic" conditions to the autonomic nervous system and the rage reaction must be considered.20

  2. [The right to medical rehabilitation according to the 2007 act to strengthen health insurance competition, GKV-WSG].

    PubMed

    Liebold, D

    2008-02-01

    Since April 1, 2007 medical rehabilitation is a standard insurance benefit of the statutory health insurance scheme (covered by the SGB V, book 5 of the German social code), with the right of the beneficiary to comply especially with the intentions, the principles and the preconditions of the benefits as stipulated in the SGB IX (book 9 of the German social code covering rehabilitation and participation of persons with disabilities). In claiming benefits the applicable rules primarily are those of the SGB IX, as long as the SGB V does not contain different rules. In light of the demands of the SGB IX, the prevailing case law of the Federal Social Court concerning technical aids and assistive devices cannot persist any longer. The so-called "basic-compensation" is contradictory to the specifications of the SGB IX. Medical rehabilitation does not only consist of complex benefits, but every single benefit pursuant to section sign 26 Abs. 2, Abs. 3 SGB IX is a medical rehabilitation benefit if its priority intention is to achieve the beneficiary's participation in society.

  3. Enkephalins in the inferior mesenteric ganglion of the cat and in the area of the lower digestive tract innervated by this ganglion: quantification by radio-immunoassay and characterization by high pressure liquid chromatography.

    PubMed

    Cupo, A; Niel, J P; Miolan, J P; Jule, Y; Jarry, T

    1988-01-01

    Met-enkephalin, Leu-enkephalin and Met-enkephalin-Arg-Gly-Leu were quantified and characterized in the cat inferior mesenteric ganglion and in the area of the lower digestive tract innervated by this ganglion, including the proximal colon, distal colon and internal anal sphincter. In the structures studied, the concentrations of enkephalins expressed as femtomole/mg of wet tissue ranged from 66 to 160 with Met-enkephalin, from 15 to 45 with Leu-enkephalin and from 2 to 12 for Met-enkephalin-arg-gly-leu. In the lower digestive tract, the Met- and Leu-enkephalin content decreased from the proximal colon to the internal anal sphincter. The Met-enkephalin versus Leu-enkephalin ratio of the structures investigated were as follows: inferior mesenteric ganglion 3.2, proximal colon 4.4, distal colon 5, internal and sphincter 4.5. In individual samples of all the structures assayed the results of high pressure liquid chromatography (HPLC) analysis pointed to the presence of authentic Met- and Leu-enkephalin. HPLC analysis could not be carried out on Met-enkephalin-Arg-Gly-Leu due to the very low concentrations of this peptide in all the structures assayed. Our results, combined with those of previous immunohistochemical and physiological studies, support the idea that enkephalins are involved in the nervous control of the motility of the lower digestive tract.

  4. Functional role of NT-3 in synapse regeneration by spiral ganglion neurons on inner hair cells after excitotoxic trauma in vitro

    PubMed Central

    Wang, Qiong; Green, Steven H.

    2011-01-01

    Spiral ganglion neurons (SGNs) are postsynaptic to hair cells and project to the brainstem. The inner hair cell (IHC) to SGN synapse is susceptible to glutamate excitotoxicity and to acoustic trauma, with potentially adverse consequences to long-term SGN survival. We used a cochlear explant culture from P6 rat pups consisting of a portion of organ of Corti maintained intact with the corresponding portion of spiral ganglion to investigate excitotoxic damage to IHC-SGN synapses in vitro. The normal innervation pattern is preserved in vitro. Brief treatment with NMDA and kainate results in loss of IHC–SGN synapses and degeneration of the distal type 1 SGN peripheral axons, mimicking damage to SGN peripheral axons caused by excitotoxicity or noise in vivo. The number of IHC presynaptic ribbons is not significantly altered. Reinnervation of IHCs occurs and regenerating axons remain restricted to the IHC row. However, the number of postsynaptic densities (PSDs) does not fully recover and not all axons regrow to the IHCs. Addition of either NT-3 or BDNF increases axon growth and synaptogenesis. Selective blockade of endogenous NT-3 signaling with TrkC-IgG reduced regeneration of axons and PSDs, but TrkB-IgG, which blocks BDNF, has no such effect, indicating that endogenous NT-3 is necessary for SGN axon growth and synaptogenesis. Remarkably, TrkC-IgG reduced axon growth and synaptogenesis even in the presence of BDNF, indicating that endogenous NT-3 has a distinctive role, not mimicked by BDNF, in promoting SGN axon growth in the organ of Corti and synaptogenesis on IHCs. PMID:21613508

  5. Effects of alpha-lipoic acid on retinal ganglion cells, retinal thicknesses, and VEGF production in an experimental model of diabetes.

    PubMed

    Kan, Emrah; Alici, Ömer; Kan, Elif Kılıç; Ayar, Ahmet

    2017-12-01

    The purpose of the present study was to investigate the effect of alpha-lipoic acid (ALA) on the thicknesses of various retinal layers and on the numbers of retinal ganglion cells and vascular endothelial growth factor levels in experimental diabetic mouse retinas. Twenty-one male BALB/C mice were made diabetic by the intraperitoneal administration of streptozotocin (200 mg/kg). One week after the induction of diabetes, the mice were divided randomly into three groups: control group (non-diabetic mice treated with alpha-lipoic acid, n = 7), diabetic group (diabetic mice without treatment, n = 7), and alpha-lipoic acid treatment group (diabetic mice with alpha-lipoic acid treatment, n = 7). At the end of the 8th week, the thicknesses of the inner nuclear layer (INL), outer nuclear layer (ONL), and full-length retina were measured; also retinal ganglion cells and VEGF expressions were counted on the histological sections of the mouse retinas and compared with each other. The thicknesses of the full-length retina, ONL, and INL were significantly reduced in the diabetic group compared to the control and ALA treatment groups (p = 0.001), whereas the thicknesses of these layers did not show a significant difference between ALA treatment and control groups. The number of ganglion cells in the diabetic group was significantly lower than those in the control and ALA treatment groups (p = 0.001). The VEGF expression was significantly higher in the diabetic group and mostly observed in the ganglion cell and inner nuclear layers compared to the control and ALA treatment groups (p = 0.001). Therefore, the number of ganglion cells and VEGF levels did not show significant differences between the ALA treatment and control groups (p = 0.7). Our results show that alpha-lipoic acid treatment may have an impact on reducing VEGF levels, protecting ganglion cells, and preserving the thicknesses of the inner and outer layers in diabetic mouse retinas.

  6. Slit/Robo Signaling Mediates Spatial Positioning of Spiral Ganglion Neurons during Development of Cochlear Innervation

    PubMed Central

    Wang, Sheng-zhi; Ibrahim, Leena A.; Kim, Young J.; Gibson, Daniel A.; Leung, Haiwen C.; Yuan, Wei; Zhang, Ke K.; Tao, Huizhong W.

    2013-01-01

    During the development of periphery auditory circuits, spiral ganglion neurons (SGNs) extend their neurites to innervate cochlear hair cells (HCs) with their soma aggregated into a cluster spatially segregated from the cochlear sensory epithelium. The molecular mechanisms underlying this spatial patterning remain unclear. In this study, in situ hybridization in the mouse cochlea suggests that Slit2 and its receptor, Robo1/2, exhibit apparently complementary expression patterns in the spiral ganglion and its nearby region, the spiral limbus. In Slit2 and Robo1/2 mutants, the spatial restriction of SGNs was disrupted. Mispositioned SGNs were found to scatter in the space between the cochlear epithelium and the main body of spiral ganglion, and the neurites of mispositioned SGNs were misrouted and failed to innervate HCs. Furthermore, in Robo1/2 mutants, SGNs were displaced toward the cochlear epithelium as an entirety. Examination of different embryonic stages in the mutants revealed that the mispositioning of SGNs was due to a progressive displacement to ectopic locations after their initial normal settlement at an earlier stage. Our results suggest that Slit/Robo signaling imposes a restriction force on SGNs to ensure their precise positioning for correct SGN-HC innervations. PMID:23884932

  7. Effects of applying nerve blocks to prevent postherpetic neuralgia in patients with acute herpes zoster: a systematic review and meta-analysis

    PubMed Central

    Kim, Hyun Jung; Ahn, Hyeong Sik; Lee, Jae Young; Choi, Seong Soo; Cheong, Yu Seon; Kwon, Koo; Yoon, Syn Hae

    2017-01-01

    Background Postherpetic neuralgia (PHN) is a common and painful complication of acute herpes zoster. In some cases, it is refractory to medical treatment. Preventing its occurrence is an important issue. We hypothesized that applying nerve blocks during the acute phase of herpes zoster could reduce PHN incidence by attenuating central sensitization and minimizing nerve damage and the anti-inflammatory effects of local anesthetics and steroids. Methods This systematic review and meta-analysis evaluates the efficacy of using nerve blocks to prevent PHN. We searched the MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov and KoreaMed databases without language restrictions on April, 30 2014. We included all randomized controlled trials performed within 3 weeks after the onset of herpes zoster in order to compare nerve blocks vs active placebo and standard therapy. Results Nine trials were included in this systematic review and meta-analysis. Nerve blocks reduced the duration of herpes zoster-related pain and PHN incidence of at 3, 6, and 12 months after final intervention. Stellate ganglion block and single epidural injection did not achieve positive outcomes, but administering paravertebral blockage and continuous/repeated epidural blocks reduced PHN incidence at 3 months. None of the included trials reported clinically meaningful serious adverse events. Conclusions Applying nerve blocks during the acute phase of the herpes zoster shortens the duration of zoster-related pain, and somatic blocks (including paravertebral and repeated/continuous epidural blocks) are recommended to prevent PHN. In future studies, consensus-based PHN definitions, clinical cutoff points that define successful treatment outcomes and standardized outcome-assessment tools will be needed. PMID:28119767

  8. The blocking action of choline 2:6-xylyl ether bromide on adrenergic nerves

    PubMed Central

    Exley, K. A.

    1957-01-01

    Choline 2:6-xylyl ether bromide (TM 10), given systemically to cats in doses of 5 to 15 mg./kg., abolishes the effects of adrenergic nerve stimulation whilst leaving the reactions of the effector organs to adrenaline unimpaired. The effects of a single dose may take up to one hour to become fully established and last for more than twenty-four hours. Apart from transitory ganglionic blockade, cholinergic autonomic nerves are unaffected even by large doses of TM 10. Doses of TM 10 which produce effective blockade do not impair conduction along adrenergic nerve trunks; the drug must, therefore, act at, or close to, the nerve terminals. TM 10 prevents the output of noradrenaline from the spleen on stimulating the splenic nerves; but, in acute experiments, it does not influence the liberation of pressor amines from the stimulated suprarenals. Examination of some ethers related to TM 10 revealed no correlation between TM 10-like adrenergic blocking activity and local anaesthetic activity. The action of TM 10 on adrenergic nerves does not, therefore, seem to be accounted for by axonal block. ImagesFIG. 8 PMID:13460234

  9. Electrical receptive fields of retinal ganglion cells: Influence of presynaptic neurons

    PubMed Central

    Apollo, Nicholas V.; Garrett, David J.

    2018-01-01

    Implantable retinal stimulators activate surviving neurons to restore a sense of vision in people who have lost their photoreceptors through degenerative diseases. Complex spatial and temporal interactions occur in the retina during multi-electrode stimulation. Due to these complexities, most existing implants activate only a few electrodes at a time, limiting the repertoire of available stimulation patterns. Measuring the spatiotemporal interactions between electrodes and retinal cells, and incorporating them into a model may lead to improved stimulation algorithms that exploit the interactions. Here, we present a computational model that accurately predicts both the spatial and temporal nonlinear interactions of multi-electrode stimulation of rat retinal ganglion cells (RGCs). The model was verified using in vitro recordings of ON, OFF, and ON-OFF RGCs in response to subretinal multi-electrode stimulation with biphasic pulses at three stimulation frequencies (10, 20, 30 Hz). The model gives an estimate of each cell’s spatiotemporal electrical receptive fields (ERFs); i.e., the pattern of stimulation leading to excitation or suppression in the neuron. All cells had excitatory ERFs and many also had suppressive sub-regions of their ERFs. We show that the nonlinearities in observed responses arise largely from activation of presynaptic interneurons. When synaptic transmission was blocked, the number of sub-regions of the ERF was reduced, usually to a single excitatory ERF. This suggests that direct cell activation can be modeled accurately by a one-dimensional model with linear interactions between electrodes, whereas indirect stimulation due to summated presynaptic responses is nonlinear. PMID:29432411

  10. Photopolymerized microfeatures for directed spiral ganglion neurite and Schwann cell growth.

    PubMed

    Tuft, Bradley W; Li, Shufeng; Xu, Linjing; Clarke, Joseph C; White, Scott P; Guymon, Bradley A; Perez, Krystian X; Hansen, Marlan R; Guymon, C Allan

    2013-01-01

    Cochlear implants (CIs) provide auditory perception to individuals with severe hearing impairment. However, their ability to encode complex auditory stimuli is limited due, in part, to poor spatial resolution caused by electrical current spread in the inner ear. Directing nerve cell processes towards target electrodes may reduce the problematic current spread and improve stimulatory specificity. In this work, photopolymerization was used to fabricate micro- and nano-patterned methacrylate polymers to probe the extent of spiral ganglion neuron (SGN) neurite and Schwann cell (SGSC) contact guidance based on variations in substrate topographical cues. Micropatterned substrates are formed in a rapid, single-step reaction by selectively blocking light with photomasks which have parallel line-space gratings with periodicities of 10-100 μm. Channel amplitudes of 250 nm-10 μm are generated by modulating UV exposure time, light intensity, and photoinitiator concentration. Gradual transitions are observed between ridges and grooves using scanning electron and atomic force microscopy. The transitions stand in contrast to vertical features generated via etching lithographic techniques. Alignment of neural elements increases significantly with increasing feature amplitude and constant periodicity, as well as with decreasing periodicity and constant amplitude. SGN neurite alignment strongly correlates (r = 0.93) with maximum feature slope. Multiple neuronal and glial types orient to the patterns with varying degrees of alignment. This work presents a method to fabricate gradually-sloping micropatterns for cellular contact guidance studies and demonstrates spatial control of inner ear neural elements in response to micro- and nano-scale surface topography. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. [The significance of quality of life from a socio-legal perspective].

    PubMed

    Axer, Peter

    2014-01-01

    Only rarely is the term quality of life explicitly mentioned in the Social Security Code (Sozialgesetzbuch, SGB). In the statutory health insurance law (Book V of the Social Security Code, SGB V), the term is explicitly regulated within the context of the entitlement to pharmaceuticals. While there are pharmaceuticals that have the priority to increase the quality of life but are excluded from the provision of healthcare (Section 34 (1) Sentence 7 SGB V), the improvement of the quality of life has to be taken into account for the cost-benefit assessment (Section 35b SGB V) as well as for the early pharmaceutical benefit assessment (Section 35a SGB V) and for the formation of reference price groups (Section 35 SGB V) for and in the case of an entitlement to benefits in the event of illness. Copyright © 2014. Published by Elsevier GmbH.

  12. PKCepsilon-dependent potentiation of TTX-resistant Nav1.8 current by neurokinin-1 receptor activation in rat dorsal root ganglion neurons.

    PubMed

    Cang, Chun-Lei; Zhang, Hua; Zhang, Yu-Qiu; Zhao, Zhi-Qi

    2009-06-30

    Substance P (SP), which mainly exists in a subtype of small-diameter dorsal root ganglion (DRG) neurons, is an important signal molecule in pain processing in the spinal cord. Our previous results have proved the expression of SP receptor neurokinin-1 (NK-1) on DRG neurons and its interaction with transient receptor potential vanilloid 1 (TRPV1) receptor. In this study we investigated the effect of NK-1 receptor agonist on Na(v)1.8, a tetrodotoxin (TTX)-resistant sodium channel, in rat small-diameter DRG neurons employing whole-cell patch clamp recordings. NK-1 agonist [Sar(9), Met(O2)(11)]-substance P (Sar-SP) significantly enhanced the Na(v)1.8 currents in a subgroup of small-diameter DRG neurons under both the normal and inflammatory situation, and the enhancement was blocked by NK-1 antagonist Win51708 and protein kinase C (PKC) inhibitor bisindolylmaleimide (BIM), but not the protein kinase A (PKA) inhibitor H89. In particular, the inhibitor of PKCepsilon, a PKC isoform, completely blocked this effect. Under current clamp model, Sar-SP reduced the amount of current required to evoke action potentials and increased the firing rate in a subgroup of DRG neurons. These data suggest that activation of NK-1 receptor potentiates Na(v)1.8 sodium current via PKCepsilon-dependent signaling pathway, probably participating in the generation of inflammatory hyperalgesia.

  13. Developmental changes in expression of GABAA receptor-channels in rat intrinsic cardiac ganglion neurones

    PubMed Central

    Fischer, Harald; Harper, Alexander A; Anderson, Colin R; Adams, David J

    2005-01-01

    The effects of γ-aminobutyric acid (GABA) on the electrophysiological properties of intracardiac neurones were investigated in the intracardiac ganglion plexus in situ and in dissociated neurones from neonatal, juvenile and adult rat hearts. Focal application of GABA evoked a depolarizing, excitatory response in both intact and dissociated intracardiac ganglion neurones. Under voltage clamp, both GABA and muscimol elicited inward currents at −60 mV in a concentration-dependent manner. The fast, desensitizing currents were mimicked by the GABAA receptor agonists muscimol and taurine, and inhibited by the GABAA receptor antagonists, bicuculline and picrotoxin. The GABAA0 antagonist (1,2,5,6-tetrahydropyridin-4-yl)methyl phosphonic acid (TPMPA), had no effect on GABA-induced currents, suggesting that GABAA receptor-channels mediate the response. The GABA-evoked current amplitude recorded from dissociated neurones was age dependent whereby the peak current density measured at −100 mV was ∼ 20 times higher for intracardiac neurones obtained from neonatal rats (P2–5) compared with adult rats (P45–49). The decrease in GABA sensitivity occurred during the first two postnatal weeks and coincides with maturation of the sympathetic innervation of the rat heart. Immunohistochemical staining using antibodies against GABA demonstrate the presence of GABA in the intracardiac ganglion plexus of the neonatal rat heart. Taken together, these results suggest that GABA and taurine may act as modulators of neurotransmission and cardiac function in the developing mammalian intrinsic cardiac nervous system. PMID:15731187

  14. Expression and function of system N glutamine transporters (SN1/SN2 or SNAT3/SNAT5) in retinal ganglion cells.

    PubMed

    Umapathy, Nagavedi S; Dun, Ying; Martin, Pamela M; Duplantier, Jennifer N; Roon, Penny; Prasad, Puttur; Smith, Sylvia B; Ganapathy, Vadivel

    2008-11-01

    Glutamine transport is essential for the glutamate-glutamine cycle, which occurs between neurons and glia. System N, consisting of SN1 (SNAT3) and SN2 (SNAT5), is the principal mediator of glutamine transport in retinal Müller cells. Mediators of glutamine transport in retinal ganglion cells were investigated. The relative contributions of various transport systems for glutamine uptake (systems N, A, L, y+L, ASCT, and ATB(0,+)) were examined in RGC-5 cells based on differential features of the individual transport systems. mRNA for the genes encoding members of these transport systems were analyzed by RT-PCR. Based on these data, SN1 and SN2 were analyzed in mouse retina, RGC-5 cells, and primary mouse ganglion cells (GCs) by in situ hybridization (ISH), immunofluorescence (IF), and Western blotting. Three transport systems--N, A, and L--participated in glutamine uptake in RGC-5 cells. System N was the principal contributor; systems A and L contributed considerably less. ISH and IF revealed SN1 and SN2 expression in the ganglion, inner nuclear, and photoreceptor cell layers. SN1 and SN2 colocalized with the ganglion cell marker Thy 1.2 and with the Müller cell marker vimentin, confirming their presence in both retinal cell types. SN1 and SN2 proteins were detected in primary mouse GCs. These findings suggest that in addition to its role in glutamine uptake in retinal glial cells, system N contributes significantly to glutamine uptake in ganglion cells and, hence, contributes to the retinal glutamate-glutamine cycle.

  15. Association Between Regular Cannabis Use and Ganglion Cell Dysfunction.

    PubMed

    Schwitzer, Thomas; Schwan, Raymund; Albuisson, Eliane; Giersch, Anne; Lalanne, Laurence; Angioi-Duprez, Karine; Laprevote, Vincent

    2017-01-01

    Because cannabis use is a major public health concern and cannabis is known to act on central neurotransmission, studying the retinal ganglion cells in individuals who regularly use cannabis is of interest. To determine whether the regular use of cannabis could alter the function of retinal ganglion cells in humans. For this case-control study, individuals who regularly use cannabis, as well as healthy controls, were recruited, and data were collected from February 11 to October 28, 2014. Retinal function was used as a direct marker of brain neurotransmission abnormalities in complex mental phenomena. Amplitude and implicit time of the N95 wave on results of pattern electroretinography. Twenty-eight of the 52 participants were regular cannabis users (24 men and 4 women; median age, 22 years [95% CI, 21-24 years]), and the remaining 24 were controls (20 men and 4 women; median age, 24 years [95% CI, 23-27 years]). There was no difference between groups in terms of age (P = .13) or sex (P = .81). After adjustment for the number of years of education and alcohol use, there was a significant increase for cannabis users of the N95 implicit time on results of pattern electroretinography (median, 98.6 milliseconds [95% CI, 93.4-99.5]) compared with controls (median, 88.4 milliseconds [95% CI, 85.0-91.1]), with 8.4 milliseconds as the median of the differences (95% CI, 4.9-11.5; P < .001, Wald logistic regression). A receiver operating characteristic curve analysis (area under the curve, 0.84 [95% CI, 0.73-0.95]; P < .001) revealed, for a cutoff value of 91.13 milliseconds, a sensitivity of 78.6% (95% CI, 60.5%-89.8%) and a specificity of 75.0% (95% CI, 55.1%-88.0%) for correctly classifying both cannabis users and controls in their corresponding group. The positive predictive value was 78.6% (95% CI, 60.5%-89.8%), and the negative predictive value was 75.0% (95% CI, 55.1%-88.0%). Our results demonstrate a delay in transmission of action potentials by the

  16. Delayed rectifier K channels contribute to contrast adaptation in mammalian retinal ganglion cells

    PubMed Central

    Weick, Michael; Demb, Jonathan B.

    2011-01-01

    SUMMARY Retinal ganglion cells adapt by reducing their sensitivity during periods of high contrast. Contrast adaptation in the firing response depends on both presynaptic and intrinsic mechanisms. Here, we investigated intrinsic mechanisms for contrast adaptation in OFF Alpha ganglion cells in the in vitro guinea pig retina. Using either visual stimulation or current injection, we show that brief depolarization evoked spiking and suppressed firing during subsequent depolarization. The suppression could be explained by Na channel inactivation, as shown in salamander cells. However, brief hyperpolarization in the physiological range (5–10 mV) also suppressed firing during subsequent depolarization. This suppression was sensitive selectively to blockers of delayed-rectifier K channels (KDR). Somatic membrane patches showed TEA-sensitive KDR currents with activation near −25 mV and removal of inactivation at voltages negative to Vrest. Brief periods of hyperpolarization apparently remove KDR inactivation and thereby increase the channel pool available to suppress excitability during subsequent depolarization. PMID:21745646

  17. Pine Oil Effects on Chemical and Thermal Injury in Mice and Cultured Mouse Dorsal Root Ganglion Neurons

    PubMed Central

    Clark, SP; Bollag, WB; Westlund, KN; Ma, F; Falls, G; Xie, D; Johnson, M; Isales, CM; Bhattacharyya, MH

    2013-01-01

    A commercial resin-based pine oil derived from Pinus palustris and Pinus elliottii was the major focus of this investigation. Extracts of pine resins, needles and bark are folk medicines commonly used to treat skin ailments, including burns. The American Burn Association estimates that 500,000 people with burn injuries receive medical treatment each year; one-half of US burn victims are children, most with scald burns. This systematic study was initiated as follow-up to personal anecdotal evidence acquired over more than 10 years by MH Bhattacharyya regarding pine oil’s efficacy for treating burns. The results demonstrate that pine oil counteracted dermal inflammation in both a mouse ear model of contact irritant-induced dermal inflammation and a 2nd degree scald burn to the mouse paw. Furthermore, pine oil significantly counteracted the tactile allodynia and soft tissue injury caused by the scald burn. In mouse dorsal root ganglion (DRG) neuronal cultures, pine oil added to the medium blocked ATP-activated, but not capsaicin-activated, pain pathways, demonstrating specificity. These results together support the hypothesis that a pine-oil-based treatment can be developed to provide effective in-home care for 2nd degree burns. PMID:23595692

  18. Atypical fibrosarcomas derived from cutaneous ganglion cell-like cells in 2 domestic Djungarian hamsters (Phodopus sungorus).

    PubMed

    Kondo, Hirotaka; Onuma, Mamoru; Shibuya, Hisashi; Sato, Tsuneo; Abbott, Jeffrey R

    2011-07-01

    Androgen-dependent atypical fibromas are benign tumors derived from ganglion-cell-like cells that are particular to Djungarian hamsters (Phodopus sungorus). Masses excised from 2 hamsters were composed of pleomorphic ganglion cell-like cells supported by small to moderate amounts of collagenous matrix. Intracytoplasmic fibrils were present in silver-stained sections, and immunohistochemistry showed that the cells expressed vimentin, androgen receptor, and, in one case, estrogen receptor α. In contrast to previously reported atypical fibromas, these tumors had features of anaplasia and were locally invasive. We diagnosed the tumors as atypical fibrosarcomas and consider them an unusual malignant counterpart of atypical fibroma. Copyright 2011 by the American Association for Laboratory Animal Science

  19. Adult Human Nasal Mesenchymal-Like Stem Cells Restore Cochlear Spiral Ganglion Neurons After Experimental Lesion

    PubMed Central

    Bas, Esperanza; Van De Water, Thomas R.; Lumbreras, Vicente; Rajguru, Suhrud; Goss, Garrett; Hare, Joshua M.

    2014-01-01

    A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic. PMID:24172073

  20. GDF15 is elevated in mice following retinal ganglion cell death and in glaucoma patients

    PubMed Central

    Ban, Norimitsu; Siegfried, Carla J.; Lin, Jonathan B.; Shui, Ying-Bo; Sein, Julia; Pita-Thomas, Wolfgang; Sene, Abdoulaye; Santeford, Andrea; Gordon, Mae; Lamb, Rachel; Dong, Zhenyu; Kelly, Shannon C.; Cavalli, Valeria; Yoshino, Jun

    2017-01-01

    Glaucoma is the second leading cause of blindness worldwide. Physicians often use surrogate endpoints to monitor the progression of glaucomatous neurodegeneration. These approaches are limited in their ability to quantify disease severity and progression due to inherent subjectivity, unreliability, and limitations of normative databases. Therefore, there is a critical need to identify specific molecular markers that predict or measure glaucomatous neurodegeneration. Here, we demonstrate that growth differentiation factor 15 (GDF15) is associated with retinal ganglion cell death. Gdf15 expression in the retina is specifically increased after acute injury to retinal ganglion cell axons and in a murine chronic glaucoma model. We also demonstrate that the ganglion cell layer may be one of the sources of secreted GDF15 and that GDF15 diffuses to and can be detected in aqueous humor (AH). In validating these findings in human patients with glaucoma, we find not only that GDF15 is increased in AH of patients with primary open angle glaucoma (POAG), but also that elevated GDF15 levels are significantly associated with worse functional outcomes in glaucoma patients, as measured by visual field testing. Thus, GDF15 maybe a reliable metric of glaucomatous neurodegeneration, although further prospective validation studies will be necessary to determine if GDF15 can be used in clinical practice. PMID:28469085

  1. Expression of zinc transporter ZnT7 in mouse superior cervical ganglion

    USDA-ARS?s Scientific Manuscript database

    The superior cervical ganglion (SCG) neurons contain a considerable amount of zinc ions, but little is known about zinc homeostasis in the SCG. It is known that zinc transporter 7 (ZnT7, Slc30a7), a member of the Slc30 ZnT family, is involved in mobilizing zinc ions from the cytoplasm into the Golgi...

  2. Chemokine CXCL13 mediates orofacial neuropathic pain via CXCR5/ERK pathway in the trigeminal ganglion of mice.

    PubMed

    Zhang, Qian; Cao, De-Li; Zhang, Zhi-Jun; Jiang, Bao-Chun; Gao, Yong-Jing

    2016-07-11

    Trigeminal nerve damage-induced neuropathic pain is a severely debilitating chronic orofacial pain syndrome. Spinal chemokine CXCL13 and its receptor CXCR5 were recently demonstrated to play a pivotal role in the pathogenesis of spinal nerve ligation-induced neuropathic pain. Whether and how CXCL13/CXCR5 in the trigeminal ganglion (TG) mediates orofacial pain are unknown. The partial infraorbital nerve ligation (pIONL) was used to induce trigeminal neuropathic pain in mice. The expression of ATF3, CXCL13, CXCR5, and phosphorylated extracellular signal-regulated kinase (pERK) in the TG was detected by immunofluorescence staining and western blot. The effect of shRNA targeting on CXCL13 or CXCR5 on pain hypersensitivity was checked by behavioral testing. pIONL induced persistent mechanical allodynia and increased the expression of ATF3, CXCL13, and CXCR5 in the TG. Inhibition of CXCL13 or CXCR5 by shRNA lentivirus attenuated pIONL-induced mechanical allodynia. Additionally, pIONL-induced neuropathic pain and the activation of ERK in the TG were reduced in Cxcr5 (-/-) mice. Furthermore, MEK inhibitor (PD98059) attenuated mechanical allodynia and reduced TNF-α and IL-1β upregulation induced by pIONL. TNF-α inhibitor (Etanercept) and IL-1β inhibitor (Diacerein) attenuated pIONL-induced orofacial pain. Finally, intra-TG injection of CXCL13 induced mechanical allodynia, increased the activation of ERK and the production of TNF-α and IL-1β in the TG of WT mice, but not in Cxcr5 (-/-) mice. Pretreatment with PD98059, Etanercept, or Diacerein partially blocked CXCL13-induced mechanical allodynia, and PD98059 also reduced CXCL13-induced TNF-α and IL-1β upregulation. CXCL13 and CXCR5 contribute to orofacial pain via ERK-mediated proinflammatory cytokines production. Targeting CXCL13/CXCR5/ERK/TNF-α and IL-1β pathway in the trigeminal ganglion may offer effective treatment for orofacial neuropathic pain.

  3. Temporal Evaluation of Neurosensory Complications After Mandibular Third Molar Extraction: Current Problems for Diagnosis and Treatment.

    PubMed

    Akashi, Masaya; Hiraoka, Yujiro; Hasegawa, Takumi; Komori, Takahide

    2016-01-01

    This retrospective study aimed to report the incidence of neurosensory complications after third molar extraction and also to identify current problems and discuss appropriate management of these complications. Patients who underwent extraction of deeply impacted mandibular third molars under general anesthesia were included. The following epidemiological data were retrospectively gathered from medical charts: type of neurosensory complication, treatment for complication, and outcome. A total 369 mandibular third molars were extracted in 210 patients under general anesthesia during this study period. Thirty-one of the 369 teeth (8.4%) in 31 patients had neurosensory complications during the first postoperative week resulting from inferior alveolar nerve damage. Neurosensory complications lasting from 1 to 3 months postoperatively included 17 cases of hypoesthesia and 8 of dysesthesia in 19 patients. Five cases of hypoesthesia and 4 of dysesthesia in 5 patients persisted over 1 year postoperatively. Sixteen of 369 teeth (4.3%) in 16 patients had persistent neurosensory complications after third molar extraction under general anesthesia. Stellate ganglion block was performed in 4 patients. Early initiation of stellate ganglion block (within 2 weeks postoperatively) produced better outcomes than late stellate ganglion block (over 6 months postoperatively). Refractory neurosensory complications after third molar extraction often combine both hypoesthesia and dysesthesia. Current problems in diagnosis and treatment included delayed detection of dysesthesia and the lack of uniform timing of stellate ganglion block. In the future, routinely inquiring about dysesthesia and promptly providing affected patients with information about stellate ganglion block might produce better outcomes.

  4. Temporal Evaluation of Neurosensory Complications After Mandibular Third Molar Extraction: Current Problems for Diagnosis and Treatment

    PubMed Central

    Akashi, Masaya; Hiraoka, Yujiro; Hasegawa, Takumi; Komori, Takahide

    2016-01-01

    Objective: This retrospective study aimed to report the incidence of neurosensory complications after third molar extraction and also to identify current problems and discuss appropriate management of these complications. Method: Patients who underwent extraction of deeply impacted mandibular third molars under general anesthesia were included. The following epidemiological data were retrospectively gathered from medical charts: type of neurosensory complication, treatment for complication, and outcome. Results: A total 369 mandibular third molars were extracted in 210 patients under general anesthesia during this study period. Thirty-one of the 369 teeth (8.4%) in 31 patients had neurosensory complications during the first postoperative week resulting from inferior alveolar nerve damage. Neurosensory complications lasting from 1 to 3 months postoperatively included 17 cases of hypoesthesia and 8 of dysesthesia in 19 patients. Five cases of hypoesthesia and 4 of dysesthesia in 5 patients persisted over 1 year postoperatively. Sixteen of 369 teeth (4.3%) in 16 patients had persistent neurosensory complications after third molar extraction under general anesthesia. Stellate ganglion block was performed in 4 patients. Early initiation of stellate ganglion block (within 2 weeks postoperatively) produced better outcomes than late stellate ganglion block (over 6 months postoperatively). Conclusion: Refractory neurosensory complications after third molar extraction often combine both hypoesthesia and dysesthesia. Current problems in diagnosis and treatment included delayed detection of dysesthesia and the lack of uniform timing of stellate ganglion block. In the future, routinely inquiring about dysesthesia and promptly providing affected patients with information about stellate ganglion block might produce better outcomes. PMID:28217188

  5. Functional Pattern of Increasing Concentrations of Brain-Derived Neurotrophic Factor in Spiral Ganglion: Implications for Research on Cochlear Implants.

    PubMed

    Ramku, Emina; Ramku, Refik; Spanca, Dugagjin; Zhjeqi, Valbona

    2017-04-15

    As previously various studies have suggested application of brain-derived neurotrophic factor (BDNF) may be considered as a promising future therapy for hearing deficits, in particular for the improvement of cochlear neurone loss during cochlear implantation. The present study's aim was to establish the upper threshold of the concentration of BDNF in Naval Medical Research Institute (NMRI) mice spiral ganglion outgrowth. Spiral ganglion explants were prepared from post-natal day 4 (p4) (NMRI) mice of both sexes under the approval and guidelines of the regional council of Hearing Research Institute Tubingen. Spiral ganglion explants were cultured at postnatal days 4 in the presence of different concentrations of BDNF as described under methods. We chose an age of postnatal day (P4) and concentrations of BDNF 0; 6; 12.5; 25 and 50 ƞg/ml. Averaged neurite outgrowth is measured in 4 different cultures that were treated with different concentrations. Results show that with increasing concentrations of BDNF, the neurite density increases. The present finding show evidence that BDNF has a clear incremental effect on the number of neurites of spiral ganglia in the prehearing organ, but less on the neurite length. The upper threshold of exogenous BNDF concentration on spiral ganglion explant is 25 ƞg/ml. This means that concentration beyond this level has no further incremental impact. Therefore our suggestion for hydrogel concentration in NMRA mice in future research should be 25 ƞg/ml.

  6. Comparative expression analysis of POU4F1, POU4F2 and ISL1 in developing mouse cochleovestibular ganglion neurons

    PubMed Central

    Deng, Min; Yang, Hua; Xie, Xiaoling; Liang, Guoqing; Gan, Lin

    2014-01-01

    POU-homeodomain and LIM-homeodomain transcription factors are expressed in developing projection neurons within retina, inner ear, dorsal root ganglion, and trigeminal ganglion, and play synergistic roles in their differentiation and survival. Here, using immunohistochemistry, we present a comparative analysis of the spatiotemporal expression pattern of POU4F1, POU4F2, and ISL1 during the development of cochleovestibular ganglion (CVG) neurons in mouse inner ear. At early stages, when otic neurons are first detected in the otic epithelium (OE) and migrate into periotic mesenchyme to form the CVG, POU4F1 and ISL1 are co-expressed in a majority of the delaminated CVG neurons, which are marked by NEUROD1 expression, but POU4F1 is absent in the otic epithelium. The onset of POU4F2 expression starts after that of POU4F1 and ISL1, and is observed in the NEUROD1-negative, post-mitotic CVG neurons. When the CVG neurons innervate the vestibular and cochlear sensory organs, the expression of POU4F1, POU4F2, and ISL1 continues in both vestibular and spiral ganglion cells. Later in development, POU4F1 expression becomes down-regulated in a majority of spiral ganglion (SG) neurons and more neurons express POU4F2 expression while ISL1 expression is maintained. The differential as well as overlapping expression of POU4F1, POU4F2, and ISL1 combined with previous studies suggests possible functional interaction and regulatory relationship of these transcription factors in the development of inner ear neurons. PMID:24709358

  7. Expression and Function of System N Glutamine Transporters (SN1/SN2 or SNAT3/SNAT5) in Retinal Ganglion Cells

    PubMed Central

    Umapathy, Nagavedi S.; Dun, Ying; Martin, Pamela M.; Duplantier, Jennifer N.; Roon, Penny; Prasad, Puttur; Smith, Sylvia B.; Ganapathy, Vadivel

    2008-01-01

    Purpose Glutamine transport is essential for the glutamate-glutamine cycle, which occurs between neurons and glia. System N, consisting of SN1 (SNAT3) and SN2 (SNAT5), is the principal mediator of glutamine transport in retinal Müller cells. Mediators of glutamine transport in retinal ganglion cells were investigated. Methods The relative contributions of various transport systems for glutamine uptake (systems N, A, L, y+L, ASCT, and ATB0,+) were examined in RGC-5 cells based on differential features of the individual transport systems. mRNA for the genes encoding members of these transport systems were analyzed by RT-PCR. Based on these data, SN1 and SN2 were analyzed in mouse retina, RGC-5 cells, and primary mouse ganglion cells (GCs) by in situ hybridization (ISH), immunofluorescence (IF), and Western blotting. Results Three transport systems—N, A, and L—participated in glutamine uptake in RGC-5 cells. System N was the principal contributor; systems A and L contributed considerably less. ISH and IF revealed SN1 and SN2 expression in the ganglion, inner nuclear, and photoreceptor cell layers. SN1 and SN2 colocalized with the ganglion cell marker Thy 1.2 and with the Müller cell marker vimentin, confirming their presence in both retinal cell types. SN1 and SN2 proteins were detected in primary mouse GCs. Conclusions These findings suggest that in addition to its role in glutamine uptake in retinal glial cells, system N contributes significantly to glutamine uptake in ganglion cells and, hence, contributes to the retinal glutamate-glutamine cycle. PMID:18689705

  8. The Three-Dimensional Culture System with Matrigel and Neurotrophic Factors Preserves the Structure and Function of Spiral Ganglion Neuron In Vitro.

    PubMed

    Sun, Gaoying; Liu, Wenwen; Fan, Zhaomin; Zhang, Daogong; Han, Yuechen; Xu, Lei; Qi, Jieyu; Zhang, Shasha; Gao, Bradley T; Bai, Xiaohui; Li, Jianfeng; Chai, Renjie; Wang, Haibo

    2016-01-01

    Whole organ culture of the spiral ganglion region is a resourceful model system facilitating manipulation and analysis of live sprial ganglion neurons (SGNs). Three-dimensional (3D) cultures have been demonstrated to have many biomedical applications, but the effect of 3D culture in maintaining the SGNs structure and function in explant culture remains uninvestigated. In this study, we used the matrigel to encapsulate the spiral ganglion region isolated from neonatal mice. First, we optimized the matrigel concentration for the 3D culture system and found the 3D culture system protected the SGNs against apoptosis, preserved the structure of spiral ganglion region, and promoted the sprouting and outgrowth of SGNs neurites. Next, we found the 3D culture system promoted growth cone growth as evidenced by a higher average number and a longer average length of filopodia and a larger growth cone area. 3D culture system also significantly elevated the synapse density of SGNs. Last, we found that the 3D culture system combined with neurotrophic factors had accumulated effects in promoting the neurites outgrowth compared with 3D culture or NFs treatment only groups. Together, we conclude that the 3D culture system preserves the structure and function of SGN in explant culture.

  9. In vivo fluorescence imaging of primate retinal ganglion cells and retinal pigment epithelial cells

    NASA Astrophysics Data System (ADS)

    Gray, Daniel C.; Merigan, William; Wolfing, Jessica I.; Gee, Bernard P.; Porter, Jason; Dubra, Alfredo; Twietmeyer, Ted H.; Ahamd, Kamran; Tumbar, Remy; Reinholz, Fred; Williams, David R.

    2006-08-01

    The ability to resolve single cells noninvasively in the living retina has important applications for the study of normal retina, diseased retina, and the efficacy of therapies for retinal disease. We describe a new instrument for high-resolution, in vivo imaging of the mammalian retina that combines the benefits of confocal detection, adaptive optics, multispectral, and fluorescence imaging. The instrument is capable of imaging single ganglion cells and their axons through retrograde transport in ganglion cells of fluorescent dyes injected into the monkey lateral geniculate nucleus (LGN). In addition, we demonstrate a method involving simultaneous imaging in two spectral bands that allows the integration of very weak signals across many frames despite inter-frame movement of the eye. With this method, we are also able to resolve the smallest retinal capillaries in fluorescein angiography and the mosaic of retinal pigment epithelium (RPE) cells with lipofuscin autofluorescence.

  10. Combined application of BDNF to the eye and brain enhances ganglion cell survival and function in the cat after optic nerve injury.

    PubMed

    Weber, Arthur J; Viswanáthan, Suresh; Ramanathan, Chidambaram; Harman, Christine D

    2010-01-01

    To determine whether application of BDNF to the eye and brain provides a greater level of neuroprotection after optic nerve injury than treatment of the eye alone. Retinal ganglion cell survival and pattern electroretinographic responses were compared in normal cat eyes and in eyes that received (1) a mild nerve crush and no treatment, (2) a single intravitreal injection of BDNF at the time of the nerve injury, or (3) intravitreal treatment combined with 1 to 2 weeks of continuous delivery of BDNF to the visual cortex, bilaterally. Relative to no treatment, administration of BDNF to the eye alone resulted in a significant increase in ganglion cell survival at both 1 and 2 weeks after nerve crush (1 week, 79% vs. 55%; 2 weeks, 60% vs. 31%). Combined treatment of the eye and visual cortex resulted in a modest additional increase (17%) in ganglion cell survival in the 1-week eyes, a further significant increase (55%) in the 2-week eyes, and ganglion cell survival levels for both that were comparable to normal (92%-93% survival). Pattern ERG responses for all the treated eyes were comparable to normal at 1 week after injury; however, at 2 weeks, only the responses of eyes receiving the combined BDNF treatment remained so. Although treatment of the eye alone with BDNF has a significant impact on ganglion cell survival after optic nerve injury, combined treatment of the eye and brain may represent an even more effective approach and should be considered in the development of future optic neuropathy-related neuroprotection strategies.

  11. G(o) transduces GABAB-receptor modulation of N-type calcium channels in cultured dorsal root ganglion neurons.

    PubMed

    Menon-Johansson, A S; Berrow, N; Dolphin, A C

    1993-11-01

    High-voltage-activated (HVA) calcium channel currents (IBa) were recorded from acutely replated cultured dorsal root ganglion (DRG) neurons. IBa was irreversibly inhibited by 56.9 +/- 2.7% by 1 microM omega-conotoxin-GVIA (omega-CTx-GVIA), whereas the 1,4-dihydropyridine antagonist nicardipine was ineffective. The selective gamma-aminobutyric acidB (GABAB) agonist, (-)-baclofen (50 microM), inhibited the HVA IBa by 30.7 +/- 5.4%. Prior application of omega-CTx-GVIA completely occluded inhibition of the HVA IBa by (-)-baclofen, indicating that in this preparation (-)-baclofen inhibits N-type current. To investigate which G protein subtype was involved, cells were replated in the presence of anti-G protein antisera. Under these conditions the antibodies were shown to enter the cells through transient pores created during the replating procedure. Replating DRGs in the presence of anti-G(o) antiserum, raised against the C-terminal decapeptide of the G alpha o subunit, reduced (-)-baclofen inhibition of the HVA IBa, whereas replating DRGs in the presence of the anti-Gi antiserum did not. Using anti-G alpha o antisera (1:2000) and confocal laser microscopy, G alpha o localisation was investigated in both unreplated and replated neurons. G alpha o immunoreactivity was observed at the plasma membrane, neurites, attachment plaques and perinuclear region, and was particularly pronounced at points of cell-to-cell contact. The plasma membrane G alpha o immunoreactivity was completely blocked by preincubation with the immunising G alpha o undecapeptide (1 microgram.ml-1) for 1 h at 37 degrees C. A similar treatment also blocked recognition of G alpha o in brain membranes on immunoblots.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Organ of Corti explants direct tonotopically graded morphology of spiral ganglion neurons in vitro.

    PubMed

    Smith, Felicia L; Davis, Robin L

    2016-08-01

    The spiral ganglion is a compelling model system to examine how morphological form contributes to sensory function. While the ganglion is composed mainly of a single class of type I neurons that make simple one-to-one connections with inner hair cell sensory receptors, it has an elaborate overall morphological design. Specific features, such as soma size and axon outgrowth, are graded along the spiral contour of the cochlea. To begin to understand the interplay between different regulators of neuronal morphology, we cocultured neuron explants with peripheral target tissues removed from distinct cochlear locations. Interestingly, these "hair cell microisolates" were capable of both increasing and decreasing neuronal somata size, without adversely affecting survival. Moreover, axon characteristics elaborated de novo by the primary afferents in culture were systematically regulated by the sensory endorgan. Apparent peripheral nervous system (PNS)-like and central nervous system (CNS)-like axonal profiles were established in our cocultures allowing an analysis of putative PNS/CNS axon length ratios. As predicted from the in vivo organization, PNS-like axon bundles elaborated by apical cocultures were longer than their basal counterparts and this phenotype was methodically altered when neuron explants were cocultured with microisolates from disparate cochlear regions. Thus, location-dependent signals within the organ of Corti may set the "address" of neurons within the spiral ganglion, allowing them to elaborate the appropriate tonotopically associated morphological features in order to carry out their signaling function. J. Comp. Neurol. 524:2182-2207, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  13. Macular ganglion cell imaging study: glaucoma diagnostic accuracy of spectral-domain optical coherence tomography.

    PubMed

    Jeoung, Jin Wook; Choi, Yun Jeong; Park, Ki Ho; Kim, Dong Myung

    2013-07-01

    We evaluated the diagnostic accuracy of macular ganglion cell-inner plexiform layer (GCIPL) measurements using a high-definition optical coherence tomography (Cirrus HD-OCT) ganglion cell analysis algorithm for detecting early and moderate-to-severe glaucoma. Totals of 119 normal subjects and 306 glaucoma patients (164 patients with early glaucoma and 142 with moderate-to-severe glaucoma) were enrolled from the Macular Ganglion Cell Imaging Study. Macular GCIPL, peripapillary retinal nerve fiber layer (RNFL) thickness, and optic nerve head (ONH) parameters were measured in each subject. Areas under the receiver operating characteristic curves (AUROCs) were calculated and compared. Based on the internal normative database, the sensitivity and specificity for detecting early and moderate-to-severe glaucoma were calculated. There was no statistically significant difference between the AUROCs for the best OCT parameters. For detecting early glaucoma, the sensitivity of the Cirrus GCIPL parameters ranged from 26.8% to 73.2% and that of the Cirrus RNFL parameters ranged from 6.1% to 61.6%. For the early glaucoma group, the best parameter from the GCIPL generally had a higher sensitivity than those of the RNFL and ONH parameters with comparable specificity (P < 0.05, McNemar's test). There were no significant differences between the AUROCs for Cirrus GCIPL, RNFL, and ONH parameters, indicating that these maps have similar diagnostic potentials for glaucoma. The minimum GCIPL showed better glaucoma diagnostic performance than the other parameters at comparable specificities. However, other GCIPL parameters showed performances comparable to those of the RNFL parameters.

  14. Separability of stimulus parameter encoding by on-off directionally selective rabbit retinal ganglion cells

    PubMed Central

    Nowak, Przemyslaw; Dobbins, Allan C.; Gawne, Timothy J.; Grzywacz, Norberto M.

    2011-01-01

    The ganglion cell output of the retina constitutes a bottleneck in sensory processing in that ganglion cells must encode multiple stimulus parameters in their responses. Here we investigate encoding strategies of On-Off directionally selective retinal ganglion cells (On-Off DS RGCs) in rabbits, a class of cells dedicated to representing motion. The exquisite axial discrimination of these cells to preferred vs. null direction motion is well documented: it is invariant with respect to speed, contrast, spatial configuration, spatial frequency, and motion extent. However, these cells have broad direction tuning curves and their responses also vary as a function of other parameters such as speed and contrast. In this study, we examined whether the variation in responses across multiple stimulus parameters is systematic, that is the same for all cells, and separable, such that the response to a stimulus is a product of the effects of each stimulus parameter alone. We extracellularly recorded single On-Off DS RGCs in a superfused eyecup preparation while stimulating them with moving bars. We found that spike count responses of these cells scaled as independent functions of direction, speed, and luminance. Moreover, the speed and luminance functions were common across the whole sample of cells. Based on these findings, we developed a model that accurately predicted responses of On-Off DS RGCs as products of separable functions of direction, speed, and luminance (r = 0.98; P < 0.0001). Such a multiplicatively separable encoding strategy may simplify the decoding of these cells' outputs by the higher visual centers. PMID:21325684

  15. Effects of 4-phenyl butyric acid on high glucose-induced alterations in dorsal root ganglion neurons.

    PubMed

    Sharma, Dilip; Singh, Jitendra Narain; Sharma, Shyam S

    2016-12-02

    Mechanisms and pathways involving in diabetic neuropathy are still not fully understood but can be unified by the process of overproduction of reactive oxygen species (ROS) such as superoxide, endoplasmic reticulum (ER) stress, downstream intracellular signaling pathways and their modulation. Susceptibility of dorsal root ganglion (DRG) to internal/external hyperglycemic environment stress contributes to the pathogenesis and progression of diabetic neuropathy. ER stress leads to abnormal ion channel function, gene expression, transcriptional regulation, metabolism and protein folding. 4-phenyl butyric acid (4-PBA) is a potent and selective chemical chaperone; which may inhibit ER stress. It may be hypothesized that 4-PBA could attenuate via channels in DRG in diabetic neuropathy. Effects of 4-PBA were determined by applying different parameters of oxidative stress, cell viability, apoptosis assays and channel expression in cultured DRG neurons. Hyperglycemia-induced apoptosis in the DRG neuron was inhibited by 4-PBA. Cell viability of DRG neurons was not altered by 4-PBA. Oxidative stress was significantly blocked by the 4-PBA. Sodium channel expression was not altered by the 4-PBA. Our data provide evidence that the hyperglycemia-induced alteration may be reduced by the 4-PBA without altering the sodium channel expression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Petrosal ganglion: a more complex role than originally imagined.

    PubMed

    Retamal, Mauricio A; Reyes, Edison P; Alcayaga, Julio

    2014-01-01

    The petrosal ganglion (PG) is a peripheral sensory ganglion, composed of pseudomonopolar sensory neurons that innervate the posterior third of the tongue and the carotid sinus and body. According to their electrical properties PG neurons can be ascribed to one of two categories: (i) neurons with action potentials presenting an inflection (hump) on its repolarizing phase and (ii) neurons with fast and brisk action potentials. Although there is some correlation between the electrophysiological properties and the sensory modality of the neurons in some species, no general pattern can be easily recognized. On the other hand, petrosal neurons projecting to the carotid body are activated by several transmitters, with acetylcholine and ATP being the most conspicuous in most species. Petrosal neurons are completely surrounded by a multi-cellular sheet of glial (satellite) cells that prevents the formation of chemical or electrical synapses between neurons. Thus, PG neurons are regarded as mere wires that communicate the periphery (i.e., carotid body) and the central nervous system. However, it has been shown that in other sensory ganglia satellite glial cells and their neighboring neurons can interact, partly by the release of chemical neuro-glio transmitters. This intercellular communication can potentially modulate the excitatory status of sensory neurons and thus the afferent discharge. In this mini review, we will briefly summarize the general properties of PG neurons and the current knowledge about the glial-neuron communication in sensory neurons and how this phenomenon could be important in the chemical sensory processing generated in the carotid body.

  17. Inhibitory Effects of Honokiol on the Voltage-Gated Potassium Channels in Freshly Isolated Mouse Dorsal Root Ganglion Neurons.

    PubMed

    Sheng, Anqi; Zhang, Yan; Li, Guang; Zhang, Guangqin

    2018-02-01

    Voltage-gated potassium (K V ) currents, subdivided into rapidly inactivating A-type currents (I A ) and slowly inactivating delayed rectifier currents (I K ), play a fundamental role in modulating pain by controlling neuronal excitability. The effects of Honokiol (Hon), a natural biphenolic compound derived from Magnolia officinalis, on K V currents were investigated in freshly isolated mouse dorsal root ganglion neurons using the whole-cell patch clamp technique. Results showed that Hon inhibited I A and I K in concentration-dependent manner. The IC 50 values for block of I A and I K were 30.5 and 25.7 µM, respectively. Hon (30 µM) shifted the steady-state activation curves of I A and I K to positive potentials by 17.6 and 16.7 mV, whereas inactivation and recovery from the inactivated state of I A were unaffected. These results suggest that Hon preferentially interacts with the active states of the I A and I K channels, and has no effect on the resting state and inactivated state of the I A channel. Blockade on K + channels by Hon may contribute to its antinociceptive effect, especially anti-inflammatory pain.

  18. Signalling mechanism for somatostatin receptor 5-mediated suppression of AMPA responses in rat retinal ganglion cells.

    PubMed

    Deng, Qin-Qin; Sheng, Wen-Long; Zhang, Gong; Weng, Shi-Jun; Yang, Xiong-Li; Zhong, Yong-Mei

    2016-08-01

    Somatostatin (SRIF) is involved in a variety of physiological functions via the activation of five subtypes of specific receptors (sst1-5). Here, we investigated the effects of SRIF on AMPA receptor (AMPAR)-mediated currents (AMPA currents) in isolated rat retinal ganglion cells (GCs) using patch-clamp techniques. Immunofluorescence double labelling demonstrated the expression of sst5 in rat GCs. Consistent to this, whole cell AMPA currents of GCs were dose-dependently suppressed by SRIF, and the effect was reversed by the sst5 antagonist BIM-23056. Intracellular dialysis of GDP-β-S or pre-incubation with the Gi/o inhibitor pertussis toxin (PTX) abolished the SRIF effect. The SRIF effect was mimicked by the administration of either 8-Br-cAMP or forskolin, but was eliminated by the protein kinase A (PKA) antagonists H-89/KT5720/Rp-cAMP. Moreover, SRIF increased intracellular Ca(2+) levels and did not suppress the AMPA currents when GCs were infused with an intracellular Ca(2+)-free solution or in the presence of ryanodine receptor modulators caffeine/ryanodine. Furthermore, the SRIF effect was eliminated when the activity of calmodulin (CaM), calcineurin and protein phosphatase 1 (PP1) was blocked with W-7, FK-506 and okadaic acid, respectively. SRIF persisted to suppress the AMPA currents when cGMP-protein kinase G (PKG) and phosphatidylinositol (PI)-/phosphatidylcholine (PC)-phospholipase C (PLC) signalling pathways were blocked. In rat flat-mount retinas, SRIF suppressed AMPAR-mediated light-evoked excitatory postsynaptic currents (L-EPSCs) in GCs. We conclude that a distinct Gi/o/cAMP-PKA/ryanodine/Ca(2+)/CaM/calcineurin/PP1 signalling pathway comes into play due to the activation of sst5 to mediate the SRIF effect on GCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Suprascapular Nerve Entrapment Caused by Protrusion of an Intraosseous Ganglion of the Glenoid into the Spinoglenoid Notch: A Rare Cause of Posterior Shoulder Pain

    PubMed Central

    Terabayashi, Nobuo; Nishimoto, Yutaka; Akiyama, Haruhiko

    2017-01-01

    We describe a case of suprascapular nerve entrapment caused by protrusion of an intraosseous ganglion of the glenoid into the spinoglenoid notch. A 47-year-old man with left shoulder pain developed an intraosseous cyst in the left glenoid, which came into contact with the suprascapular nerve. The area at which the patient experienced spontaneous shoulder pain was innervated by the suprascapular nerve, and 1% xylocaine injection into the spinoglenoid notch under ultrasonographic guidance relieved the pain. Therefore, we concluded that the protrusion of an intraosseous cyst of the glenoid into the spinoglenoid notch was a cause of the pain, and performed curettage. Consequently, the shoulder pain was resolved promptly without suprascapular nerve complications, and the cyst was histologically diagnosed as an intraosseous ganglion. This case demonstrated that the intraosseous ganglion of the glenoid was a benign lesion but could be a cause of suprascapular nerve entrapment syndrome. Curettage is a useful treatment option for a ganglion inside bone and very close to the suprascapular nerve. PMID:28620557

  20. Unmasking of spiral ganglion neuron firing dynamics by membrane potential and neurotrophin-3.

    PubMed

    Crozier, Robert A; Davis, Robin L

    2014-07-16

    Type I spiral ganglion neurons have a unique role relative to other sensory afferents because, as a single population, they must convey the richness, complexity, and precision of auditory information as they shape signals transmitted to the brain. To understand better the sophistication of spiral ganglion response properties, we compared somatic whole-cell current-clamp recordings from basal and apical neurons obtained during the first 2 postnatal weeks from CBA/CaJ mice. We found that during this developmental time period neuron response properties changed from uniformly excitable to differentially plastic. Low-frequency, apical and high-frequency basal neurons at postnatal day 1 (P1)-P3 were predominantly slowly accommodating (SA), firing at low thresholds with little alteration in accommodation response mode induced by changes in resting membrane potential (RMP) or added neurotrophin-3 (NT-3). In contrast, P10-P14 apical and basal neurons were predominately rapidly accommodating (RA), had higher firing thresholds, and responded to elevation of RMP and added NT-3 by transitioning to the SA category without affecting the instantaneous firing rate. Therefore, older neurons appeared to be uniformly less excitable under baseline conditions yet displayed a previously unrecognized capacity to change response modes dynamically within a remarkably stable accommodation framework. Because the soma is interposed in the signal conduction pathway, these specializations can potentially lead to shaping and filtering of the transmitted signal. These results suggest that spiral ganglion neurons possess electrophysiological mechanisms that enable them to adapt their response properties to the characteristics of incoming stimuli and thus have the capacity to encode a wide spectrum of auditory information. Copyright © 2014 the authors 0270-6474/14/349688-15$15.00/0.

  1. Tumor necrosis factor-α stimulation of calcitonin gene-related peptide expression and secretion from rat trigeminal ganglion neurons

    PubMed Central

    Bowen, Elizabeth J.; Schmidt, Thomas W.; Firm, Christina S.; Russo, Andrew F.; Durham, Paul L.

    2006-01-01

    Expression of the neuropeptide calcitonin gene-related peptide (CGRP) in trigeminal ganglion is implicated in neurovascular headaches and temporomandibular joint disorders. Elevation of cytokines contributes to the pathology of these diseases. However, a connection between cytokines and CGRP gene expression in trigeminal ganglion nerves has not been established. We have focused on the effects of the cytokine tumor necrosis factorα (TNFα). TNFR1 receptors were found on the majority of CGRP-containing rat trigeminal ganglion neurons. Treatment of cultures with TNFα stimulated CGRP secretion. In addition, the intracellular signaling intermediate from the TNFR1 receptor, ceramide, caused a similar increase in CGRP release. TNFα caused a coordinate increase in CGRP promoter activity. TNFα treatment activated the transcription factor NF-κB, as well as the Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways. The importance of TNFα induction of MAP kinase pathways was demonstrated by inhibiting MAP kinases with pharmacological reagents and gene transfer with an adenoviral vector encoding MAP kinase phosphatase-1 (MKP-1). We propose that selective and regulated inhibition of MAP kinases in trigeminal neurons may be therapeutically beneficial for inflammatory disorders involving elevated CGRP levels. PMID:16277606

  2. Ganglion cyst arising from the composite occipito-atlanto-axial joint cavity in a cat.

    PubMed

    Aikawa, T; Sadahiro, S; Nishimura, M; Miyazaki, Y; Shibata, M

    2014-01-01

    A four-year-old, female spayed Domestic Longhaired cat was referred for evaluation with a two month history of initial inability to jump progressing to ambulatory tetraparesis. Magnetic resonance imaging studies demonstrated a cystic lesion arising from the composite occipito-atlanto-axial joint cavity and extending to the region of the occipital bone and the axis. The lesion surrounded the spinal canal, causing moderate dorsal spinal cord compression at the atlanto-occipital joint. A dynamic myelographic study demonstrated attenuation of the dorsal contrast column at the atlanto-occipital joint when the cervical spine was positioned in extension. Partial excision of the cyst capsule by a ventral approach resulted in long-term (64 months) resolution of clinical signs. Histological evaluation was consistent with a ganglion cyst. An intra-spinal ganglion cyst arising from the composite occipito-atlanto-axial joint cavity may be considered as an uncommon differential diagnosis for cats with cervical myelopathy.

  3. Delayed-rectifier K channels contribute to contrast adaptation in mammalian retinal ganglion cells.

    PubMed

    Weick, Michael; Demb, Jonathan B

    2011-07-14

    Retinal ganglion cells adapt by reducing their sensitivity during periods of high contrast. Contrast adaptation in the firing response depends on both presynaptic and intrinsic mechanisms. Here, we investigated intrinsic mechanisms for contrast adaptation in OFF Alpha ganglion cells in the in vitro guinea pig retina. Using either visual stimulation or current injection, we show that brief depolarization evoked spiking and suppressed firing during subsequent depolarization. The suppression could be explained by Na channel inactivation, as shown in salamander cells. However, brief hyperpolarization in the physiological range (5-10 mV) also suppressed firing during subsequent depolarization. This suppression was selectively sensitive to blockers of delayed-rectifier K channels (K(DR)). In somatic membrane patches, we observed tetraethylammonium-sensitive K(DR) currents that activated near -25 mV. Recovery from inactivation occurred at potentials hyperpolarized to V(rest). Brief periods of hyperpolarization apparently remove K(DR) inactivation and thereby increase the channel pool available to suppress excitability during subsequent depolarization. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Activation of the ζ receptor 1 suppresses NMDA responses in rat retinal ganglion cells.

    PubMed

    Zhang, X-J; Liu, L-L; Jiang, S-X; Zhong, Y-M; Yang, X-L

    2011-03-17

    The sigma receptor 1 (σR1) has been shown to modulate the activity of several voltage- and ligand-gated channels. Using patch-clamp techniques in rat retinal slice preparations, we demonstrated that activation of σR1 by SKF10047 (SKF) or PRE-084 suppressed N-methyl-D-aspartate (NMDA) receptor-mediated current responses from both ON and OFF type ganglion cells (GCs), dose-dependently, and the effect could be blocked by the σR1 antagonist BD1047 or the σR antagonist haloperidol. The suppression by SKF of NMDA currents was abolished with pre-incubation of the G protein inhibitor GDP-β-S or the Gi/o activator mastoparan. We further explored the intracellular signaling pathway responsible for the SKF-induced suppression of NMDA responses. Application of either cAMP/the PKA inhibitor Rp-cAMP or cGMP/the PKG inhibitor KT5823 did not change the SKF-induced effect, suggesting the involvement of neither cAMP/PKA nor cGMP/PKG pathway. In contrast, suppression of NMDA responses by SKF was abolished by internal infusion of the phosphatidylinostiol-specific phospholipase C (PLC) inhibitor U73122, but not by the phosphatidylcholine-PLC inhibitor D609. SKF-induced suppression of NMDA responses was dependent on intracellular Ca2+ concentration ([Ca2+]i), as evidenced by the fact that the effect was abolished when [Ca2+]i was buffered with 10 mM BAPTA. The SKF effect was blocked by xestospongin-C/heparin, IP3 receptor antagonists, but unchanged by ryanodine/caffeine, ryanodine receptor modulators. Furthermore, application of protein kinase C inhibitors Bis IV and Gö6976 eliminated the SKF effect. These results suggest that the suppression of NMDA responses of rat retinal GCs caused by the activation of σR1 may be mediated by a distinct [Ca2+]i-dependent PLC-PKC pathway. This effect of SKF could help ameliorate malfunction of GCs caused by excessive stimulation of NMDA receptors under pathological conditions. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights

  5. The Gastric Ganglion of Octopus vulgaris: Preliminary Characterization of Gene- and Putative Neurochemical-Complexity, and the Effect of Aggregata octopiana Digestive Tract Infection on Gene Expression

    PubMed Central

    Baldascino, Elena; Di Cristina, Giulia; Tedesco, Perla; Hobbs, Carl; Shaw, Tanya J.; Ponte, Giovanna; Andrews, Paul L. R.

    2017-01-01

    The gastric ganglion is the largest visceral ganglion in cephalopods. It is connected to the brain and is implicated in regulation of digestive tract functions. Here we have investigated the neurochemical complexity (through in silico gene expression analysis and immunohistochemistry) of the gastric ganglion in Octopus vulgaris and tested whether the expression of a selected number of genes was influenced by the magnitude of digestive tract parasitic infection by Aggregata octopiana. Novel evidence was obtained for putative peptide and non-peptide neurotransmitters in the gastric ganglion: cephalotocin, corticotrophin releasing factor, FMRFamide, gamma amino butyric acid, 5-hydroxytryptamine, molluscan insulin-related peptide 3, peptide PRQFV-amide, and tachykinin–related peptide. Receptors for cholecystokininA and cholecystokininB, and orexin2 were also identified in this context for the first time. We report evidence for acetylcholine, dopamine, noradrenaline, octopamine, small cardioactive peptide related peptide, and receptors for cephalotocin and octopressin, confirming previous publications. The effects of Aggregata observed here extend those previously described by showing effects on the gastric ganglion; in animals with a higher level of infection, genes implicated in inflammation (NFκB, fascin, serpinB10 and the toll-like 3 receptor) increased their relative expression, but TNF-α gene expression was lower as was expression of other genes implicated in oxidative stress (i.e., superoxide dismutase, peroxiredoxin 6, and glutathione peroxidase). Elevated Aggregata levels in the octopuses corresponded to an increase in the expression of the cholecystokininA receptor and the small cardioactive peptide-related peptide. In contrast, we observed decreased relative expression of cephalotocin, dopamine β-hydroxylase, peptide PRQFV-amide, and tachykinin-related peptide genes. A discussion is provided on (i) potential roles of the various molecules in food intake

  6. KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1/2 and IL-1β in the rat trigeminal ganglion.

    PubMed

    Lukács, M; Warfvinge, K; Kruse, L S; Tajti, J; Fülöp, F; Toldi, J; Vécsei, L; Edvinsson, L

    2016-12-01

    Neurogenic inflammation has for decades been considered an important part of migraine pathophysiology. In the present study, we asked the question if administration of a novel kynurenic acid analogue (SZR72), precursor of an excitotoxin antagonist and anti-inflammatory substance, can modify the neurogenic inflammatory response in the trigeminal ganglion. Inflammation in the trigeminal ganglion was induced by local dural application of Complete Freunds Adjuvant (CFA). Levels of phosphorylated MAP kinase pERK1/2 and IL-1β expression in V1 region of the trigeminal ganglion were investigated using immunohistochemistry and Western blot. Pretreatment with one dose of SZR72 abolished the CFA-induced pERK1/2 and IL-1β activation in the trigeminal ganglion. No significant change was noted in case of repeated treatment with SZR72 as compared to a single dose. This is the first study that demonstrates that one dose of KYNA analog before application of CFA can give anti-inflammatory response in a model of trigeminal activation, opening a new line for further investigations regarding possible effects of KYNA derivates.

  7. Increased production of omega-3 fatty acids protects retinal ganglion cells after optic nerve injury in mice.

    PubMed

    Peng, Shanshan; Shi, Zhe; Su, Huanxing; So, Kwok-Fai; Cui, Qi

    2016-07-01

    Injury to the central nervous system causes progressive degeneration of injured axons, leading to loss of the neuronal bodies. Neuronal survival after injury is a prerequisite for successful regeneration of injured axons. In this study, we investigated the effects of increased production of omega-3 fatty acids and elevation of cAMP on retinal ganglion cell (RGC) survival and axonal regeneration after optic nerve (ON) crush injury in adult mice. We found that increased production of omega-3 fatty acids in mice enhanced RGC survival, but not axonal regeneration, over a period of 3 weeks after ON injury. cAMP elevation promoted RGC survival in wild type mice, but no significant difference in cell survival was seen in mice over-producing omega-3 fatty acids and receiving intravitreal injections of CPT-cAMP, suggesting that cAMP elevation protects RGCs after injury but does not potentiate the actions of the omega-3 fatty acids. The observed omega-3 fatty acid-mediated neuroprotection is likely achieved partially through ERK1/2 signaling as inhibition of this pathway by PD98059 hindered, but did not completely block, RGC protection. Our study thus enhances our current understanding of neural repair after CNS injury, including the visual system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Treatment of supragastric belching with cognitive behavioral therapy improves quality of life and reduces acid gastroesophageal reflux.

    PubMed

    Glasinovic, E; Wynter, E; Arguero, J; Ooi, J; Nakagawa, K; Yazaki, E; Hajek, P; Psych, C Clin; Woodland, P; Sifrim, D

    2018-04-01

    Excessive supragastric belching (SGB) manifests as troublesome belching, and can be associated with reflux and significant impact on quality of life (QOL). In some GERD patients, SGB-associated reflux contributes to up to 1/3 of the total esophageal acid exposure. We hypothesized that a cognitive-behavioral intervention (CBT) might reduce SGB, improve QOL, and reduce acid gastroesophageal reflux (GOR). We aimed to assess the effectiveness of CBT in patients with pathological SGB. Patients with SGB were recruited at the Royal London Hospital. Patients attended CBT sessions focused on recognition of warning signals and preventative exercises. Objective outcomes were the number of SGBs, esophageal acid exposure time (AET), and proportion of AET related to SGBs. Subjective evaluation was by patient-reported questionnaires. Of 51 patients who started treatment, 39 completed the protocol, of whom 31 had a follow-up MII-pH study. The mean number of SGBs decreased significantly after CBT (before: 116 (47-323) vs. after 45 (22-139), P<0.0003). Sixteen of 31 patients were shown to have a reduction in SGB by >50%. In patients with increased AET at baseline, AET after CBT was decreased: 9.0-6.1% (P=0.005). Mean visual analog scale severity scores decreased after CBT (before: 260 (210-320) mm vs. after: 140 (80-210) mm, P<0.0001). Cognitive behavioral therapy reduced the number of SGB and improved social and daily activities. Careful analysis of MII-pH allows identification of a subgroup of GERD patients with acid reflux predominantly driven by SGB. In these patients, CBT can reduce esophageal acid exposure.

  9. Tumor necrosis factor-alpha stimulation of calcitonin gene-related peptide expression and secretion from rat trigeminal ganglion neurons.

    PubMed

    Bowen, Elizabeth J; Schmidt, Thomas W; Firm, Christina S; Russo, Andrew F; Durham, Paul L

    2006-01-01

    Expression of the neuropeptide calcitonin gene-related peptide (CGRP) in trigeminal ganglion is implicated in neurovascular headaches and temporomandibular joint disorders. Elevation of cytokines contributes to the pathology of these diseases. However, a connection between cytokines and CGRP gene expression in trigeminal ganglion nerves has not been established. We have focused on the effects of the cytokine tumor necrosis factor-alpha (TNF-alpha). TNFR1 receptors were found on the majority of CGRP-containing rat trigeminal ganglion neurons. Treatment of cultures with TNF-alpha stimulated CGRP secretion. In addition, the intracellular signaling intermediate from the TNFR1 receptor, ceramide, caused a similar increase in CGRP release. TNF-alpha caused a coordinate increase in CGRP promoter activity. TNF-alpha treatment activated the transcription factor NF-kappaB, as well as the Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways. The importance of TNF-alpha induction of MAP kinase pathways was demonstrated by inhibiting MAP kinases with pharmacological reagents and gene transfer with an adenoviral vector encoding MAP kinase phosphatase-1 (MKP-1). We propose that selective and regulated inhibition of MAP kinases in trigeminal neurons may be therapeutically beneficial for inflammatory disorders involving elevated CGRP levels.

  10. Computerized tomography-guided sphenopalatine ganglion pulsed radiofrequency treatment in 16 patients with refractory cluster headaches: Twelve- to 30-month follow-up evaluations.

    PubMed

    Fang, Luo; Jingjing, Lu; Ying, Shen; Lan, Meng; Tao, Wang; Nan, Ji

    2016-02-01

    Sphenopalatine ganglion percutaneous radiofrequency thermocoagulation treatment can improve the symptoms of cluster headaches to some extent. However, as an ablation treatment, radiofrequency thermocoagulation treatment also has side effects. To preliminarily evaluate the efficacy and safety of a non-ablative computerized tomography-guided pulsed radiofrequency treatment of sphenopalatine ganglion in patients with refractory cluster headaches. We included and analysed 16 consecutive cluster headache patients who failed to respond to conservative therapy from the Pain Management Center at the Beijing Tiantan Hospital between April 2012 and September 2013 treated with pulsed radiofrequency treatment of sphenopalatine ganglion. Eleven of 13 episodic cluster headaches patients and one of three chronic cluster headaches patient were completely relieved of the headache within an average of 6.3 ± 6.0 days following the treatment. Two episodic cluster headache patients and two chronic cluster headache patients showed no pain relief following the treatment. The mean follow-up time was 17.0 ± 5.5 months. All patients enrolled in this study showed no treatment-related side effects or complications. Our data show that patients with refractory episodic cluster headaches were quickly, effectively and safely relieved from the cluster period after computerized tomography-guided pulsed radiofrequency treatment of sphenopalatine ganglion, suggesting that it may be a therapeutic option if conservative treatments fail. © International Headache Society 2015.

  11. Orexin-A potentiates L-type calcium/barium currents in rat retinal ganglion cells.

    PubMed

    Liu, F; Weng, S-J; Yang, X-L; Zhong, Y-M

    2015-10-01

    Two neuropeptides, orexin-A and orexin-B (also called hypocretin-1 and -2), have been implicated in sleep/wake regulation, feeding behaviors via the activation of two subtypes of G-protein-coupled receptors: orexin 1 and orexin 2 receptors (OX1R and OX2R). While the expression of orexins and orexin receptors is immunohistochemically revealed in retinal neurons, the function of these peptides in the retina is largely unknown. Using whole-cell patch-clamp recordings in rat retinal slices, we demonstrated that orexin-A increased L-type-like barium currents (IBa,L) in ganglion cells (GCs), and the effect was blocked by the selective OX1R antagonist SB334867, but not by the OX2R antagonist TCS OX2 29. The orexin-A effect was abolished by intracellular dialysis of GDP-β-S/GPAnt-2A, a Gq protein inhibitor, suggesting the mediation of Gq. Additionally, during internal dialysis of the phosphatidylinositol (PI)-phospholipase C (PLC) inhibitor U73122, orexin-A did not change the IBa,L of GCs, whereas the orexin-A effect persisted in the presence of the phosphatidylcholine (PC)-PLC inhibitor D609. The orexin-A-induced potentiation was not seen with internal infusion of Ca(2+)-free solution or when inositol 1,4,5-trisphosphate (IP3)-sensitive Ca(2+) release from intracellular stores was blocked by heparin/xestospongins-C. Moreover, the orexin-A effect was mimicked by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate, but was eliminated when PKC was inhibited by bisindolylmaleimide IV (Bis-IV)/Gö6976. Neither adenosine 3',5'-cyclic monophosphate (cAMP)-protein kinase A (PKA) nor guanosine 3',5'-cyclic monophosphate (cGMP)-protein kinase G (PKG) signaling pathway was likely involved, as orexin-A persisted to potentiate the IBa,L of GCs no matter these two pathways were activated or inhibited. These results suggest that, by activating OX1R, orexin-A potentiates the IBa,L of rat GCs through a distinct Gq/PI-PLC/IP3/Ca(2+)/PKC signaling pathway. Copyright

  12. Reliable, responsive pacemaking and pattern generation with minimal cell numbers: the crustacean cardiac ganglion.

    PubMed

    Cooke, Ian M

    2002-04-01

    Investigations of the electrophysiology of crustacean cardiac ganglia over the last half-century are reviewed for their contributions to elucidating the cellular mechanisms and interactions by which a small (as few as nine cells) neuronal network accomplishes extremely reliable, rhythmical, patterned activation of muscular activity-in this case, beating of the neurogenic heart. This ganglion is thus a model for pacemaking and central pattern generation. Favorable anatomy has permitted voltage- and space-clamp analyses of voltage-dependent ionic currents that endow each neuron with the intrinsic ability to respond with rhythmical, patterned impulse activity to nonpatterned stimulation. The crustacean soma and initial axon segment do not support impulse generation but integrate input from stretch-sensitive dendrites and electrotonic and chemically mediated synapses on axonal processes in neuropils. The soma and initial axon produce a depolarization-activated, calcium-mediated, sustained potential, the "driver potential," so-called because it drives a train of impulses at the "trigger zone" of the axon. Extreme reliability results from redundancy and the electrotonic coupling and synaptic interaction among all the neurons. Complex modulation by central nervous system inputs and by neurohormones to adjust heart pumping to physiological demands has long been demonstrated, but much remains to be learned about the cellular and molecular mechanisms of action. The continuing relevance of the crustacean cardiac ganglion as a relatively simple model for pacemaking and central pattern generation is confirmed by the rapidly widening documentation of intrinsic potentials such as plateau potentials in neurons of all major animal groups. The suite of ionic currents (a slowly inactivating calcium current and various potassium currents, with variations) observed for the crustacean cardiac ganglion have been implicated in or proven to underlie a majority of the intrinsic potentials

  13. Plasma Skimming in a Spiral Groove Bearing of a Centrifugal Blood Pump.

    PubMed

    Murashige, Tomotaka; Sakota, Daisuke; Kosaka, Ryo; Nishida, Masahiro; Kawaguchi, Yasuo; Yamane, Takashi; Maruyama, Osamu

    2016-09-01

    Plasma skimming is a phenomenon in which discharge hematocrit is lower than feed hematocrit in microvessels. Plasma skimming has been investigated at a bearing gap in a spiral groove bearing (SGB), as this has the potential to prevent hemolysis in the SGB of a blood pump. However, it is not clear whether plasma skimming occurs in a blood pump with the SGB, because the hematocrit has not been obtained. The purpose of this study is to verify plasma skimming in an SGB of a centrifugal blood pump by developing a hematocrit measurement method in an SGB. Erythrocyte observation using a high-speed microscope and a bearing gap measurement using a laser confocal displacement meter was performed five times. In these tests, bovine blood as a working fluid was diluted with autologous plasma to adjust the hematocrit to 1.0%. A resistor was adjusted to achieve a pressure head of 100 mm Hg and a flow rate of 5.0 L/min at a rotational speed of 2800 rpm. Hematocrit on the ridge region in the SGB was measured using an image analysis based on motion image of erythrocytes, mean corpuscular volume, the measured bearing gap, and a cross-sectional area of erythrocyte. Mean hematocrit on the ridge region in the SGB was linearly reduced from 0.97 to 0.07% with the decreasing mean bearing gap from 38 to 21 μm when the rotational speed was changed from 2250 to 3000 rpm. A maximum plasma skimming efficiency of 93% was obtained with a gap of 21 μm. In conclusion, we succeeded in measuring the hematocrit on the ridge region in the SGB of the blood pump. Hematocrit decreased on the ridge region in the SGB and plasma skimming occurred with a bearing gap of less than 30 μm in the hydrodynamically levitated centrifugal blood pump. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  14. Prevention of Excitotoxicity in Primary Retinal Ganglion Cells by (+)-Pentazocine, a Sigma Receptor-1-Specific Ligand

    PubMed Central

    Dun, Ying; Thangaraju, Muthusamy; Prasad, Puttur; Ganapathy, Vadivel; Smith, Sylvia B.

    2013-01-01

    Purpose σRs are non-opioid, non-phencyclidine binding sites with robust neuroprotective properties. Previously, we induced death in the RGC-5 cell line using very high concentrations (1 mM) of the excitatory amino acids glutamate (Glu) and homocysteine (Hcy) and demonstrated that the σR1 ligand (+)-pentazocine ((+)-PTZ) could protect against cell death. The purpose of the present study was to establish a physiologically relevant paradigm for testing the neuroprotective effect of (+)-PTZ in retinal ganglion cells. Methods Primary ganglion cells (1°GCs) were isolated by immunopanning from retinas of 1-day-old mice, maintained in culture for 3 days and then exposed to 10, 20, 25 or 50 µM Glu or 10, 25, 50 or 100 µM Hcy for 6 or 18 h in the presence or absence of (+)-PTZ (0.5, 1, 3 µM). Cell viability was measured using the Live/Dead and ApopTag Fluorescein In Situ Assays. Expression of σR1 was assessed by immunocytochemistry, RT-PCR and western blotting. Morphological appearance of live ganglion cells and their processes was examined over time (0, 3, 6, 18 h) by differential interference contrast (DIC) microscopy following exposure to excitotoxins in the presence or absence of (+)-PTZ. Results 1°GCs showed robust σR1 expression. The cells are exquisitely sensitive to Glu or Hcy toxicity (6 h treatment with 25 or 50 µM Glu or 50 or 100 µM Hcy induced marked cell death). 1°GCs pre-treated 1 h with (+)-PTZ followed by 18 h co-treatment with 25 µM Glu and (+)-PTZ showed a marked decrease in cell death: (25 µM Glu alone: 50%; 25 µM Glu/0.5 µM (+)-PTZ: 38%; 25 µM Glu/1 µM (+)-PTZ: 20%; 25 µM Glu/3 µM (+)-PTZ: 18%). Similar results were obtained with Hcy. σR1 mRNA and protein levels did not change in the presence of the excitotoxins. DIC examination of cells exposed to excitotoxins revealed substantial disruption of neuronal processes; co-treatment with (+)-PTZ revealed marked preservation of these processes. The stereoselective effect of (+)-PTZ for

  15. Empirical Derivation of Correction Factors for Human Spiral Ganglion Cell Nucleus and Nucleolus Count Units.

    PubMed

    Robert, Mark E; Linthicum, Fred H

    2016-01-01

    Profile count method for estimating cell number in sectioned tissue applies a correction factor for double count (resulting from transection during sectioning) of count units selected to represent the cell. For human spiral ganglion cell counts, we attempted to address apparent confusion between published correction factors for nucleus and nucleolus count units that are identical despite the role of count unit diameter in a commonly used correction factor formula. We examined a portion of human cochlea to empirically derive correction factors for the 2 count units, using 3-dimensional reconstruction software to identify double counts. The Neurotology and House Histological Temporal Bone Laboratory at University of California at Los Angeles. Using a fully sectioned and stained human temporal bone, we identified and generated digital images of sections of the modiolar region of the lower first turn of cochlea, identified count units with a light microscope, labeled them on corresponding digital sections, and used 3-dimensional reconstruction software to identify double-counted count units. For 25 consecutive sections, we determined that double-count correction factors for nucleus count unit (0.91) and nucleolus count unit (0.92) matched the published factors. We discovered that nuclei and, therefore, spiral ganglion cells were undercounted by 6.3% when using nucleolus count units. We determined that correction factors for count units must include an element for undercounting spiral ganglion cells as well as the double-count element. We recommend a correction factor of 0.91 for the nucleus count unit and 0.98 for the nucleolus count unit when using 20-µm sections. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  16. Nanoparticle optical notch filters

    NASA Astrophysics Data System (ADS)

    Kasinadhuni, Pradeep Kumar

    Developing novel light blocking products involves the design of a nanoparticle optical notch filter, working on the principle of localized surface plasmon resonance (LSPR). These light blocking products can be used in many applications. One such application is to naturally reduce migraine headaches and light sensitivity. Melanopsin ganglion cells present in the retina of the human eye, connect to the suprachiasmatic nucleus (SCN-the body's clock) in the brain, where they participate in the entrainment of the circadian rhythms. As the Melanopsin ganglion cells are involved in triggering the migraine headaches in photophobic patients, it is necessary to block the part of visible spectrum that activates these cells. It is observed from the action potential spectrum of the ganglion cells that they absorb light ranging from 450-500nm (blue-green part) of the visible spectrum with a λmax (peak sensitivity) of around 480nm (blue line). Currently prescribed for migraine patients is the FL-41 coating, which blocks a broad range of wavelengths, including wavelengths associated with melanopsin absorption. The nanoparticle optical notch filter is designed to block light only at 480nm, hence offering an effective prescription for the treatment of migraine headaches.

  17. Muscarinic receptor-mediated excitation of rat intracardiac ganglion neurons.

    PubMed

    Hirayama, Michiko; Ogata, Masanori; Kawamata, Tomoyuki; Ishibashi, Hitoshi

    2015-08-01

    Modulation of the membrane excitability of rat parasympathetic intracardiac ganglion neurons by muscarinic receptors was studied using an amphotericin B-perforated patch-clamp recording configuration. Activation of muscarinic receptors by oxotremorine-M (OxoM) depolarized the membrane, accompanied by repetitive action potentials. OxoM evoked inward currents under voltage-clamp conditions at a holding potential of -60 mV. Removal of extracellular Ca(2+) markedly increased the OxoM-induced current (IOxoM). The inward IOxoM in the absence of extracellular Ca(2+) was fully inhibited by removal of extracellular Na(+), indicating the involvement of non-selective cation channels. The IOxoM was inhibited by organic cation channel antagonists including SKF-96365 and ML-204. The IOxoM was antagonized by muscarinic receptor antagonists with the following potency: 4-DAMP > pirenzepine = darifenacin > methoctramine. Muscarinic toxin 7 (MT-7), a highly selective inhibitor for M1 receptor, produced partial inhibition of the IOxoM. In the presence of MT-7, concentration-inhibition curve of the M3-preferring antagonist darifenacin was shifted to the left. These results suggest the contribution of M1 and M3 receptors to the OxoM response. The IOxoM was inhibited by U-73122, a phospholipase C inhibitor. The membrane-permeable IP3 receptor blocker xestospongin C also inhibited the IOxoM. Furthermore, pretreatment with thapsigargin and BAPTA-AM inhibited the IOxoM, while KN-62, a blocker of Ca(2+)/calmodulin-dependent protein kinase II, had no effect. These results suggest that the activation mechanism involves a PLC pathway, release of Ca(2+) from intracellular Ca(2+) stores and calmodulin. The cation channels activated by muscarinic receptors may play an important role in neuronal membrane depolarization in rat intracardiac ganglion neurons. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Long-term outcome and prognostic factors after C2 ganglion decompression in 68 consecutive patients with intractable occipital neuralgia.

    PubMed

    Choi, Kyu-Sun; Ko, Yong; Kim, Young-Soo; Yi, Hyeong-Joong

    2015-01-01

    Occipital neuralgia is a rare cause of severe headache characterized by paroxysmal shooting or stabbing pain in the distribution of the greater occipital or lesser occipital nerve. In cases of intractable occipital neuralgia, a definite cause has not been uncovered, so various types of treatment have been applied. The aim of this study is to evaluate the prognostic factors, safety, and long-term clinical efficacy of second cervical (C2) ganglion decompression for intractable occipital neuralgia. Retrospective analysis was performed in 68 patients with medically refractory occipital neuralgia who underwent C2 ganglion decompression. Factors based on patients' demography, pre- and postoperative headache severity/characteristics, medication use, and postoperative complications were investigated. Therapeutic success was defined as pain relief by at least 50 % without ongoing medication. The visual analog scale (VAS) score was significantly reduced between the preoperative and most recent follow-up period. One year later, excellent or good results were achieved in 57 patients (83.9 %), but poor in 11 patients (16.1 %). The long-term outcome after 5 years was only slightly less than the 1-year outcome; 47 of the 68 patients (69.1 %) obtained therapeutic success. Longer duration of headache (over 13 years; p = 0.029) and presence of retro-orbital/frontal radiation (p = 0.040) were significantly associated with poor prognosis. In the current study, C2 ganglion decompression provided durable, adequate pain relief with minimal complications in patients suffering from intractable occipital neuralgia. Due to the minimally invasive and nondestructive nature of this surgical procedure, C2 ganglion decompression is recommended as an initial surgical treatment option for intractable occipital neuralgia before attempting occipital nerve stimulation. However, further study is required to manage the pain recurrence associated with longstanding nerve injury.

  19. Retinal ganglion cell dendritic fields in old-world monkeys are oriented radially.

    PubMed

    Schall, J D; Perry, V H; Leventhal, A G

    1986-03-12

    We analyzed the dendritic field morphology of 297 ganglion cells from peripheral regions of monkey retina. Most of the dendritic fields were elongated, and there was a significant tendency for the dendritic fields to be oriented radially, i.e., like the spokes of a wheel with the fovea at the hub. An overrepresentation of radial orientations in the peripheral retina of primates might explain why humans are best able to detect stimuli which are oriented radially using peripheral vision.

  20. Involvement of P2X7 receptors in retinal ganglion cell apoptosis induced by activated Müller cells.

    PubMed

    Xue, Bo; Xie, Yuting; Xue, Ying; Hu, Nan; Zhang, Guowei; Guan, Huaijin; Ji, Min

    2016-12-01

    Müller cell reactivation (gliosis) is an early response in glaucomatous retina. Previous studies have demonstrated that activation of P2X 7 receptors results in retinal ganglion cell (RGC) apoptosis. Here, the issues of whether and how activated Müller cells may contribute to RGC apoptosis through P2X 7 receptors were investigated. Either intravitreal injection of (S)-3,5-dihydroxyphenylglycine (DHPG), a group I metabotropic glutamate receptor (mGluR I) agonist, in normal rat retinas, or DHPG treatment of purified cultured rat retinal Müller cells induced an increase in glial fibrillary acidic protein (GFAP) expression, indicative of Müller cell gliosis. In addition, an increase in adenosine triphosphate (ATP) release from purified cultured Müller cells was detected during DHPG treatment (for 10 min to 48 h), which was mediated by the intracellular mGluR5/Gq/PI-PLC/PKC signaling pathway. Intravitreal injection of DHPG mimicked the reduction in the number of fluorogold retrogradely labeled RGCs in chronic ocular hypertension (COH) rats. Treatment with the conditioned culture medium (CM) obtained from the DHPG-activated Müller cell medium induced an increase in the number of TUNEL-positive cells in cultured RGCs, which was mimicked by benzoylbenzoyl adenosine triphosphate (BzATP), a P2X 7 receptor agonist, but was partially blocked by brilliant blue G (BBG), a P2X 7 receptor antagonist. Moreover, the CM treatment of cultured RGCs significantly increased Bax protein level and decreased Bcl-2 protein level, which was also mimicked by BzATP and partially blocked by BBG, respectively. These results suggest that reactivated Müller cells may release excessive ATP, in turn leading to RGC apoptosis through activating P2X 7 receptors in these cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Excitatory synaptic inputs to mouse on-off direction-selective retinal ganglion cells lack direction tuning.

    PubMed

    Park, Silvia J H; Kim, In-Jung; Looger, Loren L; Demb, Jonathan B; Borghuis, Bart G

    2014-03-12

    Direction selectivity represents a fundamental visual computation. In mammalian retina, On-Off direction-selective ganglion cells (DSGCs) respond strongly to motion in a preferred direction and weakly to motion in the opposite, null direction. Electrical recordings suggested three direction-selective (DS) synaptic mechanisms: DS GABA release during null-direction motion from starburst amacrine cells (SACs) and DS acetylcholine and glutamate release during preferred direction motion from SACs and bipolar cells. However, evidence for DS acetylcholine and glutamate release has been inconsistent and at least one bipolar cell type that contacts another DSGC (On-type) lacks DS release. Here, whole-cell recordings in mouse retina showed that cholinergic input to On-Off DSGCs lacked DS, whereas the remaining (glutamatergic) input showed apparent DS. Fluorescence measurements with the glutamate biosensor intensity-based glutamate-sensing fluorescent reporter (iGluSnFR) conditionally expressed in On-Off DSGCs showed that glutamate release in both On- and Off-layer dendrites lacked DS, whereas simultaneously recorded excitatory currents showed apparent DS. With GABA-A receptors blocked, both iGluSnFR signals and excitatory currents lacked DS. Our measurements rule out DS release from bipolar cells onto On-Off DSGCs and support a theoretical model suggesting that apparent DS excitation in voltage-clamp recordings results from inadequate voltage control of DSGC dendrites during null-direction inhibition. SAC GABA release is the apparent sole source of DS input onto On-Off DSGCs.

  2. The site of the 5-hydroxytryptamine receptor on the intramural nervous plexus of the guinea-pig isolated ileum

    PubMed Central

    Brownlee, G.; Johnson, E. S.

    1963-01-01

    Dose/response measurements were made on the guinea-pig isolated ileum with six agonists, acetylcholine, 5-hydroxytryptamine, nicotine, dimethylphenylpiperazinium, choline phenyl ether and histamine. The dose effects were repeated in the presence of each of twelve antagonists and one anticholinesterase. Acetylcholine and histamine were chosen because of their direct mode of action on smooth muscle, nicotine, dimethylphenylpiperazinium and choline phenyl ether were used as examples of drugs that act at the ganglionic acetylcholine receptor. 5-Hydroxytryptamine was the drug investigated. Hyoscine blocked the contractions caused by acetylcholine, 5-hydroxytryptamine and the ganglion-stimulants but left the responses to histamine unchanged. The anticholinesterase N,N'-diisopropylphosphorodiamidic fluoride (mipafox) potentiated all the agonists except histamine. The strength of potentiation decreased in the order 5-hydroxytryptamine, nicotine, dimethylphenylpiperazinium and choline phenyl ether, and acetylcholine. The local anaesthetic procaine inhibited to the same extent contractions elicited by 5-hydroxytryptamine, nicotine, dimethylphenylpiperazinium and choline phenyl ether. These results showed that 5-hydroxytryptamine, like nicotine, choline phenyl ether and dimethylphenylpiperazinium, mediated its response through the nervous plexus. Of those tested 5-hydroxytryptamine was the only specific antagonist to 5-hydroxytryptamine; lysergic acid derivatives produced spasm and prolonged changes in tone; phenoxybenzamine caused non-specific block. The diverse modes of action of a number of ganglion-blocking agents were selectively used. Thus hexamethonium, pentolinium, and nicotine in its competitive phase, blocked contractions due to nicotine, dimethylphenylpiperazinium and choline phenyl ether and left those due to 5-hydroxytryptamine, acetylcholine and histamine unchanged. The depolarizing ganglion-blocking agents, dimethylphenylpiperazinium and nicotine, inhibited the

  3. Inhibitory masking controls the threshold sensitivity of retinal ganglion cells

    PubMed Central

    Pan, Feng; Toychiev, Abduqodir; Zhang, Yi; Atlasz, Tamas; Ramakrishnan, Hariharasubramanian; Roy, Kaushambi; Völgyi, Béla; Akopian, Abram

    2016-01-01

    Key points Retinal ganglion cells (RGCs) in dark‐adapted retinas show a range of threshold sensitivities spanning ∼3 log units of illuminance.Here, we show that the different threshold sensitivities of RGCs reflect an inhibitory mechanism that masks inputs from certain rod pathways.The masking inhibition is subserved by GABAC receptors, probably on bipolar cell axon terminals.The GABAergic masking inhibition appears independent of dopaminergic circuitry that has been shown also to affect RGC sensitivity.The results indicate a novel mechanism whereby inhibition controls the sensitivity of different cohorts of RGCs. This can limit and thereby ensure that appropriate signals are carried centrally in scotopic conditions when sensitivity rather than acuity is crucial. Abstract The responses of rod photoreceptors, which subserve dim light vision, are carried through the retina by three independent pathways. These pathways carry signals with largely different sensitivities. Retinal ganglion cells (RGCs), the output neurons of the retina, show a wide range of sensitivities in the same dark‐adapted conditions, suggesting a divergence of the rod pathways. However, this organization is not supported by the known synaptic morphology of the retina. Here, we tested an alternative idea that the rod pathways converge onto single RGCs, but inhibitory circuits selectively mask signals so that one pathway predominates. Indeed, we found that application of GABA receptor blockers increased the sensitivity of most RGCs by unmasking rod signals, which were suppressed. Our results indicate that inhibition controls the threshold responses of RGCs under dim ambient light. This mechanism can ensure that appropriate signals cross the bottleneck of the optic nerve in changing stimulus conditions. PMID:27350405

  4. Petrographic and geochemical analyisis for determination of provenance of the Slovenj Gradec Miocene Basin fill (Western Central Paratethys)

    NASA Astrophysics Data System (ADS)

    Ivančič, Kristina; Trajanova, Mirka; Skaberne, Dragomir; Šmuc, Andrej

    2017-04-01

    (Trajanova, 2013). Consequently, the area of the wider SGB was still an integral part of the Central Paratethys until late Miocene. References Fedo, C.M., Nesbitt, H.W. & Young, G.M., 1995. Unravelling the effects of potassium metasomatism in sedimentary rocks and paleosols, with implications for paleoweathering conditions and provenance. Geology, 23(10), pp.921-924. Nesbitt, H. W., & Young, G. M., 1984. Prediction of some weathering trends of plutonic and volcanic rocks based on thermodynamic and kinetic considerations. Geochimica et Cosmochimica Acta, 48 (7), 1523-1534. Pettijohn, F.J., Potter, P.E., Siever, R., 1972. Sand and Sandstone, second ed., Springer, New York, heidelberg, Berlin 618, pp. Roser, B.P. & Korsch, R.J., 1988. Provenance signatures of sandstone-mudstonen suites determined using discriminant function of major-element data. Chemical Geology, 67(1-2), pp.119-139. Trajanova, M. 2013: Starost pohorskega magmatizma; nov pogled na nastanek pohorskega tektonskega bloka (Age of the Pohorje Mountains magmatism; new view on the origin of the Pohorje tectonic block). PhD thesis. 183 pp., Ljubljana. Verma, S.P. & Armstrong-Altrin, J.S., 2013. New multi-dimensional diagrams for tectonic discrimination of siliciclastic sediments and their application to Precambrian basins. Chemical Geology, 355, pp.117-133. Verma, S. P., & Armstrong-Altrin, J. S. (2016). Geochemical discrimination of siliciclastic sediments from active and passive margin settings. Sedimentary Geology, 332, 1-12.

  5. New light for old eyes: comparing melanopsin-mediated non-visual benefits of blue-light and UV-blocking intraocular lenses.

    PubMed

    Schmoll, Conrad; Khan, Ashraf; Aspinall, Peter; Goudie, Colin; Koay, Peter; Tendo, Christelle; Cameron, James; Roe, Jenny; Deary, Ian; Dhillon, Bal

    2014-01-01

    Melanopsin-expressing photosensitive retinal ganglion cells form a blue-light-sensitive non-visual system mediating diverse physiological effects including circadian entrainment and cognitive alertness. Reduced blue wavelength retinal illumination through cataract formation is thought to blunt these responses while cataract surgery and intraocular lens (IOL) implantation have been shown to have beneficial effects on sleep and cognition. We aimed to use the reaction time (RT) task and the Epworth Sleepiness Score (ESS) as a validated objective platform to compare non-visual benefits of UV- and blue-blocking IOLs. Patients were prospectively randomised to receive either a UV- or blue-blocking IOL, performing an RT test and ESS questionnaire before and after surgery. Optical blurring at the second test controlled for visual improvement. Non-operative age-matched controls were recruited for comparison. 80 participants completed the study. Those undergoing first-eye phacoemulsification demonstrated significant improvements in RT over control (p=0.001) and second-eye surgery patients (p=0.03). Moreover, reduced daytime sleepiness was measured by ESS for the first-eye surgery group (p=0.008) but not for the second-eye group (p=0.09). Choice of UV- or blue-blocking IOL made no significant difference to magnitude of cognitive improvement (p=0.272). Phacoemulsification, particularly first-eye surgery, has a strong positive effect on cognition and daytime alertness, regardless of IOL type.

  6. Myelin-induced inhibition in a spiral ganglion organ culture - Approaching a natural environment in vitro.

    PubMed

    Kramer, Benedikt; Tropitzsch, Anke; Müller, Marcus; Löwenheim, Hubert

    2017-08-15

    The performance of a cochlear implant depends on the defined interaction between afferent neurons of the spiral ganglion and the inserted electrode. Neurite outgrowth can be induced by neurotrophins such as brain-derived neurotrophic factor (BDNF) via tropomyosin kinase receptor B (TrkB). However, neurotrophin signaling through the p75 neurotrophin receptor (p75) inhibits neurite outgrowth in the presence of myelin. Organotypic cultures derived from postnatal (P3-5) mice were used to study myelin-induced inhibition in the cochlear spiral ganglion. Neurite outgrowth was analyzed and quantified utilizing an adapted Sholl analysis. Stimulation of neurite outgrowth was quantified after application of BDNF, the selective TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) and a selective inhibitor of the Rho-associated kinase (Y27632), which inhibits the p75 pathway. Myelin-induced inhibition was assessed by application of myelin-associated glycoprotein (MAG-Fc) to stimulate the inhibitory p75 pathway. Inhibition of neurite outgrowth was achieved by the selective TrkB inhibitor K252a. Stimulation of neurite outgrowth was observed after treatment with BDNF, 7,8 DHF and a combination of BDNF and Y27632. The 7,8-DHF-induced growth effects could be inhibited by K252a. Furthermore, inhibition of neurite outgrowth was observed after supplementation with MAG-Fc. Myelin-induced inhibition could be overcome by 7,8-DHF and the combination of BDNF and Y27632. In this study, myelin-induced inhibition of neurite outgrowth was established in a spiral ganglion model. We reveal that 7,8-DHF is a viable novel compound for the stimulation of neurite outgrowth in a myelin-induced inhibitory environment. The combination of TrkB stimulation and ROCK inhibition can be used to overcome myelin inhibition. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Role of dorsal root ganglion K2P1.1 in peripheral nerve injury-induced neuropathic pain

    PubMed Central

    Mao, Qingxiang; Yuan, Jingjing; Xiong, Ming; Wu, Shaogen; Chen, Liyong; Bekker, Alex; Yang, Tiande

    2017-01-01

    Peripheral nerve injury-caused hyperexcitability and abnormal ectopic discharges in the primary sensory neurons of dorsal root ganglion (DRG) play a key role in neuropathic pain development and maintenance. The two-pore domain background potassium (K2P) channels have been identified as key determinants of the resting membrane potential and neuronal excitability. However, whether K2P channels contribute to neuropathic pain is still elusive. We reported here that K2P1.1, the first identified mammalian K2P channel, was highly expressed in mouse DRG and distributed in small-, medium-, and large-sized DRG neurons. Unilateral lumbar (L) 4 spinal nerve ligation led to a significant and time-dependent reduction of K2P1.1 mRNA and protein in the ipsilateral L4 DRG, but not in the contralateral L4 or ipsilateral L3 DRG. Rescuing this reduction through microinjection of adeno-associated virus-DJ expressing full-length K2P1.1 mRNA into the ipsilateral L4 DRG blocked spinal nerve ligation-induced mechanical, thermal, and cold pain hypersensitivities during the development and maintenance periods. This DRG viral microinjection did not affect acute pain and locomotor function. Our findings suggest that K2P1.1 participates in neuropathic pain development and maintenance and may be a potential target in the management of this disorder. PMID:28326939

  8. Bioelectronic block of paravertebral sympathetic nerves mitigates post-myocardial infarction ventricular arrhythmias.

    PubMed

    Chui, Ray W; Buckley, Una; Rajendran, Pradeep S; Vrabec, Tina; Shivkumar, Kalyanam; Ardell, Jeffrey L

    2017-11-01

    Autonomic dysfunction contributes to induction of ventricular tachyarrhythmia (VT). To determine the efficacy of charge-balanced direct current (CBDC), applied to the T1-T2 segment of the paravertebral sympathetic chain, on VT inducibility post-myocardial infarction (MI). In a porcine model, CBDC was applied in acute animals (n = 7) to optimize stimulation parameters for sympathetic blockade and in chronic MI animals (n = 7) to evaluate the potential for VTs. Chronic MI was induced by microsphere embolization of the left anterior descending coronary artery. At termination, in anesthetized animals and following thoracotomy, an epicardial sock array was placed over both ventricles and a quadripolar carousel electrode positioned underlying the right T1-T2 paravertebral chain. In acute animals, the efficacy of CBDC carousel (CBDCC) block was assessed by evaluating cardiac function during T2 paravertebral ganglion stimulation with and without CBDCC. In chronic MI animals, VT inducibility was assessed by extrasystolic (S1-S2) stimulations at baseline and under >66% CBDCC blockade of T2-evoked sympathoexcitation. CBDCC demonstrated a current-dependent and reversible block without impacting basal cardiac function. VT was induced at baseline in all chronic MI animals. One animal died after baseline induction. Of the 6 remaining animals, only 1 was reinducible with simultaneous CBDCC application (P < .002 from baseline). The ventricular effective refractory period (VERP) was prolonged with CBDCC (323 ± 26 ms) compared to baseline (271 ± 32 ms) (P < .05). Axonal block of the T1-T2 paravertebral chain with CBDCC reduced VT in a chronic MI model. CBDCC prolonged VERP, without altering baseline cardiac function, resulting in improved electrical stability. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  9. Citral sensing by Transient [corrected] receptor potential channels in dorsal root ganglion neurons.

    PubMed

    Stotz, Stephanie C; Vriens, Joris; Martyn, Derek; Clardy, Jon; Clapham, David E

    2008-05-07

    Transient receptor potential (TRP) ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1), and produces long-lasting inhibition of TRPV1-3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol) each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate), consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin.

  10. Citral Sensing by TRANSient Receptor Potential Channels in Dorsal Root Ganglion Neurons

    PubMed Central

    Stotz, Stephanie C.; Vriens, Joris; Martyn, Derek; Clardy, Jon; Clapham, David E.

    2008-01-01

    Transient receptor potential (TRP) ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1), and produces long-lasting inhibition of TRPV1–3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol) each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate), consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin. PMID:18461159

  11. Muscarinic modulation of TREK currents in mouse sympathetic superior cervical ganglion neurons.

    PubMed

    Rivas-Ramírez, P; Cadaveira-Mosquera, A; Lamas, J A; Reboreda, A

    2015-07-01

    Muscarinic receptors play a key role in the control of neurotransmission in the autonomic ganglia, which has mainly been ascribed to the regulation of potassium M-currents and voltage-dependent calcium currents. Muscarinic agonists provoke depolarization of the membrane potential and a reduction in spike frequency adaptation in postganglionic neurons, effects that may be explained by M-current inhibition. Here, we report the presence of a riluzole-activated current (IRIL ) that flows through the TREK-2 channels, and that is also inhibited by muscarinic agonists in neurons of the mouse superior cervical ganglion (mSCG). The muscarinic agonist oxotremorine-M (Oxo-M) inhibited the IRIL by 50%, an effect that was abolished by pretreatment with atropine or pirenzepine, but was unaffected in the presence of himbacine. Moreover, these antagonists had similar effects on single-channel TREK-2 currents. IRIL inhibition was unaffected by pretreatment with pertussis toxin. The protein kinase C blocker bisindolylmaleimide did not have an effect, and neither did the inositol triphosphate antagonist 2-aminoethoxydiphenylborane. Nevertheless, the IRIL was markedly attenuated by the phospholipase C (PLC) inhibitor ET-18-OCH3. Finally, the phosphatidylinositol-3-kinase/phosphatidylinositol-4-kinase inhibitor wortmannin strongly attenuated the IRIL , whereas blocking phosphatidylinositol 4,5-bisphosphate (PIP2 ) depletion consistently prevented IRIL inhibition by Oxo-M. These results demonstrate that TREK-2 currents in mSCG neurons are inhibited by muscarinic agonists that activate M1 muscarinic receptors, reducing PIP2 levels via a PLC-dependent pathway. The similarities between the signaling pathways regulating the IRIL and the M-current in the same neurons reflect an important role of this new pathway in the control of autonomic ganglia excitability. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. Caspases in retinal ganglion cell death and axon regeneration

    PubMed Central

    Thomas, Chloe N; Berry, Martin; Logan, Ann; Blanch, Richard J; Ahmed, Zubair

    2017-01-01

    Retinal ganglion cells (RGC) are terminally differentiated CNS neurons that possess limited endogenous regenerative capacity after injury and thus RGC death causes permanent visual loss. RGC die by caspase-dependent mechanisms, including apoptosis, during development, after ocular injury and in progressive degenerative diseases of the eye and optic nerve, such as glaucoma, anterior ischemic optic neuropathy, diabetic retinopathy and multiple sclerosis. Inhibition of caspases through genetic or pharmacological approaches can arrest the apoptotic cascade and protect a proportion of RGC. Novel findings have also highlighted a pyroptotic role of inflammatory caspases in RGC death. In this review, we discuss the molecular signalling mechanisms of apoptotic and inflammatory caspase responses in RGC specifically, their involvement in RGC degeneration and explore their potential as therapeutic targets. PMID:29675270

  13. Polysensory response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia.

    PubMed

    Huang, M H; Horackova, M; Negoescu, R M; Wolf, S; Armour, J A

    1996-09-01

    To determine the response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia. Extracellular recordings were made from 54 spontaneously active and 5 normally quiescent dorsal root ganglion neurones (T2-T5) in 22 anaesthetized open-chest dogs under control conditions and during epicardial mechanical or chemical stimulation and myocardial ischaemia. The activity of 78% of spontaneously active and all quiescent neurones with left ventricular sensory fields was modified by left ventricular ischaemia. Forty-six spontaneously active neurones (85%) were polysensory with respect to mechanical and chemical stimuli. The 5 quiescent neurones responded only to chemical stimuli. Spontaneously active neurones associated with left ventricular mechanosensory endings (37 neurones) generated four different activity patterns in response to similar mechanical stimuli (high or low pressure active, high-low pressure active, high-low pressure inactive). A fifth group generated activity which was not related to chamber dynamics. Adenosine, adenosine 5'-triphosphate, substance P and bradykinin modified 72, 61, 65 and 63% of the spontaneously active neurones, respectively. Maximum local mechanical or chemical stimuli enhanced activity to similar degrees, as did ischaemia. Each ischaemia-sensitive neurone displayed unique activity patterns in response to similar mechanical or chemical stimuli. Most myocardial ischemia-sensitive dorsal root ganglion neurones associated with epicardial neurites sense mechanical and multiple chemical stimuli, a small population sensing only mechanical or chemical stimuli. Activity patterns generated by these neurones depend on their primary sensory characteristics or those of other neurones that may converge on them, as well as the type and magnitude of the stimuli that impinge upon their sensory fields, both normally and during ischaemia.

  14. Topographic specializations of catecholaminergic cells and ganglion cells and distribution of calcium binding proteins in the crepuscular rock cavy (Kerodon rupestris) retina.

    PubMed

    Oliveira, Francisco Gilberto; Nascimento-Júnior, Expedito Silva do; Cavalcante, Judney Cley; Guzen, Fausto Pierdoná; Cavalcante, Jeferson de Souza; Soares, Joacil Germano; Cavalcanti, José Rodolfo Lopes de Paiva; Freitas, Leandro Moura de; Costa, Miriam Stela Maris de Oliveira; Andrade-da-Costa, Belmira Lara da Silveira

    2018-07-01

    The rock cavy (Kerodon rupestris) is a crepuscular Hystricomorpha rodent that has been used in comparative analysis of retinal targets, but its retinal organization remains to be investigated. In order to better characterize its visual system, the present study analyzed neurochemical features related to the topographic organization of catecholaminergic cells and ganglion cells, as well the distribution of calcium-binding proteins in the outer and inner retina. Retinal sections and/or wholemounts were processed using tyrosine hydroxylase (TH), GABA, calbindin, parvalbumin and calretinin immunohistochemistry or Nissl staining. Two types of TH-immunoreactive (TH-IR) cells were found which differ in soma size, dendritic arborization, intensity of TH immunoreactivity and stratification pattern in the inner plexiform layer. The topographic distribution of all TH-IR cells defines a visual streak along the horizontal meridian in the superior retina. The ganglion cells are also distributed in a visual streak and the visual acuity estimated considering their peak density is 4.13 cycles/degree. A subset of TH-IR cells express GABA or calbindin. Calretinin is abundant in most of retinal layers and coexists with calbindin in horizontal cells. Parvalbumin is less abundant and expressed by presumed amacrine cells in the INL and some ganglion cells in the GCL. The topographic distribution of TH-IR cells and ganglion cells in the rock cavy retina indicate a suitable adaptation for using a broad extension of its inferior visual field in aspects that involve resolution, adjustment to ambient light intensity and movement detection without specialized eye movements. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Hyoscine butylbromide potently blocks human nicotinic acetylcholine receptors in SH-SY5Y cells.

    PubMed

    Weiser, Thomas; Just, Stefan

    2009-02-06

    Hyoscine butylbromide (HBB; tradenames: Buscopan/Buscapina is an antispasmodic drug for the treatment of abdominal pain associated with gastrointestinal cramping. As a hyoscine derivative, this compound competitively inhibits muscarinic acetylcholine (ACh) receptors on smooth muscle cells in the gastrointestinal tract. Preliminary investigations suggested that it might also inhibit nicotinic ACh receptors. This study investigated the effect of HBB on nicotinic ACh receptor-mediated membrane currents in SH-SY5Y cells. ACh and nicotine application-induced comparable membrane currents with EC(50) values of 25.9+/-0.6 and 40.1+/-0.4microM, respectively. When coapplied with 100microM ACh, HBB concentration-dependently suppressed currents with an IC(50) value of 0.19+/-0.04microM, and was approximately seven-times more potent than the ganglionic blocker, hexamethonium (IC(50)=1.3+/-0.3microM). Increasing the agonist concentration to 5mM did not affect the amount of block by HBB, which suggests a non-competitive mode of action. These functional in vitro data demonstrate for the first time that HBB blocks neuronal nicotinic ACh receptors in the same concentration range as it inhibits muscarinic ACh receptors. If one hypothesizes that HBB might also affect nicotinic receptors in autonomic neurons in vivo (e. g. in the enteric nervous system), this effect could contribute to its spasmolytic activity.

  16. 31 CFR 510.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Blocked account; blocked property. 510.301 Section 510.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... Definitions § 510.301 Blocked account; blocked property. The terms blocked account and blocked property shall...

  17. 31 CFR 510.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Blocked account; blocked property. 510.301 Section 510.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... Definitions § 510.301 Blocked account; blocked property. The terms blocked account and blocked property shall...

  18. 31 CFR 510.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Blocked account; blocked property. 510.301 Section 510.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... Definitions § 510.301 Blocked account; blocked property. The terms blocked account and blocked property shall...

  19. Threshold voltage variation depending on single grain boundary and stored charges in an adjacent cell for vertical silicon–oxide–nitride–oxide–silicon NAND flash memory

    NASA Astrophysics Data System (ADS)

    Oh, Hyeongwan; Kim, Jiwon; Baek, Rock-Hyun; Lee, Jeong-Soo

    2018-04-01

    The effects of single grain boundary (SGB) position and stored electron charges in an adjacent cell in silicon–oxide–nitride–oxide–silicon (SONOS) structures on the variations of threshold voltage (V th) were investigated using technology computer-aided design (TCAD) simulation. As the bit line voltage increases, the SGB position causing the maximum V th variation was shifted from the center to the source side in the channel, owing to the drain-induced grain barrier lowering effect. When the SGB is located in the spacer region, the potential interaction from both the SGB and the stored electron charges in the adjacent cell becomes significant and thus resulting in larger V th variation. In contrast, when the SGB is located at the center of the channel, the peak position of potential barrier is shifted to the center, so that the influence of the adjacent cell is diminished. As the gate length is scaled down to 20 nm, the influence of stored charges in adjacent cells becomes significant, resulting in larger V th variations.

  20. Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats.

    PubMed

    Matsushita, Yumi; Manabe, Miki; Kitamura, Naoki; Shibuya, Izumi

    2018-01-01

    Transient receptor potential vanilloid type 1 (TRPV1) is a polymodal receptor channel that responds to multiple types of stimuli, such as heat, acid, mechanical pressure and some vanilloids. Capsaicin is the most commonly used vanilloid to stimulate TRPV1. TRPV1 channels are expressed in dorsal root ganglion neurons that extend to Aδ- and C-fibers and have a role in the transduction of noxious inputs to the skin into the electrical signals of the sensory nerve. Although noradrenergic nervous systems, including the descending antinociceptive system and the sympathetic nervous system, are known to modulate pain sensation, the functional association between TRPV1 and noradrenaline in primary sensory neurons has rarely been examined. In the present study, we examined the effects of noradrenaline on capsaicin-evoked currents in cultured dorsal root ganglion neurons of the rat by the whole-cell voltage clamp method. Noradrenaline at concentrations higher than 0.1 pM significantly reduced the amplitudes of the inward capsaicin currents recorded at -60 mV holding potential. This inhibitory action was reversed by either yohimbine (an α2 antagonist, 10 nM) or propranolol (a β antagonist, 10 nM). The α2 agonists, clonidine (1 pM) and dexmedetomidine (1 pM) inhibited capsaicin currents, and yohimbine (1 nM) reversed the effects of clonidine. The inhibitory action of noradrenaline was not seen in the neurons pretreated with pertussis toxin (100 μg/ml for 24 h) and the neurons dialyzed intracellularly with guanosine 5'- [β-thio] diphosphate (GDPβS, 200 μM), the catalytic subunit of protein kinase A (250 U/ml) or okadaic acid (1 μM). These results suggest that noradrenaline directly acts on dorsal root ganglion neurons to inhibit the activity of TRPV1 depending on the activation of α2-adrenoceptors followed by the inhibition of the adenylate cyclase/cAMP/protein kinase A pathway.

  1. The relationship between neurotrophic factors and CaMKII in the death and survival of retinal ganglion cells.

    PubMed

    Cooper, N G F; Laabich, A; Fan, W; Wang, X

    2008-01-01

    The scientific discourse relating to the causes and treatments for glaucoma are becoming reflective of the need to protect and preserve retinal neurons from degenerative changes, which result from the injurious environment associated with this disease. Knowledge, in particular, of the signal transduction pathways which affect death and survival of the retinal ganglion cells is critical to this discourse and to the development of a suitable neurotherapeutic strategy for this disease. The goal of this chapter is to review what is known of the chief suspects involved in initiating the cell death/survival pathways in these cells, and what still remains to be uncovered. The least controversial aspect of the subject relates to the potential role of neurotrophic factors in the protection of the retinal ganglion cells. On the other hand, the postulated triggers for signaling cell death in glaucoma remain controversial. Certainly, the restricted flow of neurotrophic factors has been cited as one possible trigger. However, the connections between glaucoma and other factors present in the retina, such as glutamate, long held to be a prospective culprit in retinal ganglion cell death are still being questioned. Whatever the outcome of this particular debate, it is clear that the downstream intersections between the cell death and survival pathways should provide important foci for future studies whose goal is to protect retinal neurons, situated as they are, in the stressful environment of a cell destroying disease. The evidence for CaMKII being one of these intersecting points is discussed.

  2. High-wattage pulsed irradiation of linearly polarized near-infrared light to stellate ganglion area for burning mouth syndrome.

    PubMed

    Momota, Yukihiro; Kani, Koichi; Takano, Hideyuki; Matsumoto, Fumihiro; Aota, Keiko; Takegawa, Daisuke; Yamanoi, Tomoko; Kondo, Chika; Tomioka, Shigemasa; Azuma, Masayuki

    2014-01-01

    The purpose of this study was to apply high-wattage pulsed irradiation of linearly polarized near-infrared light to the stellate ganglion area for burning mouth syndrome (BMS) and to assess the efficacy of the stellate ganglion area irradiation (SGR) on BMS using differential time-/frequency-domain parameters (D parameters). Three patients with BMS received high-wattage pulsed SGR; the response to SGR was evaluated by visual analogue scale (VAS) representing the intensity of glossalgia and D parameters used in heart rate variability analysis. High-wattage pulsed SGR significantly decreased the mean value of VAS in all cases without any adverse event such as thermal injury. D parameters mostly correlated with clinical condition of BMS. High-wattage pulsed SGR was safe and effective for the treatment of BMS; D parameters are useful for assessing efficacy of SGR on BMS.

  3. Recovery of cat retinal ganglion cell sensitivity following pigment bleaching.

    PubMed Central

    Bonds, A B; Enroth-Cugell, C

    1979-01-01

    1. The threshold illuminance for small spot stimulation of on-centre cat retinal ganglion cells was plotted vs. time after exposure to adapting light sufficiently strong to bleach significant amounts of rhodopsin. 2. When the entire receptive field of an X- or Y-type ganglion cell is bleached by at most 40%, recovery of the cell's rod-system proceeds in two phases: an early relatively fast one during which the response appears transient, and a late, slower one during which responses become more sustained. Log threshold during the later phase is well fit by an exponential in time (tau = 11.5-38 min). 3. After bleaches of 90% of the underlying pigment, threshold is cone-determined for as long as 40 min. Rod threshold continues to decrease for at least 85 min after the bleach. 4. The rate of recovery is slower after strong than after weak bleaches; 10 and 90% bleaches yield time constants for the later phase of 11.5 and 38 min, respectively. This contrasts with an approximate time constant of 11 min for rhodopsin regeneration following any bleach. 5. The relationship between the initial elevation of log rod threshold extrapolated from the fitted exponential curves and the initial amount of pigment bleached is monotonic, but nonlinear. 6. After a bleaching exposure, the maintained discharge is initially very regular. The firing rate first rises, then falls to the pre-bleach level, with more extended time courses of change in firing rate after stronger exposures. The discharge rate is restored before threshold has recovered fully. 7. The change in the response vs. log stimulus relationship after bleaching is described as a shift of the curve to the right, paired with a decrease in slope of the linear segment of the curve. PMID:521963

  4. Charge-balanced biphasic electrical stimulation inhibits neurite extension of spiral ganglion neurons.

    PubMed

    Shen, Na; Liang, Qiong; Liu, Yuehong; Lai, Bin; Li, Wen; Wang, Zhengmin; Li, Shufeng

    2016-06-15

    Intracochlear application of exogenous or transgenic neurotrophins, such as neurotrophin-3 (NT-3) and brain derived neurotrophic factor (BDNF), could promote the resprouting of spiral ganglion neuron (SGN) neurites in deafened animals. These resprouting neurites might reduce the gap between cochlear implant electrodes and their targeting SGNs, allowing for an improvement of spatial resolution of electrical stimulation. This study is to investigate the impact of electrical stimulation employed in CI on the extension of resprouting SGN neurites. We established an in vitro model including the devices delivering charge-balanced biphasic electrical stimulation, and spiral ganglion (SG) dissociated culture treated with BDNF and NT-3. After electrical stimulation with varying durations and intensities, we quantified neurite lengths and Schwann cell densities in SG cultures. Stimulations that were greater than 50μA or longer than 8h significantly decreased SG neurite length. Schwann cell density under 100μA electrical stimulation for 48h was significantly lower compared to that in non-stimulated group. These electrical stimulation-induced decreases of neurite extension and Schwann cell density were attenuated by various types of voltage-dependent calcium channel (VDCC) blockers, or completely prevented by their combination, cadmium or calcium-free medium. Our study suggested that charge-balanced biphasic electrical stimulation inhibited the extension of resprouting SGN neurites and decreased Schwann cell density in vitro. Calcium influx through multiple types of VDCCs was involved in the electrical stimulation-induced inhibition. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Soluble Adenylyl Cyclase Is Required for Retinal Ganglion Cell and Photoreceptor Differentiation

    PubMed Central

    Shaw, Peter X.; Fang, Jiahua; Sang, Alan; Wang, Yan; Kapiloff, Michael S.; Goldberg, Jeffrey L.

    2016-01-01

    Purpose We have previously demonstrated that soluble adenylyl cyclase (sAC) is necessary for retinal ganglion cell (RGC) survival and axon growth. Here, we further investigate the role of sAC in neuronal differentiation during retinal development. Methods Chx10 or Math5 promoter-driven Cre-Lox recombination were used to conditionally delete sAC from early and intermediate retinal progenitor cells during retinal development. We examined cell type–specific markers expressed by retinal cells to estimate their relative numbers and characterize retinal laminar morphology by immunofluorescence in adult and newborn mice. Results Retinal ganglion cell and amacrine cell markers were significantly lower in the retinas of adult Math5cre/sACfl/fl and Chx10cre/sACfl/fl mice than in those of wild-type controls. The effect on RGC development was detectable as early as postnatal day 1 and deleting sAC in either Math5- or Chx10-expressing retinal progenitor cells also reduced nerve fiber layer thickness into adulthood. The thickness of the photoreceptor layer was slightly but statistically significantly decreased in both the newborn Chx10cre/sACfl/fl and Math5cre/sACfl/fl mice, but this reduction and abnormal morphology persisted in the adults in only the Chx10cre/sACfl/fl mice. Conclusions sAC plays an important role in the early retinal development of RGCs as well as in the development of amacrine cells and to a lesser degree photoreceptors. PMID:27679853

  6. Glial interleukin-1β upregulates neuronal sodium channel 1.7 in trigeminal ganglion contributing to temporomandibular joint inflammatory hypernociception in rats.

    PubMed

    Zhang, Peng; Bi, Rui-Yun; Gan, Ye-Hua

    2018-04-20

    The proinflammatory cytokine interleukin-1β (IL-1β) drives pain by inducing the expression of inflammatory mediators; however, its ability to regulate sodium channel 1.7 (Nav1.7), a key driver of temporomandibular joint (TMJ) hypernociception, remains unknown. IL-1β induces cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). We previously showed that PGE2 upregulated trigeminal ganglionic Nav1.7 expression. Satellite glial cells (SGCs) involve in inflammatory pain through glial cytokines. Therefore, we explored here in the trigeminal ganglion (TG) whether IL-1β upregulated Nav1.7 expression and whether the IL-1β located in the SGCs upregulated Nav1.7 expression in the neurons contributing to TMJ inflammatory hypernociception. We treated rat TG explants with IL-1β with or without inhibitors, including NS398 for COX-2, PF-04418948 for EP2, and H89 and PKI-(6-22)-amide for protein kinase A (PKA), or with adenylate cyclase agonist forskolin, and used real-time PCR, Western blot, and immunohistofluorescence to determine the expressions or locations of Nav1.7, COX-2, cAMP response element-binding protein (CREB) phosphorylation, and IL-1β. We used chromatin immunoprecipitation to examine CREB binding to the Nav1.7 promoter. Finally, we microinjected IL-1β into the TGs or injected complete Freund's adjuvant into TMJs with or without previous microinjection of fluorocitrate, an inhibitor of SGCs activation, into the TGs, and evaluated nociception and gene expressions. Differences between groups were examined by one-way analysis of variance (ANOVA) or independent samples t test. IL-1β upregulated Nav1.7 mRNA and protein expressions in the TG explants, whereas NS398, PF-04418948, H89, or PKI-(6-22)-amide could all block this upregulation, and forskolin could also upregulate Nav1.7 mRNA and protein expressions. IL-1β enhanced CREB binding to the Nav1.7 promoter. Microinjection of IL-1β into the TGs or TMJ inflammation both induced hypernociception of TMJ region

  7. Curcumin Attenuates Staurosporine-Mediated Death of Retinal Ganglion Cells

    PubMed Central

    Burugula, Balabharathi; Ganesh, Bhagyalaxmi S.

    2011-01-01

    Purpose. Staurosporine (SS) causes retinal ganglion cell (RGC) death in vivo, but the underlying mechanisms have been unclear. Since previous studies on RGC-5 cells indicated that SS induces cell death by elevating proteases, this study was undertaken to investigate whether SS induces RGC loss by elevating proteases in the retina, and curcumin prevents SS-mediated death of RGCs. Methods. Transformed mouse retinal ganglion-like cells (RGC-5) were treated with 2.0 μM SS and various doses of curcumin. Two optimal doses of SS (12.5 and 100 nM) and curcumin (2.5 and 10 μM) were injected into the vitreous of C57BL/6 mice. Matrix metalloproteinase (MMP)-9, tissue plasminogen activator (tPA), and urokinase plasminogen activator (uPA) activities were assessed by zymography assays. Viability of RGC-5 cells was assessed by MTT assays. RGC and amacrine cell loss in vivo was assessed by immunostaining with Brn3a and ChAT antibodies, respectively. Frozen retinal cross sections were immunostained for nuclear factor-κB (NF-κB). Results. Staurosporine induced uPA and tPA levels in RGC-5 cells, and MMP-9, uPA, and tPA levels in the retinas and promoted the death of RGC-5 cells in vitro and RGCs and amacrine cells in vivo. In contrast, curcumin attenuated RGC and amacrine cell loss, despite elevated levels of proteases. An NF-κB inhibitory peptide reversed curcumin-mediated protective effect on RGC-5 cells, but did not inhibit protease levels. Curcumin did not inhibit protease levels in vivo, but attenuated RGC and amacrine cell loss by restoring NF-κB expression. Conclusions. The results show that curcumin attenuates RGC and amacrine cell death despite elevated levels of proteases and raises the possibility that it may be used as a plausible adjuvant therapeutic agent to prevent the loss of these cells in retinal degenerative conditions. PMID:21498608

  8. Mechanisms regulating plasminogen activators in transformed retinal ganglion cells

    PubMed Central

    Rock, Nathan; Chintala, Shravan K.

    2008-01-01

    Irreversible loss of retinal ganglion cells (RGCs) is a major clinical issue in glaucoma, but the mechanisms that lead to RGC death are currently unclear. We have previously reported that elevated levels of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) cause the death of RGCs in vivo and transformed retinal ganglion cells (RGC-5) in vitro. Yet, it is unclear how secreted proteases such as tPA and uPA directly cause RGCs' death. In this study, by employing RGC-5 cells, we report that tPA and uPA elicit their direct effect through the low-density lipoprotein-related receptor-1 (LRP-1). We also show that blockade of protease-LRP-1 interaction leads to a compete reduction in autocrine synthesis of tPA and uPA, and prevents protease-mediated death of RGC-5 cells. RGC-5 cells were cultured in serum-free medium and treated with 2.0 uM Staurosporine to induce their differentiation. Neurite outgrowth was observed by a phase contrast microscope and quantified by NeuroJ imaging software. Proteolytic activities of tPA and uPA were determined by zymography assays. Cell viability was determined by MTT assays. Compared to untreated RGC-5 cells, cells treated with Staurosporine differentiated, synthesized and secreted elevated levels of tPA and uPA, and underwent cell death. In contrast, when RGC-5 cells were treated with Staurosporine along with the receptor associated protein (RAP), proteolytic activities of both tPA and uPA were significantly reduced. Under these conditions, a significant number of RGC-5 cells survived and showed increased neurite outgrowth. These results indicate that LRP-1 regulates autocrine synthesis of tPA and uPA in RGC-5 cells and suggest that the use of RAP to antagonize the effect of proteases may be a way to prevent RGC death in glaucoma. PMID:18243176

  9. The effect of hexamethonium on the carotid chemoreceptor response to nicotine and cyanide

    PubMed Central

    Byck, R.

    1961-01-01

    The literature concerning the effects of ganglionic blocking agents on the chemoreceptors is reviewed. Hexamethonium blocks the respiratory response to intracarotid injections of small doses of nicotine in dogs anaesthetized with chloralose, but it does not block the response to sodium cyanide. PMID:13689559

  10. 31 CFR 598.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Blocked account; blocked property. 598.301 Section 598.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... REGULATIONS General Definitions § 598.301 Blocked account; blocked property. The terms blocked account and...

  11. 31 CFR 598.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Blocked account; blocked property. 598.301 Section 598.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... REGULATIONS General Definitions § 598.301 Blocked account; blocked property. The terms blocked account and...

  12. 31 CFR 598.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Blocked account; blocked property. 598.301 Section 598.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... REGULATIONS General Definitions § 598.301 Blocked account; blocked property. The terms blocked account and...

  13. 31 CFR 598.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Blocked account; blocked property. 598.301 Section 598.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued... REGULATIONS General Definitions § 598.301 Blocked account; blocked property. The terms blocked account and...

  14. Activation of cannabinoid CB1 receptors modulates evoked action potentials in rat retinal ganglion cells.

    PubMed

    Jiang, Shu-Xia; Li, Qian; Wang, Xiao-Han; Li, Fang; Wang, Zhong-Feng

    2013-08-25

    Activation of cannabinoid CB1 receptors (CB1Rs) regulates a variety of physiological functions in the vertebrate retina through modulating various types of ion channels. The aim of the present study was to investigate the effects of this receptor on cell excitability of rat retinal ganglion cells (RGCs) in retinal slices using whole-cell patch-clamp techniques. The results showed that under current-clamped condition perfusing WIN55212-2 (WIN, 5 μmol/L), a CB1R agonist, did not significantly change the spontaneous firing frequency and resting membrane potential of RGCs. In the presence of cocktail synaptic blockers, including excitatory postsynaptic receptor blockers CNQX and D-APV, and inhibitory receptor blockers bicuculline and strychnine, perfusion of WIN (5 μmol/L) hardly changed the frequencies of evoked action potentials by a series of positive current injection (from +10 to +100 pA). Phase-plane plot analysis showed that both average threshold voltage for triggering action potential and delay time to reach threshold voltage were not affected by WIN. However, WIN significantly decreased +dV/dtmax and -dV/dtmax of action potentials, suggestive of reduced rising and descending velocities of action potentials. The effects of WIN were reversed by co-application of SR141716, a CB1R selective antagonist. Moreover, WIN did not influence resting membrane potential of RGCs with synaptic inputs being blocked. These results suggest that activation of CB1Rs may regulate intrinsic excitability of rat RGCs through modulating evoked action potentials.

  15. Characterization of spontaneous excitatory synaptic currents in salamander retinal ganglion cells.

    PubMed Central

    Taylor, W R; Chen, E; Copenhagen, D R

    1995-01-01

    1. Spontaneous excitatory postsynaptic currents (sEPSCs) were recorded under voltage-clamp conditions. Consistent with activation of non-NMDA-type glutamate receptors, the sEPSCs reversed at potentials above 0 mV, were blocked by 1 microM CNQX and prolonged by 2 mM aniracetam. 2. The peak conductance of the averaged sEPSCs (n = 70-400) was 130 +/- 60 pS (mean +/- S.D.; 17 cells, ranging from 70 to 290 pS). Amplitude distributions were skewed towards larger amplitudes. 3. The decay of individual and mean sEPSCs was exponential with a mean time constant (tau d) of 3.75 +/- 0.84 ms (n = 13), which was voltage independent. The 10-90% rise time of the sEPSCs was 1.30 +/- 0.44 ms (n = 13). There was no correlation between sEPSC rise time and tau d suggesting that dendritic filtering alone did not shape the time course of sEPSCs. 4. Light-evoked EPSCs in these retinal ganglion cells are mediated by concomitant activation of NMDA and non-NMDA receptors; however, no NMDA component was discerned in the sEPSCs, even when recording at -96 mV in Mg(2+)-free solutions. The decay time course was not altered by 20 microM AP7, an NMDA antagonist, nor was an NMDA component unmasked by adding glycine or D-serine. These results suggest that NMDA and non-NMDA receptors are not coactivated by a single vesicle of transmitter during spontaneous release, and thus are probably not colocalized in the postsynaptic membrane at the sites of spontaneous release. 5. The sEPSCs were an order of magnitude faster than the non-NMDA receptor-mediated EPSCs evoked by light stimuli, and it is proposed that the EPSC time course is determined largely by the extended time course of release of synaptic vesicles from bipolar cells. The quantal content of a light-evoked non-NMDA receptor-mediated EPSC in an on-off cell is about 200 quanta. Images Figure 6 PMID:7562636

  16. Beyond Darcy's law: The role of phase topology and ganglion dynamics for two-fluid flow

    DOE PAGES

    Armstrong, Ryan T.; McClure, James E.; Berrill, Mark A.; ...

    2016-10-27

    Relative permeability quantifies the ease at which immiscible phases flow through porous rock and is one of the most well known constitutive relationships for petroleum engineers. It however exhibits troubling dependencies on experimental conditions and is not a unique function of phase saturation as commonly accepted in industry practices. The problem lies in the multi-scale nature of the problem where underlying disequilibrium processes create anomalous macroscopic behavior. Here we show that relative permeability rate dependencies are explained by ganglion dynamic flow. We utilize fast X-ray micro-tomography and pore-scale simulations to identify unique flow regimes during the fractional flow of immisciblemore » phases and quantify the contribution of ganglion flux to the overall flux of non-wetting phase. We anticipate our approach to be the starting point for the development of sophisticated multi-scale flow models that directly link pore-scale parameters to macro-scale behavior. Such models will have a major impact on how we recover hydrocarbons from the subsurface, store sequestered CO 2 in geological formations, and remove non-aqueous environmental hazards from the vadose zone.« less

  17. Effects of Icariside II on Corpus Cavernosum and Major Pelvic Ganglion Neuropathy in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Bai, Guang-Yi; Zhou, Feng; Hui, Yu; Xu, Yong-De; Lei, Hong-En; Pu, Jin-Xian; Xin, Zhong-Cheng

    2014-01-01

    Diabetic erectile dysfunction is associated with penile dorsal nerve bundle neuropathy in the corpus cavernosum and the mechanism is not well understood. We investigated the neuropathy changes in the corpus cavernosum of rats with streptozotocin-induced diabetes and the effects of Icariside II (ICA II) on improving neuropathy. Thirty-six 8-week-old Sprague-Dawley rats were randomly distributed into normal control group, diabetic group and ICA-II treated group. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (60 mg/kg). Three days later, the diabetic rats were randomly divided into 2 groups including a saline treated placebo group and an ICA II-treated group (5 mg/kg/day, by intragastric administration daily). Twelve weeks later, erectile function was measured by cavernous nerve electrostimulation with real time intracorporal pressure assessment. The penis was harvested for the histological examination (immunofluorescence and immunohistochemical staining) and transmission electron microscopy detecting. Diabetic animals exhibited a decreased density of dorsal nerve bundle in penis. The neurofilament of the dorsal nerve bundle was fragmented in the diabetic rats. There was a decreased expression of nNOS and NGF in the diabetic group. The ICA II group had higher density of dorsal nerve bundle, higher expression of NGF and nNOS in the penis. The pathological change of major pelvic nerve ganglion (including the microstructure by transmission electron microscope and the neurite outgrowth length of major pelvic nerve ganglion tissue cultured in vitro) was greatly attenuated in the ICA II-treated group (p < 0.01). ICA II treatment attenuates the diabetes-related impairment of corpus cavernosum and major pelvic ganglion neuropathy in rats with Streptozotocin-Induced Diabetes. PMID:25517034

  18. Conduction block in the peripheral nervous system in experimental allergic encephalomyelitis

    NASA Astrophysics Data System (ADS)

    Pender, M. P.; Sears, T. A.

    1982-04-01

    Experimental allergic encephalomyelitis (EAE) has been widely studied as a model of multiple sclerosis, a central nervous system (CNS) disease of unknown aetiology. The clinical features of both EAE and multiple sclerosis provide the only guide to the progress and severity of these diseases, and are used to assess the response to treatment. In such comparisons the clinical features of EAE are assumed to be due to lesions in the CNS, but in this disease there is also histological evidence of damage to the peripheral nervous system1-8. However, the functional consequences of such peripheral lesions have been entirely ignored. To examine this we have studied nerve conduction in rabbits with EAE. We report here that most of the large diameter afferent fibres are blocked in the region of the dorsal root ganglion and at the dorsal root entry zone, thus accounting for the loss of tendon jerks and also, through the severe loss of proprioceptive information, the ataxia of these animals. We conclude that whenever clinical comparisons are made between EAE and multiple sclerosis, the pathophysiology associated with the histological damage of the peripheral nervous system must be taken into account.

  19. Older age at diagnosis of Hirschsprung disease decreases risk of postoperative enterocolitis, but resection of additional ganglionated bowel does not.

    PubMed

    Haricharan, Ramanath N; Seo, Jeong-Meen; Kelly, David R; Mroczek-Musulman, Elizabeth C; Aprahamian, Charles J; Morgan, Traci L; Georgeson, Keith E; Harmon, Carroll M; Saito, Jacqueline M; Barnhart, Douglas C

    2008-06-01

    This study was conducted to determine the effect of age at diagnosis and length of ganglionated bowel resected on postoperative Hirschsprung-associated enterocolitis (HAEC). Children who underwent endorectal pull-through (ERPT) between January 1993 and December 2004 were retrospectively reviewed. t Test, analysis of variance, Kaplan-Meier, and Cox's proportional hazards analyses were performed. Fifty-two children with Hirschsprung disease (median age, 25 days; range, 2 days-16 years) were included. Nineteen (37%) had admissions for HAEC. Proportional hazards regression showed that HAEC admissions decreased by 30% with each doubling of age at diagnosis (P = .03) and increased 9-fold when postoperative stricture was present (P < .01), after controlling for type of ERPT, trisomy 21, transition zone level, and preoperative enterocolitis. Thirty-six children, with age at initial operation less than 6 months, were grouped based on length of ganglionated bowel excised (A [5 cm] and B [>5 cm]). No significant difference in the number of HAEC admissions during initial 2 years post-ERPT was seen between groups A (n = 18) and B (n = 18). The study had a power of 0.8 to detect a difference of 1 admission over 2 years. Children diagnosed with Hirschsprung disease at younger ages are at a greater risk for postoperative enterocolitis. Excising a longer margin of ganglionated bowel (>5 cm) does not seem to be beneficial in decreasing HAEC admissions.

  20. Retinal Astrocytes and GABAergic Wide-Field Amacrine Cells Express PDGFRα: Connection to Retinal Ganglion Cell Neuroprotection by PDGF-AA.

    PubMed

    Takahama, Shokichi; Adetunji, Modupe O; Zhao, Tantai; Chen, Shan; Li, Wei; Tomarev, Stanislav I

    2017-09-01

    Our previous experiments demonstrated that intravitreal injection of platelet-derived growth factor-AA (PDGF-AA) provides retinal ganglion cell (RGC) neuroprotection in a rodent model of glaucoma. Here we used PDGFRα-enhanced green fluorescent protein (EGFP) mice to identify retinal cells that may be essential for RGC protection by PDGF-AA. PDGFRα-EGFP mice expressing nuclear-targeted EGFP under the control of the PDGFRα promoter were used. Localization of PDGFRα in the neural retina was investigated by confocal imaging of EGFP fluorescence and immunofluorescent labeling with a panel of antibodies recognizing different retinal cell types. Primary cultures of mouse RGCs were produced by immunopanning. Neurobiotin injection of amacrine cells in a flat-mounted retina was used for the identification of EGFP-positive amacrine cells in the inner nuclear layer. In the mouse neural retina, PDGFRα was preferentially localized in the ganglion cell and inner nuclear layers. Immunostaining of the retina demonstrated that astrocytes in the ganglion cell layer and a subpopulation of amacrine cells in the inner nuclear layer express PDGFRα, whereas RGCs (in vivo or in vitro) did not. PDGFRα-positive amacrine cells are likely to be Type 45 gamma-aminobutyric acidergic (GABAergic) wide-field amacrine cells. These data indicate that the neuroprotective effect of PDGF-AA in a rodent model of glaucoma could be mediated by astrocytes and/or a subpopulation of amacrine cells. We suggest that after intravitreal injection of PDGF-AA, these cells secrete factors protecting RGCs.

  1. Spontaneous voltage and current fluctuations in tissue cultured mouse dorsal root ganglion cells.

    PubMed

    Mathers, D A; Barker, J L

    1984-02-13

    Fetal mouse dorsal root ganglion (DRG) neurons were maintained in primary dissociated cell culture for periods of 7 days to 3 months. Intracellular recordings from these cells revealed the presence of spontaneous subthreshold potentials in 101/177 neurons studied. When measured at the resting membrane potential, these spontaneous voltage events took two forms: (a) high frequency potential fluctuations several millivolts in peak-to-peak amplitude and (b) small, discrete hyperpolarizations. Neurons exhibiting either type of event were designated as 'active' DRG cells. No spontaneous potentials were seen in DRG cells hyperpolarized to membrane voltages more negative than -64 +/- 11.5 mV (n = 5 cells). Under voltage-clamp conditions, the subthreshold potentials of active DRG cells were replaced by fluctuations in outward current. The power spectral density, S(f) of these current fluctuations was approximated by an equation of the form S(f) = (S(o)/[1 + (f/fc) alpha] where 2 less than or equal to a less than or equal to 3 and the half-power frequency fc = 11.3 +/- 3.1 Hz at 23 degrees C (n = 17 cells). The spontaneous voltage fluctuations of active DRG cells were abolished in Ca2+-free saline, and of the divalent metal cations Sr2+, Mg2+, Ba2+, Co2+ and Mn2+, only Sr2+ could substitute for Ca2+ in the maintenance of this activity. Tetraethylammonium ions (1-10 mM) reversibly blocked the spontaneous potentials, while caffeine (10 mM) increased the frequency of these events. The spontaneous voltage fluctuations were not dependent on the presence of spinal cord neurons in the culture plate, and they were also observed in cultured DRG cells derived from adult mice.

  2. Allogeneic Transplantation of Müller-Derived Retinal Ganglion Cells Improves Retinal Function in a Feline Model of Ganglion Cell Depletion

    PubMed Central

    Becker, Silke; Eastlake, Karen; Jayaram, Hari; Jones, Megan F.; Brown, Robert A.; McLellan, Gillian J.; Charteris, David G.; Khaw, Peng T.

    2016-01-01

    Human Müller glia with stem cell characteristics (hMGSCs) have been shown to improve retinal function upon transplantation into rat models of retinal ganglion cell (RGC) depletion. However, their translational potential may depend upon successful engraftment and improvement of retinal function in experimental models with anatomical and functional features resembling those of the human eye. We investigated the effect of allogeneic transplantation of feline Müller glia with the ability to differentiate into cells expressing RGC markers, following ablation of RGCs by N-methyl-d-aspartate (NMDA). Unlike previous observations in the rat, transplantation of hMGSC-derived RGCs into the feline vitreous formed aggregates and elicited a severe inflammatory response without improving visual function. In contrast, allogeneic transplantation of feline MGSC (fMGSC)-derived RGCs into the vitrectomized eye improved the scotopic threshold response (STR) of the electroretinogram (ERG). Despite causing functional improvement, the cells did not attach onto the retina and formed aggregates on peripheral vitreous remnants, suggesting that vitreous may constitute a barrier for cell attachment onto the retina. This was confirmed by observations that cellular scaffolds of compressed collagen and enriched preparations of fMGSC-derived RGCs facilitated cell attachment. Although cells did not migrate into the RGC layer or the optic nerve, they significantly improved the STR and the photopic negative response of the ERG, indicative of increased RGC function. These results suggest that MGSCs have a neuroprotective ability that promotes partial recovery of impaired RGC function and indicate that cell attachment onto the retina may be necessary for transplanted cells to confer neuroprotection to the retina. Significance Müller glia with stem cell characteristics are present in the adult human retina, but they do not have regenerative ability. These cells, however, have potential for

  3. Testing block subdivision algorithms on block designs

    NASA Astrophysics Data System (ADS)

    Wiseman, Natalie; Patterson, Zachary

    2016-01-01

    Integrated land use-transportation models predict future transportation demand taking into account how households and firms arrange themselves partly as a function of the transportation system. Recent integrated models require parcels as inputs and produce household and employment predictions at the parcel scale. Block subdivision algorithms automatically generate parcel patterns within blocks. Evaluating block subdivision algorithms is done by way of generating parcels and comparing them to those in a parcel database. Three block subdivision algorithms are evaluated on how closely they reproduce parcels of different block types found in a parcel database from Montreal, Canada. While the authors who developed each of the algorithms have evaluated them, they have used their own metrics and block types to evaluate their own algorithms. This makes it difficult to compare their strengths and weaknesses. The contribution of this paper is in resolving this difficulty with the aim of finding a better algorithm suited to subdividing each block type. The proposed hypothesis is that given the different approaches that block subdivision algorithms take, it's likely that different algorithms are better adapted to subdividing different block types. To test this, a standardized block type classification is used that consists of mutually exclusive and comprehensive categories. A statistical method is used for finding a better algorithm and the probability it will perform well for a given block type. Results suggest the oriented bounding box algorithm performs better for warped non-uniform sites, as well as gridiron and fragmented uniform sites. It also produces more similar parcel areas and widths. The Generalized Parcel Divider 1 algorithm performs better for gridiron non-uniform sites. The Straight Skeleton algorithm performs better for loop and lollipop networks as well as fragmented non-uniform and warped uniform sites. It also produces more similar parcel shapes and patterns.

  4. Reduced N-Type Ca2+ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis.

    PubMed

    Zhang, Dongze; Tu, Huiyin; Cao, Liang; Zheng, Hong; Muelleman, Robert L; Wadman, Michael C; Li, Yu-Long

    2018-01-15

    Attenuated cardiac vagal activity is associated with ventricular arrhythmogenesis and related mortality in patients with chronic heart failure. Our recent study has shown that expression of N-type Ca 2+ channel α-subunits (Ca v 2.2-α) and N-type Ca 2+ currents are reduced in intracardiac ganglion neurons from rats with chronic heart failure. Rat intracardiac ganglia are divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion. Ventricular myocardium receives projection of neuronal terminals only from the AVG. In this study we tested whether a decrease in N-type Ca 2+ channels in AVG neurons contributes to ventricular arrhythmogenesis. Lentiviral Ca v 2.2-α shRNA (2 μL, 2×10 7  pfu/mL) or scrambled shRNA was in vivo transfected into rat AVG neurons. Nontransfected sham rats served as controls. Using real-time single-cell polymerase chain reaction and reverse-phase protein array, we found that in vivo transfection of Ca v 2.2-α shRNA decreased expression of Ca v 2.2-α mRNA and protein in rat AVG neurons. Whole-cell patch-clamp data showed that Ca v 2.2-α shRNA reduced N-type Ca 2+ currents and cell excitability in AVG neurons. The data from telemetry electrocardiographic recording demonstrated that 83% (5 out of 6) of conscious rats with Ca v 2.2-α shRNA transfection had premature ventricular contractions ( P <0.05 versus 0% of nontransfected sham rats or scrambled shRNA-transfected rats). Additionally, an index of susceptibility to ventricular arrhythmias, inducibility of ventricular arrhythmias evoked by programmed electrical stimulation, was higher in rats with Ca v 2.2-α shRNA transfection compared with nontransfected sham rats and scrambled shRNA-transfected rats. A decrease in N-type Ca 2+ channels in AVG neurons attenuates vagal control of ventricular myocardium, thereby initiating ventricular arrhythmias. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  5. TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons.

    PubMed

    Qin, Ning; Neeper, Michael P; Liu, Yi; Hutchinson, Tasha L; Lubin, Mary Lou; Flores, Christopher M

    2008-06-11

    Transient receptor potential V2 (TRPV2) has been proposed to be a high-threshold thermosensor. However, further elucidation of the channel properties and physiological role of TRPV2 have been hindered by the lack of selective pharmacological tools as well as by the species-dependent differences in the activation of this channel. In the present study, we have used cell-based calcium mobilization and electrophysiological assays to identify and characterize several novel cannabinoid TRPV2 agonists. Among these, cannabidiol was found to be the most robust and potent (EC(50) = 3.7 microM), followed by Delta(9)-tetrahydrocannabinol (EC(50) = 14 microM) and cannabinol (EC(50) = 77.7 microM). We also demonstrated that cannabidiol evoked a concentration-dependent release of calcitonin gene-related peptide (CGRP) from cultured rat dorsal root ganglion neurons in a cannabinoid receptor- and TRPV1-independent manner. Moreover, the cannabidiol-evoked CGRP release depended on extracellular calcium and was blocked by the nonselective TRP channel blocker, ruthenium red. We further provide evidence through the use of small interfering RNA knockdown and repetitive stimulation studies, to show that cannabidiol-evoked CGRP release is mediated, at least in part, by TRPV2. Together, these data suggest not only that TRPV2 may comprise a mechanism whereby cannabidiol exerts its clinically beneficial effects in vivo, but also that TRPV2 may constitute a viable, new drug target.

  6. Color vision impairment in multiple sclerosis points to retinal ganglion cell damage.

    PubMed

    Lampert, E J; Andorra, M; Torres-Torres, R; Ortiz-Pérez, S; Llufriu, S; Sepúlveda, M; Sola, N; Saiz, A; Sánchez-Dalmau, B; Villoslada, P; Martínez-Lapiscina, Elena H

    2015-11-01

    Multiple Sclerosis (MS) results in color vision impairment regardless of optic neuritis (ON). The exact location of injury remains undefined. The objective of this study is to identify the region leading to dyschromatopsia in MS patients' NON-eyes. We evaluated Spearman correlations between color vision and measures of different regions in the afferent visual pathway in 106 MS patients. Regions with significant correlations were included in logistic regression models to assess their independent role in dyschromatopsia. We evaluated color vision with Hardy-Rand-Rittler plates and retinal damage using Optical Coherence Tomography. We ran SIENAX to measure Normalized Brain Parenchymal Volume (NBPV), FIRST for thalamus volume and Freesurfer for visual cortex areas. We found moderate, significant correlations between color vision and macular retinal nerve fiber layer (rho = 0.289, p = 0.003), ganglion cell complex (GCC = GCIP) (rho = 0.353, p < 0.001), thalamus (rho = 0.361, p < 0.001), and lesion volume within the optic radiations (rho = -0.230, p = 0.030). Only GCC thickness remained significant (p = 0.023) in the logistic regression model. In the final model including lesion load and NBPV as markers of diffuse neuroaxonal damage, GCC remained associated with dyschromatopsia [OR = 0.88 95 % CI (0.80-0.97) p = 0.016]. This association remained significant when we also added sex, age, and disease duration as covariates in the regression model. Dyschromatopsia in NON-eyes is due to damage of retinal ganglion cells (RGC) in MS. Color vision can serve as a marker of RGC damage in MS.

  7. Developmental Profiling of Spiral Ganglion Neurons Reveals Insights into Auditory Circuit Assembly

    PubMed Central

    Lu, Cindy C.; Appler, Jessica M.; Houseman, E. Andres; Goodrich, Lisa V.

    2011-01-01

    The sense of hearing depends on the faithful transmission of sound information from the ear to the brain by spiral ganglion (SG) neurons. However, how SG neurons develop the connections and properties that underlie auditory processing is largely unknown. We catalogued gene expression in mouse SG neurons from embryonic day 12 (E12), when SG neurons first extend projections, up until postnatal day 15 (P15), after the onset of hearing. For comparison, we also analyzed the closely-related vestibular ganglion (VG). Gene ontology analysis confirmed enriched expression of genes associated with gene regulation and neurite outgrowth at early stages, with the SG and VG often expressing different members of the same gene family. At later stages, the neurons transcribe more genes related to mature function, and exhibit a dramatic increase in immune gene expression. Comparisons of the two populations revealed enhanced expression of TGFβ pathway components in SG neurons and established new markers that consistently distinguish auditory and vestibular neurons. Unexpectedly, we found that Gata3, a transcription factor commonly associated with auditory development, is also expressed in VG neurons at early stages. We therefore defined new cohorts of transcription factors and axon guidance molecules that are uniquely expressed in SG neurons and may drive auditory-specific aspects of their differentiation and wiring. We show that one of these molecules, the receptor guanylyl cyclase Npr2, is required for bifurcation of the SG central axon. Hence, our data set provides a useful resource for uncovering the molecular basis of specific auditory circuit assembly events. PMID:21795542

  8. Electronic neuron within a ganglion of a leech (Hirudo medicinalis).

    PubMed

    Aliaga, J; Busca, N; Minces, V; Mindlin, G B; Pando, B; Salles, A; Sczcupak, L

    2003-06-01

    We report the construction of an electronic device that models and replaces a neuron in a midbody ganglion of the leech Hirudo medicinalis. In order to test the behavior of our device, we used a well-characterized synaptic interaction between the mechanosensory, sensitive to pressure, (P) cell and the anteropagoda (because of the action potential shape) (AP) neuron. We alternatively stimulated a P neuron and our device connected to the AP neuron, and studied the response of the latter. The number and timing of the AP spikes were the same when the electronic parameters were properly adjusted. Moreover, after changes in the depolarization of the AP cell, the responses under the stimulation of both the biological neuron and the electronic device vary in a similar manner.

  9. Osthole, a herbal compound, alleviates nucleus pulposus-evoked nociceptive responses through the suppression of overexpression of acid-sensing ion channel 3 (ASIC3) in rat dorsal root ganglion

    PubMed Central

    He, Qiu-Lan; Chen, Yuling; Qin, Jian; Mo, Sui-Lin; Wei, Ming; Zhang, Jin-Jun; Li, Mei-Na; Zou, Xue-Nong; Zhou, Shu-Feng; Chen, Xiao-Wu; Sun, Lai-Bao

    2012-01-01

    Summary Background Osthole (Ost), a natural coumarin derivative, has been shown to inhibit many pro-inflammatory mediators and block voltage-gated Na+ channels. During inflammation, acidosis is an important pain inducer which activates nociceptors by gating depolarizing cationic channels, such as acid-sensing ion channel 3 (ASIC3). The aim of this study was to examine the effects of Ost on nucleus pulposus-evoked nociceptive responses and ASIC3 over-expression in the rat dorsal root ganglion, and to investigate the possible mechanism. Material/Methods Radicular pain was generated with application of nucleus pulposus (NP) to nerve root. Mechanical allodynia was evaluated using von Frey filaments with logarithmically incremental rigidity to calculate the 50% probability thresholds for mechanical paw withdrawal. ASIC3 protein expression in dorsal root ganglions (DRGs) was assessed with Western blot and immunohistochemistry. Membrane potential (MP) shift of DRG neurons induced by ASIC3-sensitive acid (pH6.5) was determined by DiBAC4 (3) fluorescence intensity (F.I.). Results The NP-evoked mechanical hyperalgesia model showed allodynia for 3 weeks, and ASIC3 expression was up-regulated in DRG neurons, reaching peak on Day 7. Epidural administration of Ost induced a remarkable and prolonged antinociceptive effect, accompanied by an inhibition of over-expressed ASIC3 protein and of abnormal shift of MP. Amiloride (Ami), an antagonist of ASIC3, strengthened the antinociceptive effect of Ost. Conclusions Up-regulation of ASIC3 expression may be associated with NP-evoked mechanical hyperalgesia. A single epidural injection of Ost decreased ASIC3 expression in DGR neurons and the pain in the NP-evoked mechanical hyperalgesia model. Osthole may be of great benefit for preventing chronic pain status often seen in lumbar disc herniation (LDH). PMID:22648244

  10. Pulsed Radiofrequency to the Dorsal Root Ganglion in Acute Herpes Zoster and Postherpetic Neuralgia.

    PubMed

    Kim, Koohyun; Jo, Daehyun; Kim, EungDon

    2017-03-01

    Latent varicella zoster virus reactivates mainly in sensory ganglia such as the dorsal root ganglion (DRG) or trigeminal ganglion. The DRG contains many receptor channels and is an important region for pain signal transduction. Sustained abnormal electrical activity to the spinal cord via the DRG in acute herpes zoster can result in neuropathic conditions such as postherpetic neuralgia (PHN). Although the efficacy of pulsed radiofrequency (PRF) application to the DRG in various pain conditions has been previously reported, the application of PRF to the DRG in patients with herpes zoster has not yet been studied. The aim of the present study was to compare the clinical effects of PRF to the DRG in patients with herpes zoster to those of PRF to the DRG in patients with PHN. Retrospective comparative study. University hospital pain center in Korea. The medical records of 58 patients who underwent PRF to the DRG due to zoster related pain (herpes zoster or PHN) were retrospectively analyzed. Patients were divided into 2 groups according to the timing of PRF after zoster onset: an early PRF group (within 90 days) and a PHN PRF group (more than 90 days). The efficacy of PRF was assessed by a numeric rating scale (NRS) and by recording patient medication doses before PRF and at one week, 4 weeks, 8 weeks, and 12 weeks after PRF. Pain intensity was decreased after PRF in all participants. However, the degree of pain reduction was significantly higher in the early PRF group. Moreover, more patients discontinued their medication in the early PRF group, and the PRF success rate was also higher in the early PRF group. The relatively small sample size from a single center, short duration of review of medical records, and the retrospective nature of the study. PRF to the DRG is a useful treatment for treatment-resistant cases of herpes zoster and PHN. Particularly in herpes zoster patients with intractable pain, application of PRF to the DRG should be considered for pain control

  11. 31 CFR 598.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... 598.301 Section 598.301 Money and Finance: Treasury Regulations Relating to Money and Finance... REGULATIONS General Definitions § 598.301 Blocked account; blocked property. The terms blocked account and blocked property mean any account or property subject to § 598.202 held in the name of a specially...

  12. Monoamine uptake inhibitors block alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation.

    PubMed

    Long, Cheng; Chen, Mei-Fang; Sarwinski, Susan J; Chen, Po-Yi; Si, Minliang; Hoffer, Barry J; Evans, M Steven; Lee, Tony J F

    2006-07-01

    We have proposed that activation of cerebral perivascular sympathetic alpha7-nicotinic acetylcholine receptors (alpha7-nAChRs) by nicotinic agonists releases norepinephrine, which then acts on parasympathetic nitrergic nerves, resulting in release of nitric oxide and vasodilation. Using patch-clamp electrophysiology, immunohistochemistry, and in vitro tissue bath myography, we tested this axo-axonal interaction hypothesis further by examining whether blocking norepinephrine reuptake enhanced alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation. The results indicated that choline- and nicotine-induced alpha7-nAChR-mediated nitrergic neurogenic relaxation in endothelium-denuded isolated porcine basilar artery rings was enhanced by desipramine and imipramine at lower concentrations (0.03-0.1 microM) but inhibited at higher concentrations (0.3-10 microM). In cultured superior cervical ganglion (SCG) neurons of the pig and rat, choline (0.1-30 mM)-evoked inward currents were reversibly blocked by 1-30 microM mecamylamine, 1-30 microM methyllycaconitine, 10-300 nM alpha-bungarotoxin, and 0.1-10 microM desipramine and imipramine, providing electrophysiological evidence for the presence of similar functional alpha7-nAChRs in cerebral perivascular sympathetic neurons of pigs and rats. In alpha7-nAChR-expressing Xenopus oocytes, choline-elicited inward currents were attenuated by alpha-bungarotoxin, imipramine, and desipramine. These monoamine uptake inhibitors appeared to directly block the alpha7-nAChR, resulting in diminished nicotinic agonist-induced cerebral nitrergic vasodilation. The enhanced nitrergic vasodilation by lower concentrations of monoamine uptake inhibitors is likely due to a greater effect on monoamine uptake than on alpha7-nAChR blockade. These results further support the hypothesis of axo-axonal interaction in nitrergic regulation of cerebral vascular tone.

  13. Amitriptyline Activates TrkA to Aid Neuronal Growth and Attenuate Anesthesia-Induced Neurodegeneration in Rat Dorsal Root Ganglion Neurons.

    PubMed

    Zheng, Xiaochun; Chen, Feng; Zheng, Ting; Huang, Fengyi; Chen, Jianghu; Tu, Wenshao

    2016-05-01

    Tricyclic antidepressant amitriptyline (AM) has been shown to exert neurotrophic activity on neurons. We thus explored whether AM may aid the neuronal development and protect anesthesia-induced neuro-injury in young spinal cord dorsal root ganglion (DRG) neurons.The DRG explants were prepared from 1-day-old rats. The effect of AM on aiding DRG neural development was examined by immunohistochemistry at dose-dependent manner. AM-induced changes in gene and protein expressions, and also phosphorylation states of tyrosine kinases receptor A (TrkA) and B (TrkB) in DRG, were examined by quantitative real-time polymerase chain reaction and western blot. The effect of AM on attenuating lidocaine-induced DRG neurodegeneration was examined by immunohistochemistry, and small interfering RNA (siRNA)-mediated TrkA/B down-regulation.Amitriptyline stimulated DRG neuronal development in dose-dependent manner, but exerted toxic effect at concentrations higher than 10 M. AM activated TrkA in DRG through phosphorylation, whereas it had little effect on TrkB-signaling pathway. AM reduced lidocaine-induced DRG neurodegeneration by regenerating neurites and growth cones. Moreover, the neuroprotection of AM on lidocaine-injured neurodegeneration was blocked by siRNA-mediated TrkA down-regulation, but not by TrkB down-regulation.Amitriptyline facilitated neuronal development and had protective effect on lidocaine-induced neurodegeneration, very likely through the activation of TrkA-signaling pathway in DRG.

  14. Amitriptyline Activates TrkA to Aid Neuronal Growth and Attenuate Anesthesia-Induced Neurodegeneration in Rat Dorsal Root Ganglion Neurons

    PubMed Central

    Zheng, Xiaochun; Chen, Feng; Zheng, Ting; Huang, Fengyi; Chen, Jianghu; Tu, Wenshao

    2016-01-01

    Abstract Tricyclic antidepressant amitriptyline (AM) has been shown to exert neurotrophic activity on neurons. We thus explored whether AM may aid the neuronal development and protect anesthesia-induced neuro-injury in young spinal cord dorsal root ganglion (DRG) neurons. The DRG explants were prepared from 1-day-old rats. The effect of AM on aiding DRG neural development was examined by immunohistochemistry at dose-dependent manner. AM-induced changes in gene and protein expressions, and also phosphorylation states of tyrosine kinases receptor A (TrkA) and B (TrkB) in DRG, were examined by quantitative real-time polymerase chain reaction and western blot. The effect of AM on attenuating lidocaine-induced DRG neurodegeneration was examined by immunohistochemistry, and small interfering RNA (siRNA)-mediated TrkA/B down-regulation. Amitriptyline stimulated DRG neuronal development in dose-dependent manner, but exerted toxic effect at concentrations higher than 10 M. AM activated TrkA in DRG through phosphorylation, whereas it had little effect on TrkB-signaling pathway. AM reduced lidocaine-induced DRG neurodegeneration by regenerating neurites and growth cones. Moreover, the neuroprotection of AM on lidocaine-injured neurodegeneration was blocked by siRNA-mediated TrkA down-regulation, but not by TrkB down-regulation. Amitriptyline facilitated neuronal development and had protective effect on lidocaine-induced neurodegeneration, very likely through the activation of TrkA-signaling pathway in DRG. PMID:27149473

  15. Glaucoma Diagnostic Capability of Global and Regional Measurements of Isolated Ganglion Cell Layer and Inner Plexiform Layer.

    PubMed

    Chien, Jason L; Ghassibi, Mark P; Patthanathamrongkasem, Thipnapa; Abumasmah, Ramiz; Rosman, Michael S; Skaat, Alon; Tello, Celso; Liebmann, Jeffrey M; Ritch, Robert; Park, Sung Chul

    2017-03-01

    To compare glaucoma diagnostic capability of global/regional macular layer parameters in different-sized grids. Serial horizontal spectral-domain optical coherence tomography scans of macula were obtained. Automated macular grids with diameters of 3, 3.45, and 6 mm were used. For each grid, 10 parameters (total volume; average thicknesses in 9 regions) were obtained for 5 layers: macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), ganglion cell-inner plexiform layer (GCIPL; GCL+IPL), and ganglion cell complex (GCC; mRNFL+GCL+IPL). Sixty-nine normal eyes (69 subjects) and 87 glaucomatous eyes (87 patients) were included. For the total volume parameter, the area under the receiver operating characteristic curves (AUCs) in 6-mm grid were larger than the AUCs in 3- and 3.45-mm grids for GCL, GCC, GCIPL, and mRNFL (all P<0.020). For the average thickness parameters, the best AUC in 6-mm grid (T2 region for GCL, IPL, and GCIPL; I2 region for mRNFL and GCC) was greater than the best AUC in 3-mm grid for GCL, GCC, and mRNFL (P<0.045). The AUC of GCL volume (0.920) was similar to those of GCC (0.920) and GCIPL (0.909) volume. The AUC of GCL T2 region thickness (0.942) was similar to those of GCC I2 region (0.942) and GCIPL T2 region (0.934) thickness. Isolated macular GCL appears to be as good as GCC and GCIPL in glaucoma diagnosis, while IPL does not. Larger macular grids may be better at detecting glaucoma. Each layer has a characteristic region with the best glaucoma diagnostic capability.

  16. Synaptic Proteins Are Tonotopically Graded in Postnatal and Adult Type I and Type II Spiral Ganglion Neurons

    PubMed Central

    Flores-Otero, Jacqueline; Davis, Robin L.

    2011-01-01

    Inherent in the design of the mammalian auditory system is the precision necessary to transduce complex sounds and transmit the resulting electrical signals to higher neural centers. Unique specializations in the organ of Corti are required to make this conversion, such that mechanical and electrical properties of hair cell receptors are tailored to their specific role in signal coding. Electrophysiological and immunocytochemical characterizations have shown that this principle also applies to neurons of the spiral ganglion, as evidenced by distinctly different firing features and synaptic protein distributions of neurons that innervate high- and low-frequency regions of the cochlea. However, understanding the fine structure of how these properties are distributed along the cochlear partition and within the type I and type II classes of spiral ganglion neurons is necessary to appreciate their functional significance fully. To address this issue, we assessed the localization of the postsynaptic AMPA receptor subunits GluR2 and GluR3 and the presynaptic protein synaptophysin by using immunocytochemical labeling in both postnatal and adult tissue. We report that these presynaptic and postsynaptic proteins are distributed oppositely in relation to the tonotopic map and that they are equally distributed in each neuronal class, thus having an overall gradation from one end of the cochlea to the other. For synaptophysin, an additional layer of heterogeneity was superimposed orthogonal to the tonotopic axis. The highest anti-synaptophysin antibody levels were observed within neurons located close to the scala tympani compared with those located close to the scala vestibuli. Furthermore, we noted that the protein distribution patterns observed in postnatal preparations were largely retained in adult tissue sections, indicating that these features characterize spiral ganglion neurons in the fully developed ear. PMID:21452215

  17. Complete adult neurogenesis within a Wallerian degenerating nerve expressed as an ectopic ganglion.

    PubMed

    Nakano, Tomonori; Kurimoto, Shigeru; Kato, Shuichi; Asano, Kenichi; Hirata, Takuma; Kiyama, Hiroshi; Hirata, Hitoshi

    2018-06-01

    Neurogenesis in the adult peripheral nervous system remains to be demonstrated. We transplanted embryonic neural stem cells into a Wallerian degenerating nerve graft and observed development of a nodular structure consisting of neurons, glia, and Schwann cells. Histological analysis revealed a structure loosely resembling the spinal cord, including a synaptic network that formed along the neuron. Furthermore, the new axons reinnervated the paralysed muscle, forming both de novo and revived neuromuscular junctions. Reinnervation of the paralysed muscle resulted in significantly greater mean wet muscle weight and muscle fibre cross-sectional area on the cell transplantation side than on the surgical control side (body weight 0.071 ± 0.011% vs. 0.051 ± 0.007%, p = .006; area 355.6 ± 345.2 vs. 114.0 ± 132.0 μm 2 , p < .001). Electrophysiological experiments demonstrated a functional connection between the neurons and muscle; hence, we identified this nodule as an ectopic ganglion. Surprisingly, in green rat experiments, most of these glial cells, but none of the neurons, expressed enhanced green fluorescent protein, suggesting that the cells constituting the ectopic ganglion were derived from both transplanted stem cells and endogenous stem cells. Such adult neurogenesis in a peripheral nerve related to neural stem cell transplantation has not been reported previously, and these results form the basis for a novel regenerative medicine approach in paralysed muscle. Copyright © 2018 John Wiley & Sons, Ltd.

  18. Macular retinal ganglion cell-inner plexiform layer thickness in patients on hydroxychloroquine therapy.

    PubMed

    Lee, Min Gyu; Kim, Sang Jin; Ham, Don-Il; Kang, Se Woong; Kee, Changwon; Lee, Jaejoon; Cha, Hoon-Suk; Koh, Eun-Mi

    2014-11-25

    We evaluated macular ganglion cell-inner plexiform layer (GC-IPL) thickness using spectral-domain optical coherence tomography (SD-OCT) in patients with chronic exposure to hydroxychloroquine (HCQ). This study included 130 subjects, who were divided into three groups: Group 1A, 55 patients with HCQ use ≥5 years; Group 1B, 46 patients with HCQ use <5 years; and Group 2, 29 normal controls. In all patients with exposure to HCQ, fundus examination, automated threshold perimetry, fundus autofluorescence photography, SD-OCT, and GC-IPL thickness measurement using the Cirrus HD-OCT ganglion cell analysis algorithm were performed. Average and minimum macular GC-IPL thickness were compared between subjects groups, and correlations between GC-IPL thickness and duration or total dose of HCQ use were analyzed. Among the 101 patients of Group 1, six patients who showed clinically evident HCQ retinopathy also showed markedly thin macular GC-IPL. In addition, weak but significant negative correlations were observed between the average and minimum GC-IPL thickness of Group 1 patients and cumulative dose of HCQ, even when analyzing without the six patients with HCQ retinopathy. However, when analyzing after exclusion of patients with high cumulative doses (>1000 g), significant correlations were not observed. This study revealed that macular GC-IPL thickness did not show definite correlations with HCQ use. However, some patients, especially with HCQ retinopathy or high cumulative doses, showed thin GC-IPL. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  19. Sonic Hedgehog Has a Dual Effect on the Growth of Retinal Ganglion Axons Depending on Its Concentration

    PubMed Central

    Kolpak, Adrianne; Zhang, Jinhua; Bao, Zheng-Zheng

    2006-01-01

    The stereotypical projection of retinal ganglion cell (RGC) axons to the optic disc has served as a good model system for studying axon guidance. By both in vitro and in vivo experiments, we show that a secreted molecule, Sonic hedgehog (Shh), may play a critical role in the process. It is expressed in a dynamic pattern in the ganglion cell layer with a relatively higher expression in the center of the retina. Through gel culture and stripe assays, we show that Shh has a dual effect on RGC axonal growth, acting as a positive factor at low concentrations and a negative factor at high concentrations. Results from time-lapse video microscopic and stripe assay experiments further suggest that the effects of Shh on axons are not likely attributable to indirect transcriptional regulation by Shh. Overexpression of Shh protein or inhibition of Shh function inside the retina resulted in a complete loss of centrally directed projection of RGC axons, suggesting that precise regulation of Shh level inside the retina is critical for the projection of RGC axons to the optic disc. PMID:15800198

  20. Rhythmic ganglion cell activity in bleached and blind adult mouse retinas.

    PubMed

    Menzler, Jacob; Channappa, Lakshmi; Zeck, Guenther

    2014-01-01

    In retinitis pigmentosa--a degenerative disease which often leads to incurable blindness--the loss of photoreceptors deprives the retina from a continuous excitatory input, the so-called dark current. In rodent models of this disease this deprivation leads to oscillatory electrical activity in the remaining circuitry, which is reflected in the rhythmic spiking of retinal ganglion cells (RGCs). It remained unclear, however, if the rhythmic RGC activity is attributed to circuit alterations occurring during photoreceptor degeneration or if rhythmic activity is an intrinsic property of healthy retinal circuitry which is masked by the photoreceptor's dark current. Here we tested these hypotheses by inducing and analysing oscillatory activity in adult healthy (C57/Bl6) and blind mouse retinas (rd10 and rd1). Rhythmic RGC activity in healthy retinas was detected upon partial photoreceptor bleaching using an extracellular high-density multi-transistor-array. The mean fundamental spiking frequency in bleached retinas was 4.3 Hz; close to the RGC rhythm detected in blind rd10 mouse retinas (6.5 Hz). Crosscorrelation analysis of neighbouring wild-type and rd10 RGCs (separation distance <200 µm) reveals synchrony among homologous RGC types and a constant phase shift (∼70 msec) among heterologous cell types (ON versus OFF). The rhythmic RGC spiking in these retinas is driven by a network of presynaptic neurons. The inhibition of glutamatergic ganglion cell input or the inhibition of gap junctional coupling abolished the rhythmic pattern. In rd10 and rd1 retinas the presynaptic network leads to local field potentials, whereas in bleached retinas additional pharmacological disinhibition is required to achieve detectable field potentials. Our results demonstrate that photoreceptor bleaching unmasks oscillatory activity in healthy retinas which shares many features with the functional phenotype detected in rd10 retinas. The quantitative physiological differences advance the

  1. Spiral ganglion cell site of excitation I: comparison of scala tympani and intrameatal electrode responses.

    PubMed

    Cartee, Lianne A; Miller, Charles A; van den Honert, Chris

    2006-05-01

    To determine the site of excitation on the spiral ganglion cell in response to electrical stimulation similar to that from a cochlear implant, single-fiber responses to electrical stimuli delivered by an electrode positioned in the scala tympani were compared to responses from stimuli delivered by an electrode placed in the internal auditory meatus. The response to intrameatal stimulation provided a control set of data with a known excitation site, the central axon of the spiral ganglion cell. For both intrameatal and scala tympani stimuli, the responses to single-pulse, summation, and refractory stimulus protocols were recorded. The data demonstrated that summation pulses, as opposed to single pulses, are likely to give the most insightful measures for determination of the site of excitation. Single-fiber summation data for both scala tympani and intrameatally stimulated fibers were analyzed with a clustering algorithm. Combining cluster analysis and additional numerical modeling data, it was hypothesized that the scala tympani responses corresponded to central excitation, peripheral excitation adjacent to the cell body, and peripheral excitation at a site distant from the cell body. Fibers stimulated by an intrameatal electrode demonstrated the greatest range of jitter measurements indicating that greater fiber independence may be achieved with intrameatal stimulation.

  2. Single cell RNA sequencing of stem cell-derived retinal ganglion cells.

    PubMed

    Daniszewski, Maciej; Senabouth, Anne; Nguyen, Quan H; Crombie, Duncan E; Lukowski, Samuel W; Kulkarni, Tejal; Sluch, Valentin M; Jabbari, Jafar S; Chamling, Xitiz; Zack, Donald J; Pébay, Alice; Powell, Joseph E; Hewitt, Alex W

    2018-02-13

    We used single cell sequencing technology to characterize the transcriptomes of 1,174 human embryonic stem cell-derived retinal ganglion cells (RGCs) at the single cell level. The human embryonic stem cell line BRN3B-mCherry (A81-H7), was differentiated to RGCs using a guided differentiation approach. Cells were harvested at day 36 and prepared for single cell RNA sequencing. Our data indicates the presence of three distinct subpopulations of cells, with various degrees of maturity. One cluster of 288 cells showed increased expression of genes involved in axon guidance together with semaphorin interactions, cell-extracellular matrix interactions and ECM proteoglycans, suggestive of a more mature RGC phenotype.

  3. Threshold setting by the surround of cat retinal ganglion cells.

    PubMed

    Barlow, H B; Levick, W R

    1976-08-01

    1. The slope of curves relating the log increment threshold to log background luminance in cat retinal ganglion cells is affected by the area and duration of the test stimulus, as it is in human pyschophysical experiments. 2. Using large area, long duration stimuli the slopes average 0-82 and approach close to 1 (Weber's Law) in the steepest cases. Small stimuli gave an average of 0-53 for on-centre units using brief stimuli, and 0-56 for off-centre units, using long stimuli. Slopes under 0-5 (square root law) were not found over an extended range of luminances. 3. On individual units the slope was generally greater for larger and longer test stimulus, but no unit showed the full extent of change from slope of 0-5 to slope of 1. 4. The above differences hold for objective measures of quantum/spike ratio, as well as for thresholds either judged by ear or assessed by calculation. 5. The steeper slope of the curves for large area, long duration test stimuli compared with small, long duration stimuli, is associated with the increased effectiveness of antagonism from the surround at high backgrounds. This change may be less pronounced in off-centre units, one of which (probably transient Y-type) showed no difference of slope, and gave parallel area-threshold curves at widely separated background luminances, confirming the importance of differential surround effectiveness in changing the slope of the curves. 6. In on-centre units, the increased relative effectiveness of the surround is associated with the part of the raised background light that falls on the receptive field centre. 7. It is suggested that the variable surround functions as a zero-offset control that sets the threshold excitation required for generating impulses, and that this is separate from gain-setting adaptive mechanisms. This may be how ganglion cells maintain high incremental sensitivity in spite of a strong maintained excitatory drive that would otherwise cause compressive response non-linearities.

  4. Y-cell receptive field and collicular projection of parasol ganglion cells in macaque monkey retina

    PubMed Central

    Crook, Joanna D.; Peterson, Beth B.; Packer, Orin S.; Robinson, Farrel R.; Troy, John B.; Dacey, Dennis M.

    2009-01-01

    The distinctive parasol ganglion cell of the primate retina transmits a transient, spectrally non-opponent signal to the magnocellular layers of the lateral geniculate nucleus (LGN). Parasol cells show well-recognized parallels with the alpha-Y cell of other mammals, yet two key alpha-Y cell properties, a collateral projection to the superior colliculus and nonlinear spatial summation, have not been clearly established for parasol cells. Here we show by retrograde photodynamic staining that parasol cells project to the superior colliculus. Photostained dendritic trees formed characteristic spatial mosaics and afforded unequivocal identification of the parasol cells among diverse collicular-projecting cell types. Loose-patch recordings were used to demonstrate for all parasol cells a distinct Y-cell receptive field ‘signature’ marked by a non-linear mechanism that responded to contrast-reversing gratings at twice the stimulus temporal frequency (second Fourier harmonic, F2) independent of stimulus spatial phase. The F2 component showed high contrast gain and temporal sensitivity and appeared to originate from a region coextensive with that of the linear receptive field center. The F2 spatial frequency response peaked well beyond the resolution limit of the linear receptive field center, showing a Gaussian center radius of ~15 μm. Blocking inner retinal inhibition elevated the F2 response, suggesting that amacrine circuitry does not generate this non-linearity. Our data are consistent with a pooled-subunit model of the parasol-Y cell receptive field in which summation from an array of transient, partially rectifying cone bipolar cells accounts for both linear and non-linear components of the receptive field. PMID:18971470

  5. FIRST OBSERVATIONAL SIGNATURE OF ROTATIONAL DECELERATION IN A MASSIVE, INTERMEDIATE-AGE STAR CLUSTER IN THE MAGELLANIC CLOUDS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wu, Xiaohan; Li, Chengyuan; De Grijs, Richard

    While the extended main-sequence turnoffs (eMSTOs) found in almost all 1–2 Gyr old star clusters in the Magellanic Clouds are often explained by postulating extended star formation histories (SFHs), the tight subgiant branches (SGBs) seen in some clusters challenge this popular scenario. Puzzlingly, the SGB of the eMSTO cluster NGC 419 is significantly broader at bluer than at redder colors. We carefully assess and confirm the reality of this observational trend. If we would assume that the widths of the features in color–magnitude space were entirely owing to a range in stellar ages, the SFHs of the eMSTO stars andmore » the blue SGB region would be significantly more prolonged than that of the red part of the SGB. This cannot be explained by assuming an internal age spread. We show that rotational deceleration of a population of rapidly rotating stars, a currently hotly debated alternative scenario, naturally explains the observed trend along the SGB. Our analysis shows that a “converging” SGB could be produced if the cluster is mostly composed of rapidly rotating stars that slow down over time owing to the conservation of angular momentum during their evolutionary expansion from main-sequence turnoff stars to red giants.« less

  6. Pyroglutamic acid promotes survival of retinal ganglion cells after optic nerve injury.

    PubMed

    Oono, Shinichirou; Kurimoto, Takuji; Nakazawa, Toru; Miyoshi, Tomomitsu; Okamoto, Norio; Kashimoto, Ryosuke; Tagami, Yuichi; Ito, Yoshimasa; Mimura, Osamu

    2009-07-01

    To determine whether pyroglutamic acid (PGA) enhances the survival of retinal ganglion cells (RGCs) after optic nerve (ON) transection in vivo and RGCs in culture. The RGCs of rats were retrogradely labeled by Fluorogold (FG)-soaked sponges placed on both superior colliculi. Seven days later, the ON was transected, and PGA was immediately injected into the vitreous. Seven or fourteen days later, the number of FG-labeled RGCs was counted on flat-mounted retinas to obtain the mean densities of FG-labeled RGCs. To determine whether the survival effect of PGA was related to excitatory amino acid transporter (EAAT), L-trans-pyrrolidine-2,4 dicarboxylate (PDC), a nonselective glutamate transport inhibitor, was injected into vitreous with the PGA. In primary retinal cultures, RGCs were identified as cells that were immunopositive to beta III tubulin three days after beginning the culture with and without PDC. The mean density of FG-labeled RGCs was reduced from 2249 +/- 210 to 920 +/- 202 cells/mm(2) (p < 0.001) on day 7 after the ON transection. The mean density RGCs was significantly higher at 1213 +/- 159 cells/mm(2) after 0.5% PGA injection immediately after the ON transaction than eyes injected with the vehicle at 1007 +/- 122 cells/mm(2) (p = 0.035). One percent PGA was the most effective concentration for survival-promoting effects on RGCs, and the mean density of the RGCs was 1464 +/- 102/mm(2) (p < 0.001). Fourteen days after 1% PGA, the mean density of FG-labeled RGCs was significantly higher than that with vehicle (204 +/- 23/mm(2) versus 145 +/- 17 cells/mm(2); p < 0.01). Simultaneous application of 1% PGA and PDC blocked the survival effects of PGA on day 7 after ON transection. The presence of PGA increased the number of beta III tubulin-positive cells. PGA promotes the survival of axotomized RGCs in adult mammalian retinas possibly mediated by the EAATs.

  7. ["Habitual" left branch block alternating with 2 "disguised" bracnch block].

    PubMed

    Lévy, S; Jullien, G; Mathieu, P; Mostefa, S; Gérard, R

    1976-10-01

    Two cases of alternating left bundle branch block and "masquerading block" (with left bundle branch morphology in the stnadard leads and right bundle branch block morphology in the precordial leads) were studied by serial tracings and his bundle electrocardiography. In case 1 "the masquerading" block was associated with a first degree AV block related to a prolongation of HV interval. This case is to our knowledge the first cas of alternating bundle branch block in which his bundle activity was recorded in man. In case 2, the patient had atrial fibrilation and His bundle recordings were performed while differents degrees of left bundle branch block were present: The mechanism of the alternation and the concept of "masquerading" block are discussed. It is suggested that this type of block represents a right bundle branch block associated with severe lesions of the "left system".

  8. PERCUTANEOUS BALLOON COMPRESSION OF GASSERIAN GANGLION FOR THE TREATMENT OF TRIGEMINAL NEURALGIA: AN EXPERIENCE FROM INDIA.

    PubMed

    Agarwal, Anurag; Dhama, Vipin; Manik, Yogesh K; Upadhyaya, M K; Singh, C S; Rastogi, V

    2015-02-01

    Trigeminal neuralgia (TN) is characterized by unilateral, lancinating, paroxysmal pain in the dermatomal distribution area of trigeminal nerve. Percutaneous balloon compression (PBC) of Gasserian ganglion is an effective, comparatively cheaper and simple therapeutic modality for treatment of TN. Compression secondary to PBC selectively injures the large myelinated A-alfa (afferent) fibers that mediate light touch and does not affect A-delta and C-fibres, which carry pain sensation. Balloon compression reduces the sensory neuronal input, thus turning off the trigger to the neuropathic trigeminal pain. In this current case series, we are sharing our experience with PBC of Gasserian Ganglion for the treatment of idiopathic TN in our patients at an academic university-based medical institution in India. During the period of August 2012 to October 2013, a total of twelve PBCs of Gasserian Ganglion were performed in eleven patients suffering from idiopathic TN. There were nine female patients and two male patients with the age range of 35-70 years (median age: 54 years). In all patients cannulation of foramen ovale was done successfully in the first attempt. In eight out of eleven (72.7%) patients ideal 'Pear-shaped' balloon visualization could be achieved. In the remaining three patients (27.3%), inflated balloon was 'Bullet-shaped'. In one patient final placement of Fogarty balloon was not satisfactory and it ruptured during inflation. This case was deferred for one week when it was completed successfully with 'Pear-shaped' balloon inflation. During the follow up period of 1-13 months, there have been no recurrences of TN. Eight out of eleven patients (72.7%) are completely off medicines (carbamazepine and baclofen) and other two patients are stable on very low doses of carbamazepine. All patients have reported marked improvement in quality of life. This case series shows that percutaneous balloon compression is a useful minimally invasive intervention for the

  9. Endoscopic sphenopalatine ganglion blockade efficacy in pain control after endoscopic sinus surgery.

    PubMed

    Al-Qudah, Mohannad

    2016-03-01

    The objective of this study was to evaluate the efficacy of bilateral endoscopic injection of lidocaine with epinephrine in the sphenopalatine ganglion at the end of endoscopic sinus surgery (ESS) in controlling postoperative pain and rescue analgesic requirements. A prospective, double blinded, placebo-controlled clinical trial of 60 patients with chronic rhinosinusitis (CRS) undergoing general anesthesia for ESS was undertaken. Patients were randomized to receive injection of 2 mL of 2% lidocaine with epinephrine or 2 mL saline at the end of surgery. Postoperatively, patients were observed for 24 hours. Pain severity was reported immediately, 6 hours, and 24 hours after surgery using a 10-cm visual analog scale (VAS). The need of rescue analgesia was recorded and compared between the 2 groups. The 2 groups were matched in demographic and intraoperative details. Postoperative pain severity average was 3.4, 3.0, and 1.6 in the saline group compared to 1.6, 1.7, and 1.0 in the lidocaine group. These differences reached statically significant for the first 2 follow-up intervals. Also, there was significant difference in the whole-day postoperative average score between the 2 groups (2.6 vs 1.4). Twelve patients in the saline group required rescue analgesia compared to 5 in the lidocaine group. The average rescue analgesia dose was 27.5 mg of tramadol in the saline group vs 11.6 in the lidocaine group. These differences were statistically significant. No complications were reported in either group. Sphenopalatine ganglion injection of lidocaine at the end of surgery is safe, simple, noninvasive, and an effective method of short-term pain control after sinus surgery. © 2015 ARS-AAOA, LLC.

  10. The venom of Ampulex compressa--effects on behaviour and synaptic transmission of cockroaches.

    PubMed

    Piek, T; Hue, B; Lind, A; Mantel, P; van Marle, J; Visser, J H

    1989-01-01

    1. The solitary wasp Ampulex compressa stings a cockroach, Periplaneta americana, twice. 2. The first sting into the ventral thorax results in a transient paralysis. During this paralysis the wasp stings the suboesophageal ganglion, which gradually results in a permanent deactivation. 3. The venom gland is a paired and highly branched organ, with a common ductus venatus. The large lumen is lined with a folded cuticula. No venom reservoir is present. 4. Extract of the venom gland induces a slow contraction of the guinea pig ileum. 5. The agonist present in the venom cannot be identified with a known agonist. 6. Venom gland extract blocks synaptic transmission from the cercal nerve to giant neurons in the sixth abdominal ganglion of the cockroach. 7. The block develops gradually, like the gradual appearance of the effects of the sting into the suboesophageal ganglion on the behaviour of the cockroach.

  11. Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons

    PubMed Central

    Liu, Pin W.

    2014-01-01

    Kv2 family “delayed-rectifier” potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60–80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. PMID:24695716

  12. Micromonospora phytophila sp. nov. and Micromonospora luteiviridis sp. nov., isolated as natural inhabitants of plant nodules.

    PubMed

    Carro, Lorena; Veyisoglu, Aysel; Riesco, Raúl; Spröer, Cathrin; Klenk, Hans-Peter; Sahin, Nevzat; Trujillo, Martha E

    2018-01-01

    Two actinobacterial isolates, strains SG15 T and SGB14 T , were recovered through a microbial diversity study of nitrogen fixing nodules from Pisum sativum plants collected in Salamanca (Spain). The taxonomic status of these isolates was determined using a polyphasic approach and both presented chemotaxonomic and morphological properties consistent with their classification in the genus Micromonospora. For strains SG15 T and SGB14 T , the highest 16S rRNA gene sequence similarities were observed with Micromonospora coxensis JCM 13248 T (99.2 %) and Micromonospora purpureochromogenes DSM 43821 T (99.4 %), respectively. However, strains SG15 T and SGB14 T were readily distinguished from their phylogenetic neighbours both genetically and phenotypically indicating that they represent two new Micromonospora species. The following names are proposed for these species: Micromonosporaphytophila sp. nov. type strain SG15 T (=CECT 9369 T ; =DSM 105363 T ), and Micromonosporaluteiviridis sp. nov. type strain SGB14 T (=CECT 9370 T ; =DSM 105362 T ).

  13. Visual Acuity and the Balance between Receptor Density and Ganglion Cell Receptive Field Overlap.

    DTIC Science & Technology

    1980-07-01

    Physiol. 229:719-731. Cleland, B . G., Dubin, M. W. and Levick , W. R. (1971) Sustained and transient neurones in the cat’s retina and lateral...NOOOIQ.79C-0370 NLASSIFIED IA. EEEEEEEEEEinnuunuuuuuu ’mLuuuu~ 4,0 111 12. 11111IL25 1.4I 111111.6 MICROCOPY RESOLUTION TEST CHART LEVEt 9 70 b *tm...1970; Burke and Hayhow, 1968; Barlow and Levick , 1969). As far as they affect the ganglion cell, these sources of noise are equivalent so they have been

  14. Response of cervicogenic headaches and occipital neuralgia to radiofrequency ablation of the C2 dorsal root ganglion and/or third occipital nerve.

    PubMed

    Hamer, John F; Purath, Traci A

    2014-03-01

    This article investigates the degree and duration of pain relief from cervicogenic headaches or occipital neuralgia following treatment with radiofrequency ablation of the C2 dorsal root ganglion and/or third occipital nerves. It also addresses the procedure's complication rate and patient's willingness to repeat the procedure if severe symptoms recur. This is a single-center retrospective observational study of 40 patients with refractory cervicogenic headaches and or occipital neuralgia. Patients were all referred by a headache specialty clinic for evaluation for radiofrequency ablation of the C2 dorsal root ganglion and/or third occipital nerves. After treatment, patients were followed for a minimum of 6 months to a year. Patient demographics and the results of radiofrequency ablation were recorded on the same day, after 3-4 days, and at 6 months to 1 year following treatment. Thirty-five percent of patients reported 100% pain relief and 70% reported 80% or greater pain relief. The mean duration of improvement is 22.35 weeks. Complication rate was 12-13%. 92.5% of patients reported they would undergo the procedure again if severe symptoms returned. Radiofrequency ablation of the C2 dorsal root ganglion and/or third occipital nerve can provide many months of greater than 50% pain relief in the vast majority of recipients with an expected length of symptom improvement of 5-6 months. © 2014 American Headache Society.

  15. The different roles of opioid receptors in the inhibitory effects induced by sacral dorsal root ganglion stimulation on nociceptive and nonnociceptive conditions in cats.

    PubMed

    Wang, Zhaoxia; Liao, Limin; Deng, Han; Li, Xing; Chen, Guoqing; Liao, Xiwen

    2018-06-04

    To examine the roles of opioid receptors in the inhibition of nociceptive and nonnociceptive bladder reflexes by sacral dorsal root ganglion (DRG) stimulation in cats. Hook electrodes were placed in the right S1 and S2 DRG of cats. The bladders were infused with physiologic saline or 0.25% acetic acid (AA). Naloxone (0.1, 0.3, and 1 mg/kg), an opioid receptor antagonist, was administered intravenously. S1 or S2 DRG stimulation was applied before and after administering the drug. Multiple cystometrograms were performed to determine the effects of DRG stimulation and opioid receptors on the micturition reflex under nociceptive and non-nociceptive conditions. AA significantly (P < 0.01) reduced bladder capacity (BC). DRG stimulation at threshold (T) and 1.5 T significantly increased BC of the saline control under nociceptive and non-nociceptive conditions. When saline was infused, naloxone (0.1-1 mg/kg) significantly (P < 0.01) reduced BC; however, naloxone did not change BC during AA irritation. During saline infusion, naloxone (0.3 and 1 mg/kg) partly blocked S1 DRG stimulation-induced inhibition but had only a slight effect on S2 DRG stimulation. During AA infusion, naloxone (0.3 and 1 mg/kg) only partially blocked S1 DRG stimulation at T intensity but not during 1.5 T stimulation. However, no doses of naloxone significantly affected S2 DRG stimulation. Opioid receptors play a role in sacral DRG stimulation on non-nociceptive condition but are not involved in the inhibitory effect of stimulation in nociceptive conditions. © 2018 Wiley Periodicals, Inc.

  16. Changes in NGF and NT-3 protein species in the superior cervical ganglion following axotomy of postganglionic axons.

    PubMed

    Walker, Ryan G; Foster, Andrew; Randolph, Chris L; Isaacson, Lori G

    2009-02-19

    Mature sympathetic neurons in the superior cervical ganglion (SCG) are regulated by target-derived neurotrophins such as nerve growth factor (NGF) and neurotrophin-3 (NT-3). High molecular weight NGF species and mature NT-3 are the predominant NGF and NT-3 protein isoforms in the SCG, yet it is unknown whether the presence of these species is dependent on intact connection with the target tissues. In an attempt to determine the role of peripheral targets in regulating the neurotrophin species found in the SCG, we investigated the NGF and NT-3 protein species present in the SCG following axotomy (transection) or injury of the post-ganglionic axons. Following a 7 day axotomy, the 22-24 kDa NGF species and the mature 14 kDa NT-3 species in the SCG were significantly reduced by 99% and 66% respectively, suggesting that intact connection with the target is necessary for the expression of these protein species. As expected, tyrosine hydroxylase (TH) protein in the SCG was significantly reduced by 80% at 7 days following axotomy. In order to distinguish between the effects of injury and loss of target connectivity, the SCG was examined following compression injury to the post-ganglionic nerves. Following injury, no reduction in the 22-24 kDa NGF or 14 kDa mature NT-3 species was observed in the SCG. TH protein was slightly, yet significantly, decreased in the SCG following injury. The findings of this study suggest that the presence of the 22-24 kDa NGF and mature 14 kDa NT-3 species in the SCG is dependent on connection with peripheral targets and may influence, at least in part, TH protein expression in adult sympathetic neurons.

  17. Synaptology of physiologically identified ganglion cells in the cat retina: a comparison of retinal X- and Y-cells.

    PubMed

    Weber, A J; Stanford, L R

    1994-05-15

    It has long been known that a number of functionally different types of ganglion cells exist in the cat retina, and that each responds differently to visual stimulation. To determine whether the characteristic response properties of different retinal ganglion cell types might reflect differences in the number and distribution of their bipolar and amacrine cell inputs, we compared the percentages and distributions of the synaptic inputs from bipolar and amacrine cells to the entire dendritic arbors of physiologically characterized retinal X- and Y-cells. Sixty-two percent of the synaptic input to the Y-cell was from amacrine cell terminals, while the X-cells received approximately equal amounts of input from amacrine and bipolar cells. We found no significant difference in the distributions of bipolar or amacrine cell inputs to X- and Y-cells, or ON-center and OFF-center cells, either as a function of dendritic branch order or distance from the origin of the dendritic arbor. While, on the basis of these data, we cannot exclude the possibility that the difference in the proportion of bipolar and amacrine cell input contributes to the functional differences between X- and Y-cells, the magnitude of this difference, and the similarity in the distributions of the input from the two afferent cell types, suggest that mechanisms other than a simple predominance of input from amacrine or bipolar cells underlie the differences in their response properties. More likely, perhaps, is that the specific response features of X- and Y-cells originate in differences in the visual responses of the bipolar and amacrine cells that provide their input, or in the complex synaptic arrangements found among amacrine and bipolar cell terminals and the dendrites of specific types of retinal ganglion cells.

  18. Lack of early pattern stimulation prevents normal development of the alpha (Y) retinal ganglion cell population in the cat.

    PubMed

    Burnat, Kalina; Van Der Gucht, Estelle; Waleszczyk, Wioletta J; Kossut, Malgorzata; Arckens, Lutgarde

    2012-08-01

    Binocular deprivation of pattern vision (BD) early in life permanently impairs global motion perception. With the SMI-32 antibody against neurofilament protein (NFP) as a marker of the motion-sensitive Y-cell pathway (Van der Gucht et al. [2001] Cereb. Cortex 17:2805-2819), we analyzed the impact of early BD on the retinal circuitry in adult, perceptually characterized cats (Burnat et al. [2005] Neuroreport 16:751-754). In controls, large retinal ganglion cells exhibited a strong NFP signal in the soma and in the proximal parts of the dendritic arbors. The NFP-immunoreactive dendrites typically branched into sublamina a of the inner plexiform layer (IPL), i.e., the OFF inner plexiform sublamina. In the retina of adult BD cats, however, most of the NFP-immunoreactive ganglion cell dendrites branched throughout the entire IPL. The NFP-immunoreactive cell bodies were less regularly distributed, often appeared in pairs, and had a significantly larger diameter compared with NFP-expressing cells in control retinas. These remarkable differences in the immunoreactivity pattern were typically observed in temporal retina. In conclusion, we show that the anatomical organization typical of premature Y-type retinal ganglion cells persists into adulthood even if normal visual experience follows for years upon an initial 6-month period of BD. Binocular pattern deprivation possibly induces a lifelong OFF functional domination, normally apparent only during development, putting early high-quality vision forward as a premise for proper ON-OFF pathway segregation. These new observations for pattern-deprived animals provide an anatomical basis for the well-described motion perception deficits in congenital cataract patients. Copyright © 2012 Wiley Periodicals, Inc.

  19. Ganglion cell-inner plexiform layer and retinal nerve fibre layer changes within the macula in retinitis pigmentosa: a spectral domain optical coherence tomography study.

    PubMed

    Yoon, Chang Ki; Yu, Hyeong Gon

    2018-03-01

    To investigate how macular ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fibre layer (RNFL) thicknesses within the macula change with retinitis pigmentosa (RP) severity. Spectral domain optical coherence tomography (SD-OCT) was used to examine 177 patients with RP and 177 normal controls. An optical coherence tomography (OCT) line scan was used to grade RP severity. Retinitis pigmentosa (RP) was categorized as more advanced if there was no identifiable inner segment ellipsoid (ISe) band (NISE) and as less advanced if an ISe band could be identified and peripheral loss of ISe was apparent (IISE). Ganglion cell-inner plexiform layer (GCIPL) and RNFL thicknesses were manually measured on OCT images and analysed. Pearson's correlation analyses were used to examine correlations between GCIPL thickness, RNFL thickness, visual acuity (VA) and visual field extent in patients and controls. Ganglion cell-inner plexiform layer (GCIPL) was significantly thicker in IISE than in control eyes (p < 0.001), but significantly thinner in NISE than in IISE eyes (p < 0.001) in both horizontal and vertical OCT scans. Retinal nerve fibre layer (RNFL) was significantly thicker in eyes with IISE and NISE than in control eyes in both horizontal and vertical meridians (all p < 0.001). Ganglion cell-inner plexiform layer (GCIPL) thickness showed a weak positive correlation with vision, and RNFL thickness showed a weak negative correlation with vision and visual field extent. Based on these results, the inner retina, including the GCIPL and RNFL, maintains its gross integrity longer than the photoreceptor layer in RP. Additionally, thickening of the inner retina may have some functional implications in patients with RP. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  20. A Protein Encoded by the Latency-Related Gene of Bovine Herpesvirus 1 Is Expressed in Trigeminal Ganglionic Neurons of Latently Infected Cattle and Interacts with Cyclin-Dependent Kinase 2 during Productive Infection

    PubMed Central

    Jiang, Yunquan; Hossain, Ashfaque; Winkler, Maria Teresa; Holt, Todd; Doster, Alan; Jones, Clinton

    1998-01-01

    Despite productive viral gene expression in the peripheral nervous system during acute infection, the bovine herpesvirus 1 (BHV-1) infection cycle is blocked in sensory ganglionic neurons and consequently latency is established. The only abundant viral transcript expressed during latency is the latency-related (LR) RNA. LR gene products inhibit S-phase entry, and binding of the LR protein (LRP) to cyclin A was hypothesized to block cell cycle progression. This study demonstrates LRP is a nuclear protein which is expressed in neurons of latently infected cattle. Affinity chromatography indicated that LRP interacts with cyclin-dependent kinase 2 (cdk2)-cyclin complexes or cdc2-cyclin complexes in transfected human cells or infected bovine cells. After partial purification using three different columns (DEAE-Sepharose, Econo S, and heparin-agarose), LRP was primarily associated with cdk2-cyclin E complexes, an enzyme which is necessary for G1-to-S-phase cell cycle progression. During acute infection of trigeminal ganglia or following dexamethasone-induced reactivation, BHV-1 induces expression of cyclin A in neurons (L. M. Schang, A. Hossain, and C. Jones, J. Virol. 70:3807–3814, 1996). Expression of S-phase regulatory proteins (cyclin A, for example) leads to neuronal apoptosis. Consequently, we hypothesize that interactions between LRP and cell cycle regulatory proteins promote survival of postmitotic neurons during acute infection and/or reactivation. PMID:9733854

  1. A protein encoded by the latency-related gene of bovine herpesvirus 1 is expressed in trigeminal ganglionic neurons of latently infected cattle and interacts with cyclin-dependent kinase 2 during productive infection.

    PubMed

    Jiang, Y; Hossain, A; Winkler, M T; Holt, T; Doster, A; Jones, C

    1998-10-01

    Despite productive viral gene expression in the peripheral nervous system during acute infection, the bovine herpesvirus 1 (BHV-1) infection cycle is blocked in sensory ganglionic neurons and consequently latency is established. The only abundant viral transcript expressed during latency is the latency-related (LR) RNA. LR gene products inhibit S-phase entry, and binding of the LR protein (LRP) to cyclin A was hypothesized to block cell cycle progression. This study demonstrates LRP is a nuclear protein which is expressed in neurons of latently infected cattle. Affinity chromatography indicated that LRP interacts with cyclin-dependent kinase 2 (cdk2)-cyclin complexes or cdc2-cyclin complexes in transfected human cells or infected bovine cells. After partial purification using three different columns (DEAE-Sepharose, Econo S, and heparin-agarose), LRP was primarily associated with cdk2-cyclin E complexes, an enzyme which is necessary for G1-to-S-phase cell cycle progression. During acute infection of trigeminal ganglia or following dexamethasone-induced reactivation, BHV-1 induces expression of cyclin A in neurons (L. M. Schang, A. Hossain, and C. Jones, J. Virol. 70:3807-3814, 1996). Expression of S-phase regulatory proteins (cyclin A, for example) leads to neuronal apoptosis. Consequently, we hypothesize that interactions between LRP and cell cycle regulatory proteins promote survival of postmitotic neurons during acute infection and/or reactivation.

  2. Metabotropic and ionotropic glutamate receptors regulate calcium channel currents in salamander retinal ganglion cells

    PubMed Central

    Shen, Wen; Slaughter, Malcolm M

    1998-01-01

    Glutamate suppressed high-voltage-activated barium currents (IBa,HVA) in tiger salamander retinal ganglion cells. Both ionotropic (iGluR) and metabotropic (mGluR) receptors contributed to this calcium channel inhibition. Trans-ACPD (1-aminocyclopentane-trans-1S,3R-dicarboxylic acid), a broad-spectrum metabotropic glutamate receptor agonist, suppressed a dihydropyridine-sensitive barium current. Kainate, an ionotropic glutamate receptor agonist, reduced an ω-conotoxin GVIA-sensitive current. The relative effectiveness of selective agonists indicated that the predominant metabotropic receptor was the L-2-amino-4-phosphonobutyrate (l-AP4)-sensitive, group III receptor. This receptor reversed the action of forskolin, but this was not responsible for calcium channel suppression. l-AP4 raised internal calcium concentration. Antagonists of phospholipase C, inositol trisphosphate (IP3) receptors and ryanodine receptors inhibited the action of metabotropic agonists, indicating that group III receptor transduction was linked to this pathway. The action of kainate was partially suppressed by BAPTA, by calmodulin antagonists and by blockers of calmodulin-dependent phosphatase. Suppression by kainate of the calcium channel current was more rapid when calcium was the charge carrier, instead of barium. The results indicate that calcium influx through kainate-sensitive glutamate receptors can activate calmodulin, which stimulates phosphatases that may directly suppress voltage-sensitive calcium channels. Thus, ionotropic and metabotropic glutamate receptors inhibit distinct calcium channels. They could act synergistically, since both increase internal calcium. These pathways provide negative feedback that can reduce calcium influx when ganglion cells are depolarized. PMID:9660896

  3. Differential block of nicotinic synapses on B versus C neurones in sympathetic ganglia of frog by alpha-conotoxins MII and ImI.

    PubMed

    Tavazoie, S F; Tavazoie, M F; McIntosh, J M; Olivera, B M; Yoshikami, D

    1997-03-01

    1. The effects of two new acetylcholine receptor antagonists, alpha-conotoxin MII and alpha-conotoxin ImI, on nicotinic synaptic transmission in the 10th paravertebral sympathetic ganglion of the leopard frog (Rana pipiens) were examined. The preganglionic nerve was electrically stimulated (at low frequency, < or = 1 min-1, to avoid use-dependent changes) while compound action potentials of B and C neurones were monitored from the postganglionic nerve. 2. alpha-Conotoxins MII and ImI, at low micromolar concentrations, reversibly blocked both B and C waves, alpha-Conotoxin MII blocked the C wave more effectively than the B wave, whereas the potency of alpha-conotoxin ImI was opposite that of MII. The observation that nicotinic antagonists can differentially block synaptic transmission of B versus C neurones with opposite selectivities strongly suggests that these neurones possess distinct nicotinic receptors. 3. In addition to fast and slow B waves described by others. C waves with two temporally distinguishable components were present in our recordings. Each alpha-conotoxin affected fast and slow B waves similarly. Likewise, toxins did not discriminate between the two components of C waves. This suggests that all neurones within each major class (B or C) may have the same nicotinic receptors. 4. Synthetic forms of alpha-conotoxins MII and ImI were used in the present study. Their ease of synthesis and their specificities should make these toxins useful probes to investigate the various subtypes of neuronal nicotinic acetylcholine receptors.

  4. Macular Ganglion Cell Imaging Study: Covariate Effects on the Spectral Domain Optical Coherence Tomography for Glaucoma Diagnosis.

    PubMed

    Jeong, Jae Hoon; Choi, Yun Jeong; Park, Ki Ho; Kim, Dong Myung; Jeoung, Jin Wook

    2016-01-01

    To evaluate the effect of multiple covariates on the diagnostic performance of the Cirrus high-definition optical coherence tomography (HD-OCT) for glaucoma detection. A prospective case-control study was performed and included 173 recently diagnosed glaucoma patients and 63 unaffected individuals from the Macular Ganglion Cell Imaging Study. Regression analysis of receiver operating characteristic were conducted to evaluate the influence of age, spherical equivalent, axial length, optic disc size, and visual field index on the macular ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) measurements. Disease severity, as measured by visual field index, had a significant effect on the diagnostic performance of all Cirrus HD-OCT parameters. Age, axial length and optic disc size were significantly associated with diagnostic accuracy of average peripapillary RNFL thickness, whereas axial length had a significant effect on the diagnostic accuracy of average GCIPL thickness. Diagnostic performance of the Cirrus HD-OCT may be more accurate in the advanced stages of glaucoma than at earlier stages. A smaller optic disc size was significantly associated with improved the diagnostic ability of average RNFL thickness measurements; however, GCIPL thickness may be less affected by age and optic disc size.

  5. Epidural block

    MedlinePlus

    ... body. This lessens the pain of contractions during childbirth. An epidural block may also be used to ... extremities. This article focuses on epidural blocks during childbirth. How is the Epidural Given? The block or ...

  6. RdgB2 is required for dim-light input into intrinsically photosensitive retinal ganglion cells

    PubMed Central

    Walker, Marquis T.; Rupp, Alan; Elsaesser, Rebecca; Güler, Ali D.; Sheng, Wenlong; Weng, Shijun; Berson, David M.; Hattar, Samer; Montell, Craig

    2015-01-01

    A subset of retinal ganglion cells is intrinsically photosensitive (ipRGCs) and contributes directly to the pupillary light reflex and circadian photoentrainment under bright-light conditions. ipRGCs are also indirectly activated by light through cellular circuits initiated in rods and cones. A mammalian homologue (RdgB2) of a phosphoinositide transfer/exchange protein that functions in Drosophila phototransduction is expressed in the retinal ganglion cell layer. This raised the possibility that RdgB2 might function in the intrinsic light response in ipRGCs, which depends on a cascade reminiscent of Drosophila phototransduction. Here we found that under high light intensities, RdgB2−/− mutant mice showed normal pupillary light responses and circadian photoentrainment. Consistent with this behavioral phenotype, the intrinsic light responses of ipRGCs in RdgB2−/− were indistinguishable from wild-type. In contrast, under low-light conditions, RdgB2−/− mutants displayed defects in both circadian photoentrainment and the pupillary light response. The RdgB2 protein was not expressed in ipRGCs but was in GABAergic amacrine cells, which provided inhibitory feedback onto bipolar cells. We propose that RdgB2 is required in a cellular circuit that transduces light input from rods to bipolar cells that are coupled to GABAergic amacrine cells and ultimately to ipRGCs, thereby enabling ipRGCs to respond to dim light. PMID:26269578

  7. Selective labeling of retinal ganglion cells with calcium indicators by retrograde loading in vitro

    PubMed Central

    Behrend, Matthew R.; Ahuja, Ashish K.; Humayun, Mark S.; Weiland, James D.; Chow, Robert H.

    2012-01-01

    Here we present a retrograde loading technique that makes it possible for the first time to rapidly load a calcium indicator in the majority of retinal ganglion cells (RGCs) in salamander retina, and then to observe physiological activity of these dye-loaded cells. Dextran-conjugated calcium indicator, dissolved in water, was applied to the optic nerve stump. Following dye loading, the isolated retina was mounted on a microelectrode array to demonstrate that electrical activity and calcium activity were preserved, as the retina responded to electrical stimuli. PMID:19428523

  8. I h and HCN channels in murine spiral ganglion neurons: tonotopic variation, local heterogeneity, and kinetic model.

    PubMed

    Liu, Qing; Manis, Paul B; Davis, Robin L

    2014-08-01

    One of the major contributors to the response profile of neurons in the auditory pathways is the I h current. Its properties such as magnitude, activation, and kinetics not only vary among different types of neurons (Banks et al., J Neurophysiol 70:1420-1432, 1993; Fu et al., J Neurophysiol 78:2235-2245, 1997; Bal and Oertel, J Neurophysiol 84:806-817, 2000; Cao and Oertel, J Neurophysiol 94:821-832, 2005; Rodrigues and Oertel, J Neurophysiol 95:76-87, 2006; Yi et al., J Neurophysiol 103:2532-2543, 2010), but they also display notable diversity in a single population of spiral ganglion neurons (Mo and Davis, J Neurophysiol 78:3019-3027, 1997), the first neural element in the auditory periphery. In this study, we found from somatic recordings that part of the heterogeneity can be attributed to variation along the tonotopic axis because I h in the apical neurons have more positive half-activation voltage levels than basal neurons. Even within a single cochlear region, however, I h current properties are not uniform. To account for this heterogeneity, we provide immunocytochemical evidence for variance in the intracellular density of the hyperpolarization-activated cyclic nucleotide-gated channel α-subunit 1 (HCN1), which mediates I h current. We also observed different combinations of HCN1 and HCN4 α-subunits from cell to cell. Lastly, based on the physiological data, we performed kinetic analysis for the I h current and generated a mathematical model to better understand varied I h on spiral ganglion function. Regardless of whether I h currents are recorded at the nerve terminals (Yi et al., J Neurophysiol 103:2532-2543, 2010) or at the somata of spiral ganglion neurons, they have comparable mean half-activation voltage and induce similar resting membrane potential changes, and thus our model may also provide insights into the impact of I h on synaptic physiology.

  9. Effects of GABA receptor antagonists on thresholds of P23H rat retinal ganglion cells to electrical stimulation of the retina

    NASA Astrophysics Data System (ADS)

    Jensen, Ralph J.; Rizzo, Joseph F., III

    2011-06-01

    An electronic retinal prosthesis may provide useful vision for patients suffering from retinitis pigmentosa (RP). In animal models of RP, the amount of current needed to activate retinal ganglion cells (RGCs) is higher than in normal, healthy retinas. In this study, we sought to reduce the stimulation thresholds of RGCs in a degenerate rat model (P23H-line 1) by blocking GABA receptor mediated inhibition in the retina. We examined the effects of TPMPA, a GABAC receptor antagonist, and SR95531, a GABAA receptor antagonist, on the electrically evoked responses of RGCs to biphasic current pulses delivered to the subretinal surface through a 400 µm diameter electrode. Both TPMPA and SR95531 reduced the stimulation thresholds of ON-center RGCs on average by 15% and 20% respectively. Co-application of the two GABA receptor antagonists had the greatest effect, on average reducing stimulation thresholds by 32%. In addition, co-application of the two GABA receptor antagonists increased the magnitude of the electrically evoked responses on average three-fold. Neither TPMPA nor SR95531, applied alone or in combination, had consistent effects on the stimulation thresholds of OFF-center RGCs. We suggest that the effects of the GABA receptor antagonists on ON-center RGCs may be attributable to blockage of GABA receptors on the axon terminals of ON bipolar cells.

  10. The production of nitric oxide in the coeliac ganglion modulates the effect of cholinergic neurotransmission on the rat ovary during the preovulatory period.

    PubMed

    Delsouc, María B; Della Vedova, María C; Ramírez, Darío; Delgado, Silvia M; Casais, Marilina

    2018-05-01

    The aim of the present work was to investigate whether the nitric oxide produced by the nitric oxide/nitric oxide synthase (NO/NOS) system present in the coeliac ganglion modulates the effects of cholinergic innervation on oxidative status, steroidogenesis and apoptotic mechanisms that take place in the rat ovary during the first proestrous. An ex vivo Coeliac Ganglion- Superior Ovarian Nerve- Ovary (CG-SON-O) system was used. Cholinergic stimulation of the CG was achieved by 10 -6  M Acetylcholine (Ach). Furthermore, 400 μM Aminoguanidine (AG) - an inhibitor of inducible-NOS was added in the CG compartment in absence and presence of Ach. It was found that Ach in the CG compartment promotes apoptosis in ovarian tissue, probably due to the oxidative stress generated. AG in the CG compartment decreases the release of NO and progesterone, and increases the release of estradiol from the ovary. The CG co-treatment with Ach and AG counteracts the effects of the ganglionic cholinergic agonist on ovarian oxidative stress, increases hormone production and decreases Fas mRNA expression. These results suggest that NO is an endogenous modulator of cholinergic neurotransmission in CG, with implication in ovarian steroidogenesis and the apoptotic mechanisms that take place in the ovary during the preovulatory period in rats. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. PKCɛ mediates substance P inhibition of GABAA receptors-mediated current in rat dorsal root ganglion.

    PubMed

    Li, Li; Zhao, Lei; Wang, Yang; Ma, Ke-tao; Shi, Wen-yan; Wang, Ying-zi; Si, Jun-qiang

    2015-02-01

    The mechanism underlying the modulatory effect of substance P (SP) on GABA-activated response in rat dorsal root ganglion (DRG) neurons was investigated. In freshly dissociated rat DRG neurons, whole-cell patch-clamp technique was used to record GABA-activated current and sharp electrode intracellular recording technique was used to record GABA-induced membrane depolarization. Application of GABA (1-1000 μmol/L) induced an inward current in a concentration-dependent manner in 114 out of 127 DRG neurons (89.8 %) examined with whole-cell patch-clamp recordings. Bath application of GABA (1-1000 μmol/L) evoked a depolarizing response in 236 out of 257 (91.8%) DRG neurons examined with intracellular recordings. Application of SP (0.001-1 μmol/L) suppressed the GABA-activated inward current and membrane depolarization. The inhibitory effects were concentration-dependent and could be blocked by the selective neurokinin 1 (NK1) receptors antagonist spantide but not by L659187 and SR142801 (1 μmol/L, n=7), selective antagonists of NK2 and NK3. The inhibitory effect of SP was significantly reduced by the calcium chelator BAPTA-AM, phospholipase C (PLC) inhibitor U73122, and PKC inhibitor chelerythrine, respectively. The PKA inhibitor H-89 did not affect the SP effect. Remarkably, the inhibitory effect of SP on GABA-activated current was nearly completely removed by a selective PKCε inhibitor epilon-V1-2 but not by safingol and LY333531, selective inhibitors of PKCα and PKCβ. Our results suggest that NK1 receptor mediates SP-induced inhibition of GABA-activated current and membrane depolarization by activating intracellular PLC-Ca²⁺-PKCε cascade. SP might regulate the excitability of peripheral nociceptors through inhibition of the "pre-synaptic inhibition" evoked by GABA, which may explain its role in pain and neurogenic inflammation.

  12. Response profiles of murine spiral ganglion neurons on multi-electrode arrays

    NASA Astrophysics Data System (ADS)

    Hahnewald, Stefan; Tscherter, Anne; Marconi, Emanuele; Streit, Jürg; Widmer, Hans Rudolf; Garnham, Carolyn; Benav, Heval; Mueller, Marcus; Löwenheim, Hubert; Roccio, Marta; Senn, Pascal

    2016-02-01

    Objective. Cochlear implants (CIs) have become the gold standard treatment for deafness. These neuroprosthetic devices feature a linear electrode array, surgically inserted into the cochlea, and function by directly stimulating the auditory neurons located within the spiral ganglion, bypassing lost or not-functioning hair cells. Despite their success, some limitations still remain, including poor frequency resolution and high-energy consumption. In both cases, the anatomical gap between the electrode array and the spiral ganglion neurons (SGNs) is believed to be an important limiting factor. The final goal of the study is to characterize response profiles of SGNs growing in intimate contact with an electrode array, in view of designing novel CI devices and stimulation protocols, featuring a gapless interface with auditory neurons. Approach. We have characterized SGN responses to extracellular stimulation using multi-electrode arrays (MEAs). This setup allows, in our view, to optimize in vitro many of the limiting interface aspects between CIs and SGNs. Main results. Early postnatal mouse SGN explants were analyzed after 6-18 days in culture. Different stimulation protocols were compared with the aim to lower the stimulation threshold and the energy needed to elicit a response. In the best case, a four-fold reduction of the energy was obtained by lengthening the biphasic stimulus from 40 μs to 160 μs. Similarly, quasi monophasic pulses were more effective than biphasic pulses and the insertion of an interphase gap moderately improved efficiency. Finally, the stimulation with an external electrode mounted on a micromanipulator showed that the energy needed to elicit a response could be reduced by a factor of five with decreasing its distance from 40 μm to 0 μm from the auditory neurons. Significance. This study is the first to show electrical activity of SGNs on MEAs. Our findings may help to improve stimulation by and to reduce energy consumption of CIs and

  13. Rhythmic Ganglion Cell Activity in Bleached and Blind Adult Mouse Retinas

    PubMed Central

    Menzler, Jacob; Channappa, Lakshmi; Zeck, Guenther

    2014-01-01

    In retinitis pigmentosa – a degenerative disease which often leads to incurable blindness- the loss of photoreceptors deprives the retina from a continuous excitatory input, the so-called dark current. In rodent models of this disease this deprivation leads to oscillatory electrical activity in the remaining circuitry, which is reflected in the rhythmic spiking of retinal ganglion cells (RGCs). It remained unclear, however, if the rhythmic RGC activity is attributed to circuit alterations occurring during photoreceptor degeneration or if rhythmic activity is an intrinsic property of healthy retinal circuitry which is masked by the photoreceptor’s dark current. Here we tested these hypotheses by inducing and analysing oscillatory activity in adult healthy (C57/Bl6) and blind mouse retinas (rd10 and rd1). Rhythmic RGC activity in healthy retinas was detected upon partial photoreceptor bleaching using an extracellular high-density multi-transistor-array. The mean fundamental spiking frequency in bleached retinas was 4.3 Hz; close to the RGC rhythm detected in blind rd10 mouse retinas (6.5 Hz). Crosscorrelation analysis of neighbouring wild-type and rd10 RGCs (separation distance <200 µm) reveals synchrony among homologous RGC types and a constant phase shift (∼70 msec) among heterologous cell types (ON versus OFF). The rhythmic RGC spiking in these retinas is driven by a network of presynaptic neurons. The inhibition of glutamatergic ganglion cell input or the inhibition of gap junctional coupling abolished the rhythmic pattern. In rd10 and rd1 retinas the presynaptic network leads to local field potentials, whereas in bleached retinas additional pharmacological disinhibition is required to achieve detectable field potentials. Our results demonstrate that photoreceptor bleaching unmasks oscillatory activity in healthy retinas which shares many features with the functional phenotype detected in rd10 retinas. The quantitative physiological differences advance the

  14. Coatings of Different Carbon Nanotubes on Platinum Electrodes for Neuronal Devices: Preparation, Cytocompatibility and Interaction with Spiral Ganglion Cells.

    PubMed

    Burblies, Niklas; Schulze, Jennifer; Schwarz, Hans-Christoph; Kranz, Katharina; Motz, Damian; Vogt, Carla; Lenarz, Thomas; Warnecke, Athanasia; Behrens, Peter

    2016-01-01

    Cochlear and deep brain implants are prominent examples for neuronal prostheses with clinical relevance. Current research focuses on the improvement of the long-term functionality and the size reduction of neural interface electrodes. A promising approach is the application of carbon nanotubes (CNTs), either as pure electrodes but especially as coating material for electrodes. The interaction of CNTs with neuronal cells has shown promising results in various studies, but these appear to depend on the specific type of neurons as well as on the kind of nanotubes. To evaluate a potential application of carbon nanotube coatings for cochlear electrodes, it is necessary to investigate the cytocompatibility of carbon nanotube coatings on platinum for the specific type of neuron in the inner ear, namely spiral ganglion neurons. In this study we have combined the chemical processing of as-delivered CNTs, the fabrication of coatings on platinum, and the characterization of the electrical properties of the coatings as well as a general cytocompatibility testing and the first cell culture investigations of CNTs with spiral ganglion neurons. By applying a modification process to three different as-received CNTs via a reflux treatment with nitric acid, long-term stable aqueous CNT dispersions free of dispersing agents were obtained. These were used to coat platinum substrates by an automated spray-coating process. These coatings enhance the electrical properties of platinum electrodes, decreasing the impedance values and raising the capacitances. Cell culture investigations of the different CNT coatings on platinum with NIH3T3 fibroblasts attest an overall good cytocompatibility of these coatings. For spiral ganglion neurons, this can also be observed but a desired positive effect of the CNTs on the neurons is absent. Furthermore, we found that the well-established DAPI staining assay does not function on the coatings prepared from single-wall nanotubes.

  15. Coatings of Different Carbon Nanotubes on Platinum Electrodes for Neuronal Devices: Preparation, Cytocompatibility and Interaction with Spiral Ganglion Cells

    PubMed Central

    Schwarz, Hans-Christoph; Kranz, Katharina; Motz, Damian; Vogt, Carla; Lenarz, Thomas; Warnecke, Athanasia; Behrens, Peter

    2016-01-01

    Cochlear and deep brain implants are prominent examples for neuronal prostheses with clinical relevance. Current research focuses on the improvement of the long-term functionality and the size reduction of neural interface electrodes. A promising approach is the application of carbon nanotubes (CNTs), either as pure electrodes but especially as coating material for electrodes. The interaction of CNTs with neuronal cells has shown promising results in various studies, but these appear to depend on the specific type of neurons as well as on the kind of nanotubes. To evaluate a potential application of carbon nanotube coatings for cochlear electrodes, it is necessary to investigate the cytocompatibility of carbon nanotube coatings on platinum for the specific type of neuron in the inner ear, namely spiral ganglion neurons. In this study we have combined the chemical processing of as-delivered CNTs, the fabrication of coatings on platinum, and the characterization of the electrical properties of the coatings as well as a general cytocompatibility testing and the first cell culture investigations of CNTs with spiral ganglion neurons. By applying a modification process to three different as-received CNTs via a reflux treatment with nitric acid, long-term stable aqueous CNT dispersions free of dispersing agents were obtained. These were used to coat platinum substrates by an automated spray-coating process. These coatings enhance the electrical properties of platinum electrodes, decreasing the impedance values and raising the capacitances. Cell culture investigations of the different CNT coatings on platinum with NIH3T3 fibroblasts attest an overall good cytocompatibility of these coatings. For spiral ganglion neurons, this can also be observed but a desired positive effect of the CNTs on the neurons is absent. Furthermore, we found that the well-established DAPI staining assay does not function on the coatings prepared from single-wall nanotubes. PMID:27385031

  16. Chlorogenic acid alters the voltage-gated potassium channel currents of trigeminal ganglion neurons

    PubMed Central

    Zhang, Yu-Jiao; Lu, Xiao-Wen; Song, Ning; Kou, Liang; Wu, Min-Ke; Liu, Fei; Wang, Hang; Shen, Jie-Fei

    2014-01-01

    Chlorogenic acid (5-caffeoylquinic acid, CGA) is a phenolic compound that is found ubiquitously in plants, fruits and vegetables and is formed via the esterification of caffeic acid and quinic acid. In addition to its notable biological functions against cardiovascular diseases, type-2 diabetes and inflammatory conditions, CGA was recently hypothesized to be an alternative for the treatment of neurological diseases such as Alzheimer's disease and neuropathic pain disorders. However, its mechanism of action is unclear. Voltage-gated potassium channel (Kv) is a crucial factor in the electro-physiological processes of sensory neurons. Kv has also been identified as a potential therapeutic target for inflammation and neuropathic pain disorders. In this study, we analysed the effects of CGA on the two main subtypes of Kv in trigeminal ganglion neurons, namely, the IK,A and IK,V channels. Trigeminal ganglion (TRG) neurons were acutely disassociated from the rat TRG, and two different doses of CGA (0.2 and 1 mmol⋅L−1) were applied to the cells. Whole-cell patch-clamp recordings were performed to observe alterations in the activation and inactivation properties of the IK,A and IK,V channels. The results demonstrated that 0.2 mmol⋅L−1 CGA decreased the peak current density of IK,A. Both 0.2 mmol⋅L−1 and 1 mmol⋅L−1 CGA also caused a significant reduction in the activation and inactivation thresholds of IK,A and IK,V. CGA exhibited a strong effect on the activation and inactivation velocities of IK,A and IK,V. These findings provide novel evidence explaining the biological effects of CGA, especially regarding its neurological effects. PMID:25394592

  17. Neural organisation in the first optic ganglion of the nocturnal bee Megalopta genalis.

    PubMed

    Greiner, Birgit; Ribi, Willi A; Wcislo, William T; Warrant, Eric J

    2004-11-01

    Each neural unit (cartridge) in the first optic ganglion (lamina) of the nocturnal bee Megalopta genalis contains nine receptor cell axons (6 short and 3 long visual fibres), and four different types of first-order interneurons, also known as L-fibres (L1 to L4) or lamina monopolar cells. The short visual fibres terminate within the lamina as three different types (svf 1, 2, 3). The three long visual fibres pass through the lamina without forming characteristic branching patterns and terminate in the second optic ganglion, the medulla. The lateral branching pattern of svf 2 into adjacent cartridges is unique for hymenopterans. In addition, all four types of L-fibres show dorso-ventrally arranged, wide, lateral branching in this nocturnal bee. This is in contrast to the diurnal bees Apis mellifera and Lasioglossum leucozonium, where only two out of four L-fibre types (L2 and L4) reach neighbouring cartridges. In M. genalis, L1 forms two sub-types, viz. L1-a and L1-b; L1-b in particular has the potential to contact several neighbouring cartridges. L2 and L4 in the nocturnal bee are similar to L2 and L4 in the diurnal bees but have dorso-ventral arborisations that are twice as wide. A new type of laterally spreading L3 has been discovered in the nocturnal bee. The extensive neural branching pattern of L-fibres in M. genalis indicates a potential role for these neurons in the spatial summation of photons from large groups of ommatidia. This specific adaptation in the nocturnal bee could significantly improve reliability of vision in dim light.

  18. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Park, Kyoung Ho; Yeo, Sang Won, E-mail: swyeo@catholic.ac.kr; Troy, Frederic A., E-mail: fatroy@ucdavis.edu

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC withmore » epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders.« less

  19. Retinal ganglion cell maps in the brain: implications for visual processing.

    PubMed

    Dhande, Onkar S; Huberman, Andrew D

    2014-02-01

    Everything the brain knows about the content of the visual world is built from the spiking activity of retinal ganglion cells (RGCs). As the output neurons of the eye, RGCs include ∼20 different subtypes, each responding best to a specific feature in the visual scene. Here we discuss recent advances in identifying where different RGC subtypes route visual information in the brain, including which targets they connect to and how their organization within those targets influences visual processing. We also highlight examples where causal links have been established between specific RGC subtypes, their maps of central connections and defined aspects of light-mediated behavior and we suggest the use of techniques that stand to extend these sorts of analyses to circuits underlying visual perception. Copyright © 2013. Published by Elsevier Ltd.

  20. Immunocytochemical localization of metabotropic (mGluR2/3 and mGluR4a) and ionotropic (GluR2/3) glutamate receptors in adrenal medullary ganglion cells.

    PubMed

    Sarría, R; Díez, J; Losada, J; Doñate-Oliver, F; Kuhn, R; Grandes, P

    2006-02-01

    The localization of metabotropic glutamate receptors of groups II (mGluR2/3) and III (mGluR4a) and the subunits 2 and 3 of alfa-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) ionotropic glutamate receptors (GluR2/3) was investigated with immunocytochemical methods in the rat adrenal gland. MGluR2/3, mGluR4a and GluR2/3 immunoreactivities were observed in large-sized, centrally located type I adrenal medullary ganglion neurons. Furthermore, the small-sized type II adrenal ganglion neurons identified by their immunoreactivity to brain nitric oxide synthase (bNOS), also expressed mGluR2/3, mGluR4a and GluR2/3. These cells were disposed in the peripheral portion of the adrenal medulla. None of the type I neurons were positively labeled for bNOS. These morphological observations suggest that activation of glutamate receptors in ganglion neurons may be instrumental in the control of adrenal endocrine systems as well as blood regulation.

  1. Alteration of cell wall xylan acetylation triggers defense responses that counterbalance the immune deficiencies of plants impaired in the β-subunit of the heterotrimeric G-protein.

    PubMed

    Escudero, Viviana; Jordá, Lucía; Sopeña-Torres, Sara; Mélida, Hugo; Miedes, Eva; Muñoz-Barrios, Antonio; Swami, Sanjay; Alexander, Danny; McKee, Lauren S; Sánchez-Vallet, Andrea; Bulone, Vincent; Jones, Alan M; Molina, Antonio

    2017-11-01

    Arabidopsis heterotrimeric G-protein complex modulates pathogen-associated molecular pattern-triggered immunity (PTI) and disease resistance responses to different types of pathogens. It also plays a role in plant cell wall integrity as mutants impaired in the Gβ- (agb1-2) or Gγ-subunits have an altered wall composition compared with wild-type plants. Here we performed a mutant screen to identify suppressors of agb1-2 (sgb) that restore susceptibility to pathogens to wild-type levels. Out of the four sgb mutants (sgb10-sgb13) identified, sgb11 is a new mutant allele of ESKIMO1 (ESK1), which encodes a plant-specific polysaccharide O-acetyltransferase involved in xylan acetylation. Null alleles (sgb11/esk1-7) of ESK1 restore to wild-type levels the enhanced susceptibility of agb1-2 to the necrotrophic fungus Plectosphaerella cucumerina BMM (PcBMM), but not to the bacterium Pseudomonas syringae pv. tomato DC3000 or to the oomycete Hyaloperonospora arabidopsidis. The enhanced resistance to PcBMM of the agb1-2 esk1-7 double mutant was not the result of the re-activation of deficient PTI responses in agb1-2. Alteration of cell wall xylan acetylation caused by ESK1 impairment was accompanied by an enhanced accumulation of abscisic acid, the constitutive expression of genes encoding antibiotic peptides and enzymes involved in the biosynthesis of tryptophan-derived metabolites, and the accumulation of disease resistance-related secondary metabolites and different osmolites. These esk1-mediated responses counterbalance the defective PTI and PcBMM susceptibility of agb1-2 plants, and explain the enhanced drought resistance of esk1 plants. These results suggest that a deficient PTI-mediated resistance is partially compensated by the activation of specific cell-wall-triggered immune responses. © 2017 The Authors The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

  2. Interventional Management for Pelvic Pain.

    PubMed

    Nagpal, Ameet S; Moody, Erika L

    2017-08-01

    Interventional procedures can be applied for diagnostic evaluation and treatment of the patient with pelvic pain, often once more conservative measures have failed to provide relief. This article reviews interventional management strategies for pelvic pain. We review superior and inferior hypogastric plexus blocks, ganglion impar blocks, transversus abdominis plane blocks, ilioinguinal, iliohypogastric and genitofemoral blocks, pudendal nerve blocks, and selective nerve root blocks. Additionally, we discuss trigger point injections, sacroiliac joint injections, and neuromodulation approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. A Novel Gravito-Optical Surface Trap for Neutral Atoms

    NASA Astrophysics Data System (ADS)

    Xie, Chun-Xia; Wang, Zhengling; Yin, Jian-Ping

    2006-04-01

    We propose a novel gravito-optical surface trap (GOST) for neutral atoms based on one-dimensional intensity gradient cooling. The surface optical trap is composed of a blue-detuned reduced semi-Gaussian laser beam (SGB), a far-blue-detuned dark hollow beam and the gravity field. The SGB is produced by the diffraction of a collimated Gaussian laser beam passing through the straight edge of a semi-infinite opaque plate and then is reduced by an imaging lens. We calculate the intensity distribution of the reduced SGB, and study the dynamic process of the SGB intensity-gradient induced Sisyphus cooling for 87Rb atoms by using Monte Carlo simulations. Our study shows that the proposed GOST can be used not only to trap cold atoms loaded from a standard magneto-optical trap, but also to cool the trapped atoms to an equilibrium temperature of 3.47 μK from ~120 μK, even to realize an all-optical two-dimensional Bose-Einstein condensation by using optical-potential evaporative cooling.

  4. Population Blocks.

    ERIC Educational Resources Information Center

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  5. Archer fish fast hunting maneuver may be guided by directionally selective retinal ganglion cells.

    PubMed

    Tsvilling, Vadim; Donchin, Opher; Shamir, Maoz; Segev, Ronen

    2012-02-01

    Archer fish are known for their unique hunting method, where one fish in a group shoots down an insect with a jet of water while all the other fish are observing the prey's motion. To reap its reward, the archer fish must reach the prey before its competitors. This requires fast computation of the direction of motion of the prey, which enables the fish to initiate a turn towards the prey with an accuracy of 99%, at about 100 ms after the prey is shot. We explored the hypothesis that direction-selective retinal ganglion cells may underlie this rapid processing. We quantified the degree of directional selectivity of ganglion cells in the archer fish retina. The cells could be categorized into three groups: sharply (5%), broadly (37%) and non-tuned (58%) directionally selective cells. To relate the electrophysiological data to the behavioral results we studied a computational model and estimated the time required to accumulate sufficient directional information to match the decision accuracy of the fish. The computational model is based on two direction-selective populations that race against each other until one reaches the threshold and drives the decision. We found that this competition model can account for the observed response time at the required accuracy. Thus, our results are consistent with the hypothesis that the fast response behavior of the archer fish relies on retinal identification of movement direction. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  6. Intractable Pruritus After Traumatic Spinal Cord Injury

    PubMed Central

    Crane, Deborah A; Jaffee, Kenneth M; Kundu, Anjana

    2009-01-01

    Background: This report describes a young woman with incomplete traumatic cervical spinal cord injury and intractable pruritus involving her dorsal forearm. Method: Case report. Findings: Anatomic distribution of the pruritus corresponded to the dermatomal distribution of her level of spinal cord injury and vertebral fusion. Symptoms were attributed to the spinal cord injury and possible cervical root injury. Pruritus was refractory to all treatments, including topical lidocaine, gabapentin, transcutaneous electrical nerve stimulation, intravenous Bier block, stellate ganglion block, and acupuncture. Conclusions: Further understanding of neuropathic pruritus is needed. Diagnostic workup of intractable pruritus should include advanced imaging to detect ongoing nerve root compression. If diagnostic studies suggest radiculopathy, epidural steroid injection should be considered. Because the autonomic nervous system may be involved in complex chronic pain or pruritic syndromes, sympatholysis via such techniques as stellate ganglion block might be effective. PMID:19777867

  7. View of cell block eight (left), cell block seven, and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of cell block eight (left), cell block seven, and southwest guard tower, looking from cell block eight roof - Eastern State Penitentiary, 2125 Fairmount Avenue, Philadelphia, Philadelphia County, PA

  8. Cell block eleven (left) and cell block fifteen, looking from ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Cell block eleven (left) and cell block fifteen, looking from cell block two into the "Death Row" exercise yard - Eastern State Penitentiary, 2125 Fairmount Avenue, Philadelphia, Philadelphia County, PA

  9. Visual responses of ganglion cells of a New-World primate, the capuchin monkey, Cebus apella.

    PubMed

    Lee, B B; Silveira, L C; Yamada, E S; Hunt, D M; Kremers, J; Martin, P R; Troy, J B; da Silva-Filho, M

    2000-11-01

    1. The genetic basis of colour vision in New-World primates differs from that in humans and other Old-World primates. Most New-World primate species show a polymorphism; all males are dichromats and most females trichromats. 2. In the retina of Old-World primates such as the macaque, the physiological correlates of trichromacy are well established. Comparison of the retinae in New- and Old-World species may help constrain hypotheses as to the evolution of colour vision and the pathways associated with it. 3. Ganglion cell behaviour was recorded from trichromatic and dichromatic members of a New-World species (the capuchin monkey, Cebus apella) and compared with macaque data. Despite some differences in quantitative detail (such as a temporal response extended to higher frequencies), results from trichromatic animals strongly resembled those from the macaque. 4. In particular, cells of the parvocellular (PC) pathway showed characteristic frequency-dependent changes in responsivity to luminance and chromatic modulation, cells of the magnocellular (MC) pathway showed frequency-doubled responses to chromatic modulation, and the surround of MC cells received a chromatic input revealed on changing the phase of heterochromatically modulated lights. 5. Ganglion cells of dichromats were colour-blind versions of those of trichromats. 6. This strong physiological homology is consistent with a common origin of trichromacy in New- and Old-World monkeys; in the New-World primate the presence of two pigments in the middle-to-long wavelength range permits full expression of the retinal mechanisms of trichromatic vision.

  10. An intracellular characterization of neurones and neural connexions within the left coeliac ganglion of cats.

    PubMed Central

    Decktor, D L; Weems, W A

    1983-01-01

    Intracellular recordings were made in vitro from neurones located within the left coeliac ganglion of the cat solar plexus. Thirty percent of the neurones within left coeliac ganglia were identified as efferent neurones. Within this neuronal population, splenic-efferent and renal-efferent neurones were identified specifically. Neurones within left coeliac ganglia were characterized as either phasic (fast adapting) neurones or tonic (slowly adapting) neurones depending upon their prolonged firing behaviour. Electrophysiological properties of neurones varied considerably. The wide range of values obtained for both input resistance and input capacitance suggest that sizeable differences in either specific membrane resistance or cell geometry exist within the over-all neurone population. Frequency distributions of input resistance, time constant, input capacitance and current threshold for tonic and phasic neurones were found to be significantly different. Compound excitatory post-synaptic potentials were produced by stimulation of the ipsilateral splanchnic nerves in 69% of the neurones tested and in 3% of the neurones tested upon stimulation of the contralateral splanchnic nerves. Electrical stimulation of nerve fibres located in the coeliac plexus, the superior mesenteric plexus or the left renal nerves generated excitatory synaptic potentials in neurones located within left coeliac ganglia. It is concluded that neurones within the left coeliac ganglion are innervated by splanchnic nerve fibres primarily contained within the left splanchnic nerves, receive excitatory synaptic input from splenic, renal and other peripheral preganglionic fibres and have extremely varied electrophysiological properties. PMID:6620179

  11. Macular Ganglion Cell Imaging Study: Covariate Effects on the Spectral Domain Optical Coherence Tomography for Glaucoma Diagnosis

    PubMed Central

    Jeong, Jae Hoon; Choi, Yun Jeong; Park, Ki Ho; Kim, Dong Myung

    2016-01-01

    Purpose To evaluate the effect of multiple covariates on the diagnostic performance of the Cirrus high-definition optical coherence tomography (HD-OCT) for glaucoma detection. Methods A prospective case-control study was performed and included 173 recently diagnosed glaucoma patients and 63 unaffected individuals from the Macular Ganglion Cell Imaging Study. Regression analysis of receiver operating characteristic were conducted to evaluate the influence of age, spherical equivalent, axial length, optic disc size, and visual field index on the macular ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) measurements. Results Disease severity, as measured by visual field index, had a significant effect on the diagnostic performance of all Cirrus HD-OCT parameters. Age, axial length and optic disc size were significantly associated with diagnostic accuracy of average peripapillary RNFL thickness, whereas axial length had a significant effect on the diagnostic accuracy of average GCIPL thickness. Conclusions Diagnostic performance of the Cirrus HD-OCT may be more accurate in the advanced stages of glaucoma than at earlier stages. A smaller optic disc size was significantly associated with improved the diagnostic ability of average RNFL thickness measurements; however, GCIPL thickness may be less affected by age and optic disc size. PMID:27490718

  12. Random forests and stochastic gradient boosting for predicting tree canopy cover: Comparing tuning processes and model performance

    Treesearch

    E. Freeman; G. Moisen; J. Coulston; B. Wilson

    2014-01-01

    Random forests (RF) and stochastic gradient boosting (SGB), both involving an ensemble of classification and regression trees, are compared for modeling tree canopy cover for the 2011 National Land Cover Database (NLCD). The objectives of this study were twofold. First, sensitivity of RF and SGB to choices in tuning parameters was explored. Second, performance of the...

  13. Block LU factorization

    NASA Technical Reports Server (NTRS)

    Demmel, James W.; Higham, Nicholas J.; Schreiber, Robert S.

    1992-01-01

    Many of the currently popular 'block algorithms' are scalar algorithms in which the operations have been grouped and reordered into matrix operations. One genuine block algorithm in practical use is block LU factorization, and this has recently been shown by Demmel and Higham to be unstable in general. It is shown here that block LU factorization is stable if A is block diagonally dominant by columns. Moreover, for a general matrix the level of instability in block LU factorization can be founded in terms of the condition number kappa(A) and the growth factor for Gaussian elimination without pivoting. A consequence is that block LU factorization is stable for a matrix A that is symmetric positive definite or point diagonally dominant by rows or columns as long as A is well-conditioned.

  14. Block Transfer Handbook: Constructing and Negotiating Block Transfer Agreements.

    ERIC Educational Resources Information Center

    Finlay, Finola

    The purpose of this handbook is to provide resources for institutions or articulation committees who are engaged in the task of investigating the feasibility of block transfer agreements. Block transfer is the process whereby a block of credits is granted to students who have successfully completed a certificate, diploma, or cluster of courses…

  15. Is compensatory hyperhidrosis after thoracic sympathicotomy in palmar hyperhidrosis patients related to the excitability of thoracic sympathetic ganglions?

    PubMed Central

    Chen, Jun-Peng; Peng, A-Jing; Xu, Chen-Hui; Li, Guo-Ying

    2017-01-01

    Background The mechanism of compensatory hyperhidrosis remains unclear. The aim of this study was to explore the relationship between compensatory hyperhidrosis and thoracic sympathetic ganglion excitability to assess the effectiveness of thoracoscopic T4 sympathicotomy for treating palmar hyperhidrosis. Methods Sixty-six cases of T4 sympathetic ganglions were prospectively collected from patients with palmar hyperhidrosis who underwent thoracoscopic T4 sympathicotomy from 2013 to 2016 in our department. The expression levels of choline acetyltransferase (ChAT), vasoactive intestinal peptide (VIP), and synaptophysin were detected using immunohistochemistry. Patients with palmar hyperhidrosis were followed-up for examination of postoperative sweating status. Results Thirty-eight cases (57.6%) of compensatory hyperhidrosis were identified. Mild compensatory hyperhidrosis occurred in 26 patients (39.4%), moderate in 11 (16.7%), and severe in 1 (1.5%). The rate of compensatory hyperhidrosis was higher in patients with axilla hyperhidrosis than those without (76.0% vs. 46.3%, P=0.018). However, the clinical data were similar between the compensatory hyperhidrosis group and the no compensatory hyperhidrosis group. In addition, the ChAT, VIP, and synaptophysin expression levels were not significantly different between the two groups (P values of 0.356, 0.071, and 0.141, respectively). Furthermore, the ChAT, VIP, and synaptophysin expression levels in the mild group were similar to those observed in the moderate/intense group (P values of 0.089, 0.124, and 0.149, respectively). The remission rate was 100% in palmar hyperhidrosis, 48.2% (27/56) in pedal hyperhidrosis, 56.0% (14/25) in axilla hyperhidrosis and 88.9% (16/18) in skin symptoms. No signs of chapped skin on the palms were found. Conclusions There was no significant correlation between compensatory hyperhidrosis and thoracic sympathetic ganglion excitability; however, compensatory hyperhidrosis is more likely to

  16. Dragon's blood inhibits chronic inflammatory and neuropathic pain responses by blocking the synthesis and release of substance P in rats.

    PubMed

    Li, Yu-Sang; Wang, Jun-Xian; Jia, Mei-Mei; Liu, Min; Li, Xiao-Jun; Tang, He-Bin

    2012-01-01

    As a traditional Chinese medicine, dragon's blood (DB) is widely used in treating various pains for thousands of years due to its potent anti-inflammatory and analgesic effects. In the present study, we observed that intragastric administration of DB at dosages of 0.14, 0.56, and 1.12 g/kg potently inhibited paw edema, hyperalgesia, cyclooxygenase-2 (COX-2) protein expression, or preprotachykinin-A mRNA expression in carrageenan-inflamed or sciatic nerve-injured (chronic constriction injury) rats, respectively. A short-term (15 s or 10 min) pre-exposure of cultured rat dorsal root ganglion (DRG) neurons to DB (0.3, 3, and 30 µg/ml) or its component cochinchinenin B (CB; 0.1, 1, and 10 µM) blocked capsaicin-evoked increases in both the intracellular calcium ion concentration and the substance P release. Moreover, a long-term (180 min) exposure of cultured rat DRG neurons to DB or CB significantly attenuated bradykinin-induced substance P release. These findings indicate that DB exerts anti-inflammatory and analgesic effects by blocking the synthesis and release of substance P through inhibition of COX-2 protein induction and intracellular calcium ion concentration. Therefore, DB may serve as a promising potent therapeutic agent for treatment of chronic pain, and its effective component CB might partly contribute to anti-inflammatory and analgesic effects.

  17. Zinc oxide nanoparticles decrease the expression and activity of plasma membrane calcium ATPase, disrupt the intracellular calcium homeostasis in rat retinal ganglion cells.

    PubMed

    Guo, Dadong; Bi, Hongsheng; Wang, Daoguang; Wu, Qiuxin

    2013-08-01

    Zinc oxide nanoparticle is one of the most important materials with diverse applications. However, it has been reported that zinc oxide nanoparticles are toxic to organisms, and that oxidative stress is often hypothesized to be an important factor in cytotoxicity mediated by zinc oxide nanoparticles. Nevertheless, the mechanism of toxicity of zinc oxide nanoparticles has not been completely understood. In this study, we investigated the cytotoxic effect of zinc oxide nanoparticles and the possible molecular mechanism involved in calcium homeostasis mediated by plasma membrane calcium ATPase in rat retinal ganglion cells. Real-time cell electronic sensing assay showed that zinc oxide nanoparticles could exert cytotoxic effect on rat retinal ganglion cells in a concentration-dependent manner; flow cytometric analysis indicated that zinc oxide nanoparticles could lead to cell damage by inducing the overproduction of reactive oxygen species. Furthermore, zinc oxide nanoparticles could also apparently decrease the expression level and their activity of plasma membrane calcium ATPase, which finally disrupt the intracellular calcium homeostasis and result in cell death. Taken together, zinc oxide nanoparticles could apparently decrease the plasma membrane calcium ATPase expression, inhibit their activity, cause the elevated intracellular calcium ion level and disrupt the intracellular calcium homeostasis. Further, the disrupted calcium homeostasis will trigger mitochondrial dysfunction, generate excessive reactive oxygen species, and finally initiate cell death. Thus, the disrupted calcium homeostasis is involved in the zinc oxide nanoparticle-induced rat retinal ganglion cell death. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Minimum Description Length Block Finder, a Method to Identify Haplotype Blocks and to Compare the Strength of Block Boundaries

    PubMed Central

    Mannila, H.; Koivisto, M.; Perola, M.; Varilo, T.; Hennah, W.; Ekelund, J.; Lukk, M.; Peltonen, L.; Ukkonen, E.

    2003-01-01

    We describe a new probabilistic method for finding haplotype blocks that is based on the use of the minimum description length (MDL) principle. We give a rigorous definition of the quality of a segmentation of a genomic region into blocks and describe a dynamic programming algorithm for finding the optimal segmentation with respect to this measure. We also describe a method for finding the probability of a block boundary for each pair of adjacent markers: this gives a tool for evaluating the significance of each block boundary. We have applied the method to the published data of Daly and colleagues. The results expose some problems that exist in the current methods for the evaluation of the significance of predicted block boundaries. Our method, MDL block finder, can be used to compare block borders in different sample sets, and we demonstrate this by applying the MDL-based method to define the block structure in chromosomes from population isolates. PMID:12761696

  19. Minimum description length block finder, a method to identify haplotype blocks and to compare the strength of block boundaries.

    PubMed

    Mannila, H; Koivisto, M; Perola, M; Varilo, T; Hennah, W; Ekelund, J; Lukk, M; Peltonen, L; Ukkonen, E

    2003-07-01

    We describe a new probabilistic method for finding haplotype blocks that is based on the use of the minimum description length (MDL) principle. We give a rigorous definition of the quality of a segmentation of a genomic region into blocks and describe a dynamic programming algorithm for finding the optimal segmentation with respect to this measure. We also describe a method for finding the probability of a block boundary for each pair of adjacent markers: this gives a tool for evaluating the significance of each block boundary. We have applied the method to the published data of Daly and colleagues. The results expose some problems that exist in the current methods for the evaluation of the significance of predicted block boundaries. Our method, MDL block finder, can be used to compare block borders in different sample sets, and we demonstrate this by applying the MDL-based method to define the block structure in chromosomes from population isolates.

  20. The Pattern of Visual Fixation Eccentricity and Instability in Optic Neuropathy and Its Spatial Relationship to Retinal Ganglion Cell Layer Thickness.

    PubMed

    Mallery, Robert M; Poolman, Pieter; Thurtell, Matthew J; Wang, Jui-Kai; Garvin, Mona K; Ledolter, Johannes; Kardon, Randy H

    2016-07-01

    The purpose of this study was to assess whether clinically useful measures of fixation instability and eccentricity can be derived from retinal tracking data obtained during optical coherence tomography (OCT) in patients with optic neuropathy (ON) and to develop a method for relating fixation to the retinal ganglion cell complex (GCC) thickness. Twenty-nine patients with ON underwent macular volume OCT with 30 seconds of confocal scanning laser ophthalmoscope (cSLO)-based eye tracking during fixation. Kernel density estimation quantified fixation instability and fixation eccentricity from the distribution of fixation points on the retina. Preferred ganglion cell layer loci (PGCL) and their relationship to the GCC thickness map were derived, accounting for radial displacement of retinal ganglion cell soma from their corresponding cones. Fixation instability was increased in ON eyes (0.21 deg2) compared with normal eyes (0.06982 deg2; P < 0.001), and fixation eccentricity was increased in ON eyes (0.48°) compared with normal eyes (0.24°; P = 0.03). Fixation instability and eccentricity each correlated moderately with logMAR acuity and were highly predictive of central visual field loss. Twenty-six of 35 ON eyes had PGCL skewed toward local maxima of the GCC thickness map. Patients with bilateral dense central scotomas had PGCL in homonymous retinal locations with respect to the fovea. Fixation instability and eccentricity measures obtained during cSLO-OCT assess the function of perifoveal retinal elements and predict central visual field loss in patients with ON. A model relating fixation to the GCC thickness map offers a method to assess the structure-function relationship between fixation and areas of preserved GCC in patients with ON.

  1. Presence of Functional Neurotrophin TrkB Receptors in the Rat Superior Cervical Ganglion

    PubMed Central

    Valle-Leija, Pablo; Cancino-Rodezno, Angeles; Sánchez-Tafolla, Berardo M.; Arias, Erwin; Elinos, Diana; Feria, Jessica; Zetina, María E.; Morales, Miguel A.; Cifuentes, Fredy

    2017-01-01

    Sympathetic neurons express the neurotrophin receptors TrkA, p75NTR, and a non-functional truncated TrkB isoform (TrkB-Tc), but are not thought to express a functional full-length TrkB receptor (TrkB-Fl). We, and others, have demonstrated that nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) modulate synaptic transmission and synaptic plasticity in neurons of the superior cervical ganglion (SCG) of the rat. To clarify whether TrkB is expressed in sympathetic ganglia and contributes to the effects of BDNF upon sympathetic function, we characterized the presence and activity of the neurotrophin receptors expressed in the adult SCG compared with their presence in neonatal and cultured sympathetic neurons. Here, we expand our previous study regarding the immunodetection of neurotrophin receptors. Immunohistochemical analysis revealed that 19% of adult ganglionic neurons expressed TrkB-Fl immunoreactivity (IR), 82% expressed TrkA-IR, and 51% expressed p75NTR-IR; TrkB-Tc would be expressed in 36% of neurons. In addition, using Western-blotting and reverse transcriptase polymerase chain reaction (RT-PCR) analyses, we confirmed the expression of TrkB-Fl and TrkB-Tc protein and mRNA transcripts in adult SCG. Neonatal neurons expressed significantly more TrkA-IR and TrkB-Fl-IR than p75NTR-IR. Finally, the application of neurotrophin, and high frequency stimulation, induced the activation of Trk receptors and the downstream PI3-kinase (phosphatidyl inositol-3-kinase) signaling pathway, thus evoking the phosphorylation of Trk and Akt. These results demonstrate that SCG neurons express functional TrkA and TrkB-Fl receptors, which may contribute to the differential modulation of synaptic transmission and long-term synaptic plasticity. PMID:28744222

  2. Can Retinal Ganglion Cell Dipoles Seed Iso-Orientation Domains in the Visual Cortex?

    PubMed Central

    Schottdorf, Manuel; Eglen, Stephen J.; Wolf, Fred; Keil, Wolfgang

    2014-01-01

    It has been argued that the emergence of roughly periodic orientation preference maps (OPMs) in the primary visual cortex (V1) of carnivores and primates can be explained by a so-called statistical connectivity model. This model assumes that input to V1 neurons is dominated by feed-forward projections originating from a small set of retinal ganglion cells (RGCs). The typical spacing between adjacent cortical orientation columns preferring the same orientation then arises via Moiré-Interference between hexagonal ON/OFF RGC mosaics. While this Moiré-Interference critically depends on long-range hexagonal order within the RGC mosaics, a recent statistical analysis of RGC receptive field positions found no evidence for such long-range positional order. Hexagonal order may be only one of several ways to obtain spatially repetitive OPMs in the statistical connectivity model. Here, we investigate a more general requirement on the spatial structure of RGC mosaics that can seed the emergence of spatially repetitive cortical OPMs, namely that angular correlations between so-called RGC dipoles exhibit a spatial structure similar to that of OPM autocorrelation functions. Both in cat beta cell mosaics as well as primate parasol receptive field mosaics we find that RGC dipole angles are spatially uncorrelated. To help assess the level of these correlations, we introduce a novel point process that generates mosaics with realistic nearest neighbor statistics and a tunable degree of spatial correlations of dipole angles. Using this process, we show that given the size of available data sets, the presence of even weak angular correlations in the data is very unlikely. We conclude that the layout of ON/OFF ganglion cell mosaics lacks the spatial structure necessary to seed iso-orientation domains in the primary visual cortex. PMID:24475081

  3. Presence of Functional Neurotrophin TrkB Receptors in the Rat Superior Cervical Ganglion.

    PubMed

    Valle-Leija, Pablo; Cancino-Rodezno, Angeles; Sánchez-Tafolla, Berardo M; Arias, Erwin; Elinos, Diana; Feria, Jessica; Zetina, María E; Morales, Miguel A; Cifuentes, Fredy

    2017-01-01

    Sympathetic neurons express the neurotrophin receptors TrkA, p75NTR, and a non-functional truncated TrkB isoform (TrkB-Tc), but are not thought to express a functional full-length TrkB receptor (TrkB-Fl). We, and others, have demonstrated that nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) modulate synaptic transmission and synaptic plasticity in neurons of the superior cervical ganglion (SCG) of the rat. To clarify whether TrkB is expressed in sympathetic ganglia and contributes to the effects of BDNF upon sympathetic function, we characterized the presence and activity of the neurotrophin receptors expressed in the adult SCG compared with their presence in neonatal and cultured sympathetic neurons. Here, we expand our previous study regarding the immunodetection of neurotrophin receptors. Immunohistochemical analysis revealed that 19% of adult ganglionic neurons expressed TrkB-Fl immunoreactivity (IR), 82% expressed TrkA-IR, and 51% expressed p75NTR-IR; TrkB-Tc would be expressed in 36% of neurons. In addition, using Western-blotting and reverse transcriptase polymerase chain reaction (RT-PCR) analyses, we confirmed the expression of TrkB-Fl and TrkB-Tc protein and mRNA transcripts in adult SCG. Neonatal neurons expressed significantly more TrkA-IR and TrkB-Fl-IR than p75NTR-IR. Finally, the application of neurotrophin, and high frequency stimulation, induced the activation of Trk receptors and the downstream PI3-kinase (phosphatidyl inositol-3-kinase) signaling pathway, thus evoking the phosphorylation of Trk and Akt. These results demonstrate that SCG neurons express functional TrkA and TrkB-Fl receptors, which may contribute to the differential modulation of synaptic transmission and long-term synaptic plasticity.

  4. Can retinal ganglion cell dipoles seed iso-orientation domains in the visual cortex?

    PubMed

    Schottdorf, Manuel; Eglen, Stephen J; Wolf, Fred; Keil, Wolfgang

    2014-01-01

    It has been argued that the emergence of roughly periodic orientation preference maps (OPMs) in the primary visual cortex (V1) of carnivores and primates can be explained by a so-called statistical connectivity model. This model assumes that input to V1 neurons is dominated by feed-forward projections originating from a small set of retinal ganglion cells (RGCs). The typical spacing between adjacent cortical orientation columns preferring the same orientation then arises via Moiré-Interference between hexagonal ON/OFF RGC mosaics. While this Moiré-Interference critically depends on long-range hexagonal order within the RGC mosaics, a recent statistical analysis of RGC receptive field positions found no evidence for such long-range positional order. Hexagonal order may be only one of several ways to obtain spatially repetitive OPMs in the statistical connectivity model. Here, we investigate a more general requirement on the spatial structure of RGC mosaics that can seed the emergence of spatially repetitive cortical OPMs, namely that angular correlations between so-called RGC dipoles exhibit a spatial structure similar to that of OPM autocorrelation functions. Both in cat beta cell mosaics as well as primate parasol receptive field mosaics we find that RGC dipole angles are spatially uncorrelated. To help assess the level of these correlations, we introduce a novel point process that generates mosaics with realistic nearest neighbor statistics and a tunable degree of spatial correlations of dipole angles. Using this process, we show that given the size of available data sets, the presence of even weak angular correlations in the data is very unlikely. We conclude that the layout of ON/OFF ganglion cell mosaics lacks the spatial structure necessary to seed iso-orientation domains in the primary visual cortex.

  5. View southeast of caps for blocks for JFK; blocks are ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View southeast of caps for blocks for JFK; blocks are used to support ship when it is repositioned to paint inaccessible areas masked by original support blocks. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Carpentry Shop, League Island, Philadelphia, Philadelphia County, PA

  6. Norrin mediates neuroprotective effects on retinal ganglion cells via activation of the Wnt/beta-catenin signaling pathway and the induction of neuroprotective growth factors in Muller cells.

    PubMed

    Seitz, Roswitha; Hackl, Simon; Seibuchner, Thomas; Tamm, Ernst R; Ohlmann, Andreas

    2010-04-28

    Norrin is a secreted protein that binds to frizzled 4 and controls development of capillaries in retina and inner ear. We provide evidence that Norrin has distinct neuroprotective properties that are independent from its effects on vascular development. The function of Norrin was investigated in a mouse model of excitotoxic retinal ganglion cell (RGC) damage after intravitreal injection of NMDA, and in cultured Müller glia or immortalized RGC-5 cells. Intravitreal injection of Norrin significantly increased the number of surviving RGC axons in the optic nerve and decreased apoptotic death of retinal neurons following NMDA-mediated damage. This effect could be blocked by adding dickkopf (DKK)-1, an inhibitor of the Wnt/beta-catenin signaling pathway. Treatment of eyes with combined Norrin/NMDA activated Wnt/beta-catenin signaling and increased the retinal expression of leukemia inhibitory factor and endothelin-2, as well as that of neurotrophic growth factors such as fibroblast growth factor-2, brain-derived neurotrophic factor, lens epithelium-derived growth factor, and ciliary neurotrophic factor. A similar activation of Wnt/beta-catenin signaling and an increased expression of neurotrophic factors was observed in cultured Müller cells after treatment with Norrin, effects that again could be blocked by adding DKK-1. In addition, conditioned cell culture medium of Norrin-treated Müller cells increased survival of differentiated RGC-5 cells. We conclude that Norrin has pronounced neuroprotective properties on retinal neurons with the distinct potential to decrease the damaging effects of NMDA-induced RGC loss. The effects of Norrin involve activation of Wnt/beta-catenin signaling and subsequent induction of neurotrophic growth factors in Müller cells.

  7. Fractalkine Signaling Regulates Macrophage Recruitment into the Cochlea and Promotes the Survival of Spiral Ganglion Neurons after Selective Hair Cell Lesion.

    PubMed

    Kaur, Tejbeer; Zamani, Darius; Tong, Ling; Rubel, Edwin W; Ohlemiller, Kevin K; Hirose, Keiko; Warchol, Mark E

    2015-11-11

    Macrophages are recruited into the cochlea in response to injury caused by acoustic trauma or ototoxicity, but the nature of the interaction between macrophages and the sensory structures of the inner ear remains unclear. The present study examined the role of fractalkine signaling in regulating the injury-evoked behavior of macrophages following the selective ablation of cochlear hair cells. We used a novel transgenic mouse model in which the human diphtheria toxin receptor (huDTR) is selectively expressed under the control of Pou4f3, a hair cell-specific transcription factor. Administration of diphtheria toxin (DT) to these mice resulted in nearly complete ablation of cochlear hair cells, with no evident pathology among supporting cells, spiral ganglion neurons, or cells of the cochlear lateral wall. Hair cell death led to an increase in macrophages associated with the sensory epithelium of the cochlea. Their numbers peaked at 14 days after DT and then declined at later survival times. Increased macrophages were also observed within the spiral ganglion, but their numbers remained elevated for (at least) 56 d after DT. To investigate the role of fractalkine signaling in macrophage recruitment, we crossed huDTR mice to a mouse line that lacks expression of the fractalkine receptor (CX3CR1). Disruption of fractalkine signaling reduced macrophage recruitment into both the sensory epithelium and spiral ganglion and also resulted in diminished survival of spiral ganglion neurons after hair cell death. Our results suggest a fractalkine-mediated interaction between macrophages and the neurons of the cochlea. It is known that damage to the inner ear leads to recruitment of inflammatory cells (macrophages), but the chemical signals that initiate this recruitment and the functions of macrophages in the damaged ear are unclear. Here we show that fractalkine signaling regulates macrophage recruitment into the cochlea and also promotes the survival of cochlear afferents after

  8. The developing dorsal ganglion of the salp Thalia democratica, and the nature of the ancestral chordate brain

    PubMed Central

    C.Lacalli, T.

    1998-01-01

    The development of the dorsal ganglion of the salp, Thalia democratica, is described from electron microscope reconstructions up to the stage of central neuropile formation. The central nervous system (CNS) rudiment is initially tubular with an open central canal. Early developmental events include: (i) the formation of a thick dorsal mantle of neuroblasts from which paired dorsal paraxial neuropiles arise; (ii) the differentiation of clusters of primary motor neurons along the ventral margin of the mantle; and (iii) the development from the latter of a series of peripheral nerves. The dorsal paraxial neuropiles ultimately connect to the large central neuropile, which develops later. Direct contact between neuroblasts and muscle appears to be involved in the development of some anterior nerves. The caudal nerves responsible for innervating more distant targets in the posterior part of the body develop without such contacts, which suggests that a different patterning mechanism may be employed in this part of the neuromuscular system. The results are compared with patterns of brain organization in other chordates. Because the salp CNS is symmetrical and generally less reduced than that of ascidian larvae, it is more easily compared with the CNS of amphioxus and vertebrates. The dorsal paraxial centres in the salp resemble the dorsolateral tectal centres in amphioxus in both position and organization; the central neuropile in salps likewise resembles the translumenal system in amphioxus. The neurons themselves are similar in that many of their neurites appear to be derived from the apical surface instead of the basal surface of the cell. Such neurons, with extensively developed apical neurites, may represent a new cell type that evolved in the earliest chordates in conjunction with the formation of translumenal or intralumenal integrative centres. In comparing the salp ganglion with vertebrates, we suggest that the main core of the ganglion is most like the mes

  9. A Shifted Block Lanczos Algorithm 1: The Block Recurrence

    NASA Technical Reports Server (NTRS)

    Grimes, Roger G.; Lewis, John G.; Simon, Horst D.

    1990-01-01

    In this paper we describe a block Lanczos algorithm that is used as the key building block of a software package for the extraction of eigenvalues and eigenvectors of large sparse symmetric generalized eigenproblems. The software package comprises: a version of the block Lanczos algorithm specialized for spectrally transformed eigenproblems; an adaptive strategy for choosing shifts, and efficient codes for factoring large sparse symmetric indefinite matrices. This paper describes the algorithmic details of our block Lanczos recurrence. This uses a novel combination of block generalizations of several features that have only been investigated independently in the past. In particular new forms of partial reorthogonalization, selective reorthogonalization and local reorthogonalization are used, as is a new algorithm for obtaining the M-orthogonal factorization of a matrix. The heuristic shifting strategy, the integration with sparse linear equation solvers and numerical experience with the code are described in a companion paper.

  10. Using ensemble models to identify and apportion heavy metal pollution sources in agricultural soils on a local scale.

    PubMed

    Wang, Qi; Xie, Zhiyi; Li, Fangbai

    2015-11-01

    This study aims to identify and apportion multi-source and multi-phase heavy metal pollution from natural and anthropogenic inputs using ensemble models that include stochastic gradient boosting (SGB) and random forest (RF) in agricultural soils on the local scale. The heavy metal pollution sources were quantitatively assessed, and the results illustrated the suitability of the ensemble models for the assessment of multi-source and multi-phase heavy metal pollution in agricultural soils on the local scale. The results of SGB and RF consistently demonstrated that anthropogenic sources contributed the most to the concentrations of Pb and Cd in agricultural soils in the study region and that SGB performed better than RF. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Modified round block mastopexy versus traditional round block mastopexy.

    PubMed

    Sterodimas, A; Nicaretta, B; Boriani, F

    2015-01-01

    Breast ptosis may be caused by several factors, including significant weight loss, pregnancy, long breastfeeding periods, and involution of the postmenopausal breast tissue. The authors performed a prospective study to evaluate patient satisfaction and the rate of complications after modified round block mastopexy versus traditional round block mastopexy. Forty-four patients fulfilled the inclusion criteria for undergoing round block mastopexy in a prospective randomized controlled study performed from 2007 to 2008. All the patients received polyurethane silicone implants. Group A included patients who underwent the traditional round block technique described by Benelli. Group B included patients who underwent the traditional round block and 4 cardinal glando-glandular permanent sutures. The overall satisfaction with body appearance after breast mastopexy was rated on a scale of 1 (poor), 2 (fair), 3 (good), 4 (very good), and 5 (excellent). Group A patient ages ranged from 28 to 52 years and in Group B ranged from 29 to 49 years. The mean implant volume was 215 cc in both Groups. The complication and satisfaction rates for both Groups are reported. The combination of the cardinal glandulo-glandular sutures along with the traditional round block appears to be key to preventing the areolar enlargement and persistent breast ptosis. The satisfaction rates in patients who underwent the modified round mastopexy appear superior when compared to the traditional round block mastopexy. Furhter long-term follow-up need to be performed in order to confirm the favorable results seen in this series of cases.

  12. Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome (CRPS) Recurrence after Amputation for CRPS, and Failure of Conventional Spinal Cord Stimulation.

    PubMed

    Goebel, Andreas; Lewis, Sarah; Phillip, Rhodri; Sharma, Manohar

    2018-01-01

    Limb amputation is sometimes being performed in long-standing complex regional pain syndrome (CRPS), although little evidence is available guiding management decisions, including how CRPS recurrence should be managed. This report details the management of a young soldier with CRPS recurrence 2 years after midtibial amputation for CRPS. Conventional spinal cord stimulation did not achieve paraesthetic coverage, or pain relief in the stump, whereas L4 dorsal root ganglion stimulation achieved both coverage and initially modest pain relief, and over time, substantial pain relief. Current evidence does not support the use of amputation to improve either pain or function in CRPS. Before a decision is made, in exceptional cases, about referral for amputation, dorsal root ganglion stimulation should be considered as a potentially effective treatment, even where conventional spinal cord stimulator treatment has failed to achieve reliable paraesthetic cover. Furthermore, this treatment may provide pain relief in those patients with CRPS recurrence in the stump after amputation. © 2017 World Institute of Pain.

  13. Application of three-dimensional rendering in joint-related ganglion cysts.

    PubMed

    Spinner, Robert J; Edwards, Phillip K; Amrami, Kimberly K

    2006-05-01

    The origin of para-articular cysts is poorly understood and controversial. The relatively common, simple (extraneural) cysts are presumed to be derived from joints, although joint connections are not always established. Rarer complex cysts are thought by many to form de novo within nerves (intraneural ganglion cysts) or within vessels (adventitial cysts) (degenerative theory). We believe that these simple and complex ganglion cysts are joint-related (articular theory). Joint connections are often not readily appreciated with routine imaging or at surgery. Not identifying and/or treating joint connections frequently leads to cyst recurrence. More sophisticated imaging may enhance visualization of these joint connections. We created a 3D rendering technique to assess potential joint connections of simple and complex cysts localized to the knee and superior tibiofibular joints in patients with fibular (peroneal) neuropathy. Two- and three-dimensional data sets from MRI examinations were segmented semiautomatically by signal intensity with further refinement based on interaction with the user to identify specific anatomic structures, such as small nerves and vessels on serial images. The bone, cysts, nerves, and vessels were each assigned different color representations, and 3D renderings were created in ANALYZE using the data sets closest to isotropic (voxel with equal length in all dimensions) resolution as the primary background rendering. We selected four cases to illustrate the spectrum of pathology. In all of these cases, we demonstrated joint connections and correlated imaging and operative findings. Surgery addressing the cyst and the joint connection resulted in excellent outcomes; postoperative MRIs done more than 6 months later confirmed that there was no recurrence. In addition to highlighting the important relationship of these cysts to neighboring anatomic structures, this 3D technique allows visualization of "occult" connections not readily appreciated

  14. Neuroprotection of a Novel Cyclopeptide C*HSDGIC* from the Cyclization of PACAP (1–5) in Cellular and Rodent Models of Retinal Ganglion Cell Apoptosis

    PubMed Central

    Cheng, Huanhuan; Ding, Yong; Yu, Rongjie; Chen, Jiansu; Wu, Chunyun

    2014-01-01

    Purpose To investigate the protective effects of a novel cyclopeptide C*HSDGIC* (CHC) from the cyclization of Pituitary adenylate cyclase-activating polypeptide (PACAP) (1–5) in cellular and rodent models of retinal ganglion cell apoptosis. Methodology/Principal Findings Double-labeling immunohistochemistry was used to detect the expression of Thy-1 and PACAP receptor type 1 in a retinal ganglion cell line RGC-5. The apoptosis of RGC-5 cells was induced by 0.02 J/cm2 Ultraviolet B irradiation. MTT assay, flow cytometry, fluorescence microscopy were used to investigate the viability, the level of reactive oxygen species (ROS) and apoptosis of RGC-5 cells respectively. CHC attenuated apoptotic cell death induced by Ultraviolet B irradiation and inhibited the excessive generation of ROS. Moreover, CHC treatment resulted in decreased expression of Bax and concomitant increase of Bcl-2, as was revealed by western-blot analysis. The in vivo apoptosis of retinal ganglion cells was induced by injecting 50 mM N-methyl-D-aspartate (NMDA) (100 nmol in a 2 µL saline solution) intravitreally, and different dosages of CHC were administered. At day 7, rats in CHC+ NMDA-treated groups showed obvious aversion to light when compared to NMDA rats. Electroretinogram recordings revealed a marked decrease in the amplitudes of a-wave, b-wave, and photopic negative response due to NMDA damage. In retina receiving intravitreal NMDA and CHC co-treatment, these values were significantly increased. CHC treatment also resulted in less NMDA-induced cell loss and a decrease in the proportion of dUTP end-labeling-positive cells in ganglion cell line. Conclusions C*HSDGIC*, a novel cyclopeptide from PACAP (1–5) attenuates apoptosis in RGC-5 cells and inhibits NMDA-induced retinal neuronal death. The beneficial effects may occur via the mitochondria pathway. PACAP derivatives like CHC may serve as a promising candidate for neuroprotection in glaucoma. PMID:25286089

  15. Characterizing the inverses of block tridiagonal, block Toeplitz matrices

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Boffi, Nicholas M.; Hill, Judith C.; Reuter, Matthew G.

    2014-12-04

    We consider the inversion of block tridiagonal, block Toeplitz matrices and comment on the behaviour of these inverses as one moves away from the diagonal. Using matrix M bius transformations, we first present an O(1) representation (with respect to the number of block rows and block columns) for the inverse matrix and subsequently use this representation to characterize the inverse matrix. There are four symmetry-distinct cases where the blocks of the inverse matrix (i) decay to zero on both sides of the diagonal, (ii) oscillate on both sides, (iii) decay on one side and oscillate on the other and (iv)more » decay on one side and grow on the other. This characterization exposes the necessary conditions for the inverse matrix to be numerically banded and may also aid in the design of preconditioners and fast algorithms. Finally, we present numerical examples of these matrix types.« less

  16. Retinal ganglion cell damage in an experimental rodent model of blast-mediated traumatic brain injury.

    PubMed

    Mohan, Kabhilan; Kecova, Helga; Hernandez-Merino, Elena; Kardon, Randy H; Harper, Matthew M

    2013-05-15

    To evaluate retina and optic nerve damage following experimental blast injury. Healthy adult mice were exposed to an overpressure blast wave using a custom-built blast chamber. The effects of blast exposure on retina and optic nerve function and structure were evaluated using the pattern electroretinogram (pERG), spectral domain optical coherence tomography (OCT), and the chromatic pupil light reflex. Assessment of the pupil response to light demonstrated decreased maximum pupil constriction diameter in blast-injured mice using red light or blue light stimuli 24 hours after injury compared with baseline in the eye exposed to direct blast injury. A decrease in the pupil light reflex was not observed chronically following blast exposure. We observed a biphasic pERG decrease with the acute injury recovering by 24 hours postblast and the chronic injury appearing at 4 months postblast injury. Furthermore, at 3 months following injury, a significant decrease in the retinal nerve fiber layer was observed using OCT compared with controls. Histologic analysis of the retina and optic nerve revealed punctate regions of reduced cellularity in the ganglion cell layer and damage to optic nerves. Additionally, a significant upregulation of proteins associated with oxidative stress was observed acutely following blast exposure compared with control mice. Our study demonstrates that decrements in retinal ganglion cell responses can be detected after blast injury using noninvasive functional and structural tests. These objective responses may serve as surrogate tests for higher CNS functions following traumatic brain injury that are difficult to quantify.

  17. Retinal Ganglion Cell Damage in an Experimental Rodent Model of Blast-Mediated Traumatic Brain Injury

    PubMed Central

    Mohan, Kabhilan; Kecova, Helga; Hernandez-Merino, Elena; Kardon, Randy H.; Harper, Matthew M.

    2013-01-01

    Purpose. To evaluate retina and optic nerve damage following experimental blast injury. Methods. Healthy adult mice were exposed to an overpressure blast wave using a custom-built blast chamber. The effects of blast exposure on retina and optic nerve function and structure were evaluated using the pattern electroretinogram (pERG), spectral domain optical coherence tomography (OCT), and the chromatic pupil light reflex. Results. Assessment of the pupil response to light demonstrated decreased maximum pupil constriction diameter in blast-injured mice using red light or blue light stimuli 24 hours after injury compared with baseline in the eye exposed to direct blast injury. A decrease in the pupil light reflex was not observed chronically following blast exposure. We observed a biphasic pERG decrease with the acute injury recovering by 24 hours postblast and the chronic injury appearing at 4 months postblast injury. Furthermore, at 3 months following injury, a significant decrease in the retinal nerve fiber layer was observed using OCT compared with controls. Histologic analysis of the retina and optic nerve revealed punctate regions of reduced cellularity in the ganglion cell layer and damage to optic nerves. Additionally, a significant upregulation of proteins associated with oxidative stress was observed acutely following blast exposure compared with control mice. Conclusions. Our study demonstrates that decrements in retinal ganglion cell responses can be detected after blast injury using noninvasive functional and structural tests. These objective responses may serve as surrogate tests for higher CNS functions following traumatic brain injury that are difficult to quantify. PMID:23620426

  18. Fluvial entrainment of low density peat blocks (block carbon)

    NASA Astrophysics Data System (ADS)

    Warburton, Jeff

    2014-05-01

    In many fluvial environments low density materials are transported in significant quantities and these form an important part of the stream load and /or have a distinct impact on sedimentation in these environments. However, there are significant gaps in understanding of how these materials are entrained and transported by streams and rivers. Eroding upland peatland environments in particular, frequently have fluvial systems in which large eroded peat blocks, often exceeding 1 m in length; form an important component of the stream material flux. Transport of this material is significant in determining rates of erosion but also has important impacts in terms of damage to infrastructure and carbon loss. This paper describes a field experiment designed to establish for the first time the conditions under which large peat blocks (c. > 0.1 m b axis) are initially entrained from a rough gravel bed. The field site is Trout Beck, in the North Pennines, Northern England which is an upland wandering river channel with occasional lateral and mid channel bars. Mean low flow stage is typically 0.2 m but during flood can rapidly rise, in one to two hours, to over 1.5 m. To study peat block entrainment a bespoke data acquisition system consisting of two pressure transducers, four release triggers and time lapse camera was set up. The pressure transducers provided a record of local depth and the release triggers were embedded in peat blocks to record initial motion and arranged on the rough stream bed. The time lapse camera provided verification of timing of block entrainment (during daylight hours) and also provided information on the mechanism of initial movement. Peat blocks were cut from a local source and were equidimensional, ranging in size from 0.1 to 0.7 m. The derived entrainment function is related to a critical depth of entrainment. Results demonstrate that peat blocks are entrained when the local depth approximates the height of the peat block. Blocks frequently shift

  19. Identification of ganglion cell neurites in human subretinal and epiretinal membranes

    PubMed Central

    Lewis, Geoffrey P; Betts, Kellen E; Sethi, Charanjit S; Charteris, David G; Lesnik‐Oberstein, Sarit Y; Avery, Robert L; Fisher, Steven K

    2007-01-01

    Aim To determine whether neural elements are present in subretinal and epiretinal proliferative vitreoretinopathy (PVR) membranes as well as in diabetic, fibrovascular membranes removed from patients during vitrectomy surgery. Methods Human subretinal and epiretinal membranes of varying durations were immunolabelled with different combinations of antibodies to glial fibrillary acidic protein, vimentin, neurofilament protein and laminin. Results Anti‐neurofilament‐labelled neurites from presumptive ganglion cells were frequently found in epiretinal membranes and occasionally found in subretinal membranes. In addition, the neurites were only observed in regions that also contained glial processes. Conclusions These data demonstrate that neuronal processes are commonly found in human peri‐retinal cellular membranes similar to that demonstrated in animal models. These data also suggest that glial cells growing out of the neural retina form a permissive substrate for neurite growth and thus may hold clues to factors that support this growth. PMID:17108012

  20. The Pattern of Visual Fixation Eccentricity and Instability in Optic Neuropathy and Its Spatial Relationship to Retinal Ganglion Cell Layer Thickness

    PubMed Central

    M. Mallery, Robert; Poolman, Pieter; J. Thurtell, Matthew; Wang, Jui-Kai; K. Garvin, Mona; Ledolter, Johannes; Kardon, Randy H.

    2016-01-01

    Purpose The purpose of this study was to assess whether clinically useful measures of fixation instability and eccentricity can be derived from retinal tracking data obtained during optical coherence tomography (OCT) in patients with optic neuropathy (ON) and to develop a method for relating fixation to the retinal ganglion cell complex (GCC) thickness. Methods Twenty-nine patients with ON underwent macular volume OCT with 30 seconds of confocal scanning laser ophthalmoscope (cSLO)-based eye tracking during fixation. Kernel density estimation quantified fixation instability and fixation eccentricity from the distribution of fixation points on the retina. Preferred ganglion cell layer loci (PGCL) and their relationship to the GCC thickness map were derived, accounting for radial displacement of retinal ganglion cell soma from their corresponding cones. Results Fixation instability was increased in ON eyes (0.21 deg2) compared with normal eyes (0.06982 deg2; P < 0.001), and fixation eccentricity was increased in ON eyes (0.48°) compared with normal eyes (0.24°; P = 0.03). Fixation instability and eccentricity each correlated moderately with logMAR acuity and were highly predictive of central visual field loss. Twenty-six of 35 ON eyes had PGCL skewed toward local maxima of the GCC thickness map. Patients with bilateral dense central scotomas had PGCL in homonymous retinal locations with respect to the fovea. Conclusions Fixation instability and eccentricity measures obtained during cSLO-OCT assess the function of perifoveal retinal elements and predict central visual field loss in patients with ON. A model relating fixation to the GCC thickness map offers a method to assess the structure–function relationship between fixation and areas of preserved GCC in patients with ON. PMID:27409502

  1. Antibodies to ependymin block the sharpening of the regenerating retinotectal projection in goldfish.

    PubMed

    Schmidt, J T; Shashoua, V E

    1988-04-19

    The regenerating optic nerve of goldfish first reestablishes a rough retinotopic map on the tectum, then goes through an activity dependent refinement that appears to involve the elimination of inappropriate branches from early regenerated arbors. Retinotopically appropriate branches and synapses may be stabilized because the normally correlated firing of neighboring ganglion cells could cause summation of their postsynaptic responses, making them more effective. Thus, refinement of the map may be similar in several ways to associative learning. In this study, we therefore tested whether ependymin, a major protein component of the extracellular fluid that has been implicated in synaptic changes thought to be associated with learning a simple task in goldfish, may also be involved in refinement of the retinotopic map. Goldfish that had undergone unilateral optic nerve crush received intraventricular infusion of antiependymin IgG or of control IgG's beginning at 21 days postcrush. Tectal recordings from these fish at 39-56 days postcrush showed that the projection had failed to sharpen, much as in the fish with activity blocked or synchronized; the average size of the multiunit receptive fields was 31 degrees vs 11 degrees normally. The field potentials elicited from these tecta by optic nerve shock were not significantly smaller than in controls, suggesting normal levels of synaptogenesis. Control projections, identically treated but infused with either unrelated IgG or Ringer's alone regenerated normally, giving multiunit receptive fields of 12 degrees. Intact (non-regenerating) projections of the experimental fish were not rendered abnormal by the IgG treatment. Histology showed the retinas and tecta of the infused fish to be normal in appearance. The results show a specific block of sharpening by antiependymin IgG. The ependymal glia of the tectum stain positively for ependymin in normal fish, particularly the cell bodies in the ependymal layer. The tectum

  2. 31 CFR 594.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account; blocked property. 594.301 Section 594.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM SANCTIONS...

  3. 31 CFR 545.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account; blocked property. 545.301 Section 545.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TALIBAN (AFGHANISTAN) SANCTIONS...

  4. 31 CFR 551.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account; blocked property. 551.301 Section 551.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY SOMALIA SANCTIONS REGULATIONS...

  5. Radiological anatomy assessment of the fissura pterygomaxillaris for a surgical approach to ganglion pterygopalatinum.

    PubMed

    Puche-Torres, Miguel; Blasco-Serra, Arantxa; Campos-Peláez, Ana; Valverde-Navarro, Alfonso A

    2017-12-01

    The ganglion pterygopalatinum has become a therapeutic target to treat various pain syndromes in recent years. It is located in the fossa pterygopalatina, and the fissura pterygomaxillaris is the main access to surgically approach this structure. Recently, the neuromodulation of the ganglion pterygopalatinum by microstimulator implantation has become the first therapeutic line in refractory cluster headache treatment. This invasive technique is performed transorally through the fissura pterygomaxillaris, and is limited by the size of the implantation device, which requires an opening of at least 2 mm. Therefore, extensive knowledge about the anatomy of the fissura pterygomaxillaris prior to surgery is necessary to predict the success of both the approach and intervention. Likewise, establishing a morphological typology of the different fissura pterygomaxillaris variations would be a valuable predictive tool in the clinical practice. In this work, an anatomical analysis was performed of the morphological characteristics of the 242 fissurae pterygomaxillares, which corresponded to 121 adult patients, 58 males and 63 females, aged between 18 and 87 years. For each subject, right and left fissures were studied with radiological computed tomography images. Aperture fissura pterygomaxillaris measurements were taken in an upper (Measure A), middle (Measure B) and lower craneo-caudal third (Measure C). Intra-subject differences were studied between the measurements taken of each patient's right and left fissures, and the inter-subject measures in which fissures were compared according to patients' age and gender. The obtained results showed no significant differences between each patient's right and left fissures in any three measurements taken. Intra-subject differences were not significant for gender or age. No statistically significant differences were found for the inter-subject measures between the measures of fissures according to patients' age. However, our data

  6. [Social security law and evidence-based health care in Germany].

    PubMed

    Welti, Felix

    2007-01-01

    The present contribution examines whether German Social Security Law requires or allows the German health care system to follow the principles of evidence-based health care. The discussion will be based on the relevant example of statutory health insurance (Book of Social Code V-SGB V). According to Sect. 2 SGB V health care provision has to follow medical standards, acknowledging medical progress. It has to be effective and efficient. Special therapies are not outlawed, but also have to follow these principles. Efficiency is defined (Sect. 12 SGB V) by the benefits being sufficient and necessary. The responsibility for achieving these goals and supplying the benefits for all people according to need lies with the health care insurance funds along with the physicians' associations (Kassenirztliche Vereinigung) and the hospitals (Sect. 70 SGB V). These organisations cooperate in the Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA, Sect. 92 SGB V), where they have to hear organisations of patients and of the disabled also. The G-BA is allowed by law to exclude therapies not meeting the SGB V criteria. The Institute for Quality and Efficiency in Health Care (IQWiG) advises the G-BA and is also responsible for generating evidence. A major political and constitutional controversy has been triggered on the legitimation of the Federal Joint Committee. In its statute the G-BA recurs on evidence-based health care. It examines therapies according to the degree of available evidence and the usability of the evidence in the respective supply setting. The Federal Social Court (Bundessozialgericht, BSG) decided that the decisions of the G-BA could not be challenged for being medically incorrect. In 2005, the Federal Constitutional Court (Bundesverfassungsgericht-BVerfG) decided that a stricter control over the G-BA by the social courts was needed and that in the case of serious disease a lower evidence level might be sufficient. BSG and G-BA will continue to accept

  7. 31 CFR 594.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Blocked account; blocked property. 594.301 Section 594.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM SANCTIONS REGULATIONS...

  8. 31 CFR 594.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Blocked account; blocked property. 594.301 Section 594.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM SANCTIONS REGULATIONS...

  9. 31 CFR 594.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Blocked account; blocked property. 594.301 Section 594.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM SANCTIONS REGULATIONS...

  10. 31 CFR 546.302 - Blocked account; blocked property.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account; blocked property. 546.302 Section 546.302 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY DARFUR SANCTIONS REGULATIONS General...

  11. 31 CFR 593.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account; blocked property. 593.301 Section 593.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FORMER LIBERIAN REGIME OF CHARLES...

  12. 31 CFR 510.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Blocked account; blocked property. 510.301 Section 510.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NORTH KOREA SANCTIONS REGULATIONS General...

  13. 31 CFR 547.302 - Blocked account; blocked property.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Blocked account; blocked property. 547.302 Section 547.302 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY DEMOCRATIC REPUBLIC OF THE CONGO...

  14. Differential Effects of RET and TRKB on Axonal Branching and Survival of Parasympathetic Neurons

    PubMed Central

    Simpson, Julie; Keefe, Julie; Nishi, Rae

    2014-01-01

    Interactions between neurons and their targets of innervation influence many aspects of neural development. To examine how synaptic activity interacts with neurotrophic signaling, we determined the effects of blocking neuromuscular transmission on survival and axonal outgrowth of ciliary neurons from the embryonic chicken ciliary ganglion. Ciliary neurons undergo a period of cell loss due to programmed cell death between embryonic Days (E) 8 and 14 and they innervate the striated muscle of the iris. The nicotinic antagonist d-tubocurarine (dTC) induces an increase in branching measured by counting neurofilament-positive voxels (NF-VU) in the iris between E14–17 while reducing ciliary neuron survival. Blocking ganglionic transmission with dihyro-β-erythroidin and α-methyllycacontine does not mimic dTC. At E8, many trophic factors stimulate neurite outgrowth and branching of neurons placed in cell culture; however, at E13, only GDNF stimulates branching selectively in cultured ciliary neurons. The GDNF-induced branching at E13 could be inhibited by BDNF. Blocking ret signaling in vivo with a dominant negative (dn)ret decreases survival of ciliary and choroid neurons at E14 and prevents dTC induced increases in NF-VU in the iris at E17. Blocking TRKB signaling with dn TRKB increases NF-VU in the iris at E17 and decreases neuronal survival at E17, but not at E14. Thus, RET promotes survival during programmed cell death in the ciliary ganglion and contributes to promoting branching when synaptic transmission is blocked while TRKB inhibits branching and promotes maintenance of neuronal survival. These studies highlight the multifunctional nature of trophic molecule function during neuronal development. PMID:22648743

  15. Phospholipase C-dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate underlies agmatine-induced suppression of N-type Ca2+ channel in rat celiac ganglion neurons.

    PubMed

    Kim, Young-Hwan; Jeong, Ji-Hyun; Ahn, Duck-Sun; Chung, Seungsoo

    2017-03-04

    Agmatine suppresses peripheral sympathetic tone by modulating Cav2.2 channels in peripheral sympathetic neurons. However, the detailed cellular signaling mechanism underlying the agmatine-induced Cav2.2 inhibition remains unclear. Therefore, in the present study, we investigated the electrophysiological mechanism for the agmatine-induced inhibition of Cav2.2 current (I Cav2.2 ) in rat celiac ganglion (CG) neurons. Consistent with previous reports, agmatine inhibited I Cav2.2 in a VI manner. The agmatine-induced inhibition of the I Cav2.2 current was also almost completely hindered by the blockade of the imidazoline I 2 receptor (IR 2 ), and an IR 2 agonist mimicked the inhibitory effect of agmatine on I Cav2.2 , implying involvement of IR 2 . The agmatine-induced I Cav2.2 inhibition was significantly hampered by the blockade of G protein or phospholipase C (PLC), but not by the pretreatment with pertussis toxin. In addition, diC8-phosphatidylinositol 4,5-bisphosphate (PIP 2 ) dialysis nearly completely hampered agmatine-induced inhibition, which became irreversible when PIP 2 resynthesis was blocked. These results suggest that in rat peripheral sympathetic neurons, agmatine-induced IR 2 activation suppresses Cav2.2 channel voltage-independently, and that the PLC-dependent PIP 2 hydrolysis is responsible for the agmatine-induced suppression of the Cav2.2 channel. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. 31 CFR 593.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Blocked account; blocked property. 593.301 Section 593.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FORMER LIBERIAN REGIME OF CHARLES TAYLOR...

  17. 31 CFR 593.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Blocked account; blocked property. 593.301 Section 593.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FORMER LIBERIAN REGIME OF CHARLES TAYLOR...

  18. 31 CFR 593.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Blocked account; blocked property. 593.301 Section 593.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FORMER LIBERIAN REGIME OF CHARLES TAYLOR...

  19. 31 CFR 593.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Blocked account; blocked property. 593.301 Section 593.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FORMER LIBERIAN REGIME OF CHARLES TAYLOR...

  20. 31 CFR 547.302 - Blocked account; blocked property.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Blocked account; blocked property. 547.302 Section 547.302 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY DEMOCRATIC REPUBLIC OF THE CONGO SANCTIONS...

  1. 31 CFR 547.302 - Blocked account; blocked property.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Blocked account; blocked property. 547.302 Section 547.302 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY DEMOCRATIC REPUBLIC OF THE CONGO SANCTIONS...

  2. 31 CFR 547.302 - Blocked account; blocked property.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Blocked account; blocked property. 547.302 Section 547.302 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY DEMOCRATIC REPUBLIC OF THE CONGO SANCTIONS...

  3. 31 CFR 547.302 - Blocked account; blocked property.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Blocked account; blocked property. 547.302 Section 547.302 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY DEMOCRATIC REPUBLIC OF THE CONGO SANCTIONS...

  4. A new entity in the differential diagnosis of geniculate ganglion tumours: fibrous connective tissue lesion of the facial nerve.

    PubMed

    de Arriba, Alvaro; Lassaletta, Luis; Pérez-Mora, Rosa María; Gavilán, Javier

    2013-01-01

    Differential diagnosis of geniculate ganglion tumours includes chiefly schwannomas, haemangiomas and meningiomas. We report the case of a patient whose clinical and imaging findings mimicked the presentation of a facial nerve schwannoma.Pathological studies revealed a lesion with nerve bundles unstructured by intense collagenisation. Consequently, it was called fibrous connective tissue lesion of the facial nerve. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  5. EFFECT OF INTRAVITREAL RANIBIZUMAB ON GANGLION CELL COMPLEX AND PERIPAPILLARY RETINAL NERVE FIBER LAYER IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

    PubMed

    Zucchiatti, Ilaria; Cicinelli, Maria V; Parodi, Maurizio Battaglia; Pierro, Luisa; Gagliardi, Marco; Accardo, Agostino; Bandello, Francesco

    2017-07-01

    To analyze the changes in ganglion cell complex and peripapillary retinal nerve fiber layer thickness, in central macular thickness and choroidal thickness on spectral domain optical coherence tomography in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab injections. All consecutive patients with untreated neovascular age-related macular degeneration received loading phase of three monthly intravitreal ranibizumab, followed by retreatments on a pro re nata protocol for 12 months. changes in ganglion cell complex and retinal nerve fiber layer at the end of follow-up. Secondary outcome: changes in best-corrected visual acuity, central macular thickness, and choroidal thickness at the end of follow-up. Choroidal thickness was measured at 500 μm, 1000 μm, and 1,500 μm intervals nasally, temporally, superiorly, and inferiorly to the fovea, respectively, on horizontal and vertical line scans centered on the fovea. Twenty-four eyes were included. Ganglion cell complex and peripapillary retinal nerve fiber layer thickness did not show statistically significant changes through 12 months (55.6 ± 18.5 and 81.9 ± 9.9 μm at baseline, 52.7 ± 19.3 and 84.6 ± 15.5 μm at month 12, P > 0.05). Central macular thickness showed progressive decrease from baseline to month 12, with maximum reduction at month 3 (P < 0.001). Statistically significant reduction in choroidal thickness was registered in the nasal 500, 1000, and 1,500 μm from the fovea, corresponding to the papillomacular region (from 169.6 ± 45.3 to 153.9 ± 46.9, P < 0.001). Intravitreal ranibizumab injections did not affect retinal nerve fiber layer and ganglion cell complex thickness in 1-year follow-up. Choroidal thickness in papillomacular area and central macular thickness was significantly reduced at the end of treatment. Further studies, with larger sample, longer follow-up, and greater number of injections, are warranted.

  6. Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: Implications for glaucoma

    NASA Astrophysics Data System (ADS)

    Schori, Hadas; Kipnis, Jonathan; Yoles, Eti; Woldemussie, Elizabeth; Ruiz, Guadalupe; Wheeler, Larry A.; Schwartz, Michal

    2001-03-01

    Our group recently demonstrated that autoimmune T cells directed against central nervous system-associated myelin antigens protect neurons from secondary degeneration. We further showed that the synthetic peptide copolymer 1 (Cop-1), known to suppress experimental autoimmune encephalomyelitis, can be safely substituted for the natural myelin antigen in both passive and active immunization for neuroprotection of the injured optic nerve. Here we attempted to determine whether similar immunizations are protective from retinal ganglion cell loss resulting from a direct biochemical insult caused, for example, by glutamate (a major mediator of degeneration in acute and chronic optic nerve insults) and in a rat model of ocular hypertension. Passive immunization with T cells reactive to myelin basic protein or active immunization with myelin oligodendrocyte glycoprotein-derived peptide, although neuroprotective after optic nerve injury, was ineffective against glutamate toxicity in mice and rats. In contrast, the number of surviving retinal ganglion cells per square millimeter in glutamate-injected retinas was significantly larger in mice immunized 10 days previously with Cop-1 emulsified in complete Freund's adjuvant than in mice injected with PBS in the same adjuvant (2,133 ± 270 and 1,329 ± 121, respectively, mean ± SEM; P < 0.02). A similar pattern was observed when mice were immunized on the day of glutamate injection (1,777 ± 101 compared with 1,414 ± 36; P <0.05), but not when they were immunized 48h later. These findings suggest that protection from glutamate toxicity requires reinforcement of the immune system by antigens that are different from those associated with myelin. The use of Cop-1 apparently circumvents this antigen specificity barrier. In the rat ocular hypertension model, which simulates glaucoma, immunization with Cop-1 significantly reduced the retinal ganglion cell loss from 27.8%±6.8% to 4.3%±1.6%, without affecting the intraocular pressure

  7. Topographic prominence discriminator for the detection of short-latency spikes of retinal ganglion cells

    NASA Astrophysics Data System (ADS)

    Choi, Myoung-Hwan; Ahn, Jungryul; Park, Dae Jin; Lee, Sang Min; Kim, Kwangsoo; Cho, Dong-il Dan; Senok, Solomon S.; Koo, Kyo-in; Goo, Yong Sook

    2017-02-01

    Objective. Direct stimulation of retinal ganglion cells in degenerate retinas by implanting epi-retinal prostheses is a recognized strategy for restoration of visual perception in patients with retinitis pigmentosa or age-related macular degeneration. Elucidating the best stimulus-response paradigms in the laboratory using multielectrode arrays (MEA) is complicated by the fact that the short-latency spikes (within 10 ms) elicited by direct retinal ganglion cell (RGC) stimulation are obscured by the stimulus artifact which is generated by the electrical stimulator. Approach. We developed an artifact subtraction algorithm based on topographic prominence discrimination, wherein the duration of prominences within the stimulus artifact is used as a strategy for identifying the artifact for subtraction and clarifying the obfuscated spikes which are then quantified using standard thresholding. Main results. We found that the prominence discrimination based filters perform creditably in simulation conditions by successfully isolating randomly inserted spikes in the presence of simple and even complex residual artifacts. We also show that the algorithm successfully isolated short-latency spikes in an MEA-based recording from degenerate mouse retinas, where the amplitude and frequency characteristics of the stimulus artifact vary according to the distance of the recording electrode from the stimulating electrode. By ROC analysis of false positive and false negative first spike detection rates in a dataset of one hundred and eight RGCs from four retinal patches, we found that the performance of our algorithm is comparable to that of a generally-used artifact subtraction filter algorithm which uses a strategy of local polynomial approximation (SALPA). Significance. We conclude that the application of topographic prominence discrimination is a valid and useful method for subtraction of stimulation artifacts with variable amplitudes and shapes. We propose that our algorithm

  8. Spatial consequences of bleaching adaptation in cat retinal ganglion cells.

    PubMed Central

    Bonds, A B; Enroth-Cugell, C

    1981-01-01

    1. Experiments were conducted to study the effects of localized bleaching on the centre responses of rod-driven cat retinal ganglion cells. 2. Stimulation as far as 2 degrees from the bleaching site yielded responses which were reduced nearly as much as those generated at the bleaching site. Bleaching in the receptive field middle reduced responsiveness at a site 1 degrees peripheral more than bleaching at that peripheral site itself. 3. The effectiveness of a bleach in reducing centre responsiveness is related to the sensitivity of the region in which the bleach is applied. 4. Response reduction after a 0.2 degree bleach followed the same temporal pattern for concentric test spots of from 0.2 to 1.8 degrees in diameter, implying a substantially uniform spread of adaptation within these bounds. 5. A linear trade-off between fraction of rhodopsin and area bleached over a range of 8:1 yields the same pattern of response reduction, implying that the non-linear nature of bleaching adaptation is a property of the adaptation pool rather than independent photoreceptors. PMID:7320894

  9. Concrete Block Pavements

    DTIC Science & Technology

    1983-03-01

    concrete paving block ( Van der Vlist 1980). The concrete paving block was readily accepted as a substitute for the scarce paving brick and today has...seen in Figure 4, its growth.has been steady ( Van der Vlist 1980). 20 15 0< 0. n 10 1𔃺 978 960 1 62 63 64 65 66 67 68 6970 71 72 73 74 7678 7778 79...Figure 4. Concrete paving block production in the Netherlands ( Van der Vlist 1980) 8. The use of concrete paving block in the Netherlands developedI

  10. Sloppy morphological tuning in identified neurons of the crustacean stomatogastric ganglion

    PubMed Central

    Otopalik, Adriane G; Goeritz, Marie L; Sutton, Alexander C; Brookings, Ted; Guerini, Cosmo; Marder, Eve

    2017-01-01

    Neuronal physiology depends on a neuron’s ion channel composition and unique morphology. Variable ion channel compositions can produce similar neuronal physiologies across animals. Less is known regarding the morphological precision required to produce reliable neuronal physiology. Theoretical studies suggest that moraphology is tightly tuned to minimize wiring and conduction delay of synaptic events. We utilize high-resolution confocal microscopy and custom computational tools to characterize the morphologies of four neuron types in the stomatogastric ganglion (STG) of the crab Cancer borealis. Macroscopic branching patterns and fine cable properties are variable within and across neuron types. We compare these neuronal structures to synthetic minimal spanning neurite trees constrained by a wiring cost equation and find that STG neurons do not adhere to prevailing hypotheses regarding wiring optimization principles. In this highly modulated and oscillating circuit, neuronal structures appear to be governed by a space-filling mechanism that outweighs the cost of inefficient wiring. DOI: http://dx.doi.org/10.7554/eLife.22352.001 PMID:28177286

  11. Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss.

    PubMed

    Bonafede, Lucas; Ficicioglu, Can H; Serrano, Leona; Han, Grace; Morgan, Jessica I W; Mills, Monte D; Forbes, Brian J; Davidson, Stefanie L; Binenbaum, Gil; Kaplan, Paige B; Nichols, Charles W; Verloo, Patrick; Leroy, Bart P; Maguire, Albert M; Aleman, Tomas S

    2015-12-01

    To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC.

  12. RdgB2 is required for dim-light input into intrinsically photosensitive retinal ganglion cells.

    PubMed

    Walker, Marquis T; Rupp, Alan; Elsaesser, Rebecca; Güler, Ali D; Sheng, Wenlong; Weng, Shijun; Berson, David M; Hattar, Samer; Montell, Craig

    2015-10-15

    A subset of retinal ganglion cells is intrinsically photosensitive (ipRGCs) and contributes directly to the pupillary light reflex and circadian photoentrainment under bright-light conditions. ipRGCs are also indirectly activated by light through cellular circuits initiated in rods and cones. A mammalian homologue (RdgB2) of a phosphoinositide transfer/exchange protein that functions in Drosophila phototransduction is expressed in the retinal ganglion cell layer. This raised the possibility that RdgB2 might function in the intrinsic light response in ipRGCs, which depends on a cascade reminiscent of Drosophila phototransduction. Here we found that under high light intensities, RdgB2(-/-) mutant mice showed normal pupillary light responses and circadian photoentrainment. Consistent with this behavioral phenotype, the intrinsic light responses of ipRGCs in RdgB2(-/-) were indistinguishable from wild-type. In contrast, under low-light conditions, RdgB2(-/-) mutants displayed defects in both circadian photoentrainment and the pupillary light response. The RdgB2 protein was not expressed in ipRGCs but was in GABAergic amacrine cells, which provided inhibitory feedback onto bipolar cells. We propose that RdgB2 is required in a cellular circuit that transduces light input from rods to bipolar cells that are coupled to GABAergic amacrine cells and ultimately to ipRGCs, thereby enabling ipRGCs to respond to dim light. © 2015 Walker et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  13. Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss

    PubMed Central

    Bonafede, Lucas; Ficicioglu, Can H.; Serrano, Leona; Han, Grace; Morgan, Jessica I. W.; Mills, Monte D.; Forbes, Brian J.; Davidson, Stefanie L.; Binenbaum, Gil; Kaplan, Paige B.; Nichols, Charles W.; Verloo, Patrick; Leroy, Bart P.; Maguire, Albert M.; Aleman, Tomas S.

    2015-01-01

    Purpose To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Methods Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Results Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Conclusions Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC. PMID:26658511

  14. Hmx1 is required for the normal development of somatosensory neurons in the geniculate ganglion

    PubMed Central

    Quina, Lely A.; Tempest, Lynne; Hsu, Yun-Wei A.; Cox, Timothy C.; Turner, Eric E.

    2012-01-01

    Hmx1 is a variant homeodomain transcription factor expressed in the developing sensory nervous system, retina, and craniofacial mesenchyme. Recently, mutations at the Hmx1 locus have been linked to craniofacial defects in humans, rats, and mice, but its role in nervous system development is largely unknown. Here we show that Hmx1 is expressed in a subset of sensory neurons in the cranial and dorsal root ganglia which does not correspond to any specific sensory modality. Sensory neurons in the dorsal root and trigeminal ganglia of Hmx1dm/dm mouse embryos have no detectable Hmx1 protein, yet they undergo neurogenesis and express sensory subtype markers normally, demonstrating that Hmx1 is not globally required for the specification of sensory neurons from neural crest precursors. Loss of Hmx1 expression has no obvious effect on the early development of the trigeminal (V), superior (IX/X), or dorsal root ganglia neurons in which it is expressed, but results in marked defects in the geniculate (VII) ganglion. Hmx1dm/dm mouse embryos possess only a vestigial posterior auricular nerve, and general somatosensory neurons in the geniculate ganglion are greatly reduced by mid-gestation. Although Hmx1 is expressed in geniculate neurons prior to cell cycle exit, it does not appear to be required for neurogenesis, and the loss of geniculate neurons is likely to be the result of increased cell death. Fate mapping of neural crest-derived tissues indicates that Hmx1-expressing somatosensory neurons at different axial levels may be derived from either the neural crest or the neurogenic placodes. PMID:22586713

  15. Cytoarchitectonic study of the trigeminal ganglion in humans.

    PubMed

    Krastev, Dimo Stoyanov; Apostolov, Alexander

    2013-01-01

    The trigeminal ganglion (TG), a cluster of pseudounipolar neurons, is located in the trigeminal impression of the temporal pyramid. It is covered by a sheath of the dura mater and arachnoid and is near the rear end of the cavernous sinus. The peripheral processes of the pseudounipolar cells are involved in the formation of the first and second branch and the sensory part of the third branch of the fifth cranial nerve, and the central ones form the sensory root of the nerve, which penetrates at the level of the middle cerebellar peduncle, aside from the pons, and terminate in the sensory nuclei of the trigeminal complex. We found that the primary sensory neurons involved in sensory innervation of the orofacial complex are a diverse group. Although they possess the general structure of pseudounipolar neurons, there are significant differences among them, seen in varying intensities of staining. Based on our investigations we classified the neurons into 7 groups, i.e. large, subdivided into light and dark, medium, also light and dark, and small light and dark, and, moreover, neurons with an irregular shape of their perikarya. Further research by applying various immunohistochemical methods will clarify whether differences in the morphological patterns of the neurons are associated with differences in the neurochemical composition of various neuronal types.

  16. Cytoarchitectonic study of the trigeminal ganglion in humans

    PubMed Central

    KRASTEV, DIMO STOYANOV; APOSTOLOV, ALEXANDER

    2013-01-01

    The trigeminal ganglion (TG), a cluster of pseudounipolar neurons, is located in the trigeminal impression of the temporal pyramid. It is covered by a sheath of the dura mater and arachnoid and is near the rear end of the cavernous sinus. The peripheral processes of the pseudounipolar cells are involved in the formation of the first and second branch and the sensory part of the third branch of the fifth cranial nerve, and the central ones form the sensory root of the nerve, which penetrates at the level of the middle cerebellar peduncle, aside from the pons, and terminate in the sensory nuclei of the trigeminal complex. We found that the primary sensory neurons involved in sensory innervation of the orofacial complex are a diverse group. Although they possess the general structure of pseudounipolar neurons, there are significant differences among them, seen in varying intensities of staining. Based on our investigations we classified the neurons into 7 groups, i.e. large, subdivided into light and dark, medium, also light and dark, and small light and dark, and, moreover, neurons with an irregular shape of their perikarya. Further research by applying various immunohistochemical methods will clarify whether differences in the morphological patterns of the neurons are associated with differences in the neurochemical composition of various neuronal types. PMID:26527926

  17. Upper stimulation threshold for retinal ganglion cell activation.

    PubMed

    Meng, Kevin; Fellner, Andreas; Rattay, Frank; Ghezzi, Diego; Meffin, Hamish; Ibbotson, Michael R; Kameneva, Tatiana

    2018-08-01

    The existence of an upper threshold in electrically stimulated retinal ganglion cells (RGCs) is of interest because of its relevance to the development of visual prosthetic devices, which are designed to restore partial sight to blind patients. The upper threshold is defined as the stimulation level above which no action potentials (direct spikes) can be elicited in electrically stimulated retina. We collected and analyzed in vitro recordings from rat RGCs in response to extracellular biphasic (anodic-cathodic) pulse stimulation of varying amplitudes and pulse durations. Such responses were also simulated using a multicompartment model. We identified the individual cell variability in response to stimulation and the phenomenon known as upper threshold in all but one of the recorded cells (n  =  20/21). We found that the latencies of spike responses relative to stimulus amplitude had a characteristic U-shape. In silico, we showed that the upper threshold phenomenon was observed only in the soma. For all tested biphasic pulse durations, electrode positions, and pulse amplitudes above lower threshold, a propagating action potential was observed in the distal axon. For amplitudes above the somatic upper threshold, the axonal action potential back-propagated in the direction of the soma, but the soma's low level of hyperpolarization prevented action potential generation in the soma itself. An upper threshold observed in the soma does not prevent spike conductance in the axon.

  18. Protection of Retinal Ganglion Cells by Caspase Substrate-Binding Peptide IQACRG from N-Methyl-d-Aspartate Receptor-Mediated Excitotoxicity

    PubMed Central

    Seki, Masaaki; Soussou, Walid; Manabe, Shin-ichi

    2010-01-01

    Purpose. This study investigated whether the enzymatically inactive caspase mimetic IQACRG protects rat retinal ganglion cells (RGCs) from excitotoxic insults. Minimally invasive delivery of the peptide to the retina was explored, and the mechanisms of neuroprotection were elucidated. Methods. IQACRG was linked to penetratin (P-IQACRG) to facilitate cellular uptake. RGC labeling by biotinylated-P-IQACRG delivered via intravitreal or subconjunctival injection was demonstrated by avidin-biotin chemistry. The authors used histologic and electrophysiological measures to evaluate the neuroprotective potential of P-IQACRG against RGC death induced by N-methyl-d-aspartate (NMDA) in vitro and in vivo. In addition, they monitored activity of an enzyme that is downstream of caspase-1, matrix metalloproteinase-9 (MMP-9), and protein levels of the caspase-3/7 substrate, myocyte enhancer factor 2C (MEF2C), to determine the effectiveness of IQACRG in blocking excessive caspase activity. Results. IQACRG significantly reduced NMDA-induced RGC death in culture and in vivo. Ex vivo electrophysiological recording of the retina on multielectrode arrays demonstrated functional rescue of RGCs by IQACRG. The authors also found that delivery of IQACRG to the retina inhibited NMDA-triggered MMP-9 activity and prevented cleavage of MEF2C protein that would otherwise have been engendered by caspase activation preceding RGC death. Strikingly, subconjunctival injection of P-IQACRG was very effective in preventing NMDA-induced RGC death in vivo. Conclusions. These data demonstrate that IQACRG protects RGCs from excitotoxicity in vitro and in vivo. The positive results with subconjunctival administration of P-IQACRG suggest that in the future this treatment may be useful clinically in diseases such as glaucoma and retinal ischemia. PMID:19815732

  19. BAX to basics: How the BCL2 gene family controls the death of retinal ganglion cells

    PubMed Central

    Maes, Margaret E.; Schlamp, Cassandra L.; Nickells, Robert W.

    2017-01-01

    Retinal ganglion cell (RGC) death is the principal consequence of injury to the optic nerve. For several decades, we have understood that the RGC death process was executed by apoptosis, suggesting that there may be ways to therapeutically intervene in this cell death program and provide a more direct treatment to the cells and tissues affected in diseases like glaucoma. A major part of this endeavor has been to elucidate the molecular biological pathways active in RGCs from the point of axonal injury to the point of irreversible cell death. A major component of this process is the complex interaction of members of the BCL2 gene family. Three distinct family members of proteins orchestrate the most critical junction in the apoptotic program of RGCs, culminating in the activation of pro-apoptotic BAX. Once active, BAX causes irreparable damage to mitochondria, while precipitating downstream events that finish off a dying ganglion cell. This review is divided into two major parts. First, we summarize the extent of knowledge of how BCL2 gene family proteins interact to facilitate the activation and function of BAX. This area of investigation has rapidly changed over the last few years and has yielded a dramatically different mechanistic understanding of how the intrinsic apoptotic program is run in mammalian cells. Second, we provided a comprehensive analysis of nearly two decades of investigation of the role of BAX in the process of RGC death, much of which has provided many important insights into the overall pathophysiology of diseases like glaucoma. PMID:28064040

  20. BAX to basics: How the BCL2 gene family controls the death of retinal ganglion cells.

    PubMed

    Maes, Margaret E; Schlamp, Cassandra L; Nickells, Robert W

    2017-03-01

    Retinal ganglion cell (RGC) death is the principal consequence of injury to the optic nerve. For several decades, we have understood that the RGC death process was executed by apoptosis, suggesting that there may be ways to therapeutically intervene in this cell death program and provide a more direct treatment to the cells and tissues affected in diseases like glaucoma. A major part of this endeavor has been to elucidate the molecular biological pathways active in RGCs from the point of axonal injury to the point of irreversible cell death. A major component of this process is the complex interaction of members of the BCL2 gene family. Three distinct family members of proteins orchestrate the most critical junction in the apoptotic program of RGCs, culminating in the activation of pro-apoptotic BAX. Once active, BAX causes irreparable damage to mitochondria, while precipitating downstream events that finish off a dying ganglion cell. This review is divided into two major parts. First, we summarize the extent of knowledge of how BCL2 gene family proteins interact to facilitate the activation and function of BAX. This area of investigation has rapidly changed over the last few years and has yielded a dramatically different mechanistic understanding of how the intrinsic apoptotic program is run in mammalian cells. Second, we provided a comprehensive analysis of nearly two decades of investigation of the role of BAX in the process of RGC death, much of which has provided many important insights into the overall pathophysiology of diseases like glaucoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Hypoxia Induces a Metabolic Shift and Enhances the Stemness and Expansion of Cochlear Spiral Ganglion Stem/Progenitor Cells

    PubMed Central

    Chao, Ting-Ting; Sytwu, Huey-Kang; Li, Shiue-Li; Fang, Mei-Cho; Chen, Hang-Kang; Lin, Yi-Chun; Kuo, Chao-Yin

    2015-01-01

    Previously, we demonstrated that hypoxia (1% O2) enhances stemness markers and expands the cell numbers of cochlear stem/progenitor cells (SPCs). In this study, we further investigated the long-term effect of hypoxia on stemness and the bioenergetic status of cochlear spiral ganglion SPCs cultured at low oxygen tensions. Spiral ganglion SPCs were obtained from postnatal day 1 CBA/CaJ mouse pups. The measurement of oxygen consumption rate, extracellular acidification rate (ECAR), and intracellular adenosine triphosphate levels corresponding to 20% and 5% oxygen concentrations was determined using a Seahorse XF extracellular flux analyzer. After low oxygen tension cultivation for 21 days, the mean size of the hypoxia-expanded neurospheres was significantly increased at 5% O2; this correlated with high-level expression of hypoxia-inducible factor-1 alpha (Hif-1α), proliferating cell nuclear antigen (PCNA), cyclin D1, Abcg2, nestin, and Nanog proteins but downregulated expression of p27 compared to that in a normoxic condition. Low oxygen tension cultivation tended to increase the side population fraction, with a significant difference found at 5% O2 compared to that at 20% O2. In addition, hypoxia induced a metabolic energy shift of SPCs toward higher basal ECARs and higher maximum mitochondrial respiratory capacity but lower proton leak than under normoxia, where the SPC metabolism was switched toward glycolysis in long-term hypoxic cultivation. PMID:26236724

  2. Sex-, stress-, and sympathetic post-ganglionic-dependent changes in identity and proportions of immune cells in the dura.

    PubMed

    McIlvried, Lisa A; Cruz, J Agustin; Borghesi, Lisa A; Gold, Michael S

    2017-01-01

    Aim of investigation Due to compelling evidence in support of links between sex, stress, sympathetic post-ganglionic innervation, dural immune cells, and migraine, our aim was to characterize the impacts of these factors on the type and proportion of immune cells in the dura. Methods Dural immune cells were obtained from naïve or stressed adult male and female Sprague Dawley rats for flow cytometry. Rats with surgical denervation of sympathetic post-ganglionic neurons of the dura were also studied. Results Immune cells comprise ∼17% of all cells in the dura. These included: macrophages/granulocytes ("Macs"; 63.2% of immune cells), dendritic cells (0.88%), T-cells (4.51%), natural killer T-cells (0.51%), natural killer cells (3.08%), and B-cells (20.0%). There were significantly more Macs and fewer B- and natural killer T-cells in the dura of females compared with males. Macs and dendritic cells were significantly increased by stress in males, but not females. In contrast, T-cells were significantly increased in females with a 24-hour delay following stress. Lastly, Macs, dendritic cells, and T-cells were significantly higher in sympathectomized-naïve males, but not females. Conclusions It may not only be possible, but necessary to use different strategies for the most effective treatment of migraine in men and women.

  3. Molecular origin of photovoltaic performance in donor- block-acceptor all-conjugated block copolymers

    DOE PAGES

    Smith, Kendall A.; Lin, Yen -Hao; Mok, Jorge W.; ...

    2015-11-03

    All-conjugated block copolymers may be an effective route to self-assembled photovoltaic devices, but we lack basic information on the relationship between molecular characteristics and photovoltaic performance. Here, we synthesize a library of poly(3-hexylthiophene) (P3HT) block poly((9,9-dialkylfluorene)-2,7-diyl-alt-[4,7-bis(alkylthiophen-5-yl)-2,1,3-benzothiadiazole]-2',2''-diyl) (PFTBT) donor- block-acceptor all-conjugated block copolymers and carry out a comprehensive study of processing conditions, crystallinity, domain sizes, and side-chain structure on photovoltaic device performance. We find that all block copolymers studied exhibit an out-of-plane crystal orientation after deposition, and on thermal annealing at high temperatures the crystal orientation flips to an in-plane orientation. By varying processing conditions on polymer photovoltaic devices, we showmore » that the crystal orientation has only a modest effect (15-20%) on photovoltaic performance. The addition of side-chains to the PFTBT block is found to decrease photovoltaic power conversion efficiencies by at least an order of magnitude. Through grazing-incidence X-ray measurements we find that the addition of side-chains to the PFTBT acceptor block results in weak segregation and small (< 10 nm) block copolymer self-assembled donor and acceptor domains. This work is the most comprehensive to date on all-conjugated block copolymer systems and suggests that photovoltaic performance of block copolymers depends strongly on the miscibility of donor and acceptor blocks, which impacts donor and acceptor domain sizes and purity. Lastly, strategies for improving the device performance of block copolymer photovoltaics should seek to increase segregation between donor and acceptor polymer domains.« less

  4. Molecular origin of photovoltaic performance in donor- block-acceptor all-conjugated block copolymers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Smith, Kendall A.; Lin, Yen -Hao; Mok, Jorge W.

    All-conjugated block copolymers may be an effective route to self-assembled photovoltaic devices, but we lack basic information on the relationship between molecular characteristics and photovoltaic performance. Here, we synthesize a library of poly(3-hexylthiophene) (P3HT) block poly((9,9-dialkylfluorene)-2,7-diyl-alt-[4,7-bis(alkylthiophen-5-yl)-2,1,3-benzothiadiazole]-2',2''-diyl) (PFTBT) donor- block-acceptor all-conjugated block copolymers and carry out a comprehensive study of processing conditions, crystallinity, domain sizes, and side-chain structure on photovoltaic device performance. We find that all block copolymers studied exhibit an out-of-plane crystal orientation after deposition, and on thermal annealing at high temperatures the crystal orientation flips to an in-plane orientation. By varying processing conditions on polymer photovoltaic devices, we showmore » that the crystal orientation has only a modest effect (15-20%) on photovoltaic performance. The addition of side-chains to the PFTBT block is found to decrease photovoltaic power conversion efficiencies by at least an order of magnitude. Through grazing-incidence X-ray measurements we find that the addition of side-chains to the PFTBT acceptor block results in weak segregation and small (< 10 nm) block copolymer self-assembled donor and acceptor domains. This work is the most comprehensive to date on all-conjugated block copolymer systems and suggests that photovoltaic performance of block copolymers depends strongly on the miscibility of donor and acceptor blocks, which impacts donor and acceptor domain sizes and purity. Lastly, strategies for improving the device performance of block copolymer photovoltaics should seek to increase segregation between donor and acceptor polymer domains.« less

  5. A double-blind, placebo-controlled study of repetitive transnasal sphenopalatine ganglion blockade with tx360(®) as acute treatment for chronic migraine.

    PubMed

    Cady, Roger; Saper, Joel; Dexter, Kent; Manley, Heather R

    2015-01-01

    To determine if repetitive sphenopalatine ganglion (SPG) blocks with 0.5% bupivacaine delivered through the Tx360(®) are superior in reducing pain associated with chronic migraine (CM) compared with saline. The SPG is a small concentrated structure of neuronal tissue that resides within the pterygopalatine fossa (PPF) in close proximity to the sphenopalatine foramen and is innervated by the maxillary division of the trigeminal nerve. From an anatomical and physiological perspective, SPG blockade may be an effective acute and preventative treatment for CM. This was a double-blind, parallel-arm, placebo-controlled, randomized pilot study using a novel intervention for acute treatment in CM. Up to 41 subjects could be enrolled at 2 headache specialty clinics in the US. Eligible subjects were between 18 and 80 years of age and had a history of CM defined by the second edition of the International Classification of Headache Disorders appendix definition. They were allowed a stable dose of migraine preventive medications that was maintained throughout the study. Following a 28-day baseline period, subjects were randomized by computer-generated lists of 2:1 to receive 0.5% bupivacaine or saline, respectively. The primary end-point was to compare numeric rating scale scores at pretreatment baseline vs 15 minutes, 30 minutes, and 24 hours postprocedure for all 12 treatments. SPG blockade was accomplished with the Tx360(®) , which allows a small flexible soft plastic tube that is advanced below the middle turbinate just past the pterygopalatine fossa into the intranasal space. A 0.3 cc of anesthetic or saline was injected into the mucosa covering the SPG. The procedure is performed similarly in each nostril. The active phase of the study consisted of a series of 12 SPG blocks with 0.3 cc of 0.5% bupivacaine or saline provided 2 times per week for 6 weeks. Subjects were re-evaluated at 1 and 6 months postfinal procedure. The final dataset included 38 subjects, 26 in the

  6. A Double-Blind, Placebo-Controlled Study of Repetitive Transnasal Sphenopalatine Ganglion Blockade With Tx360® as Acute Treatment for Chronic Migraine

    PubMed Central

    Cady, Roger; Saper, Joel; Dexter, Kent; Manley, Heather R

    2015-01-01

    Objective To determine if repetitive sphenopalatine ganglion (SPG) blocks with 0.5% bupivacaine delivered through the Tx360® are superior in reducing pain associated with chronic migraine (CM) compared with saline. Background The SPG is a small concentrated structure of neuronal tissue that resides within the pterygopalatine fossa (PPF) in close proximity to the sphenopalatine foramen and is innervated by the maxillary division of the trigeminal nerve. From an anatomical and physiological perspective, SPG blockade may be an effective acute and preventative treatment for CM. Method This was a double-blind, parallel-arm, placebo-controlled, randomized pilot study using a novel intervention for acute treatment in CM. Up to 41 subjects could be enrolled at 2 headache specialty clinics in the US. Eligible subjects were between 18 and 80 years of age and had a history of CM defined by the second edition of the International Classification of Headache Disorders appendix definition. They were allowed a stable dose of migraine preventive medications that was maintained throughout the study. Following a 28-day baseline period, subjects were randomized by computer-generated lists of 2:1 to receive 0.5% bupivacaine or saline, respectively. The primary end-point was to compare numeric rating scale scores at pretreatment baseline vs 15 minutes, 30 minutes, and 24 hours postprocedure for all 12 treatments. SPG blockade was accomplished with the Tx360®, which allows a small flexible soft plastic tube that is advanced below the middle turbinate just past the pterygopalatine fossa into the intranasal space. A 0.3 cc of anesthetic or saline was injected into the mucosa covering the SPG. The procedure is performed similarly in each nostril. The active phase of the study consisted of a series of 12 SPG blocks with 0.3 cc of 0.5% bupivacaine or saline provided 2 times per week for 6 weeks. Subjects were re-evaluated at 1 and 6 months postfinal procedure. Results The final dataset

  7. Program structure-based blocking

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bertolli, Carlo; Eichenberger, Alexandre E.; O'Brien, John K.

    2017-09-26

    Embodiments relate to program structure-based blocking. An aspect includes receiving source code corresponding to a computer program by a compiler of a computer system. Another aspect includes determining a prefetching section in the source code by a marking module of the compiler. Yet another aspect includes performing, by a blocking module of the compiler, blocking of instructions located in the prefetching section into instruction blocks, such that the instruction blocks of the prefetching section only contain instructions that are located in the prefetching section.

  8. Effects of Antipsychotic Drugs Haloperidol and Clozapine on Visual Responses of Retinal Ganglion Cells in a Rat Model of Retinitis Pigmentosa.

    PubMed

    Jensen, Ralph J

    2016-12-01

    In the P23H rat model of retinitis pigmentosa, the dopamine D2 receptor antagonists sulpiride and eticlopride appear to improve visual responses of retinal ganglion cells (RGCs) by increasing light sensitivity of RGCs and transforming abnormal, long-latency ON-center RGCs into OFF-center cells. Antipsychotic drugs are believed to mediate their therapeutic benefits by blocking D2 receptors. This investigation was conducted to test whether haloperidol (a typical antipsychotic drug) and clozapine (an atypical antipsychotic drug) could similarly alter the light responses of RGCs in the P23H rat retina. Extracellular recordings were made from RGCs in isolated P23H rat retinas. Responses of RGCs to flashes of light were evaluated before and during bath application of a drug. Both haloperidol and clozapine increased light sensitivity of RGCs on average by ∼0.3 log unit. For those ON-center RGCs that exhibit an abnormally long-latency response to the onset of a small spot of light, both haloperidol and clozapine brought out a short-latency OFF response and markedly reduced the long-latency ON response. The selective serotonin 5-HT2A antagonist MDL 100907 had similar effects on RGCs. The effects of haloperidol on light responses of RGCs can be explained by its D2 receptor antagonism. The effects of clozapine on light responses of RGCs on the other hand may largely be due to its 5-HT2A receptor antagonism. Overall, the results suggest that antipsychotic drugs may be useful in improving vision in patients with retinitis pigmentosa.

  9. Gaussian curvature analysis allows for automatic block placement in multi-block hexahedral meshing.

    PubMed

    Ramme, Austin J; Shivanna, Kiran H; Magnotta, Vincent A; Grosland, Nicole M

    2011-10-01

    Musculoskeletal finite element analysis (FEA) has been essential to research in orthopaedic biomechanics. The generation of a volumetric mesh is often the most challenging step in a FEA. Hexahedral meshing tools that are based on a multi-block approach rely on the manual placement of building blocks for their mesh generation scheme. We hypothesise that Gaussian curvature analysis could be used to automatically develop a building block structure for multi-block hexahedral mesh generation. The Automated Building Block Algorithm incorporates principles from differential geometry, combinatorics, statistical analysis and computer science to automatically generate a building block structure to represent a given surface without prior information. We have applied this algorithm to 29 bones of varying geometries and successfully generated a usable mesh in all cases. This work represents a significant advancement in automating the definition of building blocks.

  10. Second-degree atrioventricular block.

    PubMed

    Zipes, D P

    1979-09-01

    1) While it is possible only one type of second-degree AV block exists electrophysiologically, the available data do not justify such a conclusion and it would seem more appropriate to remain a "splitter," and advocate separation and definition of multiple mechanisms, than to be a "lumper," and embrace a unitary concept. 2) The clinical classification of type I and type II AV block, based on present scalar electrocardiographic criteria, for the most part accurately differentiates clinically important categories of patients. Such a classification is descriptive, but serves a useful function and should be preserved, taking into account the caveats mentioned above. The site of block generally determines the clinical course for the patient. For most examples of AV block, the type I and type II classification in present use is based on the site of block. Because block in the His-Purkinje system is preceded by small or nonmeasurable increments, it is called type II AV block; but the very fact that it is preceded by small increments is because it occurs in the His-Purkinje system. Similar logic can be applied to type I AV block in the AV node. Exceptions do occur. If the site of AV block cannot be distinguished with certainity from the scalar ECG, an electrophysiologic study will generally reveal the answer.

  11. Ionic Blocks

    ERIC Educational Resources Information Center

    Sevcik, Richard S.; Gamble, Rex; Martinez, Elizabet; Schultz, Linda D.; Alexander, Susan V.

    2008-01-01

    "Ionic Blocks" is a teaching tool designed to help middle school students visualize the concepts of ions, ionic compounds, and stoichiometry. It can also assist high school students in reviewing their subject mastery. Three dimensional blocks are used to represent cations and anions, with color indicating charge (positive or negative) and size…

  12. Are monoaminergic systems involved in the lethargy induced by a parasitoid wasp in the cockroach prey?

    PubMed

    Weisel-Eichler, A; Libersat, F

    2002-05-01

    The venom of the parasitoid wasp Ampulex compressa induces long-lasting hypokinesia in the cockroach prey. Previous work indicates that the venom acts in the subesophageal ganglion to indirectly affect modulation of thoracic circuits for locomotion. However, the target of the venom in the subesophageal ganglion, and the mechanism by which the venom achieves its effects are as yet unknown. While the stung cockroaches appear generally lethargic, not all behaviors were affected, indicating that the venom targets specific motor systems and not behavior in general. Stung cockroaches were observed "freezing" in abnormal positions. Reserpine, which depletes monoamines, mimics the behavioral effects of the venom. We treated cockroaches with antagonists to dopamine and octopamine receptors, and found that the dopamine system is required for normal escape response. Dopamine injection induces prolonged grooming in normal cockroaches, but not in stung, suggesting that the venom is affecting dopamine receptors, or targets downstream of these receptors, in the subesophageal ganglion. This dopamine blocking effect fades slowly over the course of several weeks, similar to the time course of recovery from hypokinesia. The similarity in the time courses suggests that the mechanism underlying the hypokinesia may be the block of the dopamine receptors.

  13. Main-chain supramolecular block copolymers.

    PubMed

    Yang, Si Kyung; Ambade, Ashootosh V; Weck, Marcus

    2011-01-01

    Block copolymers are key building blocks for a variety of applications ranging from electronic devices to drug delivery. The material properties of block copolymers can be tuned and potentially improved by introducing noncovalent interactions in place of covalent linkages between polymeric blocks resulting in the formation of supramolecular block copolymers. Such materials combine the microphase separation behavior inherent to block copolymers with the responsiveness of supramolecular materials thereby affording dynamic and reversible materials. This tutorial review covers recent advances in main-chain supramolecular block copolymers and describes the design principles, synthetic approaches, advantages, and potential applications.

  14. Fermion-scalar conformal blocks

    DOE PAGES

    Iliesiu, Luca; Kos, Filip; Poland, David; ...

    2016-04-13

    In this study, we compute the conformal blocks associated with scalar-scalar-fermionfermion 4-point functions in 3D CFTs. Together with the known scalar conformal blocks, our result completes the task of determining the so-called ‘seed blocks’ in three dimensions. In addition, conformal blocks associated with 4-point functions of operators with arbitrary spins can now be determined from these seed blocks by using known differential operators.

  15. Prox1 Regulates the Subtype-Specific Development of Caudal Ganglionic Eminence-Derived GABAergic Cortical Interneurons

    PubMed Central

    Young, Allison; Petros, Timothy; Karayannis, Theofanis; McKenzie Chang, Melissa; Lavado, Alfonso; Iwano, Tomohiko; Nakajima, Miho; Taniguchi, Hiroki; Huang, Z. Josh; Heintz, Nathaniel; Oliver, Guillermo; Matsuzaki, Fumio; Machold, Robert P.

    2015-01-01

    Neurogliaform (RELN+) and bipolar (VIP+) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been elucidated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP). Interestingly, Prox1 promotes the maturation of CGE-derived interneuron subtypes through intrinsic differentiation programs that operate in tandem with extrinsically driven neuronal activity-dependent pathways. Thus Prox1 represents the first identified transcription factor specifically required for the embryonic and postnatal acquisition of CGE-derived cortical interneuron properties. SIGNIFICANCE STATEMENT Despite the recognition that 30% of GABAergic cortical interneurons originate from the caudal ganglionic eminence (CGE), to date, a specific transcriptional program that selectively regulates the development of these populations has not yet been identified. Moreover, while CGE-derived interneurons display unique patterns of tangential and radial migration and preferentially populate the superficial layers of the cortex, identification of a molecular program that controls these events is lacking. Here, we demonstrate that the homeodomain transcription factor Prox1 is expressed in postmitotic CGE-derived cortical interneuron precursors and is maintained into adulthood. We found that Prox1 function is differentially required during both embryonic and postnatal stages of development to

  16. Muscarinic acetylcholine receptor subtype expression in avian vestibular hair cells, nerve terminals and ganglion cells.

    PubMed

    Li, G Q; Kevetter, G A; Leonard, R B; Prusak, D J; Wood, T G; Correia, M J

    2007-04-25

    Muscarinic acetylcholine receptors (mAChRs) are widely expressed in the CNS and peripheral nervous system and play an important role in modulating the cell activity and function. We have shown that the cholinergic agonist carbachol reduces the pigeon's inwardly rectifying potassium channel (pKir2.1) ionic currents in native vestibular hair cells. We have cloned and sequenced pigeon mAChR subtypes M2-M5 and we have studied the expression of all five mAChR subtypes (M1-M5) in the pigeon vestibular end organs (semicircular canal ampullary cristae and utricular maculae), vestibular nerve fibers and the vestibular (Scarpa's) ganglion using tissue immunohistochemistry (IH), dissociated single cell immunocytochemistry (IC) and Western blotting (WB). We found that vestibular hair cells, nerve fibers and ganglion cells each expressed all five (M1-M5) mAChR subtypes. Two of the three odd-numbered mAChRs (M1, M5) were present on the hair cell cilia, supporting cells and nerve terminals. And all three odd numbered mAChRs (M1, M3 and M5) were expressed on cuticular plates, myelin sheaths and Schwann cells. Even-numbered mAChRs were seen on the nerve terminals. M2 was also shown on the cuticular plates and supporting cells. Vestibular efferent fibers and terminals were not identified in our studies. Results from WB of the dissociated vestibular epithelia, nerve fibers and vestibular ganglia were consistent with the results from IH and IC. Our findings suggest that there is considerable co-expression of the subtypes on the neural elements of the labyrinth. Further electrophysiological and pharmacological studies should delineate the mechanisms of action of muscarinic acetylcholine receptors on structures in the labyrinth.

  17. Glial cell line-derived neurotrophic factor (GDNF) induces neuritogenesis in the cochlear spiral ganglion via neural cell adhesion molecule (NCAM)

    PubMed Central

    Euteneuer, Sara; Yang, Kuo H.; Chavez, Eduardo; Leichtle, Anke; Loers, Gabriele; Olshansky, Adel; Pak, Kwang; Schachner, Melitta; Ryan, Allen F.

    2013-01-01

    Glial cell line-derived neurotrophic factor (GDNF) increases survival and neurite extension of spiral ganglion neurons (SGNs), the primary neurons of the auditory system, via yet unknown signaling mechanisms. In other cell types, signaling is achieved by the GPI-linked GDNF family receptor α1 (GFRα1) via recruitment of transmembrane receptors: Ret (re-arranged during transformation) and/or NCAM (neural cell adhesion molecule). Here we show that GDNF enhances neuritogenesis in organotypic cultures of spiral ganglia from 5-day-old rats and mice. Addition of GFRα1-Fc increases this effect. GDNF/GFRα1-Fc stimulation activates intracellular PI3K/Akt and MEK/Erk signaling cascades as detected by Western blot analysis of cultures prepared from rats at postnatal days 5 (P5, before the onset of hearing) and 20 (P20, after the onset of hearing). Both cascades mediate GDNF stimulation of neuritogenesis, since application of the Akt inhibitor Wortmannin or the Erk inhibitor U0126 abolished GDNF/GFRα1-Fc stimulated neuritogenesis in P5 rats. Since cultures of P5 NCAM-deficient mice failed to respond by neuritogenesis to GDNF/GFRα1-Fc, we conclude that NCAM serves as a receptor for GDNF signaling responsible for neuritogenesis in early postnatal spiral ganglion. PMID:23262364

  18. [Effect of bee venom injection on TrkA and TRPV1 expression in the dorsal root ganglion of rats with collagen-induced arthritis].

    PubMed

    Xian, Pei-Feng; Chen, Ying; Yang, Lu; Liu, Guo-Tao; Peng, Peng; Wang, Sheng-Xu

    2016-06-01

    To investigate the therapeutic effect of acupoint injection of bee venom on collagen-induced arthritis (CIA) in rats and explore the mechanism of bee venom therapy in the treatment of rheumatoid arthritis. Fifteen male Wistar rats were randomly divided into bee venom treatment group (BV group), CIA model group, and control group. In the former two groups, CIA was induced by injections of collagen II+IFA (0.2 mL) via the tail vein, and in the control group, normal saline was injected instead. The rats in BV group received daily injection of 0.1 mL (3 mg/mL) bee venom for 7 consecutive days. All the rats were assessed for paw thickness and arthritis index from days 14 to 21, and the pain threshold was determined on day 21. The expressions of TRPV1 and TrkA in the dorsal root ganglion at the level of L4-6 were detected using immunohistochemistry and Western blotting, respectively. The rats in CIA model group started to show paw swelling on day 10, and by day 14, all the rats in this group showed typical signs of CIA. In BV group, the rats receiving been venom therapy for 7 days showed a significantly smaller paw thickness and a low arthritis index than those in the model group. The pain threshold was the highest in the control group and the lowest in the model group. TRPV1-positive cells and TrkA expression in the dorsal root ganglion was significantly reduced in BV group as compared with that in the model group. s Injection of bee venom can decrease expression of TRPV1 and TrkA in the dorsal root ganglion to produce anti-inflammatory and analgesic effects, suggesting the potential value of bee venom in the treatment of rheumatoid arthritis.

  19. Stimulation of ganglionated plexus attenuates cardiac neural remodeling and heart failure progression in a canine model of acute heart failure post-myocardial infarction.

    PubMed

    Luo, Da; Hu, Huihui; Qin, Zhiliang; Liu, Shan; Yu, Xiaomei; Ma, Ruisong; He, Wenbo; Xie, Jing; Lu, Zhibing; He, Bo; Jiang, Hong

    2017-12-01

    Heart failure (HF) is associated with autonomic dysfunction. Vagus nerve stimulation has been shown to improve cardiac function both in HF patients and animal models of HF. The purpose of this present study is to investigate the effects of ganglionated plexus stimulation (GPS) on HF progression and autonomic remodeling in a canine model of acute HF post-myocardial infarction. Eighteen adult mongrel male dogs were randomized into the control (n=8) and GPS (n=10) groups. All dogs underwent left anterior descending artery ligation followed by 6-hour high-rate (180-220bpm) ventricular pacing to induce acute HF. Transthoracic 2-dimensional echocardiography was performed at different time points. The plasma levels of norepinephrine, B-type natriuretic peptide (BNP) and Ang-II were measured using ELISA kits. C-fos and nerve growth factor (NGF) proteins expressed in the left stellate ganglion as well as GAP43 and TH proteins expressed in the peri-infarct zone were measured using western blot. After 6h of GPS, the left ventricular end-diastolic volume, end-systolic volume and ejection fraction showed no significant differences between the 2 groups, but the interventricular septal thickness at end-systole in the GPS group was significantly higher than that in the control group. The plasma levels of norepinephrine, BNP, Ang-II were increased 1h after myocardial infarction while the increase was attenuated by GPS. The expression of c-fos and NGF proteins in the left stellate ganglion as well as GAP43 and TH proteins in cardiac peri-infarct zone in GPS group were significantly lower than that in control group. GPS inhibits cardiac sympathetic remodeling and attenuates HF progression in canines with acute HF induced by myocardial infarction and ventricular pacing. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Diagnostic ability of macular ganglion cell inner plexiform layer measurements in glaucoma using swept source and spectral domain optical coherence tomography.

    PubMed

    Yang, Zhiyong; Tatham, Andrew J; Weinreb, Robert N; Medeiros, Felipe A; Liu, Ting; Zangwill, Linda M

    2015-01-01

    To evaluate the diagnostic ability of macular ganglion cell and inner plexiform layer measurements in glaucoma, obtained using swept source (SS) and spectral domain (SD) optical coherence tomography (OCT) and to compare to circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements. The study included 106 glaucomatous eyes of 80 subjects and 41 eyes of 22 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Macular ganglion cell and inner plexiform layer (mGCIPL), macular ganglion cell complex (mGCC) and cpRNFL thickness were assessed using SS-OCT and SD-OCT, and area under the receiver operating characteristic curves (AUCs) were calculated to determine ability to differentiate glaucomatous and healthy eyes and between early glaucomatous and healthy eyes. Mean (± standard deviation) mGCIPL and mGCC thickness were thinner in both healthy and glaucomatous eyes using SS-OCT compared to using SD-OCT. Fixed and proportional biases were detected between SS-OCT and SD-OCT measures. Diagnostic accuracy (AUCs) for differentiating between healthy and glaucomatous eyes for average and sectoral mGCIPL was similar in SS-OCT (0.65 to 0.81) and SD-OCT (0.63 to 0.83). AUCs for average cpRNFL acquired using SS-OCT and SD-OCT tended to be higher (0.83 and 0.85, respectively) than for average mGCC (0.82 and 0.78, respectively), and mGCIPL (0.73 and 0.75, respectively) but these differences did not consistently reach statistical significance. Minimum SD-OCT mGCIPL and mGCC thickness (unavailable in SS-OCT) had the highest AUC (0.86) among macular measurements. Assessment of mGCIPL thickness using SS-OCT or SD-OCT is useful for detecting glaucomatous damage, but measurements are not interchangeable for patient management decisions. Diagnostic accuracies of mGCIPL and mGCC from both SS-OCT and SD-OCT were similar to that of cpRNFL for glaucoma detection.

  1. Diagnostic Ability of Macular Ganglion Cell Inner Plexiform Layer Measurements in Glaucoma Using Swept Source and Spectral Domain Optical Coherence Tomography

    PubMed Central

    Yang, Zhiyong; Tatham, Andrew J.; Weinreb, Robert N.; Medeiros, Felipe A.; Liu, Ting; Zangwill, Linda M.

    2015-01-01

    Purpose To evaluate the diagnostic ability of macular ganglion cell and inner plexiform layer measurements in glaucoma, obtained using swept source (SS) and spectral domain (SD) optical coherence tomography (OCT) and to compare to circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements. Methods The study included 106 glaucomatous eyes of 80 subjects and 41 eyes of 22 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Macular ganglion cell and inner plexiform layer (mGCIPL), macular ganglion cell complex (mGCC) and cpRNFL thickness were assessed using SS-OCT and SD-OCT, and area under the receiver operating characteristic curves (AUCs) were calculated to determine ability to differentiate glaucomatous and healthy eyes and between early glaucomatous and healthy eyes. Results Mean (± standard deviation) mGCIPL and mGCC thickness were thinner in both healthy and glaucomatous eyes using SS-OCT compared to using SD-OCT. Fixed and proportional biases were detected between SS-OCT and SD-OCT measures. Diagnostic accuracy (AUCs) for differentiating between healthy and glaucomatous eyes for average and sectoral mGCIPL was similar in SS-OCT (0.65 to 0.81) and SD-OCT (0.63 to 0.83). AUCs for average cpRNFL acquired using SS-OCT and SD-OCT tended to be higher (0.83 and 0.85, respectively) than for average mGCC (0.82 and 0.78, respectively), and mGCIPL (0.73 and 0.75, respectively) but these differences did not consistently reach statistical significance. Minimum SD-OCT mGCIPL and mGCC thickness (unavailable in SS-OCT) had the highest AUC (0.86) among macular measurements. Conclusion Assessment of mGCIPL thickness using SS-OCT or SD-OCT is useful for detecting glaucomatous damage, but measurements are not interchangeable for patient management decisions. Diagnostic accuracies of mGCIPL and mGCC from both SS-OCT and SD-OCT were similar to that of cpRNFL for glaucoma detection. PMID:25978420

  2. Combined KHFAC + DC nerve block without onset or reduced nerve conductivity after block

    NASA Astrophysics Data System (ADS)

    Franke, Manfred; Vrabec, Tina; Wainright, Jesse; Bhadra, Niloy; Bhadra, Narendra; Kilgore, Kevin

    2014-10-01

    Objective. Kilohertz frequency alternating current (KHFAC) waveforms have been shown to provide peripheral nerve conductivity block in many acute and chronic animal models. KHFAC nerve block could be used to address multiple disorders caused by neural over-activity, including blocking pain and spasticity. However, one drawback of KHFAC block is a transient activation of nerve fibers during the initiation of the nerve block, called the onset response. The objective of this study is to evaluate the feasibility of using charge balanced direct current (CBDC) waveforms to temporarily block motor nerve conductivity distally to the KHFAC electrodes to mitigate the block onset-response. Approach. A total of eight animals were used in this study. A set of four animals were used to assess feasibility and reproducibility of a combined KHFAC + CBDC block. A following randomized study, conducted on a second set of four animals, compared the onset response resulting from KHFAC alone and combined KHFAC + CBDC waveforms. To quantify the onset, peak forces and the force-time integral were measured during KHFAC block initiation. Nerve conductivity was monitored throughout the study by comparing muscle twitch forces evoked by supra-maximal stimulation proximal and distal to the block electrodes. Each animal of the randomized study received at least 300 s (range: 318-1563 s) of cumulative dc to investigate the impact of combined KHFAC + CBDC on nerve viability. Main results. The peak onset force was reduced significantly from 20.73 N (range: 18.6-26.5 N) with KHFAC alone to 0.45 N (range: 0.2-0.7 N) with the combined CBDC and KHFAC block waveform (p < 0.001). The area under the force curve was reduced from 6.8 Ns (range: 3.5-21.9 Ns) to 0.54 Ns (range: 0.18-0.86 Ns) (p < 0.01). No change in nerve conductivity was observed after application of the combined KHFAC + CBDC block relative to KHFAC waveforms. Significance. The distal application of CBDC can significantly reduce or even

  3. Roles of PACAP-containing retinal ganglion cells in circadian timing.

    PubMed

    Hannibal, Jens

    2006-01-01

    The brain's biological clock located in the suprachiasmatic nucleus (SCN) generates circadian rhythms in physiology and behavior. The clock-driven rhythms need daily adjustment (entrainment) to be synchronized with the astronomical day of 24 h. The most important stimulus for entrainment of the clock is the light-dark (LD) cycle. In this review functional elements of the light entrainment pathway will be considered with special focus on the neurotransmitter pituitary adenylate cyclase-activating polypeptide (PACAP), which is found exclusively in the monosynaptic neuronal pathway mediating light information to the SCN, the retinohypothalamic tract (RHT). The retinal ganglion cells of the RHT are intrinsically photosensitive due to the expression of melanopsin and seem to constitute a non-image forming photosensitive system in the mammalian eye regulating circadian timing, masking behavior, light-regulated melatonin secretion, and the pupillary light reflex. Evidence from in vitro and in vivo studies and studies of mice lacking PACAP and the specific PACAP receptor (PAC1) indicate that PACAP and glutamate are neurotransmitters in the RHT which in a clock and concentration-dependent manner interact during light entrainment of the clock.

  4. Neuronal couplings between retinal ganglion cells inferred by efficient inverse statistical physics methods

    PubMed Central

    Cocco, Simona; Leibler, Stanislas; Monasson, Rémi

    2009-01-01

    Complexity of neural systems often makes impracticable explicit measurements of all interactions between their constituents. Inverse statistical physics approaches, which infer effective couplings between neurons from their spiking activity, have been so far hindered by their computational complexity. Here, we present 2 complementary, computationally efficient inverse algorithms based on the Ising and “leaky integrate-and-fire” models. We apply those algorithms to reanalyze multielectrode recordings in the salamander retina in darkness and under random visual stimulus. We find strong positive couplings between nearby ganglion cells common to both stimuli, whereas long-range couplings appear under random stimulus only. The uncertainty on the inferred couplings due to limitations in the recordings (duration, small area covered on the retina) is discussed. Our methods will allow real-time evaluation of couplings for large assemblies of neurons. PMID:19666487

  5. Primary culture of glial cells from mouse sympathetic cervical ganglion: a valuable tool for studying glial cell biology.

    PubMed

    de Almeida-Leite, Camila Megale; Arantes, Rosa Maria Esteves

    2010-12-15

    Central nervous system glial cells as astrocytes and microglia have been investigated in vitro and many intracellular pathways have been clarified upon various stimuli. Peripheral glial cells, however, are not as deeply investigated in vitro despite its importance role in inflammatory and neurodegenerative diseases. Based on our previous experience of culturing neuronal cells, our objective was to standardize and morphologically characterize a primary culture of mouse superior cervical ganglion glial cells in order to obtain a useful tool to study peripheral glial cell biology. Superior cervical ganglia from neonatal C57BL6 mice were enzymatically and mechanically dissociated and cells were plated on diluted Matrigel coated wells in a final concentration of 10,000cells/well. Five to 8 days post plating, glial cell cultures were fixed for morphological and immunocytochemical characterization. Glial cells showed a flat and irregular shape, two or three long cytoplasm processes, and round, oval or long shaped nuclei, with regular outline. Cell proliferation and mitosis were detected both qualitative and quantitatively. Glial cells were able to maintain their phenotype in our culture model including immunoreactivity against glial cell marker GFAP. This is the first description of immunocytochemical characterization of mouse sympathetic cervical ganglion glial cells in primary culture. This work discusses the uses and limitations of our model as a tool to study many aspects of peripheral glial cell biology. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. Acid-sensing ion channels in trigeminal ganglion neurons innervating the orofacial region contribute to orofacial inflammatory pain.

    PubMed

    Fu, Hui; Fang, Peng; Zhou, Hai-Yun; Zhou, Jun; Yu, Xiao-Wei; Ni, Ming; Zheng, Jie-Yan; Jin, You; Chen, Jian-Guo; Wang, Fang; Hu, Zhuang-Li

    2016-02-01

    Orofacial pain is a common clinical symptom that is accompanied by tooth pain, migraine and gingivitis. Accumulating evidence suggests that acid-sensing ion channels (ASICs), especially ASIC3, can profoundly affect the physiological properties of nociception in peripheral sensory neurons. The aim of this study is to examine the contribution of ASICs in trigeminal ganglion (TG) neurons to orofacial inflammatory pain. A Western blot (WB), immunofluorescence assay of labelled trigeminal ganglion neurons, orofacial formalin test, cell preparation and electrophysiological experiments are performed. This study demonstrated that ASIC1, ASIC2a and ASIC3 are highly expressed in TG neurons innervating the orofacial region of rats. The amplitude of ASIC currents in these neurons increased 119.72% (for ASIC1-like current) and 230.59% (for ASIC3-like current) in the formalin-induced orofacial inflammatory pain model. In addition, WB and immunofluorescence assay demonstrated a significantly augmented expression of ASICs in orofacial TG neurons during orofacial inflammation compared with the control group. The relative protein density of ASIC1, ASIC2a and ASIC3 also increased 58.82 ± 8.92%, 45.30 ± 11.42% and 55.32 ± 14.71%, respectively, compared with the control group. Furthermore, pharmacological blockade of ASICs and genetic deletion of ASIC1 attenuated the inflammation response. These findings indicate that peripheral inflammation can induce the upregulation of ASICs in TG neurons, causing orofacial inflammatory pain. Additionally, the specific inhibitor of ASICs may have a significant analgesic effect on orofacial inflammatory pain. © 2016 John Wiley & Sons Australia, Ltd.

  7. Cocoa Enriched Diets Enhance Expression of Phosphatases and Decrease Expression of Inflammatory Molecules in Trigeminal Ganglion Neurons

    PubMed Central

    Cady, Ryan J.; Durham, Paul L.

    2010-01-01

    Activation of trigeminal nerves and release of neuropeptides that promote inflammation are implicated in the underlying pathology of migraine and temporomandibular joint (TMJ) disorders. The overall response of trigeminal nerves to peripheral inflammatory stimuli involves a balance between enzymes that promote inflammation, kinases, and those that restore homeostasis, phosphatases. The goal of this study was to determine the effects of a cocoa-enriched diet on the expression of key inflammatory proteins in trigeminal ganglion neurons under basal and inflammatory conditions. Rats were fed a control diet or an isocaloric diet enriched in cocoa for 14 days prior to an injection of noxious stimuli to cause acute or chronic excitation of trigeminal neurons. In animals fed a cocoa-enriched diet, basal levels of the mitogen-activated kinase (MAP) phosphatases MKP-1 and MKP-3 were elevated in neurons. Importantly, the stimulatory effects of acute or chronic peripheral inflammation on neuronal expression of the MAPK p38 and extracellular signal-regulated kinases (ERK) were significantly repressed in response to cocoa. Similarly, dietary cocoa significantly suppressed basal neuronal expression of calcitonin gene-related peptide (CGRP) as well as stimulated levels of the inducible form of nitric oxide synthase (iNOS), proteins implicated in the underlying pathology of migraine and TMJ disorders. To our knowledge, this is first evidence that a dietary supplement can cause upregulation of MKP, and that cocoa can prevent inflammatory responses in trigeminal ganglion neurons. Furthermore, our data provide evidence that cocoa contains biologically active compounds that would be beneficial in the treatment of migraine and TMJ disorders. PMID:20138852

  8. The ciliary margin zone of the mammalian retina generates retinal ganglion cells

    PubMed Central

    Marcucci, Florencia; Murcia-Belmonte, Veronica; Coca, Yaiza; Ferreiro-Galve, Susana; Wang, Qing; Kuwajima, Takaaki; Khalid, Sania; Ross, M. Elizabeth; Herrera, Eloisa; Mason, Carol

    2016-01-01

    Summary The retina of lower vertebrates grows continuously by integrating new neurons generated from progenitors in the ciliary margin zone (CMZ). Whether the mammalian CMZ provides the neural retina with retinal cells is controversial. Live-imaging of embryonic retina expressing eGFP in the CMZ shows that cells migrate laterally from the CMZ to the neural retina where differentiated retinal ganglion cells (RGCs) reside. As Cyclin D2, a cell-cycle regulator, is enriched in ventral CMZ, we analyzed Cyclin D2−/− mice to test whether the CMZ is a source of retinal cells. Neurogenesis is diminished in Cyclin D2 mutants, leading to a reduction of RGCs in the ventral retina. In line with these findings, in the albino retina, the decreased production of ipsilateral RGCs is correlated with fewer Cyclin D2+ cells. Together, these results implicate the mammalian CMZ as a neurogenic site that produces RGCs and whose proper generation depends on Cyclin D2 activity. PMID:28009286

  9. Protective Effect of Edaravone on Glutamate-Induced Neurotoxicity in Spiral Ganglion Neurons

    PubMed Central

    Bai, Xiaohui; Zhang, Chi; Chen, Aiping; Liu, Wenwen; Li, Jianfeng; Sun, Qian

    2016-01-01

    Glutamate is an important excitatory neurotransmitter in mammalian brains, but excessive amount of glutamate can cause “excitotoxicity” and lead to neuronal death. As bipolar neurons, spiral ganglion neurons (SGNs) function as a “bridge” in transmitting auditory information from the ear to the brain and can be damaged by excessive glutamate which results in sensorineural hearing loss. In this study, edaravone, a free radical scavenger, elicited both preventative and therapeutic effects on SGNs against glutamate-induced cell damage that was tested by MTT assay and trypan blue staining. Ho.33342 and PI double staining revealed that apoptosis as well as necrosis took place during glutamate treatment, and apoptosis was the main type of cell death. Oxidative stress played an important role in glutamate-induced cell damage but pretreatment with edaravone alleviated cell death. Results of western blot demonstrated that mechanisms underlying the toxicity of glutamate and the protection of edaravone were related to the PI3K pathway and Bcl-2 protein family. PMID:27957345

  10. Imaging light responses of foveal ganglion cells in the living macaque eye.

    PubMed

    Yin, Lu; Masella, Benjamin; Dalkara, Deniz; Zhang, Jie; Flannery, John G; Schaffer, David V; Williams, David R; Merigan, William H

    2014-05-07

    The fovea dominates primate vision, and its anatomy and perceptual abilities are well studied, but its physiology has been little explored because of limitations of current physiological methods. In this study, we adapted a novel in vivo imaging method, originally developed in mouse retina, to explore foveal physiology in the macaque, which permits the repeated imaging of the functional response of many retinal ganglion cells (RGCs) simultaneously. A genetically encoded calcium indicator, G-CaMP5, was inserted into foveal RGCs, followed by calcium imaging of the displacement of foveal RGCs from their receptive fields, and their intensity-response functions. The spatial offset of foveal RGCs from their cone inputs makes this method especially appropriate for fovea by permitting imaging of RGC responses without excessive light adaptation of cones. This new method will permit the tracking of visual development, progression of retinal disease, or therapeutic interventions, such as insertion of visual prostheses.

  11. Evidence of a gustatory-vestibular pathway for protein transport.

    PubMed

    Gacek, Richard; Lyon, Michael J

    2010-02-01

    To demonstrate anatomically a pathway for protein transport from the palate to the vestibular system. The vestibulofacial anastomosis and associated ganglion cells were identified in a collection of 160 horizontally sectioned human temporal bones that had been stained with hematoxylin and eosin. Wheat germ agglutinin-horseradish peroxidase (HRP) was applied to the greater superficial petrosal nerve in 4 Sprague-Dawley rats. After 30 hours, the rats were killed by intracardiac perfusion, and the seventh and eighth nerves with adjacent brainstem removed. Frozen sections cut at 30 mum through this block were then reacted for HRP, counterstained with neutral red, and mounted on slides for examination in the light microscope. Thirty-two of the 160 human temporal bones contained sections through the vestibulofacial anastomosis and its ganglion. In all cases, the ganglion was incorporated into the vestibular ganglion (VG) adjacent to the nervus intermedius. In all 4 experimental rats, HRP reaction product labeled a small number of ganglion cells in the VG adjacent to the nervus intermedius and facial nerve. These observations support the presence of a pathway from receptors in the palate to the VG.

  12. Beautiful Blocks of Bedrock

    NASA Image and Video Library

    2016-06-01

    This image captured by NASA Mars Reconnaissance Orbiter spacecraft targets a 3-kilometer diameter crater that occurs within the ejecta blanket of the much older Bakhuysen Crater, a 150-kilometer diameter impact crater in Noachis Terra. Impact craters are interesting because they provide a mechanism to uplift and expose underlying bedrock, allowing for the study of the subsurface and the geologic past. An enhanced color image shows the wall of the crater, which exposes layering as well as blocks of rock. There is a distinctive large block in the upper left of the crater wall, generally referred to as a "mega-block." It is an angular, light-toned, highly fragmented block, about 100 meters across. Several smaller light-toned blocks are also in the crater wall, possibly of the same rock type as the "mega-block." Ejecta blocks are thrown outward during the initial excavation of a crater, or are deposited as part of the ground-hugging flows of which the majority of the ejecta blanket is comprised. Through images like these, we are able to study the deeper subsurface of Mars that is not otherwise exposed. http://photojournal.jpl.nasa.gov/catalog/PIA20728

  13. Combined KHFAC+DC nerve block without onset or reduced nerve conductivity after block

    PubMed Central

    Franke, Manfred; Vrabec, Tina; Wainright, Jesse; Bhadra, Niloy; Bhadra, Narendra; Kilgore, Kevin

    2017-01-01

    Background Kilohertz Frequency Alternating Current waveforms (KHFAC) have been shown to provide peripheral nerve conductivity block in many acute and chronic animal models. KHFAC nerve block could be used to address multiple disorders caused by neural over-activity, including blocking pain and spasticity. However, one drawback of KHFAC block is a transient activation of nerve fibers during the initiation of the nerve block, called the onset response. The objective of this study is to evaluate the feasibility of using charge balanced direct current (CBDC) waveforms to temporarily block motor nerve conductivity distally to the KHFAC electrodes to mitigate the block onset-response. Methods A total of eight animals were used in this study. A set of four animals were used to assess feasibility and reproducibility of a combined KHFAC+CBDC block. A following randomized study, conducted on a second set of four animals, compared the onset response resulting from KHFAC alone and combined KHFAC+CBDC waveforms. To quantify the onset, peak forces and the force-time integral were measured during KHFAC block initiation. Nerve conductivity was monitored throughout the study by comparing muscle twitch forces evoked by supra-maximal stimulation proximal and distal to the block electrodes. Each animal of the randomized study received at least 300 seconds (range: 318 to 1563s) of cumulative DC to investigate the impact of combined KHFAC+CBDC on nerve viability. Results The peak onset force was reduced significantly from 20.73 N (range: 18.6–26.5 N) with KHFAC alone to 0.45 N (range: 0.2–0.7 N) with the combined CBDC and KHFAC block waveform (p<0.001). The area under the force curve was reduced from 6.8 Ns (range: 3.5–21.9 Ns) to 0.54 Ns (range: 0.18–0.86Ns) (p<0.01). No change in nerve conductivity was observed after application of the combined KHFAC+CBDC block relative to KHFAC waveforms. Conclusion The distal application of CBDC can significantly reduce or even completely

  14. Mechanism of blood pressure and R-R variability: insights from ganglion blockade in humans

    NASA Technical Reports Server (NTRS)

    Zhang, Rong; Iwasaki, Kenichi; Zuckerman, Julie H.; Behbehani, Khosrow; Crandall, Craig G.; Levine, Benjamin D.; Blomqvist, C. G. (Principal Investigator)

    2002-01-01

    Spontaneous blood pressure (BP) and R-R variability are used frequently as 'windows' into cardiovascular control mechanisms. However, the origin of these rhythmic fluctuations is not completely understood. In this study, with ganglion blockade, we evaluated the role of autonomic neural activity versus other 'non-neural' factors in the origin of BP and R-R variability in humans. Beat-to-beat BP, R-R interval and respiratory excursions were recorded in ten healthy subjects (aged 30 +/- 6 years) before and after ganglion blockade with trimethaphan. The spectral power of these variables was calculated in the very low (0.0078-0.05 Hz), low (0.05-0.15 Hz) and high (0.15-0.35 Hz) frequency ranges. The relationship between systolic BP and R-R variability was examined by cross-spectral analysis. After blockade, R-R variability was virtually abolished at all frequencies; however, respiration and high frequency BP variability remained unchanged. Very low and low frequency BP variability was reduced substantially by 84 and 69 %, respectively, but still persisted. Transfer function gain between systolic BP and R-R interval variability decreased by 92 and 88 % at low and high frequencies, respectively, while the phase changed from negative to positive values at the high frequencies. These data suggest that under supine resting conditions with spontaneous breathing: (1) R-R variability at all measured frequencies is predominantly controlled by autonomic neural activity; (2) BP variability at high frequencies (> 0.15 Hz) is mediated largely, if not exclusively, by mechanical effects of respiration on intrathoracic pressure and/or cardiac filling; (3) BP variability at very low and low frequencies (< 0.15 Hz) is probably mediated by both sympathetic nerve activity and intrinsic vasomotor rhythmicity; and (4) the dynamic relationship between BP and R-R variability as quantified by transfer function analysis is determined predominantly by autonomic neural activity rather than other

  15. Genetically Identified Suppressed-by-Contrast Retinal Ganglion Cells Reliably Signal Self-Generated Visual Stimuli

    PubMed Central

    Tien, Nai-Wen; Pearson, James T.; Heller, Charles R.; Demas, Jay

    2015-01-01

    Spike trains of retinal ganglion cells (RGCs) are the sole source of visual information to the brain; and understanding how the ∼20 RGC types in mammalian retinae respond to diverse visual features and events is fundamental to understanding vision. Suppressed-by-contrast (SbC) RGCs stand apart from all other RGC types in that they reduce rather than increase firing rates in response to light increments (ON) and decrements (OFF). Here, we genetically identify and morphologically characterize SbC-RGCs in mice, and target them for patch-clamp recordings under two-photon guidance. We find that strong ON inhibition (glycine > GABA) outweighs weak ON excitation, and that inhibition (glycine > GABA) coincides with decreases in excitation at light OFF. These input patterns explain the suppressive spike responses of SbC-RGCs, which are observed in dim and bright light conditions. Inhibition to SbC-RGC is driven by rectified receptive field subunits, leading us to hypothesize that SbC-RGCs could signal pattern-independent changes in the retinal image. Indeed, we find that shifts of random textures matching saccade-like eye movements in mice elicit robust inhibitory inputs and suppress spiking of SbC-RGCs over a wide range of texture contrasts and spatial frequencies. Similarly, stimuli based on kinematic analyses of mouse blinking consistently suppress SbC-RGC spiking. Receiver operating characteristics show that SbC-RGCs are reliable indicators of self-generated visual stimuli that may contribute to central processing of blinks and saccades. SIGNIFICANCE STATEMENT This study genetically identifies and morphologically characterizes suppressed-by-contrast retinal ganglion cells (SbC-RGCs) in mice. Targeted patch-clamp recordings from SbC-RGCs under two-photon guidance elucidate the synaptic mechanisms mediating spike suppression to contrast steps, and reveal that SbC-RGCs respond reliably to stimuli mimicking saccade-like eye movements and blinks. The similarity of

  16. Bundle Branch Block

    MedlinePlus

    ... known cause. Causes can include: Left bundle branch block Heart attacks (myocardial infarction) Thickened, stiffened or weakened ... myocarditis) High blood pressure (hypertension) Right bundle branch block A heart abnormality that's present at birth (congenital) — ...

  17. Protein based Block Copolymers

    PubMed Central

    Rabotyagova, Olena S.; Cebe, Peggy; Kaplan, David L.

    2011-01-01

    Advances in genetic engineering have led to the synthesis of protein-based block copolymers with control of chemistry and molecular weight, resulting in unique physical and biological properties. The benefits from incorporating peptide blocks into copolymer designs arise from the fundamental properties of proteins to adopt ordered conformations and to undergo self-assembly, providing control over structure formation at various length scales when compared to conventional block copolymers. This review covers the synthesis, structure, assembly, properties, and applications of protein-based block copolymers. PMID:21235251

  18. Ballistic Blocks Surrounding Kilauea's Caldera

    NASA Astrophysics Data System (ADS)

    Swanson, D.; Zolkos, S.; Haravitch, B.

    2010-12-01

    Thousands of lithic blocks dot the surface around Kilauea’s caldera, erupted ballistically at the end of the 1790 eruption or soon thereafter. Most of the blocks occur in the western and southern sectors, probably reflecting the proximity of vents on the caldera floor. We mapped the ejecta field, measuring most of the blocks with nominal diameters ((a+b+c)/3) more than 75 cm and many of the smaller ones, noting distinctive lithologies. The distributions, sizes, and lithologies suggest 7-8 different ballistic bursts from 3-4 generalized vent areas. We measured 15 blocks with nominal diameters (ND) of 150-201 cm, 169 blocks with ND 100-149 cm, 308 blocks with ND 75-99 cm, 684 blocks with ND 50-74 cm, and 545 blocks with ND 25-49 cm. The smaller blocks were measured only in outlying areas, where they were the largest in the neighborhood, but they occur throughout the field. Twelve blocks with ND >150 cm lie within 1.7 km west and south of the center of Halema`uma`u; a vent near this location likely erupted the blocks. Three of the largest blocks, however, are 2.2-2.7 km north of Halema`uma`u and probably came from a more northerly vent. This interpretation is supported by the distributions of all blocks with ND >100 cm, which define at least 4, and possibly 5, different dispersal lobes; three cluster near Halema`uma`u, one is slightly north, and the one with the three large blocks is still farther north. The blocks have typical lithologies for Kilauea’s summit, including coarse basalt or fine gabbro derived from the centers of thick flows, solidified lakes, or small intrusions. Three lithologies are distinctive and help define 3, possibly 4, discrete bursts. Blocks of fine-grained basalt riddled with segregation veins occur only in a lobe 1.3 km wide reaching as far as 1.8 km southwest of Halema`uma`u; this lobe overlaps slightly with one defined by block size but is mostly distinct and probably indicates a separate burst. A cluster of blocks with puffy, somewhat

  19. Azadirachtin blocks the calcium channel and modulates the cholinergic miniature synaptic current in the central nervous system of Drosophila.

    PubMed

    Qiao, Jingda; Zou, Xiaolu; Lai, Duo; Yan, Ying; Wang, Qi; Li, Weicong; Deng, Shengwen; Xu, Hanhong; Gu, Huaiyu

    2014-07-01

    Azadirachtin is a botanical pesticide, which possesses conspicuous biological actions such as insecticidal, anthelmintic, antifeedancy, antimalarial effects as well as insect growth regulation. Deterrent for chemoreceptor functions appears to be the main mechanism involved in the potent biological actions of Azadirachtin, although the cytotoxicity and subtle changes to skeletal muscle physiology may also contribute to its insecticide responses. In order to discover the effects of Azadirachtin on the central nervous system (CNS), patch-clamp recording was applied to Drosophila melanogaster, which has been widely used in neurological research. Here, we describe the electrophysiological properties of a local neuron located in the suboesophageal ganglion region of D. melanogaster using the whole brain. The patch-clamp recordings suggested that Azadirachtin modulates the properties of cholinergic miniature excitatory postsynaptic current (mEPSC) and calcium currents, which play important roles in neural activity of the CNS. The frequency of mEPSC and the peak amplitude of the calcium currents significantly decreased after application of Azadirachtin. Our study indicates that Azadirachtin can interfere with the insect's CNS via inhibition of excitatory cholinergic transmission and partly blocking the calcium channel. © 2013 Society of Chemical Industry.

  20. Blocking the buccal nerve using two methods of inferior alveolar block injection.

    PubMed

    Aker, F D

    2001-01-01

    The anatomic relations of the buccal nerve branch of the mandibular division of the trigeminal nerve were studied to explain the rationale for the discrepancy in blocking the buccal nerve using two methods of blocking the inferior alveolar nerve, the conventional method and the Gow-Gates method. The conventional method rarely blocks the buccal nerve, while the Gow-Gates method is reported to consistently block the buccal nerve. Eight head and mandibular specimens were dissected to observe the path of buccal nerve and its relationship to the path of needles in the conventional and Gow-Gates techniques. The buccal nerve descends on the medial and then anterior aspect of the deep head of the temporalis muscle (Tdh). At the latter position the buccal nerve enters the retromolar fossa and is encased in a fascial sleeve created by a dense fascial band that spans between the temporalis muscle tendons and the buccinator muscle. At the level of the conventional block injection the buccal nerve was shielded from the path of the needle by the Tdh and the fascial band. In the Gow-Gates block injection, the buccal nerve was exposed on the medial surface of the Tdh, immediately lateral to the path of the needle and proximal to the fascial sleeve. Consequently, the anatomical relations of the buccal nerve in the conventional block method essentially shield the nerve from being bathed by anesthetic solution while in the Gow-Gates method the relations are such that the buccal nerve can be exposed to anesthetic solution and thus blocked, explaining the findings in clinical dentistry. Copyright Wiley-Liss, Inc.