Clinical validation and applications for CT-based atlas for contouring the lower cranial nerves for head and neck cancer radiation therapy.

PubMed

Mourad, Waleed F; Young, Brett M; Young, Rebekah; Blakaj, Dukagjin M; Ohri, Nitin; Shourbaji, Rania A; Manolidis, Spiros; Gámez, Mauricio; Kumar, Mahesh; Khorsandi, Azita; Khan, Majid A; Shasha, Daniel; Blakaj, Adriana; Glanzman, Jonathan; Garg, Madhur K; Hu, Kenneth S; Kalnicki, Shalom; Harrison, Louis B

2013-09-01

Radiation induced cranial nerve palsy (RICNP) involving the lower cranial nerves (CNs) is a serious complication of head and neck radiotherapy (RT). Recommendations for delineating the lower CNs on RT planning studies do not exist. The aim of the current study is to develop a standardized methodology for contouring CNs IX-XII, which would help in establishing RT limiting doses for organs at risk (OAR). Using anatomic texts, radiologic data, and guidance from experts in head and neck anatomy, we developed step-by-step instructions for delineating CNs IX-XII on computed tomography (CT) imaging. These structures were then contoured on five consecutive patients who underwent definitive RT for locally-advanced head and neck cancer (LAHNC). RT doses delivered to the lower CNs were calculated. We successfully developed a contouring atlas for CNs IX-XII. The median total dose to the planning target volume (PTV) was 70Gy (range: 66-70Gy). The median CN (IX-XI) and (XII) volumes were 10c.c (range: 8-12c.c) and 8c.c (range: 7-10c.c), respectively. The median V50, V60, V66, and V70 of the CN (IX-XI) and (XII) volumes were (85, 77, 71, 65) and (88, 80, 74, 64) respectively. The median maximal dose to the CN (IX-XI) and (XII) were 72Gy (range: 66-77) and 71Gy (range: 64-78), respectively. We have generated simple instructions for delineating the lower CNs on RT planning imaging. Further analyses to explore the relationship between lower CN dosing and the risk of RICNP are recommended in order to establish limiting doses for these OARs. Published by Elsevier Ltd.

Factor XI and XII as antithrombotic targets.

PubMed

Müller, Felicitas; Gailani, David; Renné, Thomas

2011-09-01

Arterial and venous thrombosis are major causes of morbidity and mortality, and the incidence of thromboembolic diseases increases as a population ages. Thrombi are formed by activated platelets and fibrin. The latter is a product of the plasma coagulation system. Currently available anticoagulants such as heparins, vitamin K antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for terminating blood loss at sites of vascular injury. As a result, anticoagulants currently in clinical use increase the risk of bleeding, partially offsetting the benefits of reduced thrombosis. This review focuses on new targets for anticoagulation that are associated with minimal or no therapy-associated increased bleeding. Data from experimental models using mice and clinical studies of patients with hereditary deficiencies of coagulation factors XI or XII have shown that both of these clotting factors are important for thrombosis, while having minor or no apparent roles in processes that terminate blood loss (hemostasis). Hereditary deficiency of factor XII (Hageman factor) or factor XI, plasma proteases that initiate the intrinsic pathway of coagulation, impairs thrombus formation and provides protection from vascular occlusive events, while having a minimal impact on hemostasis. As the factor XII-factor XI pathway contributes to thrombus formation to a greater extent than to normal hemostasis, pharmacological inhibition of these coagulation factors may offer the exciting possibility of anticoagulation therapies with minimal or no bleeding risk.

Nerve-muscle activation by rotating permanent magnet configurations.

PubMed

Watterson, Peter A; Nicholson, Graham M

2016-04-01

The standard method of magnetic nerve activation using pulses of high current in coils has drawbacks of high cost, high electrical power (of order 1 kW), and limited repetition rate without liquid cooling. Here we report a new technique for nerve activation using high speed rotation of permanent magnet configurations, generating a sustained sinusoidal electric field using very low power (of order 10 W). A high ratio of the electric field gradient divided by frequency is shown to be the key indicator for nerve activation at high frequencies. Activation of the cane toad sciatic nerve and attached gastrocnemius muscle was observed at frequencies as low as 180 Hz for activation of the muscle directly and 230 Hz for curved nerves, but probably not in straight sections of nerve. These results, employing the first prototype device, suggest the opportunity for a new class of small low-cost magnetic nerve and/or muscle stimulators. Conventional pulsed current systems for magnetic neurostimulation are large and expensive and have limited repetition rate because of overheating. Here we report a new technique for nerve activation, namely high-speed rotation of a configuration of permanent magnets. Analytical solutions of the cable equation are derived for the oscillating electric field generated, which has amplitude proportional to the rotation speed. The prototype device built comprised a configuration of two cylindrical magnets with antiparallel magnetisations, made to rotate by interaction between the magnets' own magnetic field and three-phase currents in coils mounted on one side of the device. The electric field in a rectangular bath placed on top of the device was both numerically evaluated and measured. The ratio of the electric field gradient on frequency was approximately 1 V m(-2) Hz(-1) near the device. An exploratory series of physiological tests was conducted on the sciatic nerve and attached gastrocnemius muscle of the cane toad (Bufo marinus). Activation was

Preventing lower cranial nerve injuries during fourth ventricle tumor resection by utilizing intraoperative neurophysiological monitoring.

PubMed

Jahangiri, Faisal R; Minhas, Mazhar; Jane, John

2012-12-01

We present two cases illustrating the benefit of utilizing intraoperative neurophysiological monitoring (IONM) for prevention of injuries to the lower cranial nerves during fourth ventricle tumor resection surgeries. Multiple cranial nerve nuclei are located on the floor of the fourth ventricle with a high risk of permanent damage. Two male patients (ages 8 and 10 years) presented to the emergency department and had brain magnetic resonance imaging (MRI) scans showing brainstem/fourth ventricle tumors. During surgery, bilateral posterior tibial and median nerve somatosensory evoked potentials (SSEPs); four-limb and cranial nerves transcranial electrical motor evoked potentials (TCeMEPs); brainstem auditory evoked responses (BAERs); and spontaneous electromyography (s-EMG) were recorded. Electromyography (EMG) was monitored bilaterally from cranial nerves V VII, IX, X, XI, and XII. Total intravenous anesthesia was used. Neuromuscular blockade was used only for initial intubation. Pre-incision baselines were obtained with good morphology of waveforms. After exposure the floor of the fourth ventricle was mapped by triggered-EMG (t-EMG) using 0.4 to 1.0 mA. In both patients the tumor was entangled with cranial nerves VII to XII on the floor of the fourth ventricle. The surgeon made the decision not to resect the tumor in one case and limited the resection to 70% of the tumor in the second case on the basis of neurophysiological monitoring. This decision was made to minimize any post-operative neurological deficits due to surgical manipulation of the tumor involving the lower cranial nerves. Intraoperative spontaneous and triggered EMG was effectively utilized in preventing injuries to cranial nerves during surgical procedures. All signals remained stable during the surgical procedure. Postoperatively both patients were well with no additional cranial nerve weakness. At three months follow-up, the patients continued to have no deficits.

Evaluation of the Predictive Value of Intraoperative Changes in Motor-Evoked Potentials of Caudal Cranial Nerves for the Postoperative Functional Outcome.

PubMed

Kullmann, Marcel; Tatagiba, Marcos; Liebsch, Marina; Feigl, Guenther C

2016-11-01

The predictive value of changes in intraoperatively acquired motor-evoked potentials (MEPs) of the lower cranial nerves (LCN) IX-X (glossopharyngeal-vagus nerve) and CN XII (hypoglossal nerve) on operative outcomes was investigated. MEPs of CN IX-X and CN XII were recorded intraoperatively in 63 patients undergoing surgery of the posterior cranial fossa. We correlated the changes of the MEPs with postoperative nerve function. For CN IX-X, we found a correlation between the amplitude of the MEP ratio and uvula deviation (P = 0.028) and the amplitude duration of the MEP and gag reflex function (P = 0.027). Patients with an MEP ratio of the glossopharyngeal-vagus amplitude ≤1.47 μV had a 3.4 times increased risk of developing a uvula deviation. Patients with a final MEP duration of the CN IX-X ≤11.6 milliseconds had a 3.6 times increased risk for their gag reflex to become extinct. Our study greatly contributes to the current knowledge of intraoperative MEPs as a predictor for postoperative cranial nerve function. We were able to extent previous findings on MEP values of the facial nerve on postoperative nerve function to 3 additional cranial nerves. Finding reliable predictors for postoperative nerve function is of great importance to the overall quality of life for a patient undergoing surgery of the posterior cranial fossa. Copyright © 2016 Elsevier Inc. All rights reserved.

Muscle Activation During Peripheral Nerve Field Stimulation Occurs Due to Recruitment of Efferent Nerve Fibers, Not Direct Muscle Activation.

PubMed

Frahm, Ken Steffen; Hennings, Kristian; Vera-Portocarrero, Louis; Wacnik, Paul W; Mørch, Carsten Dahl

2016-08-01

Peripheral nerve field stimulation (PNFS) is a potential treatment for chronic low-back pain. Pain relief using PNFS is dependent on activation of non-nociceptive Aβ-fibers. However, PNFS may also activate muscles, causing twitches and discomfort. In this study, we developed a mathematical model, to investigate the activation of sensory and motor nerves, as well as direct muscle fiber activation. The extracellular field was estimated using a finite element model based on the geometry of CT scanned lumbar vertebrae. The electrode was modeled as being implanted to a depth of 10-15 mm. Three implant directions were modeled; horizontally, vertically, and diagonally. Both single electrode and "between-lead" stimulation between contralateral electrodes were modeled. The extracellular field was combined with models of sensory Aβ-nerves, motor neurons and muscle fibers to estimate their activation thresholds. The model showed that sensory Aβ fibers could be activated with thresholds down to 0.563 V, and the lowest threshold for motor nerve activation was 7.19 V using between-lead stimulation with the cathode located closest to the nerves. All thresholds for direct muscle activation were above 500 V. The results suggest that direct muscle activation does not occur during PNFS, and concomitant motor and sensory nerve fiber activation are only likely to occur when using between-lead configuration. Thus, it may be relevant to investigate the location of the innervation zone of the low-back muscles prior to electrode implantation to avoid muscle activation. © 2016 International Neuromodulation Society.

Value of free-run electromyographic monitoring of lower cranial nerves in endoscopic endonasal approach to skull base surgeries.

PubMed

Thirumala, Parthasarathy D; Mohanraj, Santhosh Kumar; Habeych, Miguel; Wichman, Kelley; Chang, Yue-Fang; Gardner, Paul; Snyderman, Carl; Crammond, Donald J; Balzer, Jeffrey

2012-08-01

Objective The main objective of this study was to evaluate the value of free-run electromyography (f-EMG) monitoring of cranial nerves (CNs) VII, IX, X, XI, and XII in skull base surgeries performed using endoscopic endonasal approach (EEA) to reduce iatrogenic CN deficits. Design We retrospectively identified 73 patients out of 990 patients who had EEA in our institution who had at least one CN monitored. In each CN group, we classified patients who had significant (SG) f-EMG activity as group I and those who did not as group II. Results We monitored a total of 342 CNs. A total of 62 nerves had SG f-EMG activity including CN VII = 18, CN IX = 16, CN X = 13, CN XI = 5, and CN XII = 10. No nerve deficit was found in the nerves that had significant activity during procedure. A total of five nerve deficits including (CN IX = 1, CN X = 2, CN XII = 2) were observed in the group that did not display SG f-EMG activity during surgery. Conclusions f-EMG seems highly sensitive to surgical manipulations and in locating CNs. It seems to have limited value in predicting postoperative neurological deficits. Future studies to evaluate the EMG of lower CNs during EEA procedures need to be done with both f-EMG and triggered EMG.

Value of Free-Run Electromyographic Monitoring of Lower Cranial Nerves in Endoscopic Endonasal Approach to Skull Base Surgeries

PubMed Central

Thirumala, Parthasarathy D.; Mohanraj, Santhosh Kumar; Habeych, Miguel; Wichman, Kelley; Chang, Yue-Fang; Gardner, Paul; Snyderman, Carl; Crammond, Donald J.; Balzer, Jeffrey

2012-01-01

Objective The main objective of this study was to evaluate the value of free-run electromyography (f-EMG) monitoring of cranial nerves (CNs) VII, IX, X, XI, and XII in skull base surgeries performed using endoscopic endonasal approach (EEA) to reduce iatrogenic CN deficits. Design We retrospectively identified 73 patients out of 990 patients who had EEA in our institution who had at least one CN monitored. In each CN group, we classified patients who had significant (SG) f-EMG activity as group I and those who did not as group II. Results We monitored a total of 342 CNs. A total of 62 nerves had SG f-EMG activity including CN VII = 18, CN IX = 16, CN X = 13, CN XI = 5, and CN XII = 10. No nerve deficit was found in the nerves that had significant activity during procedure. A total of five nerve deficits including (CN IX = 1, CN X = 2, CN XII = 2) were observed in the group that did not display SG f-EMG activity during surgery. Conclusions f-EMG seems highly sensitive to surgical manipulations and in locating CNs. It seems to have limited value in predicting postoperative neurological deficits. Future studies to evaluate the EMG of lower CNs during EEA procedures need to be done with both f-EMG and triggered EMG. PMID:23904999

Pius XII and the Jews: A Bibliographical Review.

ERIC Educational Resources Information Center

Byers, Catherine

1978-01-01

Presents a brief biographical sketch of Pope Pius XII and samples literary treatment of Pius's actions with respect to Nazi atrocities against the Jewish people during World War II. Concludes that Pope Pius XII failed to show moral leadership. Materials reviewed include historical texts, studies of the Vatican, documents related to the war period,…

Vestibular activation of sympathetic nerve activity

NASA Technical Reports Server (NTRS)

Ray, C. A.; Carter, J. R.

2003-01-01

AIM: The vestibulosympathetic reflex refers to sympathetic nerve activation by the vestibular system. Animal studies indicate that the vestibular system assists in blood pressure regulation during orthostasis. Although human studies clearly demonstrate activation of muscle sympathetic nerve activity (MSNA) during engagement of the otolith organs, the role of the vestibulosympathetic reflex in maintaining blood pressure during orthostasis is not well-established. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes indicates that it is a powerful and independent reflex. Ageing, which is associated with an increased risk for orthostatic hypotension, attenuates the vestibulosympathetic reflex. The attenuated reflex is associated with a reduction in arterial pressure. CONCLUSION: These findings suggest that the vestibulosympathetic reflex assists in blood pressure regulation in humans, but future studies examining this reflex in other orthostatically intolerant populations are necessary to address this hypothesis.

Differential suppression of upper airway motor activity during carbachol-induced, REM sleep-like atonia.

PubMed

Fenik, V; Davies, R O; Pack, A I; Kubin, L

1998-10-01

Microinjections of carbachol into the pontine tegmentum of decerebrate cats have been used to study the mechanisms underlying the suppression of postural and respiratory motoneuronal activity during the resulting rapid eye movement (REM) sleep-like atonia. During REM sleep, distinct respiratory muscles are differentially affected; e.g., the activity of the diaphragm shows little suppression, whereas the activity of some upper airway muscles is quite strong. To determine the pattern of the carbachol-induced changes in the activity of different groups of upper airway motoneurons, we simultaneously recorded the efferent activity of the recurrent laryngeal nerve (RL), pharyngeal branch of the vagus nerve (Phar), and genioglossal branch of the hypoglossal (XII) and phrenic (Phr) nerves in 12 decerebrate, paralyzed, vagotomized, and artificially ventilated cats. Pontine carbachol caused a stereotyped suppression of the spontaneous activity that was significantly larger in Phar expiratory (to 8.3% of control) and XII inspiratory motoneurons (to 15%) than in Phr inspiratory (to 87%), RL inspiratory (to 79%), or RL expiratory motoneurons (to 72%). The suppression in upper airway motor output was significantly greater than the depression caused by a level of hypocapnia that reduced Phr activity as much as carbachol. We conclude that pontine carbachol evokes a stereotyped pattern of suppression of upper airway motor activity. Because carbachol evokes a state having many neurophysiological characteristics similar to those of REM sleep, it is likely that pontine cholinoceptive neurons have similar effects on the activity of upper airway motoneurons during both states.

Nerve Fiber Activation During Peripheral Nerve Field Stimulation: Importance of Electrode Orientation and Estimation of Area of Paresthesia.

PubMed

Frahm, Ken Steffen; Hennings, Kristian; Vera-Portocarrero, Louis; Wacnik, Paul W; Mørch, Carsten Dahl

2016-04-01

Low back pain is one of the indications for using peripheral nerve field stimulation (PNFS). However, the effect of PNFS varies between patients; several stimulation parameters have not been investigated in depth, such as orientation of the nerve fiber in relation to the electrode. While placing the electrode parallel to the nerve fiber may give lower activation thresholds, anodal blocking may occur when the propagating action potential passes an anode. A finite element model was used to simulate the extracellular potential during PNFS. This was combined with an active cable model of Aβ and Aδ nerve fibers. It was investigated how the angle between the nerve fiber and electrode affected the nerve activation and whether anodal blocking could occur. Finally, the area of paresthesia was estimated and compared with any concomitant Aδ fiber activation. The lowest threshold was found when nerve and electrode were in parallel, and that anodal blocking did not appear to occur during PNFS. The activation of Aβ fibers was within therapeutic range (<10V) of PNFS; however, within this range, Aδ fiber activation also may occur. The combined area of activated Aβ fibers (paresthesia) was at least two times larger than Aδ fibers for similar stimulation intensities. No evidence of anodal blocking was observed in this PNFS model. The thresholds were lowest when the nerves and electrodes were parallel; thus, it may be relevant to investigate the overall position of the target nerve fibers prior to electrode placement. © 2015 International Neuromodulation Society.

Reduction of factor XII in antiphospholipid antibody-positive patients with thrombotic events in the rheumatology clinic.

PubMed

Takeishi, M; Mimori, A; Nakajima, K; Mimura, T; Suzuki, T

2003-02-01

Although rheumatological diagnosis often includes an assessment of antiphospholipid (aPL) antibodies, the significance of other prothrombotic factors has not been established in thrombotic patients who are not afflicted with either arteriosclerosis or vasculitis syndrome. We have observed both the presence of antiphospholipid antibodies and a reduction of factor XII in such patients. Our results identified both lupus anticoagulant-positive (50%) and anticardiolipin antibody-positive (58%) patients. In addition, 83% of patients showed factor XII antigen level reduction. Furthermore, 70% of aPL-positive thrombotic patients showed factor XII antigen level reduction. Only two cases had antiphospholipid antibody alone, and 4/12 showed just factor XII antigen reduction. Recently, it has been reported that the presence of antiphospholipid antibodies induces factor XII reduction, and that anti-factor XII autoantibody can be detected in thrombotic patients. However, our results indicate that there are smaller factor XII reductions in non-thrombotic controls who are positive for antiphospholipid antibodies. Furthermore, anti-factor XII autoantibody was not detected in patients with decreased factor XII levels. Kindred research suggested that in two patients there was a genetic component to factor XII reduction. We concluded that the presence of both antiphospholipid antibodies and reduced serum factor XII was observed in most thrombotic patients from our rheumatology clinic. It is therefore possible to consider that the coexistence of these prothrombotic factors can contribute to the onset of thrombosis.

MELANOPHORE BANDS AND AREAS DUE TO NERVE CUTTING, IN RELATION TO THE PROTRACTED ACTIVITY OF NERVES

PubMed Central

Parker, G. H.

1941-01-01

1. When appropriate chromatic nerves are cut caudal bands, cephalic areas, and the pelvic fins of the catfish Ameiurus darken. In pale fishes all these areas will sooner or later blanch. By recutting their nerves all such blanched areas will darken again. 2. These observations show that the darkening of caudal bands, areas, and fins on cutting their nerves is not due to paralysis (Brücke), to the obstruction of central influences such as inhibition (Zoond and Eyre), nor to vasomotor disturbances (Hogben), but to activities emanating from the cut itself. 3. The chief agents concerned with the color changes in Ameiurus are three: intermedin from the pituitary gland, acetylcholine from the dispersing nerves (cholinergic fibers), and adrenalin from the concentrating nerves (adrenergic fibers). The first two darken the fish; the third blanches it. In darkening the dispersing nerves appear to initiate the process and to be followed and substantially supplemented by intermedin. 4. Caudal bands blanch by lateral invasion, cephalic areas by lateral invasion and internal disintegration, and pelvic fins by a uniform process of general loss of tint equivalent to internal disintegration. 5. Adrenalin may be carried in such an oil as olive oil and may therefore act as a lipohumor; it is soluble in water and hence may act as a hydrohumor. In lateral invasion (caudal bands, cephalic areas) it probably acts as a lipohumor and in internal disintegration (cephalic areas, pelvic fins) it probably plays the part of a hydrohumor. 6. The duration of the activity of dispersing nerves after they had been cut was tested by means of the oscillograph, by anesthetizing blocks, and by cold-blocks. The nerves of Ameiurus proved to be unsatisfactory for oscillograph tests. An anesthetizing block, magnesium sulfate, is only partly satisfactory. A cold-block, 0°C., is successful to a limited degree. 7. By means of a cold-block it can be shown that dispersing autonomic nerve fibers in Ameiurus can

Reflex effects on renal nerve activity characteristics in spontaneously hypertensive rats.

PubMed

DiBona, G F; Jones, S Y; Sawin, L L

1997-11-01

The effects of arterial and cardiac baroreflex activation on the discharge characteristics of renal sympathetic nerve activity were evaluated in conscious spontaneously hypertensive and Wistar-Kyoto rats. In spontaneously hypertensive rats compared with Wistar-Kyoto rats, (1) arterial baroreflex regulation of renal sympathetic nerve activity was reset to a higher arterial pressure and the gain was decreased and (2) cardiac baroreflex regulation of renal sympathetic nerve activity exhibited a lower gain. With the use of sympathetic peak detection analysis, the inhibition of integrated renal sympathetic nerve activity, which occurred during both increased arterial pressure (arterial baroreflex) and right atrial pressure (cardiac baroreflex), was due to parallel decreases in peak height with little change in peak frequency in both spontaneously hypertensive and Wistar-Kyoto rats. Arterial and cardiac baroreflex inhibition of renal sympathetic nerve activity in Wistar-Kyoto and spontaneously hypertensive rats is due to a parallel reduction in the number of active renal sympathetic nerve fibers.

Polyphosphate colocalizes with factor XII on platelet-bound fibrin and augments its plasminogen activator activity.

PubMed

Mitchell, Joanne L; Lionikiene, Ausra S; Georgiev, Georgi; Klemmer, Anja; Brain, Chelsea; Kim, Paul Y; Mutch, Nicola J

2016-12-15

Activated factor XII (FXIIa) has plasminogen activator capacity but its relative contribution to fibrinolysis is considered marginal compared with urokinase and tissue plasminogen activator. Polyphosphate (polyP) is released from activated platelets and mediates FXII activation. Here, we investigate the contribution of polyP to the plasminogen activator function of αFXIIa. We show that both polyP 70 , of the chain length found in platelets (60-100 mer), and platelet-derived polyP significantly augment the plasminogen activation capacity of αFXIIa. PolyP 70 stimulated the autoactivation of FXII and subsequent plasminogen activation, indicating that once activated, αFXIIa remains bound to polyP 70 Indeed, complex formation between polyP 70 and αFXIIa provides protection against autodegradation. Plasminogen activation by βFXIIa was minimal and not enhanced by polyP 70 , highlighting the importance of the anion binding site. PolyP 70 did not modulate plasmin activity but stimulated activation of Glu and Lys forms of plasminogen by αFXIIa. Accordingly, polyP 70 was found to bind to FXII, αFXIIa, and plasminogen, but not βFXIIa. Fibrin and polyP 70 acted synergistically to enhance αFXIIa-mediated plasminogen activation. The plasminogen activator activity of the αFXIIa-polyP 70 complex was modulated by C1 inhibitor and histidine-rich glycoprotein, but not plasminogen activator inhibitors 1 and 2. Platelet polyP and FXII were found to colocalize on the activated platelet membrane in a fibrin-dependent manner and decorated fibrin strands extending from platelet aggregates. We show that in the presence of platelet polyP and the downstream substrate fibrin, αFXIIa is a highly efficient and favorable plasminogen activator. Our data are the first to document a profibrinolytic function of platelet polyP. © 2016 by The American Society of Hematology.

Polyphosphate colocalizes with factor XII on platelet-bound fibrin and augments its plasminogen activator activity

PubMed Central

Lionikiene, Ausra S.; Georgiev, Georgi; Klemmer, Anja; Brain, Chelsea; Kim, Paul Y.

2016-01-01

Activated factor XII (FXIIa) has plasminogen activator capacity but its relative contribution to fibrinolysis is considered marginal compared with urokinase and tissue plasminogen activator. Polyphosphate (polyP) is released from activated platelets and mediates FXII activation. Here, we investigate the contribution of polyP to the plasminogen activator function of αFXIIa. We show that both polyP70, of the chain length found in platelets (60-100 mer), and platelet-derived polyP significantly augment the plasminogen activation capacity of αFXIIa. PolyP70 stimulated the autoactivation of FXII and subsequent plasminogen activation, indicating that once activated, αFXIIa remains bound to polyP70. Indeed, complex formation between polyP70 and αFXIIa provides protection against autodegradation. Plasminogen activation by βFXIIa was minimal and not enhanced by polyP70, highlighting the importance of the anion binding site. PolyP70 did not modulate plasmin activity but stimulated activation of Glu and Lys forms of plasminogen by αFXIIa. Accordingly, polyP70 was found to bind to FXII, αFXIIa, and plasminogen, but not βFXIIa. Fibrin and polyP70 acted synergistically to enhance αFXIIa-mediated plasminogen activation. The plasminogen activator activity of the αFXIIa-polyP70 complex was modulated by C1 inhibitor and histidine-rich glycoprotein, but not plasminogen activator inhibitors 1 and 2. Platelet polyP and FXII were found to colocalize on the activated platelet membrane in a fibrin-dependent manner and decorated fibrin strands extending from platelet aggregates. We show that in the presence of platelet polyP and the downstream substrate fibrin, αFXIIa is a highly efficient and favorable plasminogen activator. Our data are the first to document a profibrinolytic function of platelet polyP. PMID:27694320

Acute baroreflex resetting: differential control of pressure and nerve activity.

PubMed

Drummond, H A; Seagard, J L

1996-03-01

This study evaluated acute resetting of carotid baroreflex control of arterial blood pressure and renal or thoracic sympathetic nerve activity in thiopental-anesthetized mongrel dogs with the use of a vascularly isolated carotid sinus preparation, the experimental model used previously to characterize acute resetting in carotid baroreceptor afferent fibers. Carotid baroreceptors were conditioned with a pulsatile pressure for 20 minutes at three pressure ranges: low (50 to 75 mm Hg), mid (100 to 125), or high (150 to 175). Blood pressure and nerve activity were recorded in response to slow ramp increases in sinus pressure; nonlinear regression and best-fit analyses were used for determination of curve fit parameters of the blood pressure and nerve activity versus sinus pressure response curves. Carotid sinus pressure thresholds for blood pressure and renal nerve activity responses at all conditioning pressures were significantly different; however, only the pressure threshold for thoracic nerve activity at the low conditioning pressure was significantly different from the responses at other conditioning pressures. Average renal activity resetting (0.506 +/- 0.072) was significantly greater than blood pressure resetting (0.335 +/- 0.046) in the same dogs, and thoracic activity (0.200 +/- 0.057) was not different from blood pressure resetting (0.194 +/- 0.031) in the same dogs. In a previous investigation, our laboratory had demonstrated that type 1 carotid baroreceptors acutely reset at a value of about 0.15. These results indicate that (1) renal and thoracic nerve activities and blood pressure acutely reset to a greater degree than type 1 carotid baroreceptors and that (2) renal activity acutely resets to a greater degree than blood pressure and thoracic nerve activity.

Perceptual consequences of disrupted auditory nerve activity.

PubMed

Zeng, Fan-Gang; Kong, Ying-Yee; Michalewski, Henry J; Starr, Arnold

2005-06-01

Perceptual consequences of disrupted auditory nerve activity were systematically studied in 21 subjects who had been clinically diagnosed with auditory neuropathy (AN), a recently defined disorder characterized by normal outer hair cell function but disrupted auditory nerve function. Neurological and electrophysical evidence suggests that disrupted auditory nerve activity is due to desynchronized or reduced neural activity or both. Psychophysical measures showed that the disrupted neural activity has minimal effects on intensity-related perception, such as loudness discrimination, pitch discrimination at high frequencies, and sound localization using interaural level differences. In contrast, the disrupted neural activity significantly impairs timing related perception, such as pitch discrimination at low frequencies, temporal integration, gap detection, temporal modulation detection, backward and forward masking, signal detection in noise, binaural beats, and sound localization using interaural time differences. These perceptual consequences are the opposite of what is typically observed in cochlear-impaired subjects who have impaired intensity perception but relatively normal temporal processing after taking their impaired intensity perception into account. These differences in perceptual consequences between auditory neuropathy and cochlear damage suggest the use of different neural codes in auditory perception: a suboptimal spike count code for intensity processing, a synchronized spike code for temporal processing, and a duplex code for frequency processing. We also proposed two underlying physiological models based on desynchronized and reduced discharge in the auditory nerve to successfully account for the observed neurological and behavioral data. These methods and measures cannot differentiate between these two AN models, but future studies using electric stimulation of the auditory nerve via a cochlear implant might. These results not only show the unique

Literature review of cranial nerve injuries during carotid endarterectomy.

PubMed

Sajid, M S; Vijaynagar, B; Singh, P; Hamilton, G

2007-01-01

In the recent prospective randomised trials on carotid endarterectomy (CEA), the incidence of cranial nerve injuries (CNI) are reported to be higher than in previously published studies. The objective of this study is to review the incidence of post CEA cranial nerve injury and to discover whether it has changed in the last 25 years after many innovations in vascular surgery. Generic terms including carotid endarterectomy, cranial nerve injuries, post CEA complications and cranial nerve deficit after neck surgery were used to search a variety of electronic databases. Based on selection criteria, decisions regarding inclusion and exclusion of primary studies were made. The incidence of CNI before and after 1995 was compared. We found 31 eligible studies from the literature. Patients who underwent CEA through any approach were included in the study. All patients had cranial nerves examined both before and after surgery. The total number of patients who had CEA before 1995 was 3521 with 10.6% CNI (352 patients) and after 1995, 7324 patients underwent CEA with 8.3% CNI (614 patients). Cranial nerves XII, X and VII were most commonly involved (rarely IX and XI). Statistical analysis showed that the incidence of CNI has decreased (X(2) = 5.89 + 0.74 = 6.63 => p-value = 0.0100). CNI is still a significant postoperative complication of carotid endarterectomy. Despite increasing use of CEA, the incidence of CNI has decreased probably because of increased awareness of the possibility of cranial nerve damage.

Methylxanthines do not affect rhythmogenic preBötC inspiratory network activity but impair bursting of preBötC-driven motoneurons.

PubMed

Panaitescu, B; Kuribayashi, J; Ruangkittisakul, A; Leung, V; Iizuka, M; Ballanyi, K

2013-01-01

Clinical stimulation of preterm infant breathing with methylxanthines like caffeine and theophylline can evoke seizures. It is unknown whether underlying neuronal hyperexcitability involves the rhythmogenic inspiratory active pre-Bötzinger complex (preBötC) in the brainstem or preBötC-driven motor networks. Inspiratory-related preBötC interneuronal plus spinal (cervical/phrenic) or cranial hypoglossal (XII) motoneuronal bursting was studied in newborn rat en bloc brainstem-spinal cords and brainstem slices, respectively. Non-respiratory bursting perturbed inspiratory cervical nerve activity in en bloc models at >0.25mM theophylline or caffeine. Rhythm in the exposed preBötC of transected en bloc preparations was less perturbed by 10mM theophylline than cervical root bursting which was more affected than phrenic nerve activity. In the preBötC of slices, even 10mM methylxanthine did not evoke seizure-like bursting whereas >1mM masked XII rhythm via large amplitude 1-10Hz oscillations. Blocking A-type γ-aminobutyric (GABAA) receptors evoked seizure-like cervical activity whereas in slices neither XII nor preBötC rhythm was disrupted. Methylxanthines (2.5-10mM), but not blockade of adenosine receptors, phosphodiesterase-4 or the sarcoplasmatic/endoplasmatic reticulum ATPase countered inspiratory depression by muscimol-evoked GABAA receptor activation that was associated with a hyperpolarization and input resistance decrease silencing preBötC neurons in slices. The latter blockers did neither affect preBötC or cranial/spinal motor network bursting nor evoke seizure-like activity or mask corresponding methylxanthine-evoked discharges. Our findings show that methylxanthine-evoked hyperexcitability originates from motor networks, leaving preBötC activity largely unaffected, and suggest that GABAA receptors contribute to methylxanthine-evoked seizure-like perturbation of spinal motoneurons whereas non-respiratory XII motoneuron oscillations are of different

Pyrazolylbenzo[d]imidazoles as new potent and selective inhibitors of carbonic anhydrase isoforms hCA IX and XII.

PubMed

Kumar, Satish; Ceruso, Mariangela; Tuccinardi, Tiziano; Supuran, Claudiu T; Sharma, Pawan K

2016-07-01

Novel pyrazolylbenzo[d]imidazole derivatives (2a-2f) were designed, synthesized and evaluated against four human carbonic anhydrase isoforms belonging to α family comprising of two cytosolic isoforms hCA I and II as well as two transmembrane tumor associated isoforms hCA IX and XII. Starting from these derivatives that showed high potency but low selectivity in favor of tumor associated isoforms hCA IX and XII, we investigated the impact of removing the sulfonamide group. Thus, analogs 3a-3f without sulfonamide moiety were synthesized and biological assay revealed a good activity as well as an excellent selectivity as inhibitors for tumor associated hCA IX and hCA XII and the same was analyzed by molecular docking studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanisms of insulin action on sympathetic nerve activity

NASA Technical Reports Server (NTRS)

Muntzel, Martin S.; Anderson, Erling A.; Johnson, Alan Kim; Mark, Allyn L.

1996-01-01

Insulin resistance and hyperinsulinemia may contribute to the development of arterial hypertension. Although insulin may elevate arterial pressure, in part, through activation of the sympathetic nervous system, the sites and mechanisms of insulin-induced sympathetic excitation remain uncertain. While sympathoexcitation during insulin may be mediated by the baroreflex, or by modulation of norepinephrine release from sympathetic nerve endings, it has been shown repeatedly that insulin increases sympathetic outflow by actions on the central nervous system. Previous studies employing norepinephrine turnover have suggested that insulin causes sympathoexcitation by acting in the hypothalamus. Recent experiments from our laboratory involving direct measurements of regional sympathetic nerve activity have provided further evidence that insulin acts in the central nervous system. For example, administration of insulin into the third cerebralventricle increased lumbar but not renal or adrenal sympathetic nerve activity in normotensive rats. Interestingly, this pattern of regional sympathetic nerve responses to central neural administration of insulin is similar to that seen with systemic administration of insulin. Further, lesions of the anteroventral third ventricle hypothalamic (AV3V) region abolished increases in sympathetic activity to systemic administration of insulin with euglycemic clamp, suggesting that AV3V-related structures are critical for insulin-induced elevations in sympathetic outflow.

Motor neuron activation in peripheral nerves using infrared neural stimulation

NASA Astrophysics Data System (ADS)

Peterson, E. J.; Tyler, D. J.

2014-02-01

Objective. Localized activation of peripheral axons may improve selectivity of peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized delivery to activate neural tissue. This study investigated INS to determine whether localized delivery limited functionality in larger mammalian nerves. Approach. The rabbit sciatic nerve was stimulated extraneurally with 1875 nm wavelength infrared light, electrical stimulation, or a combination of both. Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG) recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and Tibialis Anterior were the primary output measures. Stimulation applied included infrared-only, electrical-only, and combined infrared and electrical. Main results. 81% of nerves tested were sensitive to INS, with 1.7 ± 0.5 ISR detected per nerve. INS was selective to a single muscle within 81% of identified ISR. Activation energy threshold did not change significantly with stimulus power, but motor activation decreased significantly when radiant power was decreased. Maximum INS levels typically recruited up to 2-9% of any muscle. Combined infrared and electrical stimulation differed significantly from electrical recruitment in 7% of cases. Significance. The observed selectivity of INS indicates that it may be useful in augmenting rehabilitation, but significant challenges remain in increasing sensitivity and response magnitude to improve the functionality of INS.

Motor Neuron Activation in Peripheral Nerves Using Infrared Neural Stimulation

PubMed Central

Peterson, EJ; Tyler, DJ

2014-01-01

Objective Localized activation of peripheral axons may improve selectivity of peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized delivery to activate neural tissue. This study investigated INS to determine whether localized delivery limited functionality in larger mammalian nerves. Approach The rabbit sciatic nerve was stimulated extraneurally with 1875 nm-wavelength infrared light, electrical stimulation, or a combination of both. Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG) recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and Tibialis Anterior were the primary output measures. Stimulation applied included infrared-only, electrical-only, and combined infrared and electrical. Main results 81% of nerves tested were sensitive to INS, with 1.7± 0.5 ISR detected per nerve. INS was selective to a single muscle within 81% of identified ISR. Activation energy threshold did not change significantly with stimulus power, but motor activation decreased significantly when radiant power was decreased. Maximum INS levels typically recruited up to 2–9% of any muscle. Combined infrared and electrical stimulation differed significantly from electrical recruitment in 7% of cases. Significance The observed selectivity of INS indicates it may be useful in augmenting rehabilitation, but significant challenges remain in increasing sensitivity and response magnitude to improve the functionality of INS. PMID:24310923

Contact Activation of Blood Plasma and Factor XII by Ion-exchange Resins

PubMed Central

Yeh, Chyi-Huey Josh; Dimachkie, Ziad O.; Golas, Avantika; Cheng, Alice; Parhi, Purnendu; Vogler, Erwin A.

2011-01-01

Sepharose ion-exchange particles bearing strong Lewis acid/base functional groups (sulfopropyl, carboxymethyl, quarternary ammonium, dimethyl aminoethyl, and iminodiacetic acid) exhibiting high plasma protein adsorbent capacities are shown to be more efficient activators of blood factor XII in neat-buffer solution than either hydrophilic clean-glass particles or hydrophobic octyl sepharose particles ( FXII→surfaceactivatorFXIIa; a.k.a autoactivation, where FXII is the zymogen and FXIIa is a procoagulant protease). In sharp contrast to the clean-glass standard of comparison, ion-exchange activators are shown to be inefficient activators of blood plasma coagulation. These contrasting activation properties are proposed to be due to the moderating effect of plasma-protein adsorption on plasma coagulation. Efficient adsorption of blood plasma proteins unrelated to the coagulation cascade impedes FXII contacts with ion-exchange particles immersed in plasma, reducing autoactivation, and causing sluggish plasma coagulation. By contrast, plasma proteins do not adsorb to hydrophilic clean glass and efficient autoactivation leads directly to efficient activation of plasma coagulation. It is also shown that competitive-protein adsorption can displace FXIIa adsorbed to the surface of ion-exchange resins. As a consequence of highly-efficient autoactivation and FXIIa displacement by plasma proteins, ion-exchange particles are slightly more efficient activators of plasma coagulation than hydrophobic octyl sepharose particles that do not bear strong Lewis acid/base surface functionalities but to which plasma proteins adsorb efficiently. Plasma proteins thus play a dual role in moderating contact activation of the plasma coagulation cascade. The principal role is impeding FXII contact with activating surfaces but this same effect can displace FXIIa from an activating surface into solution where the protease can potentiate subsequent steps of the plasma coagulation cascade. PMID

Demonstrating Electrical Activity in Nerve and Muscle. Part I

ERIC Educational Resources Information Center

Robinson, D. J.

1975-01-01

Describes a demonstration for showing the electrical activity in nerve and muscle including action potentials, refractory period of a nerve, and fatigue. Presents instructions for constructing an amplifier, electronic stimulator, and force transducer. (GS)

Patterning of sympathetic nerve activity in response to vestibular stimulation

NASA Technical Reports Server (NTRS)

Kerman, I. A.; McAllen, R. M.; Yates, B. J.

2000-01-01

Growing evidence suggests a role for the vestibular system in regulation of autonomic outflow during postural adjustments. In the present paper we review evidence for the patterning of sympathetic nerve activity elicited by vestibular stimulation. In response to electrical activation of vestibular afferents, firing of sympathetic nerves located throughout the body is altered. However, activity of the renal nerve is most sensitive to vestibular inputs. In contrast, high-intensity simultaneous activation of cutaneous and muscle inputs elicits equivalent changes in firing of the renal, superior mesenteric and lumbar colonic nerves. Responses of muscle vasoconstrictor (MVC) efferents to vestibular stimulation are either inhibitory (Type I) or are comprised of a combination of excitation and inhibition (Type II). Interestingly, single MVC units located in the hindlimb exhibited predominantly Type I responses while those located in the forelimb and face exhibited Type II responses. Furthermore, brachial and femoral arterial blood flows were dissociated in response to vestibular stimulation, such that brachial vascular resistance increased while femoral resistance decreased. These studies demonstrate that vestibulosympathetic reflexes are patterned according to both the anatomical location and innervation target of a particular sympathetic nerve, and can lead to distinct changes in local blood flow.

Expression of cancer-related carbonic anhydrases IX and XII in normal skin and skin neoplasms.

PubMed

Syrjänen, Leo; Luukkaala, Tiina; Leppilampi, Mari; Kallioinen, Matti; Pastorekova, Silvia; Pastorek, Jaromir; Waheed, Abdul; Sly, William S; Parkkila, Seppo; Karttunen, Tuomo

2014-09-01

Purpose of the study was to evaluate the presence of hypoxia-inducible, tumour-associated carbonic anhydrases IX and XII in normal skin and a series of cutaneous tumours. Human tumour samples were taken during surgical operations performed on 245 patients and were immunohistochemically stained. A histological score value was calculated for statistical analyses which were performed using SPSS for Windows, versions 17.0 and 20.0. In normal skin, the highest expression of CA IX was detected in hair follicles, sebaceous glands, and basal parts of epidermis. CA XII was detected in all epithelial components of skin. Both CA IX and CA XII expression levels were significantly different in epidermal, appendigeal, and melanocytic tumour categories. Both CA IX and XII showed the most intense immunostaining in epidermal tumours, whereas virtually all melanocytic tumours were devoid of CA IX and XII immunostaining. In premalignant lesions, CA IX expression significantly increased when the tumours progressed to more severe dysplasia forms. Both CA IX and XII are highly expressed in different epithelial components of skin. They are also highly expressed in epidermal tumours, in which CA IX expression levels also correlate with the dysplasia grade. Interestingly, both isozymes are absent in melanocytic tumours. © 2014 APMIS. Published by John Wiley & Sons Ltd.

M. leprae components induce nerve damage by complement activation: identification of lipoarabinomannan as the dominant complement activator.

PubMed

Bahia El Idrissi, Nawal; Das, Pranab K; Fluiter, Kees; Rosa, Patricia S; Vreijling, Jeroen; Troost, Dirk; Morgan, B Paul; Baas, Frank; Ramaglia, Valeria

2015-05-01

Peripheral nerve damage is the hallmark of leprosy pathology but its etiology is unclear. We previously identified the membrane attack complex (MAC) of the complement system as a key determinant of post-traumatic nerve damage and demonstrated that its inhibition is neuroprotective. Here, we determined the contribution of the MAC to nerve damage caused by Mycobacterium leprae and its components in mouse. Furthermore, we studied the association between MAC and the key M. leprae component lipoarabinomannan (LAM) in nerve biopsies of leprosy patients. Intraneural injections of M. leprae sonicate induced MAC deposition and pathological changes in the mouse nerve, whereas MAC inhibition preserved myelin and axons. Complement activation occurred mainly via the lectin pathway and the principal activator was LAM. In leprosy nerves, the extent of LAM and MAC immunoreactivity was robust and significantly higher in multibacillary compared to paucibacillary donors (p = 0.01 and p = 0.001, respectively), with a highly significant association between LAM and MAC in the diseased samples (r = 0.9601, p = 0.0001). Further, MAC co-localized with LAM on axons, pointing to a role for this M. leprae antigen in complement activation and nerve damage in leprosy. Our findings demonstrate that MAC contributes to nerve damage in a model of M. leprae-induced nerve injury and its inhibition is neuroprotective. In addition, our data identified LAM as the key pathogen associated molecule that activates complement and causes nerve damage. Taken together our data imply an important role of complement in nerve damage in leprosy and may inform the development of novel therapeutics for patients.

Zebrafish collagen XII is present in embryonic connective tissue sheaths (fascia) and basement membranes.

PubMed

Bader, Hannah L; Keene, Douglas R; Charvet, Benjamin; Veit, Guido; Driever, Wolfgang; Koch, Manuel; Ruggiero, Florence

2009-01-01

Connective tissues ensure the cohesion of the tissues of the body, but also form specialized structures such as tendon and bone. Collagen XII may enhance the stability of connective tissues by bridging collagen fibrils, but its function is still unclear. Here, we used the zebrafish model to visualize its expression pattern in the whole organism. The zebrafish col12a1 gene is homologous to the small isoform of the tetrapod col12a1 gene. In agreement with the biochemical data reported for the small isoform, the zebrafish collagen XII alpha1 chain was characterized as a collagenase sensitive band migrating at approximately 200 kDa. Using newly generated polyclonal antibodies and anti-sense probes, we performed a comprehensive analysis of its expression in developing zebrafish. Collagen XII exhibited a much broader expression pattern than previously thought: it was ubiquitously expressed in the connective tissue sheaths (fascia) that encase the tissues and organs of the body. For example, it was found in sclera, meninges, epimysia and horizontal and vertical myosepta. Collagen XII was also detected in head mesenchyme, pharyngeal arches and within the spinal cord, where it was first expressed within and then at the lateral borders of the floor plate and at the dorsal midline. Furthermore, double immunofluorescence staining with laminin and immunogold electron microscopy revealed that collagen XII is associated with basement membranes. These data suggest that collagen XII is implicated in tissue cohesion by stabilizing fascia and by linking fascia to basement membranes.

Optimizing the design of bipolar nerve cuff electrodes for improved recording of peripheral nerve activity.

PubMed

Sabetian, Parisa; Popovic, Milos R; Yoo, Paul B

2017-06-01

Differential measurement of efferent and afferent peripheral nerve activity offers a promising means of improving the clinical utility of implantable neuroprostheses. The tripolar nerve cuff electrode has historically served as the gold standard for achieving high signal-to-noise ratios (SNRs) of the recordings. However, the symmetrical geometry of this electrode array (i.e. electrically-shorted side contacts) precludes it from measuring electrical signals that can be used to obtain directional information. In this study, we investigated the feasibility of using a bipolar nerve cuff electrode to achieve high-SNR of peripheral nerve activity. A finite element model was implemented to investigate the effects of electrode design parameters-electrode length, electrode edge length (EEL), and a conductive shielding layer (CSL)-on simulated single fiber action potentials (SFAP) and also artifact noise signals (ANS). Our model revealed that the EEL was particularly effective in increasing the peak-to-peak amplitude of the SFAP (319%) and reducing the common mode ANS (67%) of the bipolar cuff electrode. By adding a CSL to the bipolar cuff electrode, the SNR was found to be 65.2% greater than that of a conventional tripolar cuff electrode. In vivo experiments in anesthetized rats confirmed that a bipolar cuff electrode can achieve a SNR that is 38% greater than that achieved by a conventional tripolar cuff electrode (p  <  0.05). The current study showed that bipolar nerve cuff electrodes can be designed to achieve SNR levels that are comparable to that of tripolar configuration. Further work is needed to confirm that these bipolar design parameters can be used to record bi-directional neural activity in a physiological setting.

Cranial nerve involvement in nasopharyngeal carcinoma: response to radiotherapy and its clinical impact.

PubMed

Li, Jian-Cheng; Mayr, Nina A; Yuh, William T C; Wang, Jian Z; Jiang, Guo-Liang

2006-05-01

To evaluate the cranial nerve (CN) palsy associated with nasopharyngeal carcinoma (NPC), we studied factors that influenced the neurologic outcome of radiotherapy (RT), and the patterns and time course of neurologic recovery of CN palsy. Between July 1987 and July 1989, 93 patients who presented with CN palsy at the time of diagnosis of NPC were studied. All patients underwent external-beam RT with either cobalt-60 or 6-MV photon beams to a dose of 69 to 84 Gy at 2 Gy per fraction. The time course and pattern of neurologic recovery (complete, partial, or none) from CN palsy were evaluated. Age, sex, stage, histology, incidence and distribution of types of CNs involved, duration of CN palsy, and time course of tumor response during RT were correlated with the patterns and the time course of neurologic CN recovery by univariate and multivariate analyses. The cases of CN palsy most commonly involved CN V (38%), CN VI (26%), and CN XII (11%), which accounted for the majority of the cases (75%). The time course of CN recovery was variable and protracted. Most patients showed significant improvement upon completion of RT (51%, 19%, and 30% complete, partial, and no recovery, respectively) and further improvement 6 months after RT (58%, 17%, and 25%, respectively). Cranial nerves V, VI, and XII accounted for 75% of cases with no recovery. Recovery was best for CNs II, IX, and XI and the sympathetic nerve (100%, 87%, 100%, and 100%, respectively) and worst for CNs IV, VII, and XII (67%, 60%, and 40%, respectively, with no recovery). Neurologic CN recovery correlated significantly with the pretherapy duration (<3 months versus > or =3 months) of CN palsy (88% versus 62%; p = .002, multivariate analysis), the time course of clinical tumor regression, and neurologic symptom improvement during RT. Age, sex, T stage, N stage, histology, anterior versus posterior CN palsies, and base of skull involvement were not significant. According to our limited data, most patients with CN

Loss of carbonic anhydrase XII function in individuals with elevated sweat chloride concentration and pulmonary airway disease.

PubMed

Lee, Melissa; Vecchio-Pagán, Briana; Sharma, Neeraj; Waheed, Abdul; Li, Xiaopeng; Raraigh, Karen S; Robbins, Sarah; Han, Sangwoo T; Franca, Arianna L; Pellicore, Matthew J; Evans, Taylor A; Arcara, Kristin M; Nguyen, Hien; Luan, Shan; Belchis, Deborah; Hertecant, Jozef; Zabner, Joseph; Sly, William S; Cutting, Garry R

2016-05-15

Elevated sweat chloride levels, failure to thrive (FTT), and lung disease are characteristic features of cystic fibrosis (CF, OMIM #219700). Here we describe variants in CA12 encoding carbonic anhydrase XII in two pedigrees exhibiting CF-like phenotypes. Exome sequencing of a white American adult diagnosed with CF due to elevated sweat chloride, recurrent hyponatremia, infantile FTT and lung disease identified deleterious variants in each CA12 gene: c.908-1 G>A in a splice acceptor and a novel frameshift insertion c.859_860insACCT. In an unrelated consanguineous Omani family, two children with elevated sweat chloride, infantile FTT, and recurrent hyponatremia were homozygous for a novel missense variant (p.His121Gln). Deleterious CFTR variants were absent in both pedigrees. CA XII protein was localized apically in human bronchiolar epithelia and basolaterally in the reabsorptive duct of human sweat glands. Respiratory epithelial cell RNA from the adult proband revealed only aberrant CA12 transcripts and in vitro analysis showed greatly reduced CA XII protein. Studies of ion transport across respiratory epithelial cells in vivo and in culture revealed intact CFTR-mediated chloride transport in the adult proband. CA XII protein bearing either p.His121Gln or a previously identified p.Glu143Lys missense variant localized to the basolateral membranes of polarized Madin-Darby canine kidney (MDCK) cells, but enzyme activity was severely diminished when assayed at physiologic concentrations of extracellular chloride. Our findings indicate that loss of CA XII function should be considered in individuals without CFTR mutations who exhibit CF-like features in the sweat gland and lung. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Optimizing the design of bipolar nerve cuff electrodes for improved recording of peripheral nerve activity

NASA Astrophysics Data System (ADS)

Sabetian, Parisa; Popovic, Milos R.; Yoo, Paul B.

2017-06-01

Objective. Differential measurement of efferent and afferent peripheral nerve activity offers a promising means of improving the clinical utility of implantable neuroprostheses. The tripolar nerve cuff electrode has historically served as the gold standard for achieving high signal-to-noise ratios (SNRs) of the recordings. However, the symmetrical geometry of this electrode array (i.e. electrically-shorted side contacts) precludes it from measuring electrical signals that can be used to obtain directional information. In this study, we investigated the feasibility of using a bipolar nerve cuff electrode to achieve high-SNR of peripheral nerve activity. Approach. A finite element model was implemented to investigate the effects of electrode design parameters—electrode length, electrode edge length (EEL), and a conductive shielding layer (CSL)—on simulated single fiber action potentials (SFAP) and also artifact noise signals (ANS). Main results. Our model revealed that the EEL was particularly effective in increasing the peak-to-peak amplitude of the SFAP (319%) and reducing the common mode ANS (67%) of the bipolar cuff electrode. By adding a CSL to the bipolar cuff electrode, the SNR was found to be 65.2% greater than that of a conventional tripolar cuff electrode. In vivo experiments in anesthetized rats confirmed that a bipolar cuff electrode can achieve a SNR that is 38% greater than that achieved by a conventional tripolar cuff electrode (p  <  0.05). Significance. The current study showed that bipolar nerve cuff electrodes can be designed to achieve SNR levels that are comparable to that of tripolar configuration. Further work is needed to confirm that these bipolar design parameters can be used to record bi-directional neural activity in a physiological setting.

Reflex effects on components of synchronized renal sympathetic nerve activity.

PubMed

DiBona, G F; Jones, S Y

1998-09-01

The effects of peripheral thermal receptor stimulation (tail in hot water, n = 8, anesthetized) and cardiac baroreceptor stimulation (volume loading, n = 8, conscious) on components of synchronized renal sympathetic nerve activity (RSNA) were examined in rats. The peak height and peak frequency of synchronized RSNA were determined. The renal sympathoexcitatory response to peripheral thermal receptor stimulation was associated with an increase in the peak height. The renal sympathoinhibitory response to cardiac baroreceptor stimulation was associated with a decrease in the peak height. Although heart rate was significantly increased with peripheral thermal receptor stimulation and significantly decreased with cardiac baroreceptor stimulation, peak frequency was unchanged. As peak height reflects the number of active fibers, reflex increases and decreases in synchronized RSNA are mediated by parallel increases and decreases in the number of active renal nerve fibers rather than changes in the centrally based rhythm or peak frequency. The increase in the number of active renal nerve fibers produced by peripheral thermal receptor stimulation reflects the engagement of a unique group of silent renal sympathetic nerve fibers with a characteristic response pattern to stimulation of arterial baroreceptors, peripheral and central chemoreceptors, and peripheral thermal receptors.

77 FR 13317 - Lock+ Hydro Friends Fund XII, BOST2, LLC, et al.; Notice Announcing Filing Priority for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-06

... al.] Lock+ Hydro Friends Fund XII, BOST2, LLC, et al.; Notice Announcing Filing Priority for Preliminary Permit Applications Project No. Lock+ Hydro Friends Fund XII 14260-000 BOST2, LLC 14264-000.... 2. BOST2, LLC: Project No. 14264-000. 3. Lock+ Hydro Friends Fund XII: Project No. 14260-000. 4...

Natural history and clinical manifestations of hyponatremia and hyperchlorhidrosis due to carbonic anhydrase XII deficiency.

PubMed

Feinstein, Yael; Yerushalmi, Baruch; Loewenthal, Neta; Alkrinawi, Soliman; Birk, Ohad S; Parvari, Ruti; Hershkovitz, Eli

2014-01-01

We identified patients of Bedouin origin with a mutation in carbonic anhydrase XII (CA XII) leading to hyponatremia due to excessive salt loss via sweat. The medical records of patients were reviewed for clinical and laboratory data. A total of 11 subjects were identified; 7 symptomatic patients presented with hyponatremic dehydration in infancy. Screening of the entire kindred identified 4 asymptomatic individuals with elevated sweat chloride. All symptomatic patients had failure to thrive and moderate-severe hyponatremia (106-124 mmol·l(-1)); 6 had hypochloremia (79-94 mmol·l(-1)). All asymptomatic subjects had normal or near-normal serum sodium and chloride concentrations. Both symptomatic and asymptomatic subjects had normal renal functions and normal cortisol response on low-dose ACTH test. All symptomatic patients were treated by dietary salt, which prevents episodes of hyponatremic dehydration and promotes growth. At follow-up, the chief complaints remained heat intolerance, accumulation of salt precipitates on the face and hyperhidrosis. No evidence for chronic renal, respiratory, gastrointestinal or fertility abnormalities was found. Recognizing this newly described entity and differentiating it from cystic fibrosis and pseudohypoaldosteronism are important. Patients with CA XII mutations should be followed even after early childhood, especially in hot temperatures and intense physical activity. © 2014 S. Karger AG, Basel.

Computational investigation of the selectivity of salen and tetrahydrosalen compounds towards the tumor-associated hCA XII isozyme.

PubMed

Akdemir, Atilla; De Monte, Celeste; Carradori, Simone; Supuran, Claudiu T

2015-02-01

In previous work, 14 salen and tetrahydrosalen compounds have been synthesized and tested in enzyme inhibition assays against cytosolic human carbonic anhydrase isozymes I and II (hCA I and II) and tumor-associated isozymes IX and XII (hCA IX and XII). These compounds show selectivity against hCA XII over hCA I, II and IX. In this study, molecular modeling and docking studies were applied to understand this preference of the compounds for hCA XII. Most likely, the compounds can displace the zinc-bound water molecule of hCA XII to form a direct interaction with the Zn(2+) ion. In the other isozymes, the compounds might not be able to displace the water molecule nor are they expected to interact with the Zn(2+) ion.

In vivo predegeneration of peripheral nerves: an effective technique to obtain activated Schwann cells for nerve conduits.

PubMed

Keilhoff, G; Fansa, H; Schneider, W; Wolf, G

1999-07-01

In vivo predegeneration of peripheral nerves is presented as a convenient and effective method to obtain activated Schwann cells and an enhanced cell yield following in vitro cultivation. The experiments conducted in rats were aimed at clinical use in gaining Schwann cell suspensions for filling artificial conduits in order to bridge peripheral nerve gaps. The rat sciatic nerve used as a model was transected distally to the spinal ganglia. Predegeneration in vivo was allowed to take place for 1, 2, 3 and 4 days and up to 1, 2 and 3 weeks. The nerve was then resected and prepared for cell cultivation. Schwann cells cultivated from the contralateral untreated nerve served as control. Immunostaining for S100, nerve growth factor receptor and the adhesion molecules N-cadherin and L1 was used to characterize the general state of the cultures. Viability was assessed by fluorescein fluorescence staining, and the proliferation index was determined by bromodeoxyuridine-DNA incorporation. The Schwann cells from predegenerated nerves revealed an increased proliferation rate compared to the control, whereas fibroblast contamination was decreased. Best results were obtained 1 week after predegeneration.

77 FR 59669 - Comment Request for Information Collection; Unemployment Insurance (UI) Title XII Advances and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-28

... Collection; Unemployment Insurance (UI) Title XII Advances and Voluntary Repayment Process; Extension Without... assessed. Currently, ETA is soliciting comments concerning the collection process for data on UI Title XII... request (ICR) can be obtained by contacting Mr. Gibbons. SUPPLEMENTARY INFORMATION: I. Background Title...

Resveratrol Promotes Nerve Regeneration via Activation of p300 Acetyltransferase-Mediated VEGF Signaling in a Rat Model of Sciatic Nerve Crush Injury.

PubMed

Ding, Zhuofeng; Cao, Jiawei; Shen, Yu; Zou, Yu; Yang, Xin; Zhou, Wen; Guo, Qulian; Huang, Changsheng

2018-01-01

Peripheral nerve injuries are generally associated with incomplete restoration of motor function. The slow rate of nerve regeneration after injury may account for this. Although many benefits of resveratrol have been shown in the nervous system, it is not clear whether resveratrol could promote fast nerve regeneration and motor repair after peripheral nerve injury. This study showed that the motor deficits caused by sciatic nerve crush injury were alleviated by daily systematic resveratrol treatment within 10 days. Resveratrol increased the number of axons in the distal part of the injured nerve, indicating enhanced nerve regeneration. In the affected ventral spinal cord, resveratrol enhanced the expression of several vascular endothelial growth factor family proteins (VEGFs) and increased the phosphorylation of p300 through Akt signaling, indicating activation of p300 acetyltransferase. Inactivation of p300 acetyltransferase reversed the resveratrol-induced expression of VEGFs and motor repair in rats that had undergone sciatic nerve crush injury. The above results indicated that daily systematic resveratrol treatment promoted nerve regeneration and led to rapid motor repair. Resveratrol activated p300 acetyltransferase-mediated VEGF signaling in the affected ventral spinal cord, which may have thus contributed to the acceleration of nerve regeneration and motor repair.

Effect of endogenous angiotensin II on renal nerve activity and its cardiac baroreflex regulation.

PubMed

Dibona, G F; Jones, S Y; Sawin, L L

1998-11-01

The effects of physiologic alterations in endogenous angiotensin II activity on basal renal sympathetic nerve activity and its cardiac baroreflex regulation were studied. The effect of angiotensin II type 1 receptor blockade with intracerebroventricular losartan was examined in conscious rats consuming a low, normal, or high sodium diet that were instrumented for the simultaneous measurement of right atrial pressure and renal sympathetic nerve activity. The gain of cardiac baroreflex regulation of renal sympathetic nerve activity (% delta renal sympathetic nerve activity/mmHg mean right atrial pressure) was measured during isotonic saline volume loading. Intracerebroventricular losartan did not decrease arterial pressure but significantly decreased renal sympathetic nerve activity in low (-36+/-6%) and normal (-24+/-5%), but not in high (-2+/-3%) sodium diet rats. Compared with vehicle treatment, losartan treatment significantly increased cardiac baroreflex gain in low (-3.45+/-0.20 versus -2.89+/-0.17) and normal (-2.89+/-0.18 versus -2.54+/-0.14), but not in high (-2.27+/-0.15 versus -2.22+/-0.14) sodium diet rats. These results indicate that physiologic alterations in endogenous angiotensin II activity tonically influence basal levels of renal sympathetic nerve activity and its cardiac baroreflex regulation.

High-resolution measurement of electrically-evoked vagus nerve activity in the anesthetized dog

NASA Astrophysics Data System (ADS)

Yoo, Paul B.; Lubock, Nathan B.; Hincapie, Juan G.; Ruble, Stephen B.; Hamann, Jason J.; Grill, Warren M.

2013-04-01

Objective. Not fully understanding the type of axons activated during vagus nerve stimulation (VNS) is one of several factors that limit the clinical efficacy of VNS therapies. The main goal of this study was to characterize the electrical recruitment of both myelinated and unmyelinated fibers within the cervical vagus nerve. Approach. In anesthetized dogs, recording nerve cuff electrodes were implanted on the vagus nerve following surgical excision of the epineurium. Both the vagal electroneurogram (ENG) and laryngeal muscle activity were recorded in response to stimulation of the right vagus nerve. Main results. Desheathing the nerve significantly increased the signal-to-noise ratio of the ENG by 1.2 to 9.9 dB, depending on the nerve fiber type. Repeated VNS following nerve transection or neuromuscular block (1) enabled the characterization of A-fibers, two sub-types of B-fibers, and unmyelinated C-fibers, (2) confirmed the absence of stimulation-evoked reflex compound nerve action potentials in both the ipsilateral and contralateral vagus nerves, and (3) provided evidence of stimulus spillover into muscle tissue surrounding the stimulating electrode. Significance. Given the anatomical similarities between the canine and human vagus nerves, the results of this study provide a template for better understanding the nerve fiber recruitment patterns associated with VNS therapies.

Dangerous extracranial-intracranial anastomoses and supply to the cranial nerves: vessels the neurointerventionalist needs to know.

PubMed

Geibprasert, S; Pongpech, S; Armstrong, D; Krings, T

2009-09-01

Transarterial embolization in the external carotid artery (ECA) territory has a major role in the endovascular management of epistaxis, skull base tumors, and dural arteriovenous fistulas. Knowledge of the potential anastomotic routes, identification of the cranial nerve supply from the ECA, and the proper choice of embolic material are crucial to help the interventionalist avoid neurologic complications during the procedure. Three regions along the skull base constitute potential anastomotic routes between the extracranial and intracranial arteries: the orbital, the petrocavernous, and the upper cervical regions. Branches of the internal maxillary artery have anastomoses with the ophthalmic artery and petrocavernous internal carotid artery (ICA), whereas the branches of the ascending pharyngeal artery are connected to the petrocavernous ICA. Branches of both the ascending pharyngeal artery and the occipital artery have anastomoses with the vertebral artery. To avoid cranial nerve palsy, one must have knowledge of the supply to the lower cranial nerves: The petrous branch of the middle meningeal artery and the stylomastoid branch of the posterior auricular artery form the facial arcade as the major supply to the facial nerve, and the neuromeningeal trunk of the ascending pharyngeal artery supplies the lower cranial nerves (CN IX-XII).

Laser-activated solid protein bands for peripheral nerve repair: an vivo study.

PubMed

Lauto, A; Trickett, R; Malik, R; Dawes, J M; Owen, E R

1997-01-01

Severed tibial nerves in rats were repaired using a novel technique, utilizing a semiconductor diode-laser-activated protein solder applied longitudinally across the join. Welding was produced by selective laser denaturation of solid solder bands containing the dye indocyanine green. An in vivo study, using 48 adult male Wistar rats, compared conventional microsuture-repaired tibial nerves with laser solder-repaired nerves. Nerve repairs were characterised immediately after surgery and after 3 months. Successful regeneration with average compound muscle action potentials of 2.5 +/- 0.5 mV and 2.7 +/- 0.3 mV (mean and standard deviation) was demonstrated for the laser-soldered nerves and the sutured nerves, respectively. Histopathology confirmed comparable regeneration of axons in laser- and suture-operated nerves. The laser-based nerve repair technique was easier and faster than microsuture repair, minimising manipulation damage to the nerve.

76 FR 75563 - Notice for Delay of Payment of Title XII Interest for Three States

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-02

... DEPARTMENT OF LABOR Employment and Training Administration Notice for Delay of Payment of Title.... SUMMARY: This notice announces the approval for delay of Title XII interest payment for three states... Title XII advances made during the last five months of the Federal fiscal year (FY) (May, June, July...

40 CFR Appendix Xii to Part 86 - Tables for Production Compliance Auditing of Heavy-Duty Engines and Heavy-Duty Vehicles...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 19 2010-07-01 2010-07-01 false Tables for Production Compliance Auditing of Heavy-Duty Engines and Heavy-Duty Vehicles, Including Light-Duty Trucks XII Appendix XII to... Appendix XII to Part 86—Tables for Production Compliance Auditing of Heavy-Duty Engines and Heavy-Duty...

Hypothalamic stimulation and baroceptor reflex interaction on renal nerve activity.

NASA Technical Reports Server (NTRS)

Wilson, M. F.; Ninomiya, I.; Franz, G. N.; Judy, W. V.

1971-01-01

The basal level of mean renal nerve activity (MRNA-0) measured in anesthetized cats was found to be modified by the additive interaction of hypothalamic and baroceptor reflex influences. Data were collected with the four major baroceptor nerves either intact or cut, and with mean aortic pressure (MAP) either clamped with a reservoir or raised with l-epinephrine. With intact baroceptor nerves, MRNA stayed essentially constant at level MRNA-0 for MAP below an initial pressure P1, and fell approximately linearly to zero as MAP was raised to P2. Cutting the baroceptor nerves kept MRNA at MRNA-0 (assumed to represent basal central neural output) independent of MAP. The addition of hypothalamic stimulation produced nearly constant increments in MRNA for all pressure levels up to P2, with complete inhibition at some level above P2. The increments in MRNA depended on frequency and location of the stimulus. A piecewise linear model describes MRNA as a linear combination of hypothalamic, basal central neural, and baroceptor reflex activity.

Patterns of motor activity in the isolated nerve cord of the octopus arm.

PubMed

Gutfreund, Yoram; Matzner, Henry; Flash, Tamar; Hochner, Binyamin

2006-12-01

The extremely flexible octopus arm provides a unique opportunity for studying movement control in a highly redundant motor system. We describe a novel preparation that allows analysis of the peripheral nervous system of the octopus arm and its interaction with the muscular and mechanosensory elements of the arm's intrinsic muscular system. First we examined the synaptic responses in muscle fibers to identify the motor pathways from the axial nerve cord of the arm to the surrounding musculature. We show that the motor axons project to the muscles via nerve roots originating laterally from the arm nerve cord. The motor field of each nerve is limited to the region where the nerve enters the arm musculature. The same roots also carry afferent mechanosensory information from the intrinsic muscle to the axial nerve cord. Next, we characterized the pattern of activity generated in the dorsal roots by electrically stimulating the axial nerve cord. The evoked activity, although far reaching and long lasting, cannot alone account for the arm extension movements generated by similar electrical stimulation. The mismatch between patterns of activity in the isolated cord and in an intact arm may stem from the involvement of mechanosensory feedback in natural arm extension.

Nerve transection repair using laser-activated chitosan in a rat model.

PubMed

Bhatt, Neel K; Khan, Taleef R; Mejias, Christopher; Paniello, Randal C

2017-08-01

Cranial nerve transection during head and neck surgery is conventionally repaired with microsuture. Previous studies have demonstrated recovery with laser nerve welding (LNW), a novel alternative to microsuture. LNW has been reported to have poorer tensile strength, however. Laser-activated chitosan, an adhesive biopolymer, may promote nerve recovery while enhancing the tensile strength of the repair. Using a rat posterior tibial nerve injury model, we compared four different methods of nerve repair in this pilot study. Animal study. Animals underwent unilateral posterior tibial nerve transection. The injury was repaired by potassium titanyl phosphate (KTP) laser alone (n = 20), KTP + chitosan (n = 12), microsuture + chitosan (n = 12), and chitosan alone (n = 14). Weekly walking tracks were conducted to measure functional recovery (FR). Tensile strength (TS) was measured at 6 weeks. At 6 weeks, KTP laser alone had the best recovery (FR = 93.4% ± 8.3%). Microsuture + chitosan, KTP + chitosan, and chitosan alone all showed good FR (87.4% ± 13.5%, 84.6% ± 13.0%, and 84.1% ± 10.0%, respectively). One-way analysis of variance was performed (F(3,56) = 2.6, P = .061). A TS threshold of 3.8 N was selected as a control mean recovery. Three groups-KTP alone, KTP + chitosan, and microsuture + chitosan-were found to meet threshold 60% (95% confidence interval [CI]: 23.1%-88.3%), 75% (95% CI: 46.8%-91.1%), and 100% (95% CI: 75.8%-100.0%), respectively. In the posterior tibial nerve model, all repair methods promoted nerve recovery. Laser-activated chitosan as a biopolymer anchor provided good TS and appears to be a novel alternative to microsuture. This repair method may have surgical utility following cranial nerve injury during head and neck surgery. NA Laryngoscope, 127:E253-E257, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Influence of Different Geometric Representations of the Volume Conductor on Nerve Activation during Electrical Stimulation

PubMed Central

Gómez-Tames, José; González, José; Yu, Wenwei

2014-01-01

Volume conductor models with different geometric representations, such as the parallel layer model (PM), the cylindrical layer model (CM), or the anatomically based model (AM), have been employed during the implementation of bioelectrical models for electrical stimulation (FES). Evaluating their strengths and limitations to predict nerve activation is fundamental to achieve a good trade-off between accuracy and computation time. However, there are no studies aimed at clarifying the following questions. (1) Does the nerve activation differ between CM and PM? (2) How well do CM and PM approximate an AM? (3) What is the effect of the presence of blood vessels and nerve trunk on nerve activation prediction? Therefore, in this study, we addressed these questions by comparing nerve activation between CM, PM, and AM models by FES. The activation threshold was used to evaluate the models under different configurations of superficial electrodes (size and distance), nerve depths, and stimulation sites. Additionally, the influences of the sciatic nerve, femoral artery, and femoral vein were inspected for a human thigh. The results showed that the CM and PM had a high error rate, but the variation of the activation threshold followed the same tendency for electrode size and interelectrode distance variation as AM. PMID:25276222

Hericium erinaceus (Bull.: Fr.) Pers., a medicinal mushroom, activates peripheral nerve regeneration.

PubMed

Wong, Kah-Hui; Kanagasabapathy, Gowri; Naidu, Murali; David, Pamela; Sabaratnam, Vikineswary

2016-10-01

To study the ability of aqueous extract of Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats. Aqueous extract of Hericium erinaceus was given by daily oral administration following peroneal nerve crush injury in Sprague-Dawley rats. The expression of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways; and c-Jun and c-Fos genes were studied in dorsal root ganglia (DRG) whereas the activity of protein synthesis was assessed in peroneal nerves by immunohistochemical method. Peripheral nerve injury leads to changes at the axonal site of injury and remotely located DRG containing cell bodies of sensory afferent neurons. Immunofluorescence studies showed that DRG neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt, MAPK, c-Jun and c-Fos as compared with negative control group (P <0.05). The intensity of nuclear ribonucleoprotein in the distal segments of crushed nerves of treated groups was significantly higher than in the negative control group (P <0.05). H. erinaceus is capable of promoting peripheral nerve regeneration after injury. Potential signaling pathways include Akt, MAPK, c-Jun, and c-Fos, and protein synthesis have been shown to be involved in its action.

The Secondary Structure of Human Hageman Factor (Factor XII) and its Alteration by Activating Agents

PubMed Central

McMillin, Carl R.; Saito, Hidehiko; Ratnoff, Oscar D.; Walton, Alan G.

1974-01-01

Hageman factor (factor XII) is activated by exposure to surfaces such as glass or by solutions of certain compounds, notably ellagic acid. Changes in the structure of Hageman factor accompanying activation have been examined in this study by circular dichroism spectroscopy. The spectrum of unactivated Hageman factor in aqueous solutions suggests that its conformation is mainly aperiodic. Various perturbants altered the conformation of Hageman factor in differing ways, demonstrating the sensitivity of Hageman factor to its environment. After activation of Hageman factor with solutions of ellagic acid, a negative trough appeared in the region of the circular dichroism spectrum commonly assigned to tyrosine residues, along with other minor changes in the peptide spectral region. Some of these changes are similar to changes that occurred upon partial neutralization of the basic residues at alkali pH. Activation of Hageman factor by adsorption to quartz surfaces (in an aqueous environment) also produced changes similar to those in the ellagic acid-activated Hageman factor, including the negative ellipticity in the tyrosine region. These observations suggest that the activation process may be related to a change in status of some of the basic amino acid residues, coupled with a specific change in the environment of some tyrosine residues. The importance of these changes during the activation process remains to be determined. The sensitivity of Hageman factor to its environment is consistent with the view that the initiation of clotting by exposure of plasma to appropriate agents is brought about by alterations in the conformation of Hageman factor that occur in the apparent absence of Fletcher factor or other recognized clotting factors. Images PMID:4373492

Effect of upper extremity nerve damage on activity participation, pain, depression, and quality of life.

PubMed

Bailey, Ryan; Kaskutas, Vicki; Fox, Ida; Baum, Carolyn M; Mackinnon, Susan E

2009-11-01

To explore the relationship between upper extremity nerve damage and activity participation, pain, depression, and perceived quality of life. A total of 49 patients with upper extremity nerve damage completed standardized measures of activity participation, pain, depression, and quality of life. We analyzed scores for all subjects and for 2 diagnostic groups: patients with compressive neuropathy and patients with nerve injury (laceration, tumor, and brachial plexus injury), and explored predictors of overall quality of life. Participants had given up 21% of their previous daily activities; greater activity loss was reported in patients with nerve injury. Pain was moderate and 39% had signs of clinical depression. Physical and psychological quality of life ratings were below the norms. Activity loss was strongly associated with higher levels of depression and lower physical and psychological quality of life. Higher depression scores correlated strongly with lower overall quality of life. Greater pain correlated moderately with higher depression scores and weakly with quality of life; no statistical relationship was found between pain and physical quality of life. Activity participation and depression predicted 61% of the variance in overall quality of life in patients with nerve damage. The results of this study suggest that hand surgeons and therapists caring for patients with nerve compression and nerve injury should discuss strategies to improve activity participation, and decrease pain and depression, to improve overall effect on quality of life throughout the recovery process. Depression screening and referral when indicated should be included in the overall treatment plan for patients with upper extremity nerve damage. Prognostic IV.

[Imaging anatomy of the cranial nerves using 3.0 Tesla MRI: a practical review for clinicians].

PubMed

Chávez-Barba, Oscar; Martínez-Martínez, Lidieth; Cazares-Arellano, José Luis; Martínez-López, Manuel; Roldan-Valadez, Ernesto

2011-01-01

Magnetic resonance (MR) imaging is the method of choice to evaluate the cranial nerves (CN). These nerves constitute a group of structures that have acquired during their phylogenetic development a high degree of specialization. There are 12 pairs of CN to which we use their specific name or number. The olfactory (I) and optic (II) pairs are not real nerves but tracts from the encephalon. The spinal nerve (XI) derives from superior cervical segment of the spine. The other 9 pairs of CN are related with the brain stem. Although the skull base foramina can be seen on computed tomography, the nerves themselves can only be visualized in detail on MR. That means, in order to see the different segments of nerves I to XII, the right sequences must be used. It is important to provide detailed clinical information to the radiologist so that a tailored MR study can be performed. In this review, the basic imaging anatomy of the 12 CN is discussed and illustrated briefly with an emphasis on more advanced extra-axial anatomy, illustrated with high-resolution MR images. Clinicians looking for complete anatomic descriptions and/or MR illustrations are advised to consult specialized textbooks considering it is not possible to describe all of the anatomy in one article. This manuscript is intended to be a practical review for clinicians.

Characterization of the interactions of type XII collagen with two small proteoglycans from fetal bovine tendon, decorin and fibromodulin.

PubMed

Font, B; Eichenberger, D; Rosenberg, L M; van der Rest, M

1996-11-01

In addition to the major collagens, such as type I or type II, connective tissues contain a number of less abundant collagens and proteoglycans, whose association contributes to the different properties of the tissues. Type XII and type XIV collagens have been described in soft connective tissues, and type XIV collagen has been shown to interact specifically with decorin through its glycosaminoglycan chain (Font et al., J. Biol. Chem. 268, 25015-25018, 1993). Interactions between these collagens and the small proteoglycans have been characterized further by studying the binding of type XII collagen to decorin by solid phase assays. Our results show a saturable binding of the proteoglycan through its glycosaminoglycan chain to type XII collagen, which does not seem to involve the large non-collagenous NC3 domain of the molecule. This interaction is strongly inhibited by heparin. Furthermore, we report that another small proteoglycan, fibromodulin, isolated from tendon under non-denaturing conditions, is able to bind to type XII collagen. This interaction has been characterized and, unlike that observed with decorin, type XII collagen-fibromodulin interaction seems to take place with the core protein of the proteoglycan. In addition, we report that type XII-type I collagen interactions are not necessarily mediated by decorin as previously suggested.

Functional significance of the pattern of renal sympathetic nerve activation.

PubMed

Dibona, G F; Sawin, L L

1999-08-01

To assess the renal functional significance of the pattern of renal sympathetic nerve activation, computer-generated stimulus patterns (delivered at constant integrated voltage) were applied to the decentralized renal sympathetic nerve bundle and renal hemodynamic and excretory responses determined in anesthetized rats. When delivered at the same integrated voltage, stimulus patterns resembling those observed in in vivo multifiber recordings of renal sympathetic nerve activity (diamond-wave patterns) produced greater renal vasoconstrictor responses than conventional square-wave patterns. Within diamond-wave patterns, increasing integrated voltage by increasing amplitude produced twofold greater renal vasoconstrictor responses than by increasing duration. With similar integrated voltages that were subthreshold for renal vasoconstriction, neither diamond- nor square-wave pattern altered glomerular filtration rate, whereas diamond- but not square-wave pattern reversibly decreased urinary sodium excretion by 25 +/- 3%. At the same number of pulses per second, intermittent stimulation produced faster and greater renal vasoconstriction than continuous stimulation. At the same number of pulses per second, increases in rest period during intermittent stimulation proportionally augmented the renal vasoconstrictor response compared with that observed with continuous stimulation; the maximum augmentation of 55% occurred at a rest period of 500 ms. These results indicate that the pattern of renal sympathetic nerve stimulation (activity) significantly influences the rapidity, magnitude, and selectivity of the renal vascular and tubular responses.

Development of Kinematic Graphs of Median Nerve during Active Finger Motion: Implications of Smartphone Use

PubMed Central

2016-01-01

Background Certain hand activities cause deformation and displacement of the median nerve at the carpal tunnel due to the gliding motion of tendons surrounding it. As smartphone usage escalates, this raises the public’s concern whether hand activities while using smartphones can lead to median nerve problems. Objective The aims of this study were to 1) develop kinematic graphs and 2) investigate the associated deformation and rotational information of median nerve in the carpal tunnel during hand activities. Methods Dominant wrists of 30 young adults were examined with ultrasonography by placing a transducer transversely on their wrist crease. Ultrasound video clips were recorded when the subject performing 1) thumb opposition with the wrist in neutral position, 2) thumb opposition with the wrist in ulnar deviation and 3) pinch grip with the wrist in neutral position. Six still images that were separated by 0.2-second intervals were then captured from the ultrasound video for the determination of 1) cross-sectional area (CSA), 2) flattening ratio (FR), 3) rotational displacement (RD) and 4) translational displacement (TD) of median nerve in the carpal tunnel, and these collected information of deformation, rotational and displacement of median nerve were compared between 1) two successive time points during a single hand activity and 2) different hand motions at the same time point. Finally, kinematic graphs were constructed to demonstrate the mobility of median nerve during different hand activities. Results Performing different hand activities during this study led to a gradual reduction in CSA of the median nerve, with thumb opposition together with the wrist in ulnar deviation causing the greatest extent of deformation of the median nerve. Thumb opposition with the wrist in ulnar deviation also led to the largest extent of TD when compared to the other two hand activities of this study. Kinematic graphs showed that the motion pathways of median nerve during

Neurophysiological mechanism of possibly confounding peripheral activation of the facial nerve during corticobulbar tract monitoring.

PubMed

Téllez, Maria J; Ulkatan, Sedat; Urriza, Javier; Arranz-Arranz, Beatriz; Deletis, Vedran

2016-02-01

To improve the recognition and possibly prevent confounding peripheral activation of the facial nerve caused by leaking transcranial electrical stimulation (TES) current during corticobulbar tract monitoring. We applied a single stimulus and a short train of electrical stimuli directly to the extracranial portion of the facial nerve. We compared the peripherally elicited compound muscle action potential (CMAP) of the facial nerve with the responses elicited by TES during intraoperative monitoring of the corticobulbar tract. A single stimulus applied directly to the facial nerve at subthreshold intensities did not evoke a CMAP, whereas short trains of subthreshold stimuli repeatedly evoked CMAPs. This is due to the phenomenon of sub- or near-threshold super excitability of the cranial nerve. Therefore, the facial responses evoked by short trains TES, when the leaked current reaches the facial nerve at sub- or near-threshold intensity, could lead to false interpretation. Our results revealed a potential pitfall in the current methodology for facial corticobulbar tract monitoring that is due to the activation of the facial nerve by subthreshold trains of stimuli. This study proposes a new criterion to exclude peripheral activation during corticobulbar tract monitoring. The failure to recognize and avoid facial nerve activation due to leaking current in the peripheral portion of the facial nerve during TES decreases the reliability of corticobulbar tract monitoring by increasing the possibility of false interpretation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Evaluation of high-density, multi-contact nerve cuffs for activation of grasp muscles in monkeys

NASA Astrophysics Data System (ADS)

Brill, N. A.; Naufel, S. N.; Polasek, K.; Ethier, C.; Cheesborough, J.; Agnew, S.; Miller, L. E.; Tyler, D. J.

2018-06-01

Objective. The objective of this work was to evaluate whether nerve cuffs can selectively activate hand muscles for functional electrical stimulation (FES). FES typically involves identifying and implanting electrodes in many individual muscles, but nerve cuffs only require implantation at a single site around the nerve. This method is surgically more attractive. Nerve cuffs may also more effectively stimulate intrinsic hand muscles, which are difficult to implant and stimulate without spillover to adjacent muscles. Approach. To evaluate its ability to selectively activate muscles, we implanted and tested the flat interface nerve electrode (FINE), which is designed to selectively stimulate peripheral nerves that innervate multiple muscles (Tyler and Durand 2002 IEEE Trans. Neural Syst. Rehabil. Eng. 10 294-303). We implanted FINEs on the nerves and bipolar intramuscular wires for recording compound muscle action potentials (CMAPs) from up to 20 muscles in each arm of six monkeys. We then collected recruitment curves while the animals were anesthetized. Main result. A single FINE implanted on an upper extremity nerve in the monkey can selectively activate muscles or small groups of muscles to produce multiple, independent hand functions. Significance. FINE cuffs can serve as a viable supplement to intramuscular electrodes in FES systems, where they can better activate intrinsic and extrinsic muscles with lower currents and less extensive surgery.

Higher sympathetic nerve activity during ventricular (VVI) than during dual-chamber (DDD) pacing

NASA Technical Reports Server (NTRS)

Taylor, J. A.; Morillo, C. A.; Eckberg, D. L.; Ellenbogen, K. A.

1996-01-01

OBJECTIVES: We determined the short-term effects of single-chamber ventricular pacing and dual-chamber atrioventricular (AV) pacing on directly measured sympathetic nerve activity. BACKGROUND: Dual-chamber AV cardiac pacing results in greater cardiac output and lower systemic vascular resistance than does single-chamber ventricular pacing. However, it is unclear whether these hemodynamic advantages result in less sympathetic nervous system outflow. METHODS: In 13 patients with a dual-chamber pacemaker, we recorded the electrocardiogram, noninvasive arterial pressure (Finapres), respiration and muscle sympathetic nerve activity (microneurography) during 3 min of underlying basal heart rate and 3 min of ventricular and AV pacing at rates of 60 and 100 beats/min. RESULTS: Arterial pressure was lowest and muscle sympathetic nerve activity was highest at the underlying basal heart rate. Arterial pressure increased with cardiac pacing and was greater with AV than with ventricular pacing (change in mean blood pressure +/- SE: 10 +/- 3 vs. 2 +/- 2 mm Hg at 60 beats/min; 21 +/- 5 vs. 14 +/- 2 mm Hg at 100 beats/min; p < 0.05). Sympathetic nerve activity decreased with cardiac pacing and the decline was greater with AV than with ventricular pacing (60 beats/min -40 +/- 11% vs. -17 +/- 7%; 100 beats/min -60 +/- 9% vs. -48 +/- 10%; p < 0.05). Although most patients showed a strong inverse relation between arterial pressure and muscle sympathetic nerve activity, three patients with severe left ventricular dysfunction (ejection fraction < or = 30%) showed no relation between arterial pressure and sympathetic activity. CONCLUSIONS: Short-term AV pacing results in lower sympathetic nerve activity and higher arterial pressure than does ventricular pacing, indicating that cardiac pacing mode may influence sympathetic outflow simply through arterial baroreflex mechanisms. We speculate that the greater incidence of adverse outcomes in patients treated with single-chamber ventricular

Factor XII (Hageman factor) is a missing link between stress and hypercoagulability and plays an important role in the pathophysiology of ischemic stroke.

PubMed

Eggers, Arnold E

2006-01-01

A new hypothesis is presented on the function of factor XII, which is postulated to be a "missing link" between acute stress and transient hypercoagulability. The implications of this idea are developed to show how chronic stress, which involves activation of hypertension and migraine as well as hypercoagulability, can cause of cerebrovascular disease. "Acute stress" is defined as "the normal short-term physiological response to the perception of major threats or demands". "Chronic stress" is "the abnormal ongoing physiological response to the continuing perception of unresolvable major threats or demands". The factor XII hypothesis is as follows: Acute stress includes release of epinephrine by the adrenal medulla. Epinephrine activates platelets by binding to alpha-2A adrenergic receptors. Activated platelets convert pre-bound factor XII to its active form, which then initiates the intrinsic coagulation cascade. This can be called the "activated platelet initiation pathway" for coagulation. Neither tissue factor nor pre-formed thrombin is required. Thrombosis proceeds to completion, but only a minute amount of thrombin is formed, and the process normally stops at this point. In people who lapse into a state of chronic stress, essential hypertension, which is also a manifestation of stress, synergizes with hypercoagulability: there is both a baseline rise in blood pressure and systemic platelet activation as well as superimposed labile rises of both. Upregulation of these two stress parameters is atherogenic: epinephrine-activated platelets stimulating thrombin formation interact with endothelial cells activated by angiotensin II to cause, first, smooth muscle cell proliferation, which is a histological hallmark of atherosclerosis, and, lastly, a symptomatic thrombotic occlusion-the stroke. The migraine symptoms which often accompany this process are a marker of chronic stress and ongoing pathophysiologic damage. Therapeutic predictions are made regarding novel

ANATOMICAL STUDY OF CRANIAL NERVE EMERGENCE AND SKULL FORAMINA IN THE HORSE USING MAGNETIC RESONANCE IMAGING AND COMPUTED TOMOGRAPHY.

PubMed

Gonçalves, Rita; Malalana, Fernando; McConnell, James Fraser; Maddox, Thomas

2015-01-01

For accurate interpretation of magnetic resonance (MR) images of the equine brain, knowledge of the normal cross-sectional anatomy of the brain and associated structures (such as the cranial nerves) is essential. The purpose of this prospective cadaver study was to describe and compare MRI and computed tomography (CT) anatomy of cranial nerves' origins and associated skull foramina in a sample of five horses. All horses were presented for euthanasia for reasons unrelated to the head. Heads were collected posteuthanasia and T2-weighted MR images were obtained in the transverse, sagittal, and dorsal planes. Thin-slice MR sequences were also acquired using transverse 3D-CISS sequences that allowed mutliplanar reformatting. Transverse thin-slice CT images were acquired and multiplanar reformatting was used to create comparative images. Magnetic resonance imaging consistently allowed visualization of cranial nerves II, V, VII, VIII, and XII in all horses. The cranial nerves III, IV, and VI were identifiable as a group despite difficulties in identification of individual nerves. The group of cranial nerves IX, X, and XI were identified in 4/5 horses although the region where they exited the skull was identified in all cases. The course of nerves II and V could be followed on several slices and the main divisions of cranial nerve V could be distinguished in all cases. In conclusion, CT allowed clear visualization of the skull foramina and occasionally the nerves themselves, facilitating identification of the nerves for comparison with MRI images. © 2015 American College of Veterinary Radiology.

Dynamic analysis of renal nerve activity responses to baroreceptor denervation in hypertensive rats.

PubMed

DiBona, G F; Jones, S Y

2001-04-01

Sinoaortic and cardiac baroreflexes exert important control over renal sympathetic nerve activity. Alterations in these reflex mechanisms contribute to renal sympathoexcitation in hypertension. Nonlinear dynamic analysis was used to examine the chaotic behavior of renal sympathetic nerve activity in normotensive Sprague-Dawley and Wistar-Kyoto rats and spontaneously hypertensive rats before and after complete baroreceptor denervation (sinoaortic and cardiac baroreceptor denervation). The peak interval sequence of synchronized renal sympathetic nerve discharge was extracted and used for analysis. In all rat strains, this yielded systems whose correlation dimensions converged to similar low values over the embedding dimension range of 10 to 15 and whose greatest Lyapunov exponents were positive. In Sprague-Dawley and Wistar-Kyoto rats, compete baroreceptor denervation was associated with decreases in the correlation dimensions (Sprague-DAWLEY: 2.42+/-0.04 to 2.16+/-0.04; Wistar-KYOTO: 2.44+/-0.04 to 2.34+/-0.04) and in the greatest Lyapunov exponents (Sprague-DAWLEY: 0.199+/-0.004 to 0.130+/-0.015; Wistar-KYOTO: 0.196+/-0.002 to 0.136+/-0.010). Spontaneously hypertensive rats had a similar correlation dimension, which was unaffected by complete baroreceptor denervation (2.42+/-0.02 versus 2.42+/-0.03), and a lower value for the greatest Lyapunov exponent, which decreased to a lesser extent after complete baroreceptor denervation (0.183+/-0.006 versus 0.158+/-0.006). These results indicate that removal of sinoaortic and cardiac baroreceptor regulation of renal sympathetic nerve activity is associated with a greater decrease in the chaotic behavior of renal sympathetic nerve activity in normotensive compared with hypertensive rats. This suggests that the central neural mechanisms that regulate renal sympathetic nerve activity in response to alterations in cardiovascular reflex inputs are different in spontaneously hypertensive rats from those in Sprague-Dawley and

Rostral dorsolateral pontine neurons with sympathetic nerve-related activity.

PubMed

Barman, S M; Gebber, G L; Kitchens, H

1999-02-01

Spike-triggered averaging, arterial pulse-triggered analysis, and coherence analysis were used to classify rostral dorsolateral pontine (RDLP) neurons into groups whose naturally occurring discharges were correlated to only the 10-Hz rhythm (n = 29), to only the cardiac-related rhythm (n = 15), and to both rhythms (n = 15) in inferior cardiac sympathetic nerve discharge (SND) of urethan-anesthetized cats. Most of the neurons with activity correlated to only the cardiac-related rhythm were located medial to the other two groups of neurons. The firing rates of most RDLP neurons with activity correlated to only the 10-Hz rhythm (9 of 12) or both rhythms (7 of 8) were decreased during baroreceptor reflex-induced inhibition of SND produced by aortic obstruction; thus, they are presumed to be sympathoexcitatory. The firing rates of four of seven RDLP neurons with activity correlated to only the cardiac-related rhythm increased during baroreceptor reflex activation; thus, they may be sympathoinhibitory. We conclude that the RDLP contains a functionally heterogeneous population of neurons with sympathetic nerve-related activity. These neurons could not be antidromically activated by stimulation of the thoracic spinal cord.

75 FR 37456 - Green Retrofit Program of Title XII of the American Recovery and Reinvestment Act of 2009

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-29

... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5376-N-55] Green Retrofit Program of Title XII of the American Recovery and Reinvestment Act of 2009 AGENCY: Office of the Chief Information... Title of Proposal: Green Retrofit Program of Title XII of the American Recovery and Reinvestment Act of...

Ionotropic and metabotropic receptor mediated airway sensory nerve activation.

PubMed

Lee, Min-Goo; Kollarik, Marian; Chuaychoo, Benjamas; Undem, Bradley J

2004-01-01

There are several receptors capable of inducing activating generator potentials in cough-associated afferent terminals in the airways. The chemical receptors leading to generator potentials can be subclassified into ionotropic and metabotropic types. An ionotropic receptor has an agonist-binding domain, and also serves directly as an ion channel that is opened upon binding of the agonist. Examples of ionotropic receptors found in airway sensory nerve terminals include receptors for serotonin (5-HT3 receptors), ATP (P2X receptors), acetylcholine (nicotinic receptors), receptors for capsaicin and related vanilloids (TRPV1 receptors), and acid receptors (acid sensing ion channels). Afferent nerve terminals can also be depolarized via activation of metabotropic or G-protein coupled receptors (GPCRs). Among the GPCRs that can lead to activation of airway afferent fibers include bradykinin B2 and adenosine A1 receptors. The signaling events leading to GPCR-mediated membrane depolarization are more complex than that seen with ionotropic receptors. The GPCR-mediated effects are thought to occur through classical second messenger systems such as activation of phospholipase C. This may lead to membrane depolarization through interaction with specific ionotropic receptors (such as TRPV1) and/or various types of calcium activated channels.

[XII National Forum on Health Education].

PubMed

Ramiro-H, Manuel

2015-01-01

In Guadalajara, on August 19, 20 and 21 was held the XII Foro Nacional de Educación en Salud, in line with the interest that both, the Dirección General and the Dirección de Prestaciones Médicas of the IMSS, have in training and updating the human resources for the care of the beneficiaries. The Unidad de Educación, Investigación y Políticas de Salud organized a meeting in which the actors of these tasks, the institutional staff and authorities from various universities worked together with the IMSS.

Severe localised granulomatosis with polyangiitis (Wegener's granulomatosis) manifesting with extensive cranial nerve palsies and cranial diabetes insipidus: a case report and literature review.

PubMed

Peters, James E; Gupta, Vivek; Saeed, Ibtisam T; Offiah, Curtis; Jawad, Ali S M

2018-05-01

Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) is a multisystem vasculitis of small- to medium-sized blood vessels. Cranial involvement can result in cranial nerve palsies and, rarely, pituitary infiltration. We describe the case of a 32 year-old woman with limited but severe GPA manifesting as progressive cranial nerve palsies and pituitary dysfunction. Our patient initially presented with localised ENT involvement, but despite treatment with methotrexate, she deteriorated. Granulomatous inflammatory tissue around the skull base resulted in cavernous sinus syndrome, facial nerve palsy, palsies of cranial nerves IX-XII (Collet-Sicard syndrome), and the rare complication of cranial diabetes insipidus due to pituitary infiltration. The glossopharyngeal, vagus and accessory nerve palsies resulted in severe dysphagia and she required nasogastric tube feeding. Her neurological deficits substantially improved with treatment including high dose corticosteroid, cyclophosphamide and rituximab. This case emphasises that serious morbidity can arise from localised cranial Wegener's granulomatosis in the absence of systemic disease. In such cases intensive induction immunosuppression is required. Analysis of previously reported cases of pituitary involvement in GPA reveals that this rare complication predominantly affects female patients.

Activation of vagus nerve by semapimod alters substance P levels and decreases breast cancer metastasis.

PubMed

Erin, Nuray; Duymuş, Ozlem; Oztürk, Saffet; Demir, Necdet

2012-11-10

Chronic inflammation is involved in initiation as well as in progression of cancer. Semapimod, a tetravalent guanylhydrazon and formerly known as CNI-1493, inhibits the release of inflammatory cytokines from activated macrophages and this effect is partly mediated by the vagus nerve. Our previous findings demonstrated that inactivation of vagus nerve activity as well sensory neurons enhanced visceral metastasis of 4THM breast carcinoma. Hence semapimod by activating vagus nerve may inhibit breast cancer metastasis. Here, effects of semapimod on breast cancer metastasis, the role of vagal sensory neurons on this effect and changes in mediators of the neuroimmune connection, such as substance P (SP) as well as neprilysin-like activity, were examined. Vagotomy was performed on half of the control animals that were treated with semapimod following orthotopic injection of 4THM breast carcinoma cells. Semapimod decreased lung and liver metastases in control but not in vagotomized animals with an associated increased SP levels in sensory nerve endings. Semapimod also increased neprilysin-like activity in lung tissue of control animals but not in tumor-bearing animals. This is the first report demonstrating that semapimod enhances vagal sensory nerve activity and may have anti-tumoral effects under in-vivo conditions. Further studies, however, are required to elucidate the conditions and the mechanisms involved in anti-tumoral effects of semapimod. Copyright © 2012 Elsevier B.V. All rights reserved.

Carbonic anhydrase inhibitors: guaiacol and catechol derivatives effectively inhibit certain human carbonic anhydrase isoenzymes (hCA I, II, IX and XII).

PubMed

Scozzafava, Andrea; Passaponti, Maurizio; Supuran, Claudiu T; Gülçin, İlhami

2015-01-01

Carbonic anhydrases (CAs) are widespread metalloenzymes in higher vertebrates including humans. A series of phenolic compounds, including guaiacol, 4-methylguaiacol, 4-propylguaiacol, eugenol, isoeugenol, vanillin, syringaldehyde, catechol, 3-methyl catechol, 4-methyl catechol and 3-methoxy catechol were investigated for their inhibition of all the catalytically active mammalian isozymes of the Zn(2+)-containing CA (EC 4.2.1.1). All the phenolic compounds effectively inhibited human carbonic anhydrase isoenzymes (hCA I, II, IX and XII), with Kis in the range of 2.20-515.98 μM. The various isozymes showed diverse inhibition profiles. Among the tested phenolic derivatives, compounds 4-methyl catechol and 3-methoxy catechol showed potent activity as inhibitors of the tumour-associated transmembrane isoforms (hCA IX and XII) in the submicromolar range, with high selectivity. The results obtained from this research may lead to the design of more effective carbonic anhydrase isoenzyme inhibitors (CAIs) based on such phenolic compound scaffolds.

Mechanisms underpinning sympathetic nervous activity and its modulation using transcutaneous vagus nerve stimulation.

PubMed

Deuchars, Susan A; Lall, Varinder K; Clancy, Jennifer; Mahadi, Mohd; Murray, Aaron; Peers, Lucy; Deuchars, Jim

2018-03-01

What is the topic of this review? This review briefly considers what modulates sympathetic nerve activity and how it may change as we age or in pathological conditions. It then focuses on transcutaneous vagus nerve stimulation, a method of neuromodulation in autonomic cardiovascular control. What advances does it highlight? The review considers the pathways involved in eliciting the changes in autonomic balance seen with transcutaneous vagus nerve stimulation in relationship to other neuromodulatory techniques. The autonomic nervous system, consisting of the sympathetic and parasympathetic branches, is a major contributor to the maintenance of cardiovascular variables within homeostatic limits. As we age or in certain pathological conditions, the balance between the two branches changes such that sympathetic activity is more dominant, and this change in dominance is negatively correlated with prognosis in conditions such as heart failure. We have shown that non-invasive stimulation of the tragus of the ear increases parasympathetic activity and reduces sympathetic activity and that the extent of this effect is correlated with the baseline cardiovascular parameters of different subjects. The effects could be attributable to activation of the afferent branch of the vagus and, potentially, other sensory nerves in that region. This indicates that tragus stimulation may be a viable treatment in disorders where autonomic activity to the heart is compromised. © 2017 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Evaluation of thromboelastography in two factor XII-deficient cats.

PubMed

Blois, Shauna L; Holowaychuk, Marie K; Wood, R Darren

2015-01-01

The current report describes thromboelastography (TEG) findings in two cats with factor XII (FXII) deficiency. The first cat was diagnosed with bilateral perinephric pseudocysts; hemostatic testing was performed prior to performing renal aspirates. The second cat was healthy; hemostatic testing was performed prior to inclusion into a research project. Both cats had markedly prolonged partial thromboplastin times and hypocoagulable TEG tracings when samples were activated with kaolin. However, when tissue factor (TF) was used to activate the sample, both cats had normal-to-hypercoagulable TEG tracings. The cats each had a subnormal FXII level. TEG is becoming widely used to investigate hemostasis in veterinary patients, and TEG results in cats with FXII deficiency have not been previously reported. FXII deficiency is the most common hereditary hemostatic defect in cats. While FXII deficiency does not lead to in vivo hemorrhagic tendencies, it can lead to marked prolongation in activated partial thromboplastin and activated clotting times, and cannot be differentiated from true hemorrhagic diatheses without measuring individual factor activity. With the increased use of TEG to evaluate hemostasis in veterinary patients, it is important to recognize the effects of FXII deficiency on this testing modality. The finding of a hypocoagulable kaolin-activated TEG tracing and a concurrent normal TF-activated TEG tracing in samples should prompt clinicians to consider ruling out FXII deficiency.

Evaluation of thromboelastography in two factor XII-deficient cats

PubMed Central

Holowaychuk, Marie K; Wood, R Darren

2015-01-01

Case summary The current report describes thromboelastography (TEG) findings in two cats with factor XII (FXII) deficiency. The first cat was diagnosed with bilateral perinephric pseudocysts; hemostatic testing was performed prior to performing renal aspirates. The second cat was healthy; hemostatic testing was performed prior to inclusion into a research project. Both cats had markedly prolonged partial thromboplastin times and hypocoagulable TEG tracings when samples were activated with kaolin. However, when tissue factor (TF) was used to activate the sample, both cats had normal-to-hypercoagulable TEG tracings. The cats each had a subnormal FXII level. Relevance and novel information TEG is becoming widely used to investigate hemostasis in veterinary patients, and TEG results in cats with FXII deficiency have not been previously reported. FXII deficiency is the most common hereditary hemostatic defect in cats. While FXII deficiency does not lead to in vivo hemorrhagic tendencies, it can lead to marked prolongation in activated partial thromboplastin and activated clotting times, and cannot be differentiated from true hemorrhagic diatheses without measuring individual factor activity. With the increased use of TEG to evaluate hemostasis in veterinary patients, it is important to recognize the effects of FXII deficiency on this testing modality. The finding of a hypocoagulable kaolin-activated TEG tracing and a concurrent normal TF-activated TEG tracing in samples should prompt clinicians to consider ruling out FXII deficiency. PMID:28491358

Laser-activated protein solder for peripheral nerve repair

NASA Astrophysics Data System (ADS)

Trickett, Rodney I.; Lauto, Antonio; Dawes, Judith M.; Owen, Earl R.

1995-05-01

A 100 micrometers core optical fiber-coupled 75 mW diode laser operating at a wavelength of 800 nm has been used in conjunction with a protein solder to stripe weld severed rat tibial nerves, reducing the long operating time required for microsurgical nerve repair. Welding is produced by selective laser denaturation of the albumin based solder which contains the dye indocyanine green. Operating time for laser soldering was 10 +/- 5 min. (n equals 20) compared to 23 +/- 9 min. (n equals 10) for microsuturing. The laser solder technique resulted in patent welds with a tensile strength of 15 +/- 5 g, while microsutured nerves had a tensile strength of 40 +/- 10 g. Histopathology of the laser soldered nerves, conducted immediately after surgery, displayed solder adhesion to the outer membrane with minimal damage to the inner axons of the nerves. An in vivo study is under way comparing laser solder repaired tibial nerves to conventional microsuture repair. At the time of submission 15 laser soldered nerves and 7 sutured nerves were characterized at 3 months and showed successful regeneration with compound muscle action potentials of 27 +/- 8 mV and 29 +/- 8 mW respectively. A faster, less damaging and long lasting laser based anastomotic technique is presented.

CK-2127107 amplifies skeletal muscle response to nerve activation in humans.

PubMed

Andrews, Jinsy A; Miller, Timothy M; Vijayakumar, Vipin; Stoltz, Randall; James, Joyce K; Meng, Lisa; Wolff, Andrew A; Malik, Fady I

2018-05-01

Three studies evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of CK-2127107 (CK-107), a next-generation fast skeletal muscle troponin activator (FSTA), in healthy participants. We tested the hypothesis that CK-107 would amplify the force-frequency response of muscle in humans. To assess the force-frequency response, participants received single doses of CK-107 and placebo in a randomized, double-blind, 4-period, crossover study. The force-frequency response of foot dorsiflexion following stimulation of the deep fibular nerve to activate the tibialis anterior muscle was assessed. CK-107 significantly increased tibialis anterior muscle response with increasing dose and plasma concentration in a frequency-dependent manner; the largest increase in peak force was ∼60% at 10 Hz. CK-107 appears more potent and produced larger increases in force than tirasemtiv-a first-generation FSTA-in a similar pharmacodynamic study, thereby supporting its development for improvement of muscle function of patients. Muscle Nerve 57: 729-734, 2018. © 2017 The Authors. Muscle & Nerve published by Wiley Periodicals, Inc.

Carotid artery and lower cranial nerve exposure with increasing surgical complexity to the parapharyngeal space.

PubMed

Lemos-Rodriguez, Ana M; Sreenath, Satyan B; Rawal, Rounak B; Overton, Lewis J; Farzal, Zainab; Zanation, Adam M

2017-03-01

To investigate the extent of carotid artery exposure attained, including the identification of the external carotid branches and lower cranial nerves in five sequential external approaches to the parapharyngeal space, and to provide an anatomical algorithm. Anatomical study. Six latex-injected adult cadaver heads were dissected in five consecutive approaches: transcervical approach with submandibular gland removal, posterior extension of the transcervical approach, transcervical approach with parotidectomy, parotidectomy with lateral mandibulotomy, and parotidectomy with mandibulectomy. The degree of carotid artery exposure attained, external carotid branches, and lower cranial nerves visualized was documented. The transcervical approach exposed 1.5 cm (Standard Deviation (SD) 0.5) of internal carotid artery (ICA) and 1.25 cm (SD 0.25) of external carotid artery (ECA). The superior thyroid and facial arteries and cranial nerve XII and XI were identified. The posterior extension exposed 2.9 cm (SD 0.7) of ICA and 2.7 cm (SD 1.0) of ECA. Occipital and ascending pharyngeal arteries were visualized. The transparotid approach exposed 4.0 cm (SD 1.1) of ICA and 3.98 cm (SD 1.8) of ECA. Lateral mandibulotomy exposed the internal maxillary artery, cranial nerve X, the sympathetic trunk, and 4.6 cm (SD 2.4) of ICA. Mandibulectomy allowed for complete ECA exposure, cranial nerve IX, lingual nerve, and 6.9 cm (SD 1.3) of ICA. Approaches for the parapharyngeal space must be based on anatomic and biological patient factors. This study provides a guide for the skull base surgeon for an extended approach based on the desired anatomic exposure. N/A. Laryngoscope, 127:585-591, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

77 FR 10741 - Lock+ Hydro Friends Fund XII, BOST2, LLC, Riverbank Hydro No. 21, LLC, FFP Project 96, LLC...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-23

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project Nos. 14260-000, 14264-000, 14267-000, 14273-000] Lock+ Hydro Friends Fund XII, BOST2, LLC, Riverbank Hydro No. 21, LLC, FFP Project... Greene and Hale counties, Alabama. The applications were filed by Lock+ Hydro Friends Fund XII for...

FOREWORD: The 12th International Workshop on Desorption Induced by Electronic Transitions (DIET XII) (Pine Mountain, Georgia, USA, 19-23 April 2009) The 12th International Workshop on Desorption Induced by Electronic Transitions (DIET XII) (Pine Mountain, Georgia, USA, 19-23 April 2009)

NASA Astrophysics Data System (ADS)

Orlando, Thomas M.; Diebold, Ulrike

2010-03-01

The 12th International Workshop on Desorption Induced by Electronic Transitions (DIET XII) took place from 19-23 April 2009 in Pine Mountain, Georgia, USA. This was the 12th conference in a strong and vibrant series, which dates back to the early 1980s. DIET XII continued the tradition of exceptional interdisciplinary science and focused on the study of desorption and dynamics induced by electronic excitations of surfaces and interfaces. The format involved invited lectures, contributed talks and a poster session on the most recent developments and advances in this area of surface physics. The Workshop International Steering Committee and attendees wish to dedicate DIET XII to the memory of the late Professor Theodore (Ted) Madey. Ted was one of the main pioneers of this field and was one of the primary individuals working to keep this area of science exciting and adventurous. His overall contributions to surface science were countless and his contributions to the DIET field and community were enormous. He is missed and remembered by many friends and colleagues throughout the world. The papers collected in this issue cover many of the highlights of DIET XII. Topics include ultrafast electron transfer at surfaces and interfaces, quantum and spatially resolved mapping of surface dynamics and desorption, photon-, electron- and ion-beam induced processes at complex interfaces, the role of non-thermal desorption in astrochemistry and astrophysics and laser-/ion-based methods of examining soft matter and biological media. Although the workshop attracted many scientists active in the general area of non-thermal surface processes, DIET XII also attracted many younger scientists (i.e., postdoctoral fellows, advanced graduate students, and a select number of advanced undergraduate students). This field has had an impact in a number of areas including nanoscience, device physics, astrophysics, and now biophysics. We believe that this special issue of Journal of Physics

Laser-activated protein bands for peripheral nerve repair

NASA Astrophysics Data System (ADS)

Lauto, Antonio; Trickett, Rodney I.; Malik, Richard; Dawes, Judith M.; Owen, Earl R.

1996-01-01

A 100 micrometer core optical fiber-coupled 75 mW diode laser operating at a wavelength of 800 nm has been used in conjunction with a protein solder to stripe weld severed rat tibial nerves, reducing the long operating time required for microsurgical nerve repair. Welding is produced by selective laser denaturation of the protein based solder which contains the dye indocyanine green. Operating time for laser soldering was 10 plus or minus 5 min. (n equals 24) compared to 23 plus or minus 9 min (n equals 13) for microsuturing. The laser solder technique resulted in patent welds with a tensile strength of 15 plus or minus 5 g, while microsutured nerves had a tensile strength of 40 plus or minus 10 g. Histopathology of the laser soldered nerves, conducted immediately after surgery, displayed solder adhesion to the outer membrane with minimal damage to the inner axons of the nerves. An in vivo study, with a total of fifty-seven adult male wistar rats, compared laser solder repaired tibial nerves to conventional microsuture repair. Twenty-four laser soldered nerves and thirteen sutured nerves were characterized at three months and showed successful regeneration with average compound muscle action potentials (CMAP) of 2.4 plus or minus 0.7 mV and 2.7 plus or minus 0.8 mV respectively. Histopathology of the in vivo study, confirmed the comparable regeneration of axons in laser and suture operated nerves. A faster, less damaging and long lasting laser based anastomotic technique is presented.

A voltage-controlled capacitive discharge method for electrical activation of peripheral nerves.

PubMed

Rosellini, Will M; Yoo, Paul B; Engineer, Navzer; Armstrong, Scott; Weiner, Richard L; Burress, Chester; Cauller, Larry

2011-01-01

A voltage-controlled capacitive discharge (VCCD) method was investigated as an alternative to rectangular stimulus pulses currently used in peripheral nerve stimulation therapies.  In two anesthetized Gottingen mini pigs, the threshold (total charge per phase) for evoking a compound nerve action potential (CNAP) was compared between constant current (CC) and VCCD methods. Electrical pulses were applied to the tibial and posterior cutaneous femoralis nerves using standard and modified versions of the Medtronic 3778 Octad.  In contrast to CC stimulation, the combined application of VCCD pulses with a modified Octad resulted in a marked decrease (-73 ± 7.4%) in the stimulation threshold for evoking a CNAP. This was consistent for different myelinated fiber types and locations of stimulation.  The VCCD method provides a highly charge-efficient means of activating myelinated fibers that could potentially be used within a wireless peripheral nerve stimulator system. © 2011 International Neuromodulation Society.

Cranial nerve clock. Part II: functional MR imaging of brain activation during a declarative memory task.

PubMed

Weiss, K L; Welsh, R C; Eldevik, P; Bieliauskas, L A; Steinberg, B A

2001-12-01

The authors performed this study to assess brain activation during encoding and successful recall with a declarative memory paradigm that has previously been demonstrated to be effective for teaching students about the cranial nerves. Twenty-four students underwent functional magnetic resonance (MR) imaging during encoding and recall of the name, number, and function of the 12 cranial nerves. The students viewed mnemonic graphic and text slides related to individual nerves, as well as their respective control slides. For the recall paradigm, students were prompted with the numbers 1-12 (test condition) intermixed with the number 14 (control condition). Subjects were tested about their knowledge of cranial nerves outside the MR unit before and after functional MR imaging. Students learned about the cranial nerves while undergoing functional MR imaging (mean post- vs preparadigm score, 8.1 +/- 3.4 [of a possible 12] vs 0.75 +/- 0.94, bilateral prefrontal cortex, left greater than right; P < 2.0 x 10(-12)) and maintained this knowledge at I week. The encoding and recall paradigms elicited distributed networks of brain activation. Encoding revealed statistically significant activation in the bilateral prefrontal cortex, left greater than right [corrected]; bilateral occipital and parietal associative cortices, parahippocampus region, fusiform gyri, and cerebellum. Successful recall activated the left much more than the right prefrontal, parietal associative, and anterior cingulate cortices; bilateral precuneus and cerebellum; and right more than the left posterior cingulate. A predictable pattern of brain activation at functional MR imaging accompanies the encoding and successful recall of the cranial nerves with this declarative memory paradigm.

Endothelial Cell Permeability during Hantavirus Infection Involves Factor XII-Dependent Increased Activation of the Kallikrein-Kinin System

PubMed Central

Taylor, Shannon L.; Wahl-Jensen, Victoria; Copeland, Anna Maria; Jahrling, Peter B.; Schmaljohn, Connie S.

2013-01-01

Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are diseases caused by hantavirus infections and are characterized by vascular leakage due to alterations of the endothelial barrier. Hantavirus-infected endothelial cells (EC) display no overt cytopathology; consequently, pathogenesis models have focused either on the influx of immune cells and release of cytokines or on increased degradation of the adherens junction protein, vascular endothelial (VE)-cadherin, due to hantavirus-mediated hypersensitization of EC to vascular endothelial growth factor (VEGF). To examine endothelial leakage in a relevant in vitro system, we co-cultured endothelial and vascular smooth muscle cells (vSMC) to generate capillary blood vessel-like structures. In contrast to results obtained in monolayers of cultured EC, we found that despite viral replication in both cell types as well as the presence of VEGF, infected in vitro vessels neither lost integrity nor displayed evidence of VE-cadherin degradation. Here, we present evidence for a novel mechanism of hantavirus-induced vascular leakage involving activation of the plasma kallikrein-kinin system (KKS). We show that incubation of factor XII (FXII), prekallikrein (PK), and high molecular weight kininogen (HK) plasma proteins with hantavirus-infected EC results in increased cleavage of HK, higher enzymatic activities of FXIIa/kallikrein (KAL) and increased liberation of bradykinin (BK). Measuring cell permeability in real-time using electric cell-substrate impedance sensing (ECIS), we identified dramatic increases in endothelial cell permeability after KKS activation and liberation of BK. Furthermore, the alterations in permeability could be prevented using inhibitors that directly block BK binding, the activity of FXIIa, or the activity of KAL. Lastly, FXII binding and autoactivation is increased on the surface of hantavirus-infected EC. These data are the first to demonstrate KKS activation during

Facial nerve activity disrupts psychomotor rhythms in the forehead microvasculature.

PubMed

Drummond, Peter D; O'Brien, Geraldine

2011-10-28

Forehead blood flow was monitored in seven participants with a unilateral facial nerve lesion during relaxation, respiratory biofeedback and a sad documentary. Vascular waves at 0.1Hz strengthened during respiratory biofeedback, in tune with breathing cycles that also averaged 0.1Hz. In addition, a psychomotor rhythm at 0.15Hz was more prominent in vascular waveforms on the denervated than intact side of the forehead, both before and during relaxation and the sad documentary. These findings suggest that parasympathetic activity in the facial nerve interferes with the psychomotor rhythm in the forehead microvasculature. Copyright © 2011 Elsevier B.V. All rights reserved.

Retinal venous thrombosis in a young patient with coagulation factor XII deficiency.

PubMed

Borrego-Sanz, L; Santos-Bueso, E; Sáenz-Francés, F; Martínez-de-la-Casa, J M; García-Feijoo, J; Gegúndez-Fernández, J A; García-Sánchez, J

2014-08-01

A 35-year-old woman, with no relevant medical history, was referred for sudden vision loss in the left eye. Ophthalmological examination showed best corrected visual acuity of 1.0 in the right eye and 0.3 in left eye, with normal anterior pole and intraocular pressure. Fundus examination of the left eye revealed a venous thrombosis in the superior temporal branch, with dilated and tortuous retinal veins. The patient was referred to the hematology unit for thrombophilia study, and was diagnosed with a coagulation XII or Hageman factor deficiency. The development of retinal vessel occlusions, in patients under 50 years of age, is frequently associated with thrombophilia or hypercoagulability disorders. Factor XII deficiency is a rare condition, and its presence could contribute to a higher risk of thromboembolic events. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

PubMed Central

Longhurst, John C.

2013-01-01

Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32–3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 μmol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP (n = 7) or bradykinin (n = 7). These data suggest that peripheral opioid peptides suppress the

Identification of cytokine-specific sensory neural signals by decoding murine vagus nerve activity.

PubMed

Zanos, Theodoros P; Silverman, Harold A; Levy, Todd; Tsaava, Tea; Battinelli, Emily; Lorraine, Peter W; Ashe, Jeffrey M; Chavan, Sangeeta S; Tracey, Kevin J; Bouton, Chad E

2018-05-22

The nervous system maintains physiological homeostasis through reflex pathways that modulate organ function. This process begins when changes in the internal milieu (e.g., blood pressure, temperature, or pH) activate visceral sensory neurons that transmit action potentials along the vagus nerve to the brainstem. IL-1β and TNF, inflammatory cytokines produced by immune cells during infection and injury, and other inflammatory mediators have been implicated in activating sensory action potentials in the vagus nerve. However, it remains unclear whether neural responses encode cytokine-specific information. Here we develop methods to isolate and decode specific neural signals to discriminate between two different cytokines. Nerve impulses recorded from the vagus nerve of mice exposed to IL-1β and TNF were sorted into groups based on their shape and amplitude, and their respective firing rates were computed. This revealed sensory neural groups responding specifically to TNF and IL-1β in a dose-dependent manner. These cytokine-mediated responses were subsequently decoded using a Naive Bayes algorithm that discriminated between no exposure and exposures to IL-1β and TNF (mean successful identification rate 82.9 ± 17.8%, chance level 33%). Recordings obtained in IL-1 receptor-KO mice were devoid of IL-1β-related signals but retained their responses to TNF. Genetic ablation of TRPV1 neurons attenuated the vagus neural signals mediated by IL-1β, and distal lidocaine nerve block attenuated all vagus neural signals recorded. The results obtained in this study using the methodological framework suggest that cytokine-specific information is present in sensory neural signals within the vagus nerve. Copyright © 2018 the Author(s). Published by PNAS.

Division XII: Commission 46: Education & Development of Astronomy

NASA Astrophysics Data System (ADS)

Ros, Rosa M.; Hearnshaw, John; Stavinschi, Magda; Garcia, Beatriz; Gerbaldi, Michele; de Greve, Jean-Pierre; Guinan, Edward; Haubold, Hans; Jones, Barrie; Marshall, Laurence A.; Pasachoff, Jay

2015-08-01

C46 is a Commission of the Executive Committee of the IAU under Division XII Union-Wide Activities. Aiming at improvement of astronomy education and research at all levels worldwide (through the various projects it initiates),maintains, develops, as well as through the dissemination of information. C46 has 332 members and it was managed by the Organizing Committee, formed by the Commission President (Rosa M. Ros, from Spain), the Vice-Presiden (John Hearnshaw, from New Zealand), the Retiring President (Magda Stavinschi, from Romania), the Vice-President of the IAU (George Miley, from Netherland) and the PG chairs: • Worldwide Development of Astronomy WWDA: John Hearnshaw • Teaching Astronomy for Development TAD: Edward Guinan and Laurence A. Marshall • International Schools for Young Astronomers ISYA; chair: Jean-Pierre de Greve • Network for Astronomy School Education NASE: Rosa M. Ros and Beatriz Garcia • Public Understanding at the times of Solar Eclipses and transit Phenomena PUTSE: Jay Pasachoff • National Liaison and Newsletter: Barrie Jones • Collaborative Programs: Hans Haubold

Renal hemodynamic effects of activation of specific renal sympathetic nerve fiber groups.

PubMed

DiBona, G F; Sawin, L L

1999-02-01

To examine the effect of activation of a unique population of renal sympathetic nerve fibers on renal blood flow (RBF) dynamics, anesthetized rats were instrumented with a renal sympathetic nerve activity (RSNA) recording electrode and an electromagnetic flow probe on the ipsilateral renal artery. Peripheral thermal receptor stimulation (external heat) was used to activate a unique population of renal sympathetic nerve fibers and to increase total RSNA. Total RSNA was reflexly increased to the same degree with somatic receptor stimulation (tail compression). Arterial pressure and heart rate were increased by both stimuli. Total RSNA was increased to the same degree by both stimuli but external heat produced a greater renal vasoconstrictor response than tail compression. Whereas both stimuli increased spectral density power of RSNA at both cardiac and respiratory frequencies, modulation of RBF variability by fluctuations of RSNA was small at these frequencies, with values for the normalized transfer gain being approximately 0.1 at >0.5 Hz. During tail compression coherent oscillations of RSNA and RBF were found at 0.3-0.4 Hz with normalized transfer gain of 0.33 +/- 0.02. During external heat coherent oscillations of RSNA and RBF were found at both 0.2 and 0.3-0.4 Hz with normalized transfer gains of 0. 63 +/- 0.05 at 0.2 Hz and 0.53 +/- 0.04 to 0.36 +/- 0.02 at 0.3-0.4 Hz. Renal denervation eliminated the oscillations in RBF at both 0.2 and 0.3-0.4 Hz. These findings indicate that despite similar increases in total RSNA, external heat results in a greater renal vasoconstrictor response than tail compression due to the activation of a unique population of renal sympathetic nerve fibers with different frequency-response characteristics of the renal vasculature.

Selective neural activation in a histologically derived model of peripheral nerve

NASA Astrophysics Data System (ADS)

Butson, Christopher R.; Miller, Ian O.; Normann, Richard A.; Clark, Gregory A.

2011-06-01

Functional electrical stimulation (FES) is a general term for therapeutic methods that use electrical stimulation to aid or replace lost ability. For FES systems that communicate with the nervous system, one critical component is the electrode interface through which the machine-body information transfer must occur. In this paper, we examine the influence of inhomogeneous tissue conductivities and positions of nodes of Ranvier on activation of myelinated axons for neuromuscular control as a function of electrode configuration. To evaluate these effects, we developed a high-resolution bioelectric model of a fascicle from a stained cross-section of cat sciatic nerve. The model was constructed by digitizing a fixed specimen of peripheral nerve, extruding the image along the axis of the nerve, and assigning each anatomical component to one of several different tissue types. Electrodes were represented by current sources in monopolar, transverse bipolar, and longitudinal bipolar configurations; neural activation was determined using coupled field-neuron simulations with myelinated axon cable models. We found that the use of an isotropic tissue medium overestimated neural activation thresholds compared with the use of physiologically based, inhomogeneous tissue medium, even after controlling for mean impedance levels. Additionally, the positions of the cathodic sources relative to the nodes of Ranvier had substantial effects on activation, and these effects were modulated by the electrode configuration. Our results indicate that physiologically based tissue properties cause considerable variability in the neural response, and the inclusion of these properties is an important component in accurately predicting activation. The results are used to suggest new electrode designs to enable selective stimulation of small diameter fibers.

OATYC Journal, Vol. XII, Nos. 1-2, Fall 1986-Spring 1987.

ERIC Educational Resources Information Center

Fullen, James, Ed.

1987-01-01

"OATYC Journal," published by the the Ohio Association of Two-Year Colleges, is designed as a forum for the exchange of concepts, methods, and findings relevant to the two-year college classroom. Along with commentaries and letters of reaction from the readership, the two issues of Volume XII present the following: (1) "Focus:…

76 FR 73614 - Lock Hydro Friends Fund XII; BOST2 LLC; Riverbank Hydro No. 21 LLC; FFP Project 96 LLC; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-29

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project Nos. 14260-000; 14264-000; 14267-000; 14273-000] Lock Hydro Friends Fund XII; BOST2 LLC; Riverbank Hydro No. 21 LLC; FFP Project 96..., Motions To Intervene, and Competing Applications On September 1, 2011, Lock Hydro Friends Fund XII (Lock...

Neuroprotective effect of lurasidone via antagonist activities on histamine in a rat model of cranial nerve involvement.

PubMed

He, Baoming; Yu, Liang; Li, Suping; Xu, Fei; Yang, Lili; Ma, Shuai; Guo, Yi

2018-04-01

Cranial nerve involvement frequently involves neuron damage and often leads to psychiatric disorder caused by multiple inducements. Lurasidone is a novel antipsychotic agent approved for the treatment of cranial nerve involvement and a number of mental health conditions in several countries. In the present study, the neuroprotective effect of lurasidone by antagonist activities on histamine was investigated in a rat model of cranial nerve involvement. The antagonist activities of lurasidone on serotonin 5‑HT7, serotonin 5‑HT2A, serotonin 5‑HT1A and serotonin 5‑HT6 were analyzed, and the preclinical therapeutic effects of lurasidone were examined in a rat model of cranial nerve involvement. The safety, maximum tolerated dose (MTD) and preliminary antitumor activity of lurasidone were also assessed in the cranial nerve involvement model. The therapeutic dose of lurasidone was 0.32 mg once daily, administered continuously in 14‑day cycles. The results of the present study found that the preclinical prescriptions induced positive behavioral responses following treatment with lurasidone. The MTD was identified as a once daily administration of 0.32 mg lurasidone. Long‑term treatment with lurasidone for cranial nerve involvement was shown to improve the therapeutic effects and reduce anxiety in the experimental rats. In addition, treatment with lurasidone did not affect body weight. The expression of the language competence protein, Forkhead‑BOX P2, was increased, and the levels of neuroprotective SxIP motif and microtubule end‑binding protein were increased in the hippocampal cells of rats with cranial nerve involvement treated with lurasidone. Lurasidone therapy reinforced memory capability and decreased anxiety. Taken together, lurasidone treatment appeared to protect against language disturbances associated with negative and cognitive impairment in the rat model of cranial nerve involvement, providing a basis for its use in the clinical treatment of

Studies on the Release of Renin by Direct and Reflex Activation of Renal Sympathetic Nerves.

ERIC Educational Resources Information Center

Donald, David E.

1979-01-01

Presents data on release of renin during direct and indirect stimulation of renal nerves. Conclusions show that renin release is influenced by change in activity of carotid and cardiopulmonary baroreceptor systems, and excitation of discrete areas of brain and hypothalamus by changes in renal sympathetic nerve. (Author/SA)

Inhibition of carbonic anhydrase isoforms I, II, IX and XII with novel Schiff bases: identification of selective inhibitors for the tumor-associated isoforms over the cytosolic ones.

PubMed

Sarikaya, Busra; Ceruso, Mariangela; Carta, Fabrizio; Supuran, Claudiu T

2014-11-01

A series of new Schiff bases was obtained from sulfanilamide, 3-fluorosulfanilamide or 4-(2-aminoethyl)-benzenesulfonamide and aromatic/heterocyclic aldehydes incorporating both hydrophobic and hydrophilic moieties. The obtained sulfonamides were investigated as inhibitors of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic CA I and II, as well as the transmembrane, tumor-associated CA IX and XII. Most derivatives were medium potency or weak hCA I/II inhibitors, but several of them showed nanomolar affinity for CA IX and/or XII, making them an interesting example of isoform-selective compounds. The nature of the aryl/hetaryl moiety present in the initial aldehyde was the main factor influencing potency and isoform selectivity. The best and most CA IX-selective compounds incorporated moieties such as 4-methylthiophenyl, 4-cyanophenyl-, 4-(2-pyridyl)-phenyl and the 4-aminoethylbenzenesulfonamide scaffold. The best hCA XII inhibitors, also showing selectivity for this isoform, incorporated 2-methoxy-4-nitrophenyl-, 2,3,5,6-tetrafluorophenyl and 4-(2-pyridyl)-phenyl functionalities and were also derivatives of 4-aminoethylbenzenesulfonamide. The sulfanilamide and 3-fluorosulfanilamide derived Schiff bases were less active compared to the corresponding 4-aminoethyl-benzenesulfonamide derivatives. As hCA IX/XII selective inhibition is attractive for obtaining antitumor agents/diagnostic tools with a new mechanism of action, compounds of the type described here may be considered interesting preclinical candidates. Copyright © 2014 Elsevier Ltd. All rights reserved.

Demonstration of resonant photopumping of Mo VII by Mo XII for a VUV laser near 600 {Angstrom}

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

Ilcisin, K.J.; Aumayr, F.; Schwob, J.L.

1993-09-01

We present data of experiments on the resonant photopumping of Mo VII by Mo XII as a method of generating a coherent VUV source near 600 {angstrom}. The experiment is based on a scheme proposed by Feldman and Reader in which the 4p{sup 6} -- 4p{sup 5}6s transition in Mo VII in resonantly photopumped by the 5s {sup 2}S{sub 1/2} -- 4p {sup 2}P{sub 1/2} transition in Mo XII. Results of the laser produced plasma experiments show the successful enhancement of the population of the Mo VII 4p{sup 5}6s upper lasing level when pumped by an adjacent Mo VII plasma.more » No enhancement was seen in a control experiment where the Mo VII plasma was pumped by a Zr X plasma. Improvements of the intensity of the Mo XII pump source, achieved using an additional pump laser, lead to the generation of a population inversion for the VUV transition.« less

Sensorimotor Peripheral Nerve Function and Physical Activity in Older Men

PubMed Central

Lange-Maia, Brittney S.; Cauley, Jane A.; Newman, Anne B.; Boudreau, Robert M.; Jakicic, John M.; Glynn, Nancy W.; Zivkovic, Sasa; Dam, Tien; Caserotti, Paolo; Cawthon, Peggy M.; Orwoll, Eric S.; Strotmeyer, Elsa S.

2017-01-01

We determined whether sensorimotor peripheral nerve (PN) function was associated with physical activity (PA) in older men. The Osteoporotic Fractures in Men Study Pittsburgh, PA, site (n=328, age 78.8±4.7 years), conducted PN testing, including: peroneal motor and sural sensory nerve conduction (latencies, amplitudes: CMAP and SNAP for motor and sensory amplitude, respectively), 1.4g/10g monofilament (dorsum of the great toe), and neuropathy symptoms. ANOVA and multivariate linear regression modeled PN associations with PA (Physical Activity Scale for the Elderly (PASE) and SenseWear Armband). After multivariable adjustment, better motor latency was associated with higher PASE scores (160.5±4.8 vs 135.6±6.7, p<0.01). Those without vs. with neuropathy symptoms had higher PASE scores (157.6±5.3 vs 132.9±7.1, p<0.01). Better vs. worse SNAP was associated with slightly more daily vigorous activity (9.5±0.8 vs. 7.3±0.7, p=0.05). Other PN measures were not associated with PA. Certain PN measures were associated with lower PA, suggesting a potential pathway for disability. PMID:26964668

[Blood-nerve barrier and peripheral nerve regeneration].

PubMed

Kanda, Takashi

2013-01-01

Blood-nerve barrier (BNB) restricts the movement of soluble mediators and leukocytes from the blood contents to the peripheral nervous system (PNS) parenchyma and thus maintains the endoneurial homeostasis. However, it interferes the supply of various neurotrophic factors from the blood constituents and stops the drainage of toxic substances out of the PNS parenchyma, resulting in the inhibition of peripheral nerve regeneration. If the manipulation of BNB function is possible, regeneration of peripheral nerve may be facilitated via the alteration of peripheral nerve microenvironment and ample supply of neurotrophic substances. A possible method to manipulate the BNB for therapeutic purposes is to modify the endothelial function using siRNAs, oligonucleotides and virus vectors. Another possible method is to modify BNB pericytes: small hydrophobic substances that can reach the pericyte membrane through the endothelial monolayer and strengthen the pericytic activity, including the release of various cytokines/chemokines that influence endothelial function, may also be useful as drug candidates to control the BNB function.

Carotid baroreflex regulation of sympathetic nerve activity during dynamic exercise in humans

NASA Technical Reports Server (NTRS)

Fadel, P. J.; Ogoh, S.; Watenpaugh, D. E.; Wasmund, W.; Olivencia-Yurvati, A.; Smith, M. L.; Raven, P. B.

2001-01-01

We sought to determine whether carotid baroreflex (CBR) control of muscle sympathetic nerve activity (MSNA) was altered during dynamic exercise. In five men and three women, 23.8 +/- 0.7 (SE) yr of age, CBR function was evaluated at rest and during 20 min of arm cycling at 50% peak O(2) uptake using 5-s periods of neck pressure and neck suction. From rest to steady-state arm cycling, mean arterial pressure (MAP) was significantly increased from 90.0 +/- 2.7 to 118.7 +/- 3.6 mmHg and MSNA burst frequency (microneurography at the peroneal nerve) was elevated by 51 +/- 14% (P < 0.01). However, despite the marked increases in MAP and MSNA during exercise, CBR-Delta%MSNA responses elicited by the application of various levels of neck pressure and neck suction ranging from +45 to -80 Torr were not significantly different from those at rest. Furthermore, estimated baroreflex sensitivity for the control of MSNA at rest was the same as during exercise (P = 0.74) across the range of neck chamber pressures. Thus CBR control of sympathetic nerve activity appears to be preserved during moderate-intensity dynamic exercise.

Evaluation of 177Lu[Lu]-CHX-A″-DTPA-6A10 Fab as a radioimmunotherapy agent targeting carbonic anhydrase XII.

PubMed

Fiedler, L; Kellner, M; Gosewisch, A; Oos, R; Böning, G; Lindner, S; Albert, N; Bartenstein, P; Reulen, H-J; Zeidler, R; Gildehaus, F J

2018-05-01

Due to their infiltrative growth behavior, gliomas have, even after surgical resection, a high recurrence tendency. The approach of intracavitary radioimmunotherapy (RIT) is aimed at inhibiting tumor re-growth by directly administering drugs into the resection cavity (RC). Direct application of the radioconjugate into the RC has the advantage of bypassing the blood-brain barrier, which allows the administration of higher radiation doses than systemic application. Carbonic anhydrase XII (CA XII) is highly expressed on glioma cells while being absent from normal brain and thus an attractive target molecule for RIT. We evaluated a CA XII-specific 6A10 Fab (fragment antigen binding) labelled with 177 Lu as an agent for RIT. 6A10 Fab fragment was modified and radiolabelled with 177 Lu and characterized by MALDI-TOF, flow cytometry and radio-TLC. In vitro stability was determined under physiological conditions. Biodistribution studies, autoradiography tumor examinations and planar scintigraphy imaging were performed on SCID-mice bearing human glioma xenografts. The in vitro CA XII binding capacity of the modified Fab was confirmed. Radiochemical purity was determined to be >90% after 72 h of incubation under physiological conditions. Autoradiography experiments proved the specific binding of the Fab to CA XII on tumor cells. Biodistribution studies revealed a tumor uptake of 3.0%ID/g after 6 h and no detectable brain uptake. The tumor-to-contralateral ratio of 10/1 was confirmed by quantitative planar scintigraphy. The radiochemical stability in combination with a successful in vivo tumor uptake shows the potential suitability for future RIT applications with the 6A10 Fab. Copyright © 2018 Elsevier Inc. All rights reserved.

Interpretation of fusimotor activity in cat masseter nerve during reflex jaw movements.

PubMed Central

Gottlieb, S; Taylor, A

1983-01-01

Simultaneous recordings were made from fusimotor axons in the central ends of filaments of the masseter nerve, and from masseter and temporalis spindle afferents in the mesencephalic nucleus of the fifth cranial nerve in lightly anaesthetized cats. Fusimotor and alpha-motor units in the masseter nerve were differentiated on the basis of their response to passive ramp and hold stretches applied to the jaw. Spindle afferents were identified as primary or secondary according to their dynamic index after administration of suxamethonium. The activity of a given fusimotor unit during reflex movements of the jaw followed one of two distinct patterns: so-called 'tonic' units showed a general increase in activity during a movement, without detailed relation to lengthening or shortening, while 'modulated' units displayed a striking modulation of their activity with shortening, and were usually silent during subsequent lengthening. Comparison of the simultaneously recorded fusimotor and spindle afferent activity suggests that modulated units may be representative of a population of static fusimotor neurones, and tonic units of a population of dynamic fusimotor neurones. In these lightly anaesthetized animals, both primary and secondary spindle afferents showed increased firing during muscle shortening as well as during lengthening. This increase during shortening is not usually seen in conscious animals and reasons are given for the view that it is due to greater depression of alpha-motor activity than of static fusimotor activity during anaesthesia. The results are discussed in relation to the theories of 'alpha-gamma co-activation' and of 'servo-assistance'; and it is suggested that static fusimotor neurones provide a 'temporal template' of the intended movement, while dynamic fusimotor neurones set the required dynamic sensitivity to deviations from the intended movement pattern. PMID:6229627

Overlapping Mechanisms of Peripheral Nerve Regeneration and Angiogenesis Following Sciatic Nerve Transection

PubMed Central

Wang, Hongkui; Zhu, Hui; Guo, Qi; Qian, Tianmei; Zhang, Ping; Li, Shiying; Xue, Chengbin; Gu, Xiaosong

2017-01-01

Peripheral nervous system owns the ability of self-regeneration, mainly in its regenerative microenvironment including vascular network reconstruction. More recently, more attentions have been given to the close relationship between tissue regeneration and angiogenesis. To explore the overlap of molecular mechanisms and key regulation molecules between peripheral nerve regeneration and angiogenesis post peripheral nerve injury, integrative and bioinformatic analysis was carried out for microarray data of proximal stumps after sciatic nerve transection in SD rats. Nerve regeneration and angiogenesis were activated at 1 day immediately after sciatic nerve transection simultaneously. The more obvious changes of transcription regulators and canonical pathways suggested a phase transition between 1 and 4 days of both nerve regeneration and angiogenesis after sciatic nerve transection. Furthermore, 16 differentially expressed genes participated in significant biological processes of both nerve regeneration and angiogenesis, a few of which were validated by qPCR and immunofluorescent staining. It was demonstrated that STAT3, EPHB3, and Cdc42 co-expressed in Schwann cells and vascular endothelial cells to play a key role in regulation of nerve regeneration and angiogenesis simultaneously response to sciatic nerve transection. We provide a framework for understanding biological processes and precise molecular correlations between peripheral nerve regeneration and angiogenesis after peripheral nerve transection. Our work serves as an experimental basis and a valuable resource to further understand molecular mechanisms that define nerve injury-induced micro-environmental variation for achieving desired peripheral nerve regeneration. PMID:29085283

Overlapping Mechanisms of Peripheral Nerve Regeneration and Angiogenesis Following Sciatic Nerve Transection.

PubMed

Wang, Hongkui; Zhu, Hui; Guo, Qi; Qian, Tianmei; Zhang, Ping; Li, Shiying; Xue, Chengbin; Gu, Xiaosong

2017-01-01

Peripheral nervous system owns the ability of self-regeneration, mainly in its regenerative microenvironment including vascular network reconstruction. More recently, more attentions have been given to the close relationship between tissue regeneration and angiogenesis. To explore the overlap of molecular mechanisms and key regulation molecules between peripheral nerve regeneration and angiogenesis post peripheral nerve injury, integrative and bioinformatic analysis was carried out for microarray data of proximal stumps after sciatic nerve transection in SD rats. Nerve regeneration and angiogenesis were activated at 1 day immediately after sciatic nerve transection simultaneously. The more obvious changes of transcription regulators and canonical pathways suggested a phase transition between 1 and 4 days of both nerve regeneration and angiogenesis after sciatic nerve transection. Furthermore, 16 differentially expressed genes participated in significant biological processes of both nerve regeneration and angiogenesis, a few of which were validated by qPCR and immunofluorescent staining. It was demonstrated that STAT3, EPHB3, and Cdc42 co-expressed in Schwann cells and vascular endothelial cells to play a key role in regulation of nerve regeneration and angiogenesis simultaneously response to sciatic nerve transection. We provide a framework for understanding biological processes and precise molecular correlations between peripheral nerve regeneration and angiogenesis after peripheral nerve transection. Our work serves as an experimental basis and a valuable resource to further understand molecular mechanisms that define nerve injury-induced micro-environmental variation for achieving desired peripheral nerve regeneration.

Which nerve conduction parameters can predict spontaneous electromyographic activity in carpal tunnel syndrome?

PubMed

Chang, Chia-Wei; Lee, Wei-Ju; Liao, Yi-Chu; Chang, Ming-Hong

2013-11-01

We investigate electrodiagnostic markers to determine which parameters are the best predictors of spontaneous electromyographic (EMG) activity in carpal tunnel syndrome (CTS). We enrolled 229 patients with clinically proven and nerve conduction study (NCS)-proven CTS, as well as 100 normal control subjects. All subjects were evaluated using electrodiagnostic techniques, including median distal sensory latencies (DSLs), sensory nerve action potentials (SNAPs), distal motor latencies (DMLs), compound muscle action potentials (CMAPs), forearm median nerve conduction velocities (FMCVs) and wrist-palm motor conduction velocities (W-P MCVs). All CTS patients underwent EMG examination of the abductor pollicis brevis (APB) muscle, and the presence or absence of spontaneous EMG activities was recorded. Normal limits were determined by calculating the means ± 2 standard deviations from the control data. Associations between parameters from the NCS and EMG findings were investigated. In patients with clinically diagnosed CTS, abnormal median CMAP amplitudes were the best predictors of spontaneous activity during EMG examination (p<0.001; OR 36.58; 95% CI 15.85-84.43). If the median CMAP amplitude was ≤ 2.1 mV, the rate of occurrence of spontaneous EMG activity was >95% (positive predictive rate >95%). If the median CMAP amplitude was higher than the normal limit (>4.9 mV), the rate of no spontaneous EMG activity was >94% (negative predictive rate >94%). An abnormal SNAP amplitude was the second best predictor of spontaneous EMG activity (p<0.001; OR 4.13; 95% CI 2.16-7.90), and an abnormal FMCV was the third best predictor (p=0.01; OR 2.10; 95% CI 1.20-3.67). No other nerve conduction parameters had significant power to predict spontaneous activity upon EMG examination. The CMAP amplitudes of the APB are the most powerful predictors of the occurrence of spontaneous EMG activity. Low CMAP amplitudes are strongly associated with spontaneous activity, whereas high CMAP

BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit

PubMed Central

Wang, Peng; Du, Chao; Chen, Fei-Xue; Li, Chang-Qing; Yu, Yan-Bo; Han, Ting; Akhtar, Suhail; Zuo, Xiu-Li; Tan, Xiao-Di; Li, Yan-Qing

2016-01-01

The over-expressed colonic brain-derived neurotrophic factor (BDNF) has been reported to be associated with abdominal pain in patients with irritable bowel syndrome (IBS). However, the neuropathological mechanism is unclear. We here investigated the involvement of enteroglial cells (EGCs) and enteric nerves in IBS-like visceral hypersensitivity. We showed that glial fibrillary acidic protein (GFAP), tyrosine receptor kinase B (TrkB) and substance P (SP) were significantly increased in the colonic mucosa of IBS patients. The upregulation of those proteins was also observed in the colon of mice with visceral hypersensitivity, but not in the colon of BDNF+/− mice. Functionally, TrkB or EGC inhibitors, or BDNF knockdown significantly suppressed visceral hypersensitivity in mice. Using the EGC cell line, we found that recombinant human BDNF (r-HuBDNF) could directly activate EGCs via the TrkB-phospholipase Cγ1 pathway, thereby inducing a significant upregulation of SP. Moreover, supernatants from r-HuBDNF-activated EGC culture medium, rather than r-HuBDNF alone, triggered markedly augmented discharges in isolated intestinal mesenteric afferent nerves. r-HuBDNF alone could cause mesenteric afferent mechanical hypersensitivity independently, and this effect was synergistically enhanced by activated EGCs. We conclude that EGC-enteric nerve unit may be involved in IBS-like visceral hypersensitivity, and this process is likely initiated by BDNF-TrkB pathway activation. PMID:26837784

Reconstruction of peripheral nerves using acellular nerve grafts with implanted cultured Schwann cells.

PubMed

Frerichs, Onno; Fansa, Hisham; Schicht, Christoph; Wolf, Gerald; Schneider, Wolfgang; Keilhoff, Gerburg

2002-01-01

The bridging of nerve gaps is still one of the major problems in peripheral nerve surgery. The present experiment describes our attempt to engineer different biologic nerve grafts in a rat sciatic nerve model: cultured isogenic Schwann cells were implanted into 2-cm autologous acellular nerve grafts or autologous predegenerated nerve grafts. Autologous nerve grafts and predegenerated or acellular nerve grafts without implanted Schwann cells served as controls. The regenerated nerves were assessed histologically and morphometrically after 6 weeks. Predegenerated grafts showed results superior in regard to axon count and histologic appearance in comparison to standard grafts and acellular grafts. The acellular nerve grafts showed the worst histologic picture, but axon counts were in the range of standard grafts. The implantation of Schwann cells did not yield significant improvements in any group. In conclusion, the status of activation of Schwann cells and the stadium of Wallerian degeneration in a nerve graft might be key factors for regeneration, rather than total number of Schwann cells. Predegenerated nerve grafts are therefore superior to standard grafts in the rat model. Acellular grafts are able to bridge nerve gaps of up to 2 cm in the rat model, but even the addition of cultivated Schwann cells did not lead to results as good as in the group with autologous nerve grafts. Copyright 2002 Wiley-Liss, Inc. MICROSURGERY 22:311-315 2002

Chaotic behavior of renal sympathetic nerve activity: effect of baroreceptor denervation and cardiac failure.

PubMed

DiBona, G F; Jones, S Y; Sawin, L L

2000-09-01

Nonlinear dynamic analysis was used to examine the chaotic behavior of renal sympathetic nerve activity in conscious rats subjected to either complete baroreceptor denervation (sinoaortic and cardiac baroreceptor denervation) or induction of congestive heart failure (CHF). The peak interval sequence of synchronized renal sympathetic nerve discharge was extracted and used for analysis. In control rats, this yielded a system whose correlation dimension converged to a low value over the embedding dimension range of 10-15 and whose greatest Lyapunov exponent was positive. Complete baroreceptor denervation was associated with a decrease in the correlation dimension of the system (before 2.65 +/- 0.27, after 1.64 +/- 0.17; P < 0.01) and a reduction in chaotic behavior (greatest Lyapunov exponent: 0.201 +/- 0.008 bits/data point before, 0.177 +/- 0.004 bits/data point after, P < 0.02). CHF, a state characterized by impaired sinoaortic and cardiac baroreceptor regulation of renal sympathetic nerve activity, was associated with a similar decrease in the correlation dimension (control 3.41 +/- 0.23, CHF 2.62 +/- 0.26; P < 0.01) and a reduction in chaotic behavior (greatest Lyapunov exponent: 0.205 +/- 0.048 bits/data point control, 0.136 +/- 0.033 bits/data point CHF, P < 0.02). These results indicate that removal of sinoaortic and cardiac baroreceptor regulation of renal sympathetic nerve activity, occurring either physiologically or pathophysiologically, is associated with a decrease in the correlation dimensions of the system and a reduction in chaotic behavior.

Mesencephalic stimulation elicits inhibition of phrenic nerve activity in cat.

PubMed Central

Gallman, E A; Lawing, W L; Millhorn, D E

1991-01-01

1. Previous work from this laboratory has indicated that the mesencephalon is the anatomical substrate for a mechanism capable of inhibiting central respiratory drive in glomectomized cats for periods of up to 1 h or more following brief exposure to systemic hypoxia; phrenic nerve activity was used as an index of central respiratory drive. 2. The present study was undertaken to further localize the region responsible for the observed post-hypoxic inhibition of respiratory drive. We studied the phrenic nerve response to stimulations of the mesencephalon in anaesthetized, paralysed peripherally chemo-denervated cats with end-expired PCO2 and body temperature servo-controlled. 3. Stimulations of two types were employed. Electrical stimulation allowed rapid determination of sites from which phrenic inhibition could be elicited. Microinjections of excitatory amino acids were used subsequently in order to confine excitation to neuronal cell bodies and not axons of passage. 4. Stimulation of discrete regions of the ventromedial aspect of the mesencephalon in the vicinity of the red nucleus produced substantial inhibition of phrenic activity which lasted up to 45 min. Stimulation of other areas of the mesencephalon either produced no phrenic inhibition or resulted in a slight stimulation of phrenic activity. 5. The results are discussed in the context of the central respiratory response to hypoxia. PMID:1676420

Active patient decision making regarding nerve sparing during radical prostatectomy: a novel approach.

PubMed

Lavery, Hugh J; Prall, David N; Abaza, Ronney

2011-08-01

The motivation to preserve sexual function can vary widely among patients before prostatectomy. Increasing patient involvement may allow a more personalized experience and may improve satisfaction. We assessed a strategy of surgeon deference to patient choice in regard to nerve sparing to determine to what degree patients are rational actors and capable of active decision making. A total of 150 patients treated with prostatectomy participated in a standardized preoperative discussion regarding the concept of nerve sparing, extracapsular extension and the potential need for adjuvant radiation in the event of local recurrence. Each patient was given his nomogram predicted risk of extracapsular extension and then elected nerve sparing or nonnerve sparing. The corresponding procedure was performed unless grossly invasive disease was encountered. Of the 150 patients 109 chose nerve sparing (73%) and 41 chose nonnerve sparing (27%). In patients with a nomogram predicted risk of extracapsular extension less than 20%, 20% to 50% and greater than 50%, nerve sparing was elected by 88%, 41% and 25%, respectively. Patients with lower risks of extracapsular extension electing nonnerve sparing were older and had higher rates of erectile dysfunction. Empowering patients to decide on their nerve sparing status is a reasonable strategy that did not lead to a high rate of patients with a high risk of extracapsular extension electing nerve sparing. With proper counseling informed patients made reasonable decisions, and appeared to be conservative, prioritizing cancer control in the majority of instances where extracapsular extension risk was high. In addition, they may have been overly conservative in electing nonnerve sparing when the risk was low. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Phrenic and hypoglossal nerve activity during respiratory response to hypoxia in 6-OHDA unilateral model of Parkinson's disease.

PubMed

Andrzejewski, Kryspin; Budzińska, Krystyna; Kaczyńska, Katarzyna

2017-07-01

Parkinson's disease (PD) patients apart from motor dysfunctions exhibit respiratory disturbances. Their mechanism is still unknown and requires investigation. Our research was designed to examine the activity of phrenic (PHR) and hypoglossal (HG) nerves activity during a hypoxic respiratory response in the 6-hydroxydopamine (6-OHDA) model of PD. Male adult Wistar rats were injected unilaterally with 6-OHDA (20μg) or the vehicle into the right medial forebrain bundle (MFB). Two weeks after the surgery the activity of the phrenic and hypoglossal nerve was registered in anesthetized, vagotomized, paralyzed, and mechanically ventilated rats under normoxic and hypoxic conditions. Lesion effectiveness was confirmed by the cylinder test, performed before the MFB injection and 14days after, before the respiratory experiment. 6-OHDA lesioned animals showed a significant increase in normoxic inspiratory time. Expiratory time and total time of the respiratory cycle were prolonged in PD rats after hypoxia. The amplitude of the PHR activity and its minute activity were increased in comparison to the sham group at recovery time and during 30s of hypoxia. The amplitude of the HG activity was increased in response to hypoxia in 6-OHDA lesioned animals. The degeneration of dopaminergic neurons decreased the pre-inspiratory/inspiratory ratio of the hypoglossal burst amplitude during and after hypoxia. Unilateral MFB lesion changed the activity of the phrenic and hypoglossal nerves. The altered pre-inspiratory hypoglossal nerve activity indicates modifications to the central mechanisms controlling the activity of the HG nerve and may explain respiratory disorders seen in PD, i.e. apnea. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamic analysis of patterns of renal sympathetic nerve activity: implications for renal function.

PubMed

DiBona, Gerald F

2005-03-01

Methods of dynamic analysis are used to provide additional understanding of the renal sympathetic neural control of renal function. The concept of functionally specific subgroups of renal sympathetic nerve fibres conveying information encoded in the frequency domain is presented. Analog pulse modulation and pseudorandom binary sequence stimulation patterns are used for the determination of renal vascular frequency response. Transfer function analysis is used to determine the effects of non-renal vasoconstrictor and vasoconstrictor intensities of renal sympathetic nerve activity on dynamic autoregulation of renal blood flow.

Opisthorchiasis in infant remains from the medieval Zeleniy Yar burial ground of XII-XIII centuries AD

PubMed Central

Slepchenko, Sergey Mikhailovich; Gusev, Alexander Vasilevich; Ivanov, Sergey Nikolaevich; Svyatova, Evgenia Olegovna

2015-01-01

We present a paleoparasitological analysis of the medieval Zeleniy Yar burial ground of the XII-XII centuries AD located in the northern part of Western Siberia. Parasite eggs, identified as eggs of Opisthorchis felineus, were found in the samples from the pelvic area of a one year old infant buried at the site. Presence of these eggs in the soil samples from the infant’s abdomen suggests that he/she was infected with opisthorchiasis and imply consumption of undercooked fish. Ethnographic records collected among the population of the northern part of Western Siberia reveal numerous cases of feeding raw fish to their children. Zeleniy Yar case of opisthorchiasis suggests that this dietary custom has persisted from at least medieval times. PMID:26602874

Facial reanimation by muscle-nerve neurotization after facial nerve sacrifice. Case report.

PubMed

Taupin, A; Labbé, D; Babin, E; Fromager, G

2016-12-01

Recovering a certain degree of mimicry after sacrifice of the facial nerve is a clinically recognized finding. The authors report a case of hemifacial reanimation suggesting a phenomenon of neurotization from muscle-to-nerve. A woman benefited from a parotidectomy with sacrifice of the left facial nerve indicated for recurrent tumor in the gland. The distal branches of the facial nerve, isolated at the time of resection, were buried in the masseter muscle underneath. The patient recovered a voluntary hémifacial motricity. The electromyographic analysis of the motor activity of the zygomaticus major before and after block of the masseter nerve showed a dependence between mimic muscles and the masseter muscle. Several hypotheses have been advanced to explain the spontaneous reanimation of facial paralysis. The clinical case makes it possible to argue in favor of muscle-to-nerve neurotization from masseter muscle to distal branches of the facial nerve. It illustrates the quality of motricity that can be obtained thanks to this procedure. The authors describe a simple implantation technique of distal branches of the facial nerve in the masseter muscle during a radical parotidectomy with facial nerve sacrifice and recovery of resting tone but also a quality voluntary mimicry. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Nerve stripper-assisted sural nerve harvest.

PubMed

Hassanpour, Esmail; Yavari, Masoud; Karbalaeikhani, Ali; Saremi, Hossein

2014-03-01

Sural nerve has the favorite length and size for nerve graft interposition. Here two techniques, that is, "stocking seam" and "stair-step" or "stepladder," have been used for harvesting sural nerve. The first technique results in an unsightly scar at the posterior calf, and the latter one takes a long time to perform and exert undue traction to the graft during harvesting. The purpose of this article is to describe our experience in harvesting the sural nerve by a nerve stripper. A nerve stripper was used for harvesting sural nerve in 35 adult patients (in 6 patients, sural harvesting was done bilaterally), 27 men and 8 women. Thirty-one sural nerve harvests were done by closed technique (i.e., harvesting of sural nerve only by two incisions, one in the posterior of the lateral malleolus and the other in popliteal fossa), in 8 others by limited open technique, and in 2 cases, there was early laceration of the sural nerve at the beginning of the study. The contralateral sural nerve was harvested in one patient and medial antebrachial nerve in another by open technique. The mean length of the retrieved sural nerve was 34.5 cm in the closed technique group and 35 cm in the limited open technique group. We detected advancing Tinel's sign in all nerve stripper-assisted sural nerve harvested group members in both the closed and limited open groups. Sural nerve harvesting by the nerve stripper is a reliable and simple technique, and it is applicable as a routine technique. Applying controlled rotatory movements of the nerve stripper instead of pushing can result in satisfactory harvesting of the sural nerve without early laceration. Georg Thieme Verlag KG Stuttgart · New York.

Open saccharin-based secondary sulfonamides as potent and selective inhibitors of cancer-related carbonic anhydrase IX and XII isoforms.

PubMed

D'Ascenzio, Melissa; Guglielmi, Paolo; Carradori, Simone; Secci, Daniela; Florio, Rosalba; Mollica, Adriano; Ceruso, Mariangela; Akdemir, Atilla; Sobolev, Anatoly P; Supuran, Claudiu T

2017-12-01

A large number of novel secondary sulfonamides based on the open saccharin scaffold were synthesized and evaluated as selective inhibitors of four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). They were obtained by reductive ring opening of the newly synthesized N-alkylated saccharin derivatives and were shown to be inactive against the two cytosolic off-target hCA I and II (K i s > 10 µM). Interestingly, these compounds inhibited hCA IX in the low nanomolar range with K i s ranging between 20 and 298 nM and were extremely potent inhibitors of hCA XII isoenzyme (K i s ranging between 4.3 and 432 nM). Since hCA IX and XII are the cancer-related isoforms recently validated as drug targets, these results represent an important goal in the development of new anticancer candidates. Finally, a computational approach has been performed to better correlate the biological data to the binding mode of these inhibitors.

Changes in Extracellular Striatal Acetylcholine and Brain Seizure Activity Following Acute Exposure to Nerve Against in Freely Moving Guinea Pigs

DTIC Science & Technology

2010-01-01

Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Changes in extracellular striatal acetylcholine and brain seizure activity following...Acetylcholine, acetylcholinesterase, choline, guinea pig, in vivo microdialysis, nerve agents, organophosphorus compounds, sarin, seizure activity ...RESEARCH ARTICLE Changes in extracellular striatal acetylcholine and brain seizure activity following acute exposure to nerve agents in freely

Peripheral Nerve Regeneration Strategies: Electrically Stimulating Polymer Based Nerve Growth Conduits

PubMed Central

Anderson, Matthew; Shelke, Namdev B.; Manoukian, Ohan S.; Yu, Xiaojun; McCullough, Louise D.; Kumbar, Sangamesh G.

2017-01-01

Treatment of large peripheral nerve damages ranges from the use of an autologous nerve graft to a synthetic nerve growth conduit. Biological grafts, in spite of many merits, show several limitations in terms of availability and donor site morbidity, and outcomes are suboptimal due to fascicle mismatch, scarring, and fibrosis. Tissue engineered nerve graft substitutes utilize polymeric conduits in conjunction with cues both chemical and physical, cells alone and or in combination. The chemical and physical cues delivered through polymeric conduits play an important role and drive tissue regeneration. Electrical stimulation (ES) has been applied toward the repair and regeneration of various tissues such as muscle, tendon, nerve, and articular tissue both in laboratory and clinical settings. The underlying mechanisms that regulate cellular activities such as cell adhesion, proliferation, cell migration, protein production, and tissue regeneration following ES is not fully understood. Polymeric constructs that can carry the electrical stimulation along the length of the scaffold have been developed and characterized for possible nerve regeneration applications. We discuss the use of electrically conductive polymers and associated cell interaction, biocompatibility, tissue regeneration, and recent basic research for nerve regeneration. In conclusion, a multifunctional combinatorial device comprised of biomaterial, structural, functional, cellular, and molecular aspects may be the best way forward for effective peripheral nerve regeneration. PMID:27278739

A Comparison of Blood Factor XII Autoactivation in Buffer, Protein Cocktail, Serum, and Plasma Solutions

PubMed Central

Golas, Avantika; Yeh, Chyi-Huey Josh; Pitakjakpipop, Harit; Siedlecki, Christopher A.; Vogler, Erwin A.

2012-01-01

Activation of blood plasma coagulation in vitro by contact with material surfaces is demonstrably dependent on plasma-volume-to-activator-surface-area ratio. The only plausible explanation consistent with current understanding of coagulation-cascade biochemistry is that procoagulant stimulus arising from the activation complex of the intrinsic pathway is dependent on activator surface area. And yet, it is herein shown that activation of the blood zymogen factor XII (Hageman factor, FXII) dissolved in buffer, protein cocktail, heat-denatured serum, and FXI deficient plasma does not exhibit activator surface-area dependence. Instead, a highly-variable burst of procoagulant-enzyme yield is measured that exhibits no measurable kinetics, sensitivity to mixing, or solution-temperature dependence. Thus, FXII activation in both buffer and protein-containing solutions does not exhibit characteristics of a biochemical reaction but rather appears to be a “mechanochemical” reaction induced by FXII molecule interactions with hydrophilic activator particles that do not formally adsorb blood proteins from solution. Results of this study strongly suggest that activator surface-area dependence observed in contact activation of plasma coagulation does not solely arise at the FXII activation step of the intrinsic pathway. PMID:23117212

Treatment of peroneal nerve injuries with simultaneous tendon transfer and nerve exploration.

PubMed

Ho, Bryant; Khan, Zubair; Switaj, Paul J; Ochenjele, George; Fuchs, Daniel; Dahl, William; Cederna, Paul; Kung, Theodore A; Kadakia, Anish R

2014-08-06

Common peroneal nerve palsy leading to foot drop is difficult to manage and has historically been treated with extended bracing with expectant waiting for return of nerve function. Peroneal nerve exploration has traditionally been avoided except in cases of known traumatic or iatrogenic injury, with tendon transfers being performed in a delayed fashion after exhausting conservative treatment. We present a new strategy for management of foot drop with nerve exploration and concomitant tendon transfer. We retrospectively reviewed a series of 12 patients with peroneal nerve palsies that were treated with tendon transfer from 2005 to 2011. Of these patients, seven were treated with simultaneous peroneal nerve exploration and repair at the time of tendon transfer. Patients with both nerve repair and tendon transfer had superior functional results with active dorsiflexion in all patients, compared to dorsiflexion in 40% of patients treated with tendon transfers alone. Additionally, 57% of patients treated with nerve repair and tendon transfer were able to achieve enough function to return to running, compared to 20% in patients with tendon transfer alone. No patient had full return of native motor function resulting in excessive dorsiflexion strength. The results of our limited case series for this rare condition indicate that simultaneous nerve repair and tendon transfer showed no detrimental results and may provide improved function over tendon transfer alone.

"Long-term stability of stimulating spiral nerve cuff electrodes on human peripheral nerves".

PubMed

Christie, Breanne P; Freeberg, Max; Memberg, William D; Pinault, Gilles J C; Hoyen, Harry A; Tyler, Dustin J; Triolo, Ronald J

2017-07-11

Electrical stimulation of the peripheral nerves has been shown to be effective in restoring sensory and motor functions in the lower and upper extremities. This neural stimulation can be applied via non-penetrating spiral nerve cuff electrodes, though minimal information has been published regarding their long-term performance for multiple years after implantation. Since 2005, 14 human volunteers with cervical or thoracic spinal cord injuries, or upper limb amputation, were chronically implanted with a total of 50 spiral nerve cuff electrodes on 10 different nerves (mean time post-implant 6.7 ± 3.1 years). The primary outcome measures utilized in this study were muscle recruitment curves, charge thresholds, and percent overlap of recruited motor unit populations. In the eight recipients still actively involved in research studies, 44/45 of the spiral contacts were still functional. In four participants regularly studied over the course of 1 month to 10.4 years, the charge thresholds of the majority of individual contacts remained stable over time. The four participants with spiral cuffs on their femoral nerves were all able to generate sufficient moment to keep the knees locked during standing after 2-4.5 years. The dorsiflexion moment produced by all four fibular nerve cuffs in the active participants exceeded the value required to prevent foot drop, but no tibial nerve cuffs were able to meet the plantarflexion moment that occurs during push-off at a normal walking speed. The selectivity of two multi-contact spiral cuffs was examined and both were still highly selective for different motor unit populations for up to 6.3 years after implantation. The spiral nerve cuffs examined remain functional in motor and sensory neuroprostheses for 2-11 years after implantation. They exhibit stable charge thresholds, clinically relevant recruitment properties, and functional muscle selectivity. Non-penetrating spiral nerve cuff electrodes appear to be a suitable option

Influence of local noxious heat stimulation on sensory nerve activity in the feline dental pulp.

PubMed

Ahlberg, K F

1978-05-01

The present investigation was undertaken to develop an experimental model in which noxious heat stimulation was used to produce increased intradental sensory nerve activity in canine teeth of anesthetized cats. Two techniques were evaluated in which both the method of recording and the nature of the stimulus varied. Slow heating (approx 1 degree C/s) to 47 degree C of the tooth surface (combined with recording from electrodes in open dentinal cavities) did not produce any persistent nerve activity. Repeated periods of brief intense heating (approx 60 degrees C/s) (combined with recording from amalgam electrodes placed on cavity floors) resulted in an immediate response and an afterdischarge (phase 3) generally persisting for 20--60 min. Maximum phase 3 activity was characteristic for the individual cat and ranged from 0.2 to 50.2 imp/s. mean value 10.6 imp/s (S.D. +/- 9.2). A systematically higher phase 3 activity was recorded in lower compared to upper canine teeth (p less than 0.05). The maximum phase 3 response generally occurred after 3-8 stimulations; the median number of required stimuli was 3. Repeated brief heat stimulations combined with the closed cavity recording technique may be used as an experimental model by which the mechanisms behind increases in intradental sensory nerve activity associated with tissue damage can be studied.

Depletion of coagulation factor XII ameliorates brain pathology and cognitive impairment in Alzheimer disease mice.

PubMed

Chen, Zu-Lin; Revenko, Alexey S; Singh, Pradeep; MacLeod, A Robert; Norris, Erin H; Strickland, Sidney

2017-05-04

Vascular abnormalities and inflammation are found in many Alzheimer disease (AD) patients, but whether these changes play a causative role in AD is not clear. The factor XII (FXII) -initiated contact system can trigger both vascular pathology and inflammation and is activated in AD patients and AD mice. We have investigated the role of the contact system in AD pathogenesis. Cleavage of high-molecular-weight kininogen (HK), a marker for activation of the inflammatory arm of the contact system, is increased in a mouse model of AD, and this cleavage is temporally correlated with the onset of brain inflammation. Depletion of FXII in AD mice inhibited HK cleavage in plasma and reduced neuroinflammation, fibrinogen deposition, and neurodegeneration in the brain. Moreover, FXII-depleted AD mice showed better cognitive function than untreated AD mice. These results indicate that FXII-mediated contact system activation contributes to AD pathogenesis, and therefore this system may offer novel targets for AD treatment. © 2017 by The American Society of Hematology.

Cardiac-locked bursts of muscle sympathetic nerve activity are absent in familial dysautonomia

PubMed Central

Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Axelrod, Felicia B; Kaufmann, Horacio

2013-01-01

Familial dysautonomia (Riley–Day syndrome) is an hereditary sensory and autonomic neuropathy (HSAN type III), expressed at birth, that is associated with reduced pain and temperature sensibilities and absent baroreflexes, causing orthostatic hypotension as well as labile blood pressure that increases markedly during emotional excitement. Given the apparent absence of functional baroreceptor afferents, we tested the hypothesis that the normal cardiac-locked bursts of muscle sympathetic nerve activity (MSNA) are absent in patients with familial dysautonomia. Tungsten microelectrodes were inserted percutaneously into muscle or cutaneous fascicles of the common peroneal nerve in 12 patients with familial dysautonomia. Spontaneous bursts of MSNA were absent in all patients, but in five patients we found evidence of tonically firing sympathetic neurones, with no cardiac rhythmicity, that increased their spontaneous discharge during emotional arousal but not during a manoeuvre that unloads the baroreceptors. Conversely, skin sympathetic nerve activity (SSNA), recorded in four patients, appeared normal. We conclude that the loss of phasic bursts of MSNA and the loss of baroreflex modulation of muscle vasoconstrictor drive contributes to the poor control of blood pressure in familial dysautonomia, and that the increase in tonic firing of muscle vasoconstrictor neurones contributes to the increase in blood pressure during emotional excitement. PMID:23165765

Reflectance Speckle of Retinal Nerve Fiber Layer Reveals Axonal Activity

PubMed Central

Huang, Xiang-Run; Knighton, Robert W.; Zhou, Ye; Zhao, Xiao-Peng

2013-01-01

Purpose. This study investigated the retinal nerve fiber layer (RNFL) reflectance speckle and tested the hypothesis that temporal change of RNFL speckle reveals axonal dynamic activity. Methods. RNFL reflectance speckle of isolated rat retinas was studied with monochromatic illumination. A series of reflectance images was collected every 5 seconds for approximately 15 minutes. Correlation coefficients (CC) of selected areas between a reference and subsequent images were calculated and plotted as a function of the time intervals between images. An exponential function fit to the time course was used to evaluate temporal change of speckle pattern. To relate temporal change of speckle to axonal activity, in vitro living retina perfused at a normal (34°C) and a lower (24°C) temperature, paraformaldehyde-fixed retina, and retina treated with microtubule depolymerization were used. Results. RNFL reflectance was not uniform; rather nerve fiber bundles had a speckled texture that changed with time. In normally perfused retina, the time constant of the CC change was 0.56 ± 0.26 minutes. In retinas treated with lower temperature and microtubule depolymerization, the time constants increased by two to four times, indicating that the speckle pattern changed more slowly. The speckled texture in fixed retina was stationary. Conclusions. Fixation stops axonal activity; treatments with either lower temperature or microtubule depolymerization are known to decrease axonal transport. The results obtained in this study suggest that temporal change of RNFL speckle reveals structural change due to axonal activity. Assessment of RNFL reflectance speckle may offer a new means of evaluating axonal function. PMID:23532525

Resting Afferent Renal Nerve Discharge and Renal Inflammation: Elucidating the Role of Afferent and Efferent Renal Nerves in Deoxycorticosterone Acetate Salt Hypertension.

PubMed

Banek, Christopher T; Knuepfer, Mark M; Foss, Jason D; Fiege, Jessica K; Asirvatham-Jeyaraj, Ninitha; Van Helden, Dusty; Shimizu, Yoji; Osborn, John W

2016-12-01

Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA) salt rat model. Uninephrectomized male Sprague-Dawley rats (275-300 g) underwent afferent-selective RDNx (n=10), total RDNx (n=10), or Sham (n=10) and were instrumented for the measurement of mean arterial pressure and heart rate by radiotelemetry. Rats received 100-mg DOCA (SC) and 0.9% saline for 21 days. Resting afferent renal nerve activity in DOCA and vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting afferent renal nerve activity, expressed as a percent of peak afferent nerve activity, was substantially increased in DOCA than in vehicle (35.8±4.4 versus 15.3±2.8 %Amax). The DOCA-Sham hypertension (132±12 mm Hg) was attenuated by ≈50% in both total RDNx (111±8 mm Hg) and afferent-selective RDNx (117±5 mm Hg) groups. Renal inflammation induced by DOCA salt was attenuated by total RDNx and unaffected by afferent-selective RDNx. These data suggest that afferent renal nerve activity may mediate the hypertensive response to DOCA salt, but inflammation may be mediated primarily by efferent renal sympathetic nerve activity. Also, resting afferent renal nerve activity is elevated in DOCA salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension. © 2016 American Heart Association, Inc.

Methamphetamine neurotoxicity in dopamine nerve endings of the striatum is associated with microglial activation.

PubMed

Thomas, David M; Walker, Paul D; Benjamins, Joyce A; Geddes, Timothy J; Kuhn, Donald M

2004-10-01

Methamphetamine intoxication causes long-lasting damage to dopamine nerve endings in the striatum. The mechanisms underlying this neurotoxicity are not known but oxidative stress has been implicated. Microglia are the major antigen-presenting cells in brain and when activated, they secrete an array of factors that cause neuronal damage. Surprisingly, very little work has been directed at the study of microglial activation as part of the methamphetamine neurotoxic cascade. We report here that methamphetamine activates microglia in a dose-related manner and along a time course that is coincident with dopamine nerve ending damage. Prevention of methamphetamine toxicity by maintaining treated mice at low ambient temperature prevents drug-induced microglial activation. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), which damages dopamine nerve endings and cell bodies, causes extensive microglial activation in striatum as well as in the substantia nigra. In contrast, methamphetamine causes neither microglial activation in the substantia nigra nor dopamine cell body damage. Dopamine transporter antagonists (cocaine, WIN 35,428 [(-)-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane 1,5-naphthalenedisulfonate], and nomifensine), selective D1 (SKF 82958 [(+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide]), D2 (quinpirole), or mixed D1/D2 receptor agonists (apomorphine) do not mimic the effect of methamphetamine on microglia. Hyperthermia, a prominent and dangerous clinical response to methamphetamine intoxication, was also ruled out as the cause of microglial activation. Together, these data suggest that microglial activation represents an early step in methamphetamine-induced neurotoxicity. Other neurochemical effects resulting from methamphetamine-induced overflow of DA into the synapse, but which are not neurotoxic, do not play a role in this response.

[Sural nerve removal using a nerve stripper].

PubMed

Assmus, H

1983-03-01

In 19 patients the sural nerve was removed for nerve grafting by a specially designed nerve stripper. This technique provides a safe and time-saving removal of the nerve in length up to 34 cm (depending on the length of the stripper used). From a single short incision at the level of the lateral malleolus the nerve is stripped proximally tearing some small branches of the distal nerve. The relatively blunt tip avoids inadvertent transection of the nerve at a lower level or dissection of the nerve at a point where branching occurs. Finally the nerve is cut by the divided cylinder at the tip of the stripper.

A Structure-Activity Analysis of the Variation in Oxime Efficacy Against Nerve Agents

DTIC Science & Technology

2008-01-01

Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A structure- activity analysis of the variation in oxime...structure– activity analysis of the variation in oxime efficacy against nerve agents☆ Donald M. Maxwell a,⁎, Irwin Koplovitz a, Franz Worek b, Richard E...structure– activity analysi Received 22 February 2008 Revised 8 April 2008 Accepted 13 April 2008 Available online 22 April 2008 Keywords: Organophosphorus

G-CSF prevents caspase 3 activation in Schwann cells after sciatic nerve transection, but does not improve nerve regeneration.

PubMed

Frost, Hanna K; Kodama, Akira; Ekström, Per; Dahlin, Lars B

2016-10-15

Exogenous granulocyte-colony stimulating factor (G-CSF) has emerged as a drug candidate for improving the outcome after peripheral nerve injuries. We raised the question if exogenous G-CSF can improve nerve regeneration following a clinically relevant model - nerve transection and repair - in healthy and diabetic rats. In short-term experiments, distance of axonal regeneration and extent of injury-induced Schwann cell death was quantified by staining for neurofilaments and cleaved caspase 3, respectively, seven days after repair. There was no difference in axonal outgrowth between G-CSF-treated and non-treated rats, regardless if healthy Wistar or diabetic Goto-Kakizaki (GK) rats were examined. However, G-CSF treatment caused a significant 13% decrease of cleaved caspase 3-positive Schwann cells at the lesion site in healthy rats, but only a trend in diabetic rats. In the distal nerve segments of healthy rats a similar trend was observed. In long-term experiments of healthy rats, regeneration outcome was evaluated at 90days after repair by presence of neurofilaments, wet weight of gastrocnemius muscle, and perception of touch (von Frey monofilament testing weekly). The presence of neurofilaments distal to the suture line was similar in G-CSF-treated and non-treated rats. The weight ratio of ipsi-over contralateral gastrocnemius muscles, and perception of touch at any time point, were likewise not affected by G-CSF treatment. In addition, the inflammatory response in short- and long-term experiments was studied by analyzing ED1 stainable macrophages in healthy rats, but in neither case was any attenuation seen at the injury site or distal to it. G-CSF can prevent caspase 3 activation in Schwann cells in the short-term, but does not detectably affect the inflammatory response, nor improve early or late axonal outgrowth or functional recovery. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration.

PubMed

Yu, Qing; Zhang, She-Hong; Wang, Tao; Peng, Feng; Han, Dong; Gu, Yu-Dong

2017-10-01

End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.

End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration

PubMed Central

Yu, Qing; Zhang, She-hong; Wang, Tao; Peng, Feng; Han, Dong; Gu, Yu-dong

2017-01-01

End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy. PMID:29171436

Stimulation of proteinase-activated receptor 2 excites jejunal afferent nerves in anaesthetised rats

PubMed Central

Kirkup, Anthony J; Jiang, Wen; Bunnett, Nigel W; Grundy, David

2003-01-01

Proteinase-activated receptor 2 (PAR2) is a receptor for mast cell tryptase and trypsins and might participate in brain-gut communication. However, evidence that PAR2 activation can lead to afferent impulse generation is lacking. To address this issue, we examined the sensitivity of jejunal afferent nerves to a hexapeptide agonist of PAR2, SLIGRL-NH2, and the modulation of the resulting response to treatment with drugs and vagotomy. Multiunit recordings of jejunal afferent activity were made using extracellular recording techniques in anaesthetised male rats. SLIGRL-NH2 (0.001–1 mg kg−1, I.V.) increased jejunal afferent firing and intrajejunal pressure. The reverse peptide sequence (1 mg kg−1, I.V.), which does not stimulate PAR2, was inactive. Naproxen (10 mg kg−1, I.V.), but not a cocktail of ω-conotoxins GVIA and SVIB (each at 25 μg kg−1, I.V.), curtailed both the afferent response and the intrajejunal pressure rise elicited by the PAR2 agonist. Although neither treatment modulated the peak magnitude of the afferent firing, they each altered the intestinal motor response, unmasking an initial inhibitory component. Nifedipine (1 mg kg−1, I.V.) reduced the peak magnitude of the afferent nerve discharge and abolished the initial rise in intrajejunal pressure produced by SLIGRL-NH2. Vagotomy did not significantly influence the magnitude of the afferent response to the PAR2 agonist, which involves a contribution from capsaicin-sensitive fibres. In conclusion, intravenous administration of SLIGRL-NH2 evokes complex activation of predominantly spinally projecting extrinsic intestinal afferent nerves, an effect that involves both direct and indirect mechanisms. PMID:14561839

Right-sided vagus nerve stimulation inhibits induced spinal cord seizures.

PubMed

Tubbs, R Shane; Salter, E George; Killingsworth, Cheryl; Rollins, Dennis L; Smith, William M; Ideker, Raymond E; Wellons, John C; Blount, Jeffrey P; Oakes, W Jerry

2007-01-01

We have previously shown that left-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. To test our hypothesis that right-sided vagus nerve stimulation will also abort seizure activity, we have initiated seizures in the spinal cord and then performed right-sided vagus nerve stimulation in an animal model. Four pigs were anesthetized and placed in the lateral position and a small laminectomy performed in the lumbar region. Topical penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord, was next applied to the dorsal surface of the exposed cord. With the exception of the control animal, once seizure activity was discernible via motor convulsion or increased electrical activity, the right vagus nerve previously isolated in the neck was stimulated. Following multiple stimulations of the vagus nerve and with seizure activity confirmed, the cord was transected in the midthoracic region and vagus nerve stimulation performed. Right-sided vagus nerve stimulation resulted in cessation of spinal cord seizure activity in all animals. Transection of the spinal cord superior to the site of seizure induction resulted in the ineffectiveness of vagus nerve stimulation in causing cessation of seizure activity in all study animals. As with left-sided vagus nerve stimulation, right-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. Additionally, the effects of right-sided vagus nerve stimulation on induced spinal cord seizures involve descending spinal pathways. These data may aid in the development of alternative mechanisms for electrical stimulation for patients with medically intractable seizures and add to our knowledge regarding the mechanism for seizure cessation following peripheral nerve stimulation.

Role of renal sensory nerves in physiological and pathophysiological conditions

PubMed Central

2014-01-01

Whether activation of afferent renal nerves contributes to the regulation of arterial pressure and sodium balance has been long overlooked. In normotensive rats, activating renal mechanosensory nerves decrease efferent renal sympathetic nerve activity (ERSNA) and increase urinary sodium excretion, an inhibitory renorenal reflex. There is an interaction between efferent and afferent renal nerves, whereby increases in ERSNA increase afferent renal nerve activity (ARNA), leading to decreases in ERSNA by activation of the renorenal reflexes to maintain low ERSNA to minimize sodium retention. High-sodium diet enhances the responsiveness of the renal sensory nerves, while low dietary sodium reduces the responsiveness of the renal sensory nerves, thus producing physiologically appropriate responses to maintain sodium balance. Increased renal ANG II reduces the responsiveness of the renal sensory nerves in physiological and pathophysiological conditions, including hypertension, congestive heart failure, and ischemia-induced acute renal failure. Impairment of inhibitory renorenal reflexes in these pathological states would contribute to the hypertension and sodium retention. When the inhibitory renorenal reflexes are suppressed, excitatory reflexes may prevail. Renal denervation reduces arterial pressure in experimental hypertension and in treatment-resistant hypertensive patients. The fall in arterial pressure is associated with a fall in muscle sympathetic nerve activity, suggesting that increased ARNA contributes to increased arterial pressure in these patients. Although removal of both renal sympathetic and afferent renal sensory nerves most likely contributes to the arterial pressure reduction initially, additional mechanisms may be involved in long-term arterial pressure reduction since sympathetic and sensory nerves reinnervate renal tissue in a similar time-dependent fashion following renal denervation. PMID:25411364

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

Protease signaling through protease activated receptor 1 mediate nerve activation by mucosal supernatants from irritable bowel syndrome but not from ulcerative colitis patients

PubMed Central

Buhner, Sabine; Hahne, Hannes; Hartwig, Kerstin; Li, Qin; Vignali, Sheila; Ostertag, Daniela; Meng, Chen; Hörmannsperger, Gabriele; Braak, Breg; Pehl, Christian; Frieling, Thomas; Barbara, Giovanni; De Giorgio, Roberto; Demir, Ihsan Ekin; Ceyhan, Güralp Onur; Zeller, Florian; Boeckxstaens, Guy; Haller, Dirk; Kuster, Bernhard

2018-01-01

Background & aims The causes of gastrointestinal complaints in irritable bowel syndrome (IBS) remain poorly understood. Altered nerve function has emerged as an important pathogenic factor as IBS mucosal biopsy supernatants consistently activate enteric and sensory neurons. We investigated the neurally active molecular components of such supernatants from patients with IBS and quiescent ulcerative colitis (UC). Method Effects of supernatants from 7 healthy controls (HC), 20 IBS and 12 UC patients on human and guinea pig submucous neurons were studied with neuroimaging techniques. We identify differentially expressed proteins with proteome analysis. Results Nerve activation by IBS supernatants was prevented by the protease activated receptor 1 (PAR1) antagonist SCHE79797. UC supernatants also activated enteric neurons through protease dependent mechanisms but without PAR1 involvement. Proteome analysis of the supernatants identified 204 proteins, among them 17 proteases as differentially expressed between IBS, UC and HC. Of those the four proteases elastase 3a, chymotrypsin C, proteasome subunit type beta-2 and an unspecified isoform of complement C3 were significantly more abundant in IBS compared to HC and UC supernatants. Of eight proteases, which were upregulated in IBS, the combination of elastase 3a, cathepsin L and proteasome alpha subunit-4 showed the highest prediction accuracy of 98% to discriminate between IBS and HC groups. Elastase synergistically potentiated the effects of histamine and serotonin–the two other main neuroactive substances in the IBS supernatants. A serine protease inhibitor isolated from the probiotic Bifidobacterium longum NCC2705 (SERPINBL), known to inhibit elastase-like proteases, prevented nerve activation by IBS supernatants. Conclusion Proteases in IBS and UC supernatants were responsible for nerve activation. Our data demonstrate that proteases, particularly those signalling through neuronal PAR1, are biomarker candidates for

Renal sympathetic nerve ablation for treatment-resistant hypertension

PubMed Central

Krum, Henry; Schlaich, Markus; Sobotka, Paul

2013-01-01

Hypertension is a major risk factor for increased cardiovascular events with accelerated sympathetic nerve activity implicated in the pathogenesis and progression of disease. Blood pressure is not adequately controlled in many patients, despite the availability of effective pharmacotherapy. Novel procedure- as well as device-based strategies, such as percutaneous renal sympathetic nerve denervation, have been developed to improve blood pressure in these refractory patients. Renal sympathetic denervation not only reduces blood pressure but also renal as well as systemic sympathetic nerve activity in such patients. The reduction in blood pressure appears to be sustained over 3 years after the procedure, which suggests absence of re-innervation of renal sympathetic nerves. Safety appears to be adequate. This approach may also have potential in other disorders associated with enhanced sympathetic nerve activity such as congestive heart failure, chronic kidney disease and metabolic syndrome. This review will focus on the current status of percutaneous renal sympathetic nerve denervation, clinical efficacy and safety outcomes and prospects beyond refractory hypertension. PMID:23819768

AMPK activation by peri-sciatic nerve administration of ozone attenuates CCI-induced neuropathic pain in rats.

PubMed

Lu, Lijuan; Pan, Cailong; Chen, Lu; Hu, Liang; Wang, Chaoyu; Han, Yuan; Yang, Yanjing; Cheng, Zhixiang; Liu, Wen-Tao

2017-04-01

Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeutics. Ozone is widely used as an alternative therapy for many different pain conditions, with exact mechanisms still elusive. In this study, we found that a single peri-sciatic nerve injection of ozone decreased mechanical allodynia and thermal hyperalgesia, and normalized the phosphorylation of protein kinase C γ, N-methyl-D-aspartate receptor, and extracellular signal-regulated kinase in a chronic constriction injury (CCI) model in rat sciatic nerve. Meanwhile, ozone significantly suppressed CCI-induced activation of spinal microglia. More importantly, the anti-nociceptive effect of ozone depended on the activation of 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK), which was proved by the fact that the phosphorylated AMPK level increased during the ozone therapy and AMPK antagonist abolished the effect of ozone in vivo and in vitro. In addition, direct injection of AMPK agonist could replicate the anti-nociceptive effect of ozone in CCI rats. In conclusion, our observations indicate that peri-sciatic nerve injection of ozone activates AMPK to attenuate CCI-induced neuropathic pain. © The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

Neuromonitoring of cochlea and auditory nerve with multiple extracted parameters during induced hypoxia and nerve manipulation

NASA Astrophysics Data System (ADS)

Bohórquez, Jorge; Özdamar, Özcan; Morawski, Krzysztof; Telischi, Fred F.; Delgado, Rafael E.; Yavuz, Erdem

2005-06-01

A system capable of comprehensive and detailed monitoring of the cochlea and the auditory nerve during intraoperative surgery was developed. The cochlear blood flow (CBF) and the electrocochleogram (ECochGm) were recorded at the round window (RW) niche using a specially designed otic probe. The ECochGm was further processed to obtain cochlear microphonics (CM) and compound action potentials (CAP).The amplitude and phase of the CM were used to quantify the activity of outer hair cells (OHC); CAP amplitude and latency were used to describe the auditory nerve and the synaptic activity of the inner hair cells (IHC). In addition, concurrent monitoring with a second electrophysiological channel was achieved by recording compound nerve action potential (CNAP) obtained directly from the auditory nerve. Stimulation paradigms, instrumentation and signal processing methods were developed to extract and differentiate the activity of the OHC and the IHC in response to three different frequencies. Narrow band acoustical stimuli elicited CM signals indicating mainly nonlinear operation of the mechano-electrical transduction of the OHCs. Special envelope detectors were developed and applied to the ECochGm to extract the CM fundamental component and its harmonics in real time. The system was extensively validated in experimental animal surgeries by performing nerve compressions and manipulations.

Central command: control of cardiac sympathetic and vagal efferent nerve activity and the arterial baroreflex during spontaneous motor behaviour in animals.

PubMed

Matsukawa, Kanji

2012-01-01

Feedforward control by higher brain centres (termed central command) plays a role in the autonomic regulation of the cardiovascular system during exercise. Over the past 20 years, workers in our laboratory have used the precollicular-premammillary decerebrate animal model to identify the neural circuitry involved in the CNS control of cardiac autonomic outflow and arterial baroreflex function. Contrary to the traditional idea that vagal withdrawal at the onset of exercise causes the increase in heart rate, central command did not decrease cardiac vagal efferent nerve activity but did allow cardiac sympathetic efferent nerve activity to produce cardiac acceleration. In addition, central command-evoked inhibition of the aortic baroreceptor-heart rate reflex blunted the baroreflex-mediated bradycardia elicited by aortic nerve stimulation, further increasing the heart rate at the onset of exercise. Spontaneous motor activity and associated cardiovascular responses disappeared in animals decerebrated at the midcollicular level. These findings indicate that the brain region including the caudal diencephalon and extending to the rostral mesencephalon may play a role in generating central command. Bicuculline microinjected into the midbrain ventral tegmental area of decerebrate rats produced a long-lasting repetitive activation of renal sympathetic nerve activity that was synchronized with the motor nerve discharge. When lidocaine was microinjected into the ventral tegmental area, the spontaneous motor activity and associated cardiovascular responses ceased. From these findings, we conclude that cerebral cortical outputs trigger activation of neural circuits within the caudal brain, including the ventral tegmental area, which causes central command to augment cardiac sympathetic outflow at the onset of exercise in decerebrate animal models.

Reconstruction of facial nerve injuries in children.

PubMed

Fattah, Adel; Borschel, Gregory H; Zuker, Ron M

2011-05-01

Facial nerve trauma is uncommon in children, and many spontaneously recover some function; nonetheless, loss of facial nerve activity leads to functional impairment of ocular and oral sphincters and nasal orifice. In many cases, the impediment posed by facial asymmetry and reduced mimetic function more significantly affects the child's psychosocial interactions. As such, reconstruction of the facial nerve affords great benefits in quality of life. The therapeutic strategy is dependent on numerous factors, including the cause of facial nerve injury, the deficit, the prognosis for recovery, and the time elapsed since the injury. The options for treatment include a diverse range of surgical techniques including static lifts and slings, nerve repairs, nerve grafts and nerve transfers, regional, and microvascular free muscle transfer. We review our strategies for addressing facial nerve injuries in children.

Axillary nerve monitoring during arthroscopic shoulder stabilization.

PubMed

Esmail, Adil N; Getz, Charles L; Schwartz, Daniel M; Wierzbowski, Lawrence; Ramsey, Matthew L; Williams, Gerald R

2005-06-01

This study evaluated the ability of a novel intraoperative neurophysiologic monitoring method used to locate the axillary nerve, predict relative capsule thickness, and identify impending injury to the axillary nerve during arthroscopic thermal capsulorrhaphy of the shoulder. Prospective cohort study. Twenty consecutive patients with glenohumeral instability were monitored prospectively during arthroscopic shoulder surgery. Axillary nerve mapping and relative capsule thickness estimates were recorded before the stabilization portion of the procedure. During labral repair and/or thermal capsulorrhaphy, continuous and spontaneous electromyography recorded nerve activity. In addition, trans-spinal motor-evoked potentials of the fourth and fifth cervical roots and brachial plexus electrical stimulation, provided real-time information about nerve integrity. Axillary nerve mapping and relative capsule thickness were recorded in all patients. Continuous axillary nerve monitoring was successfully performed in all patients. Eleven of the 20 patients underwent thermal capsulorrhaphy alone or in combination with arthroscopic labral repair. Nine patients underwent arthroscopic labral repair alone. In 4 of the 11 patients who underwent thermal capsulorrhaphy, excessive spontaneous neurotonic electromyographic activity was noted, thereby altering the pattern of heat application by the surgeon. In 1 of these 4 patients, a small increase in the motor latency was noted after the procedure but no clinical deficit was observed. There were no neuromonitoring or clinical neurologic changes observed in the labral repair group without thermal application. At last follow-up, no patient in either group had any clinical evidence of nerve injury or complications from neurophysiologic monitoring. We successfully evaluated the use of intraoperative nerve monitoring to identify axillary nerve position, capsule thickness, and provide real-time identification of impending nerve injury and

The effects of general anaesthesia on nerve-motor response characteristics (rheobase and chronaxie) to peripheral nerve stimulation.

PubMed

Tsui, B C

2014-04-01

Using a simple surface nerve stimulation system, I examined the effects of general anaesthesia on rheobase (the minimum current required to stimulate nerve activity) and chronaxie (the minimum time for a stimulus twice the rheobase to elicit nerve activity). Nerve stimulation was used to elicit a motor response from the ulnar nerve at varying pulse widths before and after induction of general anaesthesia. Mean (SD) rheobase before and after general anaesthesia was 0.91 (0.37) mA (95% CI 0.77-1.04 mA) and 1.11 (0.53) mA (95% CI 0.92-1.30 mA), respectively. Mean (SD) chronaxie measured before and after general anaesthesia was 0.32 (0.17) ms (95% CI 0.26-0.38 ms) and 0.29 (0.13) ms (95% CI 0.24-0.33 ms), respectively. Under anaesthesia, rheobase values increased by an average of 20% (p = 0.05), but chronaxie values did not change significantly (p = 0.39). These results suggest that threshold currents used for motor response from nerve stimulation under general anaesthesia might be higher than those used in awake patients. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

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

Implantable electrode for recording nerve signals in awake animals

NASA Technical Reports Server (NTRS)

Ninomiya, I.; Yonezawa, Y.; Wilson, M. F.

1976-01-01

An implantable electrode assembly consisting of collagen and metallic electrodes was constructed to measure simultaneously neural signals from the intact nerve and bioelectrical noises in awake animals. Mechanical artifacts, due to bodily movement, were negligibly small. The impedance of the collagen electrodes, measured in awake cats 6-7 days after implantation surgery, ranged from 39.8-11.5 k ohms at a frequency range of 20-5 kHz. Aortic nerve activity and renal nerve activity, measured in awake conditions using the collagen electrode, showed grouped activity synchronous with the cardiac cycle. Results indicate that most of the renal nerve activity was from postganglionic sympathetic fibers and was inhibited by the baroceptor reflex in the same cardiac cycle.

Renal dopamine containing nerves. What is their functional significance?

PubMed

DiBona, G F

1990-06-01

Biochemical and morphological studies indicate that there are nerves within the kidney that contain dopamine and that various structures within the kidney contain dopamine receptors. However, the functional significance of these renal dopamine containing nerves in relation to renal dopamine receptors is unknown. The functional significance could be defined by demonstrating that an alteration in one or more renal functions occurring in response to reflex or electrical activation of efferent renal nerves is dependent on release of dopamine as the neurotransmitter from the renal nerve terminals acting on renal dopamine receptors. Thus, the hypothesis becomes: reflex or electrical activation of efferent renal nerves causes alterations in renal function (eg, renal blood flow, water and solute handling) that are inhibited by specific and selective dopamine receptor antagonists. As reviewed herein, the published experimental data do not support the hypothesis. Therefore, the view that alterations in one or more renal functions occurring in response to reflex or electrical activation of efferent renal nerves are dependent on release of dopamine as the neurotransmitter from the renal nerve terminals acting on renal dopamine receptors remains unproven.

Identification of a Peripheral Nerve Neurite Growth-Promoting Activity by Development and Use of an in vitro Bioassay

NASA Astrophysics Data System (ADS)

Sandrock, Alfred W.; Matthew, William D.

1987-10-01

The effective regeneration of severed neuronal axons in the peripheral nerves of adult mammals may be explained by the presence of molecules in situ that promote the effective elongation of neurites. The absence of such molecules in the central nervous system of these animals may underlie the relative inability of axons to regenerate in this tissue after injury. In an effort to identify neurite growth-promoting molecules in tissues that support effective axonal regeneration, we have developed an in vitro bioassay that is sensitive to substrate-bound factors of peripheral nerve that influence the growth of neurites. In this assay, neonatal rat superior cervical ganglion explants are placed on longitudinal cryostat sections of fresh-frozen sciatic nerve, and the regrowing axons are visualized by catecholamine histofluorescence. Axons are found to regenerate effectively over sciatic nerve tissue sections. When ganglia are similarly explanted onto cryostat sections of adult rat central nervous system tissue, however, axonal regeneration is virtually absent. We have begun to identify the molecules in peripheral nerve that promote effective axonal regeneration by examining the effect of antibodies that interfere with the activity of previously described neurite growth-promoting factors. Axonal elongation over sciatic nerve tissue was found to be sensitive to the inhibitory effects of INO (for inhibitor of neurite outgrowth), a monoclonal antibody that recognizes and inhibits a neurite growth-promoting activity from PC-12 cell-conditioned medium. The INO antigen appears to be a molecular complex of laminin and heparan sulfate proteoglycan. In contrast, a rabbit antiserum that recognizes laminin purified from mouse Engelbreth-Holm-Swarm (EHS) sarcoma, stains the Schwann cell basal lamina of peripheral nerve, and inhibits neurite growth over purified laminin substrata has no detectable effect on the rate of axonal regeneration in our assay.

Anatomic study of cranial nerve emergence and associated skull foramina in cats using CT and MRI.

PubMed

Gomes, Eymeric; Degueurce, Christophe; Ruel, Yannick; Dennis, Ruth; Begon, Dominique

2009-01-01

Magnetic resonance (MR) images of the brain of four normal cats were reviewed retrospectively to assess the emergence and course of the cranial nerves (CNs). Two-millimeter-thick images were obtained in transverse, sagittal, and dorsal planes using a 1.5 T unit. CN skull foramina, as anatomic landmarks for MR imaging, were identified by computed tomography performed on an isolated cat skull using thin wire within each skull foramen. Thin slice (1 mm slice thickness) images were obtained with a high-resolution bone filter scan protocol. The origins of CNs II, V, VII, and VIII and the group of IX, X, XI, and XII could be identified. The pathway and proximal divisions of CNs V were described. CNs III, IV, and VI were not distinguished from each other but could be seen together in the orbital fissure. CN V was characterized by slight contrast enhancement.

Chronic stability and selectivity of four-contact spiral nerve-cuff electrodes in stimulating the human femoral nerve.

PubMed

Fisher, L E; Tyler, D J; Anderson, J S; Triolo, R J

2009-08-01

This study describes the stability and selectivity of four-contact spiral nerve-cuff electrodes implanted bilaterally on distal branches of the femoral nerves of a human volunteer with spinal cord injury as part of a neuroprosthesis for standing and transfers. Stimulation charge threshold, the minimum charge required to elicit a visible muscle contraction, was consistent and low (mean threshold charge at 63 weeks post-implantation: 23.3 +/- 8.5 nC) for all nerve-cuff electrode contacts over 63 weeks after implantation, indicating a stable interface with the peripheral nervous system. The ability of individual nerve-cuff electrode contacts to selectively stimulate separate components of the femoral nerve to activate individual heads of the quadriceps was assessed with fine-wire intramuscular electromyography while measuring isometric twitch knee extension moment. Six of eight electrode contacts could selectively activate one head of the quadriceps while selectively excluding others to produce maximum twitch responses of between 3.8 and 8.1 N m. The relationship between isometric twitch and tetanic knee extension moment was quantified, and selective twitch muscle responses scaled to between 15 and 35 N m in tetanic response to pulse trains with similar stimulation parameters. These results suggest that this nerve-cuff electrode can be an effective and chronically stable tool for selectively stimulating distal nerve branches in the lower extremities for neuroprosthetic applications.

Chronic stability and selectivity of four-contact spiral nerve-cuff electrodes in stimulating the human femoral nerve

PubMed Central

Fisher, L E; Tyler, D J; Anderson, J S; Triolo, R J

2010-01-01

This study describes the stability and selectivity of four-contact spiral nerve-cuff electrodes implanted bilaterally on distal branches of the femoral nerves of a human volunteer with spinal cord injury as part of a neuroprosthesis for standing and transfers. Stimulation charge threshold, the minimum charge required to elicit a visible muscle contraction, was consistent and low (mean threshold charge at 63 weeks post-implantation: 23.3 ± 8.5 nC) for all nerve-cuff electrode contacts over 63 weeks after implantation, indicating a stable interface with the peripheral nervous system. The ability of individual nerve-cuff electrode contacts to selectively stimulate separate components of the femoral nerve to activate individual heads of the quadriceps was assessed with fine-wire intramuscular electromyography while measuring isometric twitch knee extension moment. Six of eight electrode contacts could selectively activate one head of the quadriceps while selectively excluding others to produce maximum twitch responses of between 3.8 and 8.1 Nm. The relationship between isometric twitch and tetanic knee extension moment was quantified, and selective twitch muscle responses scaled to between 15 and 35 Nm in tetanic response to pulse trains with similar stimulation parameters. These results suggest that this nerve-cuff electrode can be an effective and chronically stable tool for selectively stimulating distal nerve branches in the lower extremities for neuroprosthetic applications. PMID:19602729

Potassium Fluxes in Desheathed Frog Sciatic Nerve

PubMed Central

Hurlbut, William P.

1963-01-01

Desheathed frog (R. pipiens) sciatic nerves were soaked in Na-deficient solutions, and measurements were made of their Na and K contents and of the movements of K42. When a nerve is in Ringer's solution, the Na fluxes are equal to the K fluxes, and about 75 per cent of the K influx is due to active transport. The Na content and the Na efflux are linearly related to the Na concentration of the bathing solution, while the K content and the K fluxes are not so related. When a nerve is in a solution in which 75 per cent of the NaCl has been replaced by choline chloride or sucrose, the active K influx exceeds the active Na efflux, and the K content is maintained. When a nerve is soaked in a solution that contains Li, the K42 uptake is inhibited, and the nerve loses K and gains Li. When a Li-loaded nerve recovers in a Li-free solution, K is taken up in exchange for Li. This uptake of K requires Na in the external solution. It is concluded that the active transports of K and of Na may be due to different processes, that an accumulation of K occurs only in exchange for an intracellular cation, which need not be Na, and that Na plays a specific, but unknown, role in K transport. PMID:14043000

Effects of nerve cells and adhesion molecules on nerve conduit for peripheral nerve regeneration

PubMed Central

Fiorellini, Joseph P.

2017-01-01

Background For peripheral nerve regeneration, recent attentions have been paid to the nerve conduits made by tissue-engineering technique. Three major elements of tissue-engineering are cells, molecules, and scaffolds. Methods In this study, the attachments of nerve cells, including Schwann cells, on the nerve conduit and the effects of both growth factor and adhesion molecule on these attachments were investigated. Results The attachment of rapidly-proliferating cells, C6 cells and HS683 cells, on nerve conduit was better than that of slowly-proliferating cells, PC12 cells and Schwann cells, however, the treatment of nerve growth factor improved the attachment of slowly-proliferating cells. In addition, the attachment of Schwann cells on nerve conduit coated with fibronectin was as good as that of Schwann cells treated with glial cell line-derived neurotrophic factor (GDNF). Conclusions Growth factor changes nerve cell morphology and affects cell cycle time. And nerve growth factor or fibronectin treatment is indispensable for Schwann cell to be used for implantation in artificial nerve conduits. PMID:29090249

Benzenesulfonamide bearing 1,2,4-triazole scaffolds as potent inhibitors of tumor associated carbonic anhydrase isoforms hCA IX and hCA XII.

PubMed

SitaRam; Celik, Gulsah; Khloya, Poonam; Vullo, Daniela; Supuran, Claudiu T; Sharma, Pawan K

2014-03-15

Three series of novel heterocyclic compounds (3a-3g, 4a-4g and 5a-5g) containing benzenesulfonamide moiety and incorporating a 1,2,4-triazole ring, have been synthesized and investigated as inhibitors against four isomers of the α-class carbonic anhydrases (CAs, EC 4.2.1.1), comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (transmembrane, tumor associated isozymes). Against the human isozymes hCA I and II, compounds of two series (3a-3g and 4a-4g) showed Ki values in the range of 84-868 nM and 5.6-390 nM, respectively whereas compounds of series 5a-5g were found to be poor inhibitors (Ki values exceeding 10,000 nM in some cases). Against hCA IX and XII, all the tested compounds exhibited excellent to moderate inhibitory potential with Ki values in the range of 2.8-431 nM and 1.3-63 nM, respectively. Compounds 3d, 3f and 4f exhibited excellent inhibitory potential against all of the four isozymes hCA I, II, IX and XII, even better than the standard drug acetazolamide (AZA) whereas compound of the series 5a-5g were comparatively less potent but more selective towards hCA IX and XII. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sleep Deprivation Aggravates Median Nerve Injury-Induced Neuropathic Pain and Enhances Microglial Activation by Suppressing Melatonin Secretion

PubMed Central

Huang, Chun-Ta; Chiang, Rayleigh Ping-Ying; Chen, Chih-Li; Tsai, Yi-Ju

2014-01-01

Study Objectives: Sleep deprivation is common in patients with neuropathic pain, but the effect of sleep deprivation on pathological pain remains uncertain. This study investigated whether sleep deprivation aggravates neuropathic symptoms and enhances microglial activation in the cuneate nucleus (CN) in a median nerve chronic constriction injury (CCI) model. Also, we assessed if melatonin supplements during the sleep deprived period attenuates these effects. Design: Rats were subjected to sleep deprivation for 3 days by the disc-on-water method either before or after CCI. In the melatonin treatment group, CCI rats received melatonin supplements at doses of 37.5, 75, 150, or 300 mg/kg during sleep deprivation. Melatonin was administered at 23:00 once a day. Participants: Male Sprague-Dawley rats, weighing 180-250 g (n = 190), were used. Measurements: Seven days after CCI, behavioral testing was conducted, and immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analyses of microglial activation and measurements of proinflammatory cytokines. Results: In rats who underwent post-CCI sleep deprivation, microglia were more profoundly activated and neuropathic pain was worse than those receiving pre-CCI sleep deprivation. During the sleep deprived period, serum melatonin levels were low over the 24-h period. Administration of melatonin to CCI rats with sleep deprivation significantly attenuated activation of microglia and development of neuropathic pain, and markedly decreased concentrations of proinflammatory cytokines. Conclusions: Sleep deprivation makes rats more vulnerable to nerve injury-induced neuropathic pain, probably because of associated lower melatonin levels. Melatonin supplements to restore a circadian variation in melatonin concentrations during the sleep deprived period could alleviate nerve injury-induced behavioral hypersensitivity. Citation: Huang CT, Chiang RP, Chen CL, Tsai YJ. Sleep

Origin and pharmacological response of atrial tachyarrhythmias induced by activation of mediastinal nerves in canines.

PubMed

Armour, J Andrew; Richer, Louis-Philippe; Pagé, Pierre; Vinet, Alain; Kus, Teresa; Vermeulen, Michel; Nadeau, Réginald; Cardinal, René

2005-03-31

We sought to determine the sites of origin of atrial tachyarrhythmias induced by activating mediastinal nerves, as well as the response of such arrhythmias to autonomic modulation. Under general anaesthesia, atrioventricular block was induced after thoracotomy in 19 canines. Brief trains of 5 electrical stimuli were delivered to right-sided mediastinal nerves during the atrial refractory period. Unipolar electrograms were recorded from 191 right and left atrial epicardial sites under several conditions, i.e. (i) with intact nervous systems and following (ii) acute decentralization of the intrathoracic nervous system or administration of (iii) atropine, (iv) timolol, (v) hexamethonium. Concomitant right atrial endocardial mapping was performed in 7 of these dogs. Mediastinal nerve stimulation consistently initiated bradycardia followed by atrial tachyarrhythmias. In the initial tachyarrhythmia beats, early epicardial breakthroughs were identified in the right atrial free wall (28/50 episodes) or Bachmann bundle region (22/50), which corresponded to endocardial sites of origin associated with the right atrial subsidiary pacemaker complex, i.e. the crista terminalis and dorsal locations including the right atrial aspect of the interatrial septum. Neuronally induced responses were eliminated by atropine, modified by timolol and unaffected by acute neuronal decentralization. After hexamethonium, responses to extra-pericardial but not intra-pericardial nerve stimulation were eliminated. It is concluded that concomitant activation of cholinergic and adrenergic efferent intrinsic cardiac neurons induced by right-sided efferent neuronal stimulation initiates atrial tachyarrhythmias that originate from foci anatomically related to the right atrial pacemaker complex and tissues underlying major atrial ganglionated plexuses.

Nerve cell-mimicking liposomes as biosensor for botulinum neurotoxin complete physiological activity

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

Weingart, Oliver G., E-mail: Oliver.Weingart@hest.

Botulinum neurotoxins (BoNT) are the most toxic substances known, and their neurotoxic properties and paralysing effects are exploited for medical treatment of a wide spectrum of disorders. To accurately quantify the potency of a pharmaceutical BoNT preparation, its physiological key activities (binding to membrane receptor, translocation, and proteolytic degradation of SNARE proteins) need to be determined. To date, this was only possible using animal models, or, to a limited extent, cell-based assays. We here report a novel in vitro system for BoNT/B analysis, based on nerve-cell mimicking liposomes presenting motoneuronal membrane receptors required for BoNT binding. Following triggered membrane translocationmore » of the toxin's Light Chain, the endopeptidase activity can be quantitatively monitored employing a FRET-based reporter assay within the functionalized liposomes. We were able to detect BoNT/B physiological activity at picomolar concentrations in short time, opening the possibility for future replacement of animal experimentation in pharmaceutical BoNT testing. - Highlights: • A cell-free in vitro system was used to measure BoNT/B physiological function. • The system relies on nerve-cell mimicking liposomes as a novel detection system. • A FRET-based reporter assay is used as final readout of the test system. • BoNT/B physiological activity was detected at picogram quantities in short time. • The method opens the possibility to replace animal experimentation in BoNT testing.« less

Anoxia increases potassium conductance in hippocampal nerve cells.

PubMed

Hansen, A J; Hounsgaard, J; Jahnsen, H

1982-07-01

The effect of anoxia on nerve cell function was studied by intra- and extracellular microelectrode recordings from the CA1 and CA3 region in guinea pig hippocampal slices. Hyperpolarization and concomitant reduction of the nerve cell input resistance was observed early during anoxia. During this period the spontaneous activity first disappeared, then the evoked activity gradually disappeared. The hyperpolarization was followed by depolarization and an absence of a measurable input resistance. All the induced changes were reversed when the slice was reoxygenated. Reversal of the electro-chemical gradient for Cl- across the nerve cell membrane did not affect the course of events during anoxia. Aminopyridines blocked the anoxic hyperpolarization and attenuated the decrease of membrane resistance, but had no effect on the later depolarization. Blockers of synaptic transmission. Mn++, Mg++ and of Na+-channels (TTX) were without effect on the nerve cell changes during anoxia. It is suggested that the reduction of nerve cell excitability in anoxia is primarily due to increased K+-conductance. Thus, the nerve cells are hyperpolarized and the input resistance reduced, causing higher threshold and reduction of synaptic potentials. The mechanism of the K+-conductance activation is unknown at present.

Functional restoration of the paralyzed diaphragm in high cervical quadriplegia via phrenic nerve neurotization utilizing the functional spinal accessory nerve.

PubMed

Yang, Ming-liang; Li, Jian-jun; Zhang, Shao-cheng; Du, Liang-jie; Gao, Feng; Li, Jun; Wang, Yu-ming; Gong, Hui-ming; Cheng, Liang

2011-08-01

The authors report a case of functional improvement of the paralyzed diaphragm in high cervical quadriplegia via phrenic nerve neurotization using a functional spinal accessory nerve. Complete spinal cord injury at the C-2 level was diagnosed in a 44-year-old man. Left diaphragm activity was decreased, and the right diaphragm was completely paralyzed. When the level of metabolism or activity (for example, fever, sitting, or speech) slightly increased, dyspnea occurred. The patient underwent neurotization of the right phrenic nerve with the trapezius branch of the right spinal accessory nerve at 11 months postinjury. Four weeks after surgery, training of the synchronous activities of the trapezius muscle and inspiration was conducted. Six months after surgery, motion was observed in the previously paralyzed right diaphragm. The lung function evaluation indicated improvements in vital capacity and tidal volume. This patient was able to sit in a wheelchair and conduct outdoor activities without assisted ventilation 12 months after surgery.

Action of sympathetic nerves of inner and outer muscle of sheep carotid artery, and effect of pressure on nerve distribution.

PubMed Central

Keatinge, W R; Torrie, C

1976-01-01

1. The direction of torsion produced during active shortening of helical strips of sheep carotid arteries was measured to assess whether inner or outer muscle was contracting. 2. Noradrenaline contracted inner (non-innervated) muscle in lower concentrations than were needed to contract outer (innervated) muscle, even with desipramine present to prevent uptake of noradrenaline by the nerves and with enough cyanide present to rise the normally low O2 tension of inner muscle to that of outer muscle. 3. Activation of sympathetic nerves in the outer part of the artery by nicotine caused almost evenly balanced contraction of both parts of the wall, with slight bias to outer contraction. 4. Moderate external constriction of the artery in vivo for 10-17 days, in order to raise pressure throughout the wall to intraluminal pressure, made the entire wall nerve-free. 5. The results provide evidence that the nerves can induce substantial activation of inner muscle, which is highly sensitive to noradrenaline, and that the absence of nerves from inner muscle can be explained by the high pressure there. Images Plate 1 PMID:950610

Raman spectroscopic detection of peripheral nerves towards nerve-sparing surgery

NASA Astrophysics Data System (ADS)

Minamikawa, Takeo; Harada, Yoshinori; Takamatsu, Tetsuro

2017-02-01

The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery, namely nerve-sparing surgery, is now promising technique to avoid functional deficits of the limbs and organs following surgery as an aspect of the improvement of quality of life of patients. Detection of peripheral nerves including myelinated and unmyelinated nerves is required for the nerve-sparing surgery; however, conventional nerve identification scheme is sometimes difficult to identify peripheral nerves due to similarity of shape and color to non-nerve tissues or its limited application to only motor peripheral nerves. To overcome these issues, we proposed a label-free detection technique of peripheral nerves by means of Raman spectroscopy. We found several fingerprints of peripheral myelinated and unmyelinated nerves by employing a modified principal component analysis of typical spectra including myelinated nerve, unmyelinated nerve, and adjacent tissues. We finally realized the sensitivity of 94.2% and the selectivity of 92.0% for peripheral nerves including myelinated and unmyelinated nerves against adjacent tissues. Although further development of an intraoperative Raman spectroscopy system is required for clinical use, our proposed approach will serve as a unique and powerful tool for peripheral nerve detection for nerve-sparing surgery in the future.

Beneficial effects of gamma linolenic acid supplementation on nerve conduction velocity, Na+, K+ ATPase activity, and membrane fatty acid composition in sciatic nerve of diabetic rats.

PubMed

Coste, T; Pierlovisi, M; Leonardi, J; Dufayet, D; Gerbi, A; Lafont, H; Vague, P; Raccah, D

1999-07-01

Metabolic and vascular abnormalities are implicated in the pathogenesis of diabetic neuropathy. Two principal metabolic defects are altered lipid metabolism resulting from the impairment of delta-6-desaturase, which converts linoleic acid (LA) into gamma linolenic acid (GLA), and reduced nerve Na+, K+ ATPase activity. This reduction may be caused by a lack of incorporation of (n-6) fatty acids in membrane phospholipids. Because this ubiquitous enzyme maintains the membrane electrical potential and allows repolarization, disturbances in its activity can alter the process of nerve conduction velocity (NCV). We studied the effects of supplementation with GLA (260 mg per day) on NCV, fatty acid phospholipid composition, and Na+, K+ ATPase activity in streptozotocin-diabetic rats. Six groups of 10 rats were studied. Two groups served as controls supplemented with GLA or sunflower oil (GLA free). Two groups with different durations of diabetes were studied: 6 weeks with no supplementation and 12 weeks supplemented with sunflower oil. To test the ability of GLA to prevent or reverse the effects of diabetes, two groups of diabetic rats were supplemented with GLA, one group for 12 weeks and one group for 6 weeks, starting 6 weeks after diabetes induction. Diabetes resulted in a 25% decrease in NCV (P < 0.0001), a 45% decrease in Na+, K+ ATPase activity (P < 0.0001), and an abnormal phospholipid fatty acid composition. GLA restored NCV both in the prevention and reversal studies and partially restored Na+, K+ ATPase activity in the preventive treatment group (P < 0.0001). These effects were accompanied by a modification of phospholipid fatty acid composition in nerve membranes. Overall, the results suggest that membrane fatty acid composition plays a direct role in NCV and confirm the beneficial effect of GLA supplementation in diabetic neuropathy.

Comparing the Efficacy of Triple Nerve Transfers with Nerve Graft Reconstruction in Upper Trunk Obstetric Brachial Plexus Injury.

PubMed

O'Grady, Kathleen M; Power, Hollie A; Olson, Jaret L; Morhart, Michael J; Harrop, A Robertson; Watt, M Joe; Chan, K Ming

2017-10-01

Upper trunk obstetric brachial plexus injury can cause profound shoulder and elbow dysfunction. Although neuroma excision with interpositional sural nerve grafting is the current gold standard, distal nerve transfers have a number of potential advantages. The goal of this study was to compare the clinical outcomes and health care costs between nerve grafting and distal nerve transfers in children with upper trunk obstetric brachial plexus injury. In this prospective cohort study, children who underwent triple nerve transfers were followed with the Active Movement Scale for 2 years. Their outcomes were compared to those of children who underwent nerve graft reconstruction. To assess health care use, a cost analysis was also performed. Twelve patients who underwent nerve grafting were compared to 14 patients who underwent triple nerve transfers. Both groups had similar baseline characteristics and showed improved shoulder and elbow function following surgery. However, the nerve transfer group displayed significantly greater improvement in shoulder external rotation and forearm supination 2 years after surgery (p < 0.05). The operative time and length of hospital stay were significantly lower (p < 0.05), and the overall cost was approximately 50 percent less in the nerve transfer group. Triple nerve transfer for upper trunk obstetric brachial plexus injury is a feasible option, with better functional shoulder external rotation and forearm supination, faster recovery, and lower cost compared with traditional nerve graft reconstruction. Therapeutic, II.

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

Zelenak, Kamil, E-mail: zelenak@unm.sk; Zelenakova, Jana; DeRiggo, Julius

Internal carotid artery (ICA) lesions in the parapharyngeal space (a dissection and a pseudoaneurysm) may present as isolated lower cranial nerves (IX, X, XI, and XII) palsy (Collet-Sicard syndrome). Some arteriopathies such as fibromuscular dysplasia and tortuosity make a vessel predisposed to dissection. Extreme vessel tortuosity makes the treatment by a stent graft impossible. Two Silk stents were used in a 46 year-old man with left lower cranial nerves (IX-XII) palsy for the treatment of left ICA spontaneous dissection with pseudoaneurysm. A follow-up angiogram 5 months later confirmed pseudoaneurysm thrombosis and patency of the left ICA. The patient recovered completelymore » from the deficits.« less

Inhibitory effects and structural insights for a novel series of coumarin-based compounds that selectively target human CA IX and CA XII carbonic anhydrases.

PubMed

De Luca, Laura; Mancuso, Francesca; Ferro, Stefania; Buemi, Maria Rosa; Angeli, Andrea; Del Prete, Sonia; Capasso, Clemente; Supuran, Claudiu T; Gitto, Rosaria

2018-01-01

Coumarin derivatives are a peculiar class of inhibitors of the family of metalloenzymes carbonic anhydrases (CA, EC 4.2.1.1). Several coumarins display higher affinity and selectivity toward most relevant and druggable CA isoforms. By decorating the natural compound umbelliferone (1) we have identified a new series of coumarin-based compounds demonstrating high CA inhibitory effects with nanomolar affinity for hCA IX and hCA XII isoforms that were considered a target amenable to develop antitumor agents. The most active tested compounds proved to be potent inhibitors with K i values equal to that of the well-known inhibitor acetazolamide (AAZ), that lacks selectivity over ubiquitous hCA I and hCA II. As suggested by docking studies the coumarins, that are lacking of the canonical metal binding groups, do not interact with Zinc ion within the catalytic site as found for classical sulfonamide type inhibitors of CAs. Thus, the studied inhibitors might possess a non-classical inhibitory mode of action preventing the carbon dioxide to entry into catalytic cavity and its conversion into bicarbonate ion. Specifically, the most active inhibitor of hCA XII compound 18i (K i value of 5.5 nM) and its supposed hydrolytic products could establish a web of H-bond interactions within the enzymatic cavity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Differential Roles for the Coagulation Factors XI and XII in Regulating the Physical Biology of Fibrin.

PubMed

Sylman, Joanna L; Daalkhaijav, Uranbileg; Zhang, Ying; Gray, Elliot M; Farhang, Parsa A; Chu, Tiffany T; Zilberman-Rudenko, Jevgenia; Puy, Cristina; Tucker, Erik I; Smith, Stephanie A; Morrissey, James H; Walker, Travis W; Nan, Xiaolin L; Gruber, András; McCarty, Owen J T

2017-05-01

In the contact activation pathway of the coagulation, zymogen factor XII (FXII) is converted to FXIIa, which triggers activation of FXI leading to the activation of FIX and subsequent thrombin generation and fibrin formation. Feedback activation of FXI by thrombin has been shown to promote thrombin generation in a FXII-independent manner and FXIIa can bypass FXI to directly activate FX and prothrombin in the presence of highly negatively charged molecules, such as long-chain polyphosphates (LC polyP). We sought to determine whether activation of FXII or FXI differentially regulate the physical biology of fibrin formation. Fibrin formation was initiated with tissue factor, ellagic acid (EA), or LC polyP in the presence of inhibitors of FXI and FXII. Our data demonstrated that inhibition of FXI decreased the rate of fibrin formation and fiber network density, and increased the fibrin network strength and rate of fibrinolysis when gelation was initiated via the contact activation pathway with EA. FXII inhibition decreased the fibrin formation and fibrin density, and increased the fibrinolysis rate only when fibrin formation was initiated via the contact activation pathway with LC polyP. Overall, we demonstrate that inhibition of FXI and FXII distinctly alter the biophysical properties of fibrin.

Endogenous angiotensin affects responses to stimulation of baroreceptor afferent nerves.

PubMed

DiBona, Gerald F; Jones, Susan Y

2003-08-01

To study effects of endogenous angiotensin II on responses to standardized stimulation of afferent neural input into the central portion of the arterial and cardiac baroreflexes. Different dietary sodium intakes were used to physiologically alter endogenous angiotensin II activity. Candesartan, an angiotensin II type 1 receptor antagonist, was used to assess dependency of observed effects on angiotensin II stimulation of angiotensin II type 1 receptors. Electrical stimulation of arterial and cardiac baroreflex afferent nerves was used to provide a standardized input to the central portion of the arterial and cardiac baroreflexes. In anesthetized rats in balance on low, normal and high dietary sodium intake, arterial pressure, heart rate and renal sympathetic nerve activity responses to electrical stimulation of vagus and aortic depressor nerves were determined. Compared with plasma renin activity values in normal dietary sodium intake rats, those from low dietary sodium intake rats were higher and those from high dietary sodium intake rats were lower. During vagus nerve stimulation, the heart rate, arterial pressure and renal sympathetic nerve activity responses were similar in all three dietary sodium intake groups. During aortic depressor nerve stimulation, the heart rate and arterial pressure responses were similar in all three dietary sodium intake groups. However, the renal sympathetic nerve activity response was significantly greater in the low sodium group than in the normal and high sodium group at 4, 8 and 16 Hz. Candesartan administered to low dietary sodium intake rats had no effect on the heart rate and arterial pressure responses to either vagus or aortic depressor nerve stimulation but increased the magnitude of the renal sympathoinhibitory responses. Increased endogenous angiotensin II in rats on a low dietary sodium intake attenuates the renal sympathoinhibitory response to activation of the cardiac and sinoaortic baroreflexes by standardized vagus

Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

PubMed Central

Moore, Amy M.; MacEwan, Matthew; Santosa, Katherine B.; Chenard, Kristofer E.; Ray, Wilson Z.; Hunter, Daniel A.; Mackinnon, Susan E.; Johnson, Philip J.

2011-01-01

Background Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods Three established models of acellular nerve allograft (cold-preserved, detergent-processed, and AxoGen® -processed nerve allografts) were compared to nerve isografts and silicone nerve guidance conduits in a 14 mm rat sciatic nerve defect. Results All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent-processed allografts were similar to isografts at 6 weeks post-operatively, while AxoGen®-processed and cold-preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent-processed allografts promoted isograft-equivalent levels of motor recovery 16 weeks post-operatively. All acellular allografts promoted greater amounts of motor recovery compared to silicone conduits. Conclusions These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. PMID:21660979

Nerve Transfer Versus Nerve Graft for Reconstruction of High Ulnar Nerve Injuries.

PubMed

Sallam, Asser A; El-Deeb, Mohamed S; Imam, Mohamed A

2017-04-01

To assess the efficacy of nerve transfer versus nerve grafting in restoring motor and sensory hand function in patients with complete, isolated high ulnar nerve injuries. A retrospective chart review was performed, at a minimum 2 years of follow-up, of 52 patients suffering complete, isolated high ulnar nerve injury between January 2006 and June 2013 in one specialized hand surgery unit. Twenty-four patients underwent motor and sensory nerve transfers (NT group). Twenty-eight patients underwent sural nerve grafting (NG group). Motor recovery, return of sensibility and complications were examined as outcome measures. The Medical Research Council scale was applied to evaluate sensory and motor recovery. Grip and pinch strengths of the hand were measured. Twenty of 24 patients (83.33%) in the NT group regained M3 grade or greater for the adductor pollicis, the abductor digiti minimi, and the medial 2 lumbricals and interossei, compared with only 16 of 28 patients (57.14%) in the NG group. Means for percentage recovery of grip strengths compared with the other healthy hand were significantly higher for the NT group than the NG group. Sensory recovery of S3 or greater was achieved in more than half of each group with no significant difference between groups. Nerve transfer is favored over nerve grafting in managing high ulnar nerve injuries because of better improvement of motor power and better restoration of grip functions of the hand. Therapeutic IV. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Matrix metalloproteinase-2 is downregulated in sciatic nerve by streptozotocin induced diabetes and/or treatment with minocycline: Implications for nerve regeneration

PubMed Central

Ali, Sumia; Driscoll, Heather E.; Newton, Victoria L.; Gardiner, Natalie J.

2014-01-01

Minocycline is an inhibitor of matrix metalloproteinases (MMPs) and has been shown to have analgesic effects. Whilst increased expression of MMPs is associated with neuropathic pain, MMPs also play crucial roles in Wallerian degeneration and nerve regeneration. In this study we examined the expression of MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1/-2 in the sciatic nerve of control and streptozotocin-induced diabetic rats treated with either vehicle or minocycline by quantitative PCR and gelatin zymography. We assessed the effects of minocycline on nerve conduction velocity and intraepidermal nerve fibre (IENF) deficits in diabetic neuropathy and investigated the effects of minocycline or MMP-2 on neurite outgrowth from primary cultures of dissociated adult rat sensory neurons. We show that MMP-2 is expressed constitutively in the sciatic nerve in vivo and treatment with minocycline or diabetes leads to downregulation of MMP-2 expression and activity. The functional consequence of this is IENF deficits in minocycline-treated nondiabetic rats and an unsupportive microenvironment for regeneration in diabetes. Minocycline reduces levels of MMP-2 mRNA and nerve growth factor-induced neurite outgrowth. Furthermore, in vivo minocycline treatment reduces preconditioning-induced in vitro neurite outgrowth following a sciatic nerve crush. In contrast, the addition of active MMP-2 facilitates neurite outgrowth in the absence of neurotrophic support and pre-treatment of diabetic sciatic nerve substrata with active MMP-2 promotes a permissive environment for neurite outgrowth. In conclusion we suggest that MMP-2 downregulation may contribute to the regenerative deficits in diabetes. Minocycline treatment also downregulates MMP-2 activity and is associated with inhibitory effects on sensory neurons. Thus, caution should be exhibited with its use as the balance between beneficial and detrimental outcomes may be critical in assessing the benefits of using

VAGUS NERVE STIMULATION REGULATES HEMOSTASIS IN SWINE

PubMed Central

Czura, Christopher J.; Schultz, Arthur; Kaipel, Martin; Khadem, Anna; Huston, Jared M.; Pavlov, Valentin A.; Redl, Heinz; Tracey, Kevin J.

2010-01-01

The central nervous system regulates peripheral immune responses via the vagus nerve, the primary neural component of the cholinergic anti-inflammatory pathway. Electrical stimulation of the vagus nerve suppresses pro-inflammatory cytokine release in response to endotoxin, I/R injury, and hypovolemic shock and protects against lethal hypotension. To determine the effect of vagus nerve stimulation on coagulation pathways, anesthetized pigs were subjected to partial ear resection before and after electrical vagus nerve stimulation. We observed that electrical vagus nerve stimulation significantly decreased bleeding time (pre–electrical vagus nerve stimulation = 1033 ± 210 s versus post–electrical vagus nerve stimulation = 585 ± 111 s; P < 0.05) and total blood loss (pre–electrical vagus nerve stimulation = 48.4 ± 6.8 mL versus post–electrical vagus nerve stimulation = 26.3 ± 6.7 mL; P < 0.05). Reduced bleeding time after vagus nerve stimulation was independent of changes in heart rate or blood pressure and correlated with increased thrombin/antithrombin III complex generation in shed blood. These data indicate that electrical stimulation of the vagus nerve attenuates peripheral hemorrhage in a porcine model of soft tissue injury and that this protective effect is associated with increased coagulation factor activity. PMID:19953009

Slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with chronic heart failure: from modeling to clinical application.

PubMed

Harada, Daisuke; Asanoi, Hidetsugu; Takagawa, Junya; Ishise, Hisanari; Ueno, Hiroshi; Oda, Yoshitaka; Goso, Yukiko; Joho, Shuji; Inoue, Hiroshi

2014-10-15

Influences of slow and deep respiration on steady-state sympathetic nerve activity remain controversial in humans and could vary depending on disease conditions and basal sympathetic nerve activity. To elucidate the respiratory modulation of steady-state sympathetic nerve activity, we modeled the dynamic nature of the relationship between lung inflation and muscle sympathetic nerve activity (MSNA) in 11 heart failure patients with exaggerated sympathetic outflow at rest. An autoregressive exogenous input model was utilized to simulate entire responses of MSNA to variable respiratory patterns. In another 18 patients, we determined the influence of increasing tidal volume and slowing respiratory frequency on MSNA; 10 patients underwent a 15-min device-guided slow respiration and the remaining 8 had no respiratory modification. The model predicted that a 1-liter, step increase of lung volume decreased MSNA dynamically; its nadir (-33 ± 22%) occurred at 2.4 s; and steady-state decrease (-15 ± 5%), at 6 s. Actually, in patients with the device-guided slow and deep respiration, respiratory frequency effectively fell from 16.4 ± 3.9 to 6.7 ± 2.8/min (P < 0.0001) with a concomitant increase in tidal volume from 499 ± 206 to 1,177 ± 497 ml (P < 0.001). Consequently, steady-state MSNA was decreased by 31% (P < 0.005). In patients without respiratory modulation, there were no significant changes in respiratory frequency, tidal volume, and steady-state MSNA. Thus slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with high levels of resting sympathetic tone as in heart failure. Copyright © 2014 the American Physiological Society.

Nerve Cross-Bridging to Enhance Nerve Regeneration in a Rat Model of Delayed Nerve Repair

PubMed Central

2015-01-01

There are currently no available options to promote nerve regeneration through chronically denervated distal nerve stumps. Here we used a rat model of delayed nerve repair asking of prior insertion of side-to-side cross-bridges between a donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) nerve stump ameliorates poor nerve regeneration. First, numbers of retrogradely-labelled TIB neurons that grew axons into the nerve stump within three months, increased with the size of the perineurial windows opened in the TIB and CP nerves. Equal numbers of donor TIB axons regenerated into CP stumps either side of the cross-bridges, not being affected by target neurotrophic effects, or by removing the perineurium to insert 5-9 cross-bridges. Second, CP nerve stumps were coapted three months after inserting 0-9 cross-bridges and the number of 1) CP neurons that regenerated their axons within three months or 2) CP motor nerves that reinnervated the extensor digitorum longus (EDL) muscle within five months was determined by counting and motor unit number estimation (MUNE), respectively. We found that three but not more cross-bridges promoted the regeneration of axons and reinnervation of EDL muscle by all the CP motoneurons as compared to only 33% regenerating their axons when no cross-bridges were inserted. The same 3-fold increase in sensory nerve regeneration was found. In conclusion, side-to-side cross-bridges ameliorate poor regeneration after delayed nerve repair possibly by sustaining the growth-permissive state of denervated nerve stumps. Such autografts may be used in human repair surgery to improve outcomes after unavoidable delays. PMID:26016986

Respiratory modulation of sympathetic nerve activity is enhanced in male rat offspring following uteroplacental insufficiency.

PubMed

Menuet, C; Wlodek, M E; Fong, A Y; Allen, A M

2016-06-01

Sympathetic nerve activity to the cardiovascular system displays prominent respiratory-related modulation which leads to the generation of rhythmic oscillations in blood pressure called Traube-Hering waves. An amplification of this respiratory modulation of sympathetic activity is observed in hypertension of both genetic, the spontaneously hypertensive rat, and induced, chronic intermittent hypoxia or maternal protein restriction during gestation, origin. Male offspring of mothers with uteroplacental insufficiency, induced by bilateral uterine vessel ligation at 18 days of gestation, are also hypertensive in adulthood. In this study we examined whether these male offspring display altered respiratory modulation of sympathetic activity at pre-hypertensive ages compared to controls. Respiratory, cardiovascular and sympathetic parameters were examined using the working heart-brainstem preparation in 35 day old male rats that had reduced birth weight due to uteroplacental insufficiency. Whilst all respiratory parameters were not different between groups, we observed an enhanced respiratory-related burst of thoracic sympathetic nerve activity and amplified Traube-Hering waves in the growth-restricted group. This group also showed an increased sympathetic and bradycardic response to activation of peripheral chemoreceptors. The observations add support to the view that altered respiratory modulation of sympathetic activity represents a common mechanism involved in the development of several forms of hypertension. Copyright © 2015 Elsevier B.V. All rights reserved.

Regenerating Fish Optic Nerves and a Regeneration-Like Response in Injured Optic Nerves of Adult Rabbits

NASA Astrophysics Data System (ADS)

Schwartz, M.; Belkin, M.; Harel, A.; Solomon, A.; Lavie, V.; Hadani, M.; Rachailovich, I.; Stein-Izsak, C.

1985-05-01

Regeneration of fish optic nerve (representing regenerative central nervous system) was accompanied by increased activity of regeneration-triggering factors produced by nonneuronal cells. A graft of regenerating fish optic nerve, or a ``wrap-around'' implant containing medium conditioned by it, induced a response associated with regeneration in injured optic nerves of adult rabbits (representing a nonregenerative central nervous system). This response was manifested by an increase of general protein synthesis and of selective polypeptides in the retinas and by the ability of the retina to sprout in culture.

Implosion and heating experiments of fast ignition targets by Gekko-XII and LFEX lasers

NASA Astrophysics Data System (ADS)

Shiraga, H.; Fujioka, S.; Nakai, M.; Watari, T.; Nakamura, H.; Arikawa, Y.; Hosoda, H.; Nagai, T.; Koga, M.; Kikuchi, H.; Ishii, Y.; Sogo, T.; Shigemori, K.; Nishimura, H.; Zhang, Z.; Tanabe, M.; Ohira, S.; Fujii, Y.; Namimoto, T.; Sakawa, Y.; Maegawa, O.; Ozaki, T.; Tanaka, K. A.; Habara, H.; Iwawaki, T.; Shimada, K.; Key, M.; Norreys, P.; Pasley, J.; Nagatomo, H.; Johzaki, T.; Sunahara, A.; Murakami, M.; Sakagami, H.; Taguchi, T.; Norimatsu, T.; Homma, H.; Fujimoto, Y.; Iwamoto, A.; Miyanaga, N.; Kawanaka, J.; Kanabe, T.; Jitsuno, T.; Nakata, Y.; Tsubakimoto, K.; Sueda, K.; Kodama, R.; Kondo, K.; Morio, N.; Matsuo, S.; Kawasaki, T.; Sawai, K.; Tsuji, K.; Murakami, H.; Sarukura, N.; Shimizu, T.; Mima, K.; Azechi, H.

2013-11-01

The FIREX-1 project, the goal of which is to demonstrate fuel heating up to 5 keV by fast ignition scheme, has been carried out since 2003 including construction and tuning of LFEX laser and integrated experiments. Implosion and heating experiment of Fast Ignition targets have been performed since 2009 with Gekko-XII and LFEX lasers. A deuterated polystyrene shell target was imploded with the 0.53- μm Gekko-XII, and the 1.053- μm beam of the LFEX laser was injected through a gold cone attached to the shell to generate hot electrons to heat the imploded fuel plasma. Pulse contrast ratio of the LFEX beam was significantly improved. Also a variety of plasma diagnostic instruments were developed to be compatible with harsh environment of intense hard x-rays (γ rays) and electromagnetic pulses due to the intense LFEX beam on the target. Large background signals around the DD neutron signal in time-of-flight record of neutron detector were found to consist of neutrons via (γ,n) reactions and scattered gamma rays. Enhanced neutron yield was confirmed by carefully eliminating such backgrounds. Neutron enhancement up to 3.5 × 107 was observed. Heating efficiency was estimated to be 10-20% assuming a uniform temperature rise model.

Comparison of Extracellular Striatal Acetylcholine and Brain Seizure Activity Following Acute Exposure to the Nerve Agents Cyclosarin and Tabun in Freely Moving Guinea Pigs

DTIC Science & Technology

2010-01-01

Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Comparison of extracellular striatal acetylcholine and brain seizure activity following...lethality; nerve agents; organophosphorus compounds; seizure activity ; tabun 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER...acetylcholine and brain seizure activity following acute exposure to the nerve agents cyclosarin and tabun in freely moving guinea pigs John C

Preoperative transcutaneous electrical nerve stimulation for localizing superficial nerve paths.

PubMed

Natori, Yuhei; Yoshizawa, Hidekazu; Mizuno, Hiroshi; Hayashi, Ayato

2015-12-01

During surgery, peripheral nerves are often seen to follow unpredictable paths because of previous surgeries and/or compression caused by a tumor. Iatrogenic nerve injury is a serious complication that must be avoided, and preoperative evaluation of nerve paths is important for preventing it. In this study, transcutaneous electrical nerve stimulation (TENS) was used for an in-depth analysis of peripheral nerve paths. This study included 27 patients who underwent the TENS procedure to evaluate the peripheral nerve path (17 males and 10 females; mean age: 59.9 years, range: 18-83 years) of each patient preoperatively. An electrode pen coupled to an electrical nerve stimulator was used for superficial nerve mapping. The TENS procedure was performed on patients' major peripheral nerves that passed close to the surgical field of tumor resection or trauma surgery, and intraoperative damage to those nerves was apprehensive. The paths of the target nerve were detected in most patients preoperatively. The nerve paths of 26 patients were precisely under the markings drawn preoperatively. The nerve path of one patient substantially differed from the preoperative markings with numbness at the surgical region. During surgery, the nerve paths could be accurately mapped preoperatively using the TENS procedure as confirmed by direct visualization of the nerve. This stimulation device is easy to use and offers highly accurate mapping of nerves for surgical planning without major complications. The authors conclude that TENS is a useful tool for noninvasive nerve localization and makes tumor resection a safe and smooth procedure. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Chitin biological absorbable catheters bridging sural nerve grafts transplanted into sciatic nerve defects promote nerve regeneration.

PubMed

Wang, Zhi-Yong; Wang, Jian-Wei; Qin, Li-Hua; Zhang, Wei-Guang; Zhang, Pei-Xun; Jiang, Bao-Guo

2018-06-01

To investigate the efficacy of chitin biological absorbable catheters in a rat model of autologous nerve transplantation. A segment of sciatic nerve was removed to produce a sciatic nerve defect, and the sural nerve was cut from the ipsilateral leg and used as a graft to bridge the defect, with or without use of a chitin biological absorbable catheter surrounding the graft. The number and morphology of regenerating myelinated fibers, nerve conduction velocity, nerve function index, triceps surae muscle morphology, and sensory function were evaluated at 9 and 12 months after surgery. All of the above parameters were improved in rats in which the nerve graft was bridged with chitin biological absorbable catheters compared with rats without catheters. The results of this study indicate that use of chitin biological absorbable catheters to surround sural nerve grafts bridging sciatic nerve defects promotes recovery of structural, motor, and sensory function and improves muscle fiber morphology. © 2018 John Wiley & Sons Ltd.

External laryngeal nerve in thyroid surgery: is the nerve stimulator necessary?

PubMed

Aina, E N; Hisham, A N

2001-09-01

To find out the incidence and type of external laryngeal nerves during operations on the thyroid, and to assess the role of a nerve stimulator in detecting them. Prospective, non-randomised study. Teaching hospital, Malaysia. 317 patients who had 447 dissections between early January 1998 and late November 1999. Number and type of nerves crossing the cricothyroid space, and the usefulness of the nerve stimulator in finding them. The nerve stimulator was used in 206/447 dissections (46%). 392 external laryngeal nerves were seen (88%), of which 196/206 (95%) were detected with the stimulator. However, without the stimulator 196 nerves were detected out of 241 dissections (81%). The stimulator detected 47 (23%) Type I nerves (nerve > 1 cm from the upper edge of superior pole); 86 (42%) Type IIa nerves (nerve < 1 cm from the upper edge of superior pole); and 63 (31%) Type IIb nerves (nerve below upper edge of superior pole). 10 nerves were not detected. When the stimulator was not used the corresponding figures were 32 (13%), 113 (47%), and 51 (21%), and 45 nerves were not seen. If the nerve cannot be found we recommend dissection of capsule close to the medial border of the upper pole of the thyroid to avoid injury to the nerve. Although the use of the nerve stimulator seems desirable, it confers no added advantage in finding the nerve. In the event of uncertainty about whether a structure is the nerve, the stimulator may help to confirm it. However, exposure of the cricothyroid space is most important for good exposure in searching for the external laryngeal nerve.

The significance of nerve sugar levels for the peripheral nerve impairment of spontaneously diabetic GK (Goto-Kakizaki) rats.

PubMed

Suzuki, K; Yen-Chung, H; Toyota, T; Goto, Y; Hirata, Y; Okada, K

1990-05-01

This study was carried out to clarify the relationship between the slowing of motor nerve conduction velocity and nerve levels of sorbitol, fructose, glucose and myoinositol in spontaneously diabetic GK (Goto-Kakizaki) rats. The motor nerve conduction velocity in GK rats was constantly lower than in normal controls at three and nine months of age. This constant decrease in motor nerve conduction velocity in GK rats was closely related to glucose intolerance in GK rats soon after birth. Nerve levels of sorbitol, glucose and fructose in GK rats were significantly increased as compared to normal controls at nine months old, but not (except glucose) at three months old. The increase in nerve concentrations of sugars in GK rats was progressive with age. However, levels of glucose, sorbitol and fructose in normal Wistar rats remain unchanged with age. Although nerve myo-inositol levels in GK rats were lower at three and nine months than those of normal controls, a significant difference in myo-inositol levels was observed only at nine months. On the contrary, nerve myo-inositol level in normal Wistar rats did not show age-related change. These findings suggested that both enhanced polyol pathway activity and myo-inositol depletion play important roles in the reduction of motor nerve conduction velocity.

Structural parameters of collagen nerve grafts influence peripheral nerve regeneration.

PubMed

Stang, Felix; Fansa, Hisham; Wolf, Gerald; Reppin, Michael; Keilhoff, Gerburg

2005-06-01

Large nerve defects require nerve grafts to allow regeneration. To avoid donor nerve problems the concept of tissue engineering was introduced into nerve surgery. However, non-neuronal grafts support axonal regeneration only to a certain extent. They lack viable Schwann cells which provide neurotrophic and neurotopic factors and guide the sprouting nerve. This experimental study used the rat sciatic nerve to bridge 2 cm nerve gaps with collagen (type I/III) tubes. The tubes were different in their physical structure (hollow versus inner collagen skeleton, different inner diameters). To improve regeneration Schwann cells were implanted. After 8 weeks the regeneration process was monitored clinically, histologically and morphometrically. Autologous nerve grafts and collagen tubes without Schwann cells served as control. In all parameters autologous nerve grafts showed best regeneration. Nerve regeneration in a noteworthy quality was also seen with hollow collagen tubes and tubes with reduced lumen, both filled with Schwann cells. The inner skeleton, however, impaired nerve regeneration independent of whether Schwann cells were added or not. This indicates that not only viable Schwann cells are an imperative prerequisite but also structural parameters determine peripheral nerve regeneration.

Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells

PubMed Central

Göbel, Kerstin; Pankratz, Susann; Asaridou, Chloi-Magdalini; Herrmann, Alexander M.; Bittner, Stefan; Merker, Monika; Ruck, Tobias; Glumm, Sarah; Langhauser, Friederike; Kraft, Peter; Krug, Thorsten F.; Breuer, Johanna; Herold, Martin; Gross, Catharina C.; Beckmann, Denise; Korb-Pap, Adelheid; Schuhmann, Michael K.; Kuerten, Stefanie; Mitroulis, Ioannis; Ruppert, Clemens; Nolte, Marc W.; Panousis, Con; Klotz, Luisa; Kehrel, Beate; Korn, Thomas; Langer, Harald F.; Pap, Thomas; Nieswandt, Bernhard; Wiendl, Heinz; Chavakis, Triantafyllos; Kleinschnitz, Christoph; Meuth, Sven G.

2016-01-01

Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders. PMID:27188843

Increase of transcription factor EB (TFEB) and lysosomes in rat DRG neurons and their transportation to the central nerve terminal in dorsal horn after nerve injury.

PubMed

Jung, J; Uesugi, N; Jeong, N Y; Park, B S; Konishi, H; Kiyama, H

2016-01-28

In the spinal dorsal horn (DH), nerve injury activates microglia and induces neuropathic pain. Several studies clarified an involvement of adenosine triphosphate (ATP) in the microglial activation. However, the origin of ATP together with the release mechanism is unclear. Recent in vitro study revealed that an ATP marker, quinacrine, in lysosomes was released from neurite terminal of dorsal root ganglion (DRG) neurons to extracellular space via lysosomal exocytosis. Here, we demonstrate a possibility that the lysosomal ingredient including ATP released from DRG neurons by lysosomal-exocytosis is an additional source of the glial activation in DH after nerve injury. After rat L5 spinal nerve ligation (SNL), mRNA for transcription factor EB (TFEB), a transcription factor controlling lysosomal activation and exocytosis, was induced in the DRG. Simultaneously both lysosomal protein, LAMP1- and vesicular nuclear transporter (VNUT)-positive vesicles were increased in L5 DRG neurons and ipsilateral DH. The quinacrine staining in DH was increased and co-localized with LAMP1 immunoreactivity after nerve injury. In DH, LAMP1-positive vesicles were also co-localized with a peripheral nerve marker, Isolectin B4 (IB4) lectin. Injection of the adenovirus encoding mCherry-LAMP1 into DRG showed that mCherry-positive lysosomes are transported to the central nerve terminal in DH. These findings suggest that activation of lysosome synthesis including ATP packaging in DRG, the central transportation of the lysosome, and subsequent its exocytosis from the central nerve terminal of DRG neurons in response to nerve injury could be a partial mechanism for activation of microglia in DH. This lysosome-mediated microglia activation mechanism may provide another clue to control nociception and pain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Simulating Univariate and Multivariate Burr Type IIII and Type XII Distributions through the Method of L-Moments

ERIC Educational Resources Information Center

Pant, Mohan Dev

2011-01-01

The Burr families (Type III and Type XII) of distributions are traditionally used in the context of statistical modeling and for simulating non-normal distributions with moment-based parameters (e.g., Skew and Kurtosis). In educational and psychological studies, the Burr families of distributions can be used to simulate extremely asymmetrical and…

An implantable nerve cooler for the exercising dog.

PubMed

Borgdorff, P; Versteeg, P G

1984-01-01

An implantable nerve cooler has been constructed to block cervical vago-sympathetic activity in the exercising dog reversibly. An insulated gilt brass container implanted around the nerve is perfused with cooled alcohol via silicone tubes. The flow of alcohol is controlled by an electromagnetic valve to keep nerve temperature at the required value. Nerve temperature is measured by a thermistor attached to the housing and in contact with the nerve. It is shown that, during cooling, temperature at this location differs less than 2 degrees C from nerve core temperature. Measurement of changes in heart rate revealed that complete vagal block in the conscious animal is obtained at a nerve temperature of 2 degrees C and can be achieved within 50 s. During steady-state cooling in the exercising animal nerve temperature varied less than 0.5 degree C. When the coolers after 2 weeks of implantation were removed they showed no oxydation and could be used again.

The scalene reflex: relationship between increased median or ulnar nerve pressure and scalene muscle activity.

PubMed

Monsivais, J J; Sun, Y; Rajashekhar, T P

1995-07-01

Neck pain, headaches, upper thoracic pain, and dystonic scalene muscles are common findings in patients who have severe entrapment neuropathies of the upper extremities. This problem was taken to the laboratory in an attempt to discover the correlation between distal entrapment neuropathies, brachial plexus entrapments, and prominent scalenus muscles. When increased pressure (over 40 mmHg) was applied to the median and ulnar nerves in the forelimbs of eight goats, increased electromyographic activity was noted in the ipsilateral scalenus muscle. Pressures ranging from 100 to 150 mmHg caused increased electromyographic activity on the contralateral scalene muscle, and the authors postulate that it is mediated by the gamma afferent and efferent system. This relationship may explain the commonly found neck pain and muscle spasm in patients with peripheral neuropathies, and it represents a link between the somatic efferent nerves and the gamma motor neuron system. At present, the same phenomenon has been documented in 30 humans with the diagnosis of brachial plexus entrapment.

Impact of cardiac hypertrophy on arterial and cardiopulmonary baroreflex control of renal sympathetic nerve activity in anaesthetized rats.

PubMed

Flanagan, Evelyn T; Buckley, Maria M; Aherne, Claire M; Lainis, Fredolin; Sattar, Munavvar; Johns, Edward J

2008-09-01

This study aimed to quantify the effect of cardiac hypertrophy induced with isoprenaline and caffeine on reflex regulation of renal sympathetic nerve activity by the arterial and cardiopulmonary baroreceptors. Male Wistar rats, untreated or given water containing caffeine and subcutaneous (s.c.) isoprenaline every 72 h for 2 weeks or thyroxine s.c. for 7 days, were anaesthetized and prepared for measurement of renal sympathetic nerve activity or cardiac indices. Both isoprenaline-caffeine and thyroxine treatment blunted weight gain but increased heart weight and heart weight to body weight ratio by 40 and 14% (both P<0.01), respectively. In the isoprenaline-caffeine group, the maximal rate of change of left ventricular pressure and the contractility index were higher by 17 and 14% (both P<0.01), respectively, compared with untreated rats. In the isoprenaline-caffeine-treated rats, baroreflex gain curve sensitivity was depressed by approximately 30% (P<0/05), while the mid-point blood pressure was lower, by 15% (P<0/05), and the range of the curve was 60% (P<0.05) greater than in the untreated rats. An acute intravenous infusion of a saline load decreased renal sympathetic nerve activity by 42% (P<0.05) in the untreated rats but had no effect in the isoprenaline-caffeine- or the thyroxine-treated groups. The isoprenaline-caffeine treatment induced cardiac hypertrophy with raised cardiac performance and an associated depression in the reflex regulation of renal sympathetic nerve activity by both high- and low-pressure baroreceptors. The thyroxine-induced cardiac hypertrophy also blunted the low-pressure baroreceptor-mediated renal sympatho-inhibition. These findings demonstrate that in cardiac hypertrophy without impaired cardiac function, there is a blunted baroreceptor control of renal sympathetic outflow.

High Ulnar Nerve Injuries: Nerve Transfers to Restore Function.

PubMed

Patterson, Jennifer Megan M

2016-05-01

Peripheral nerve injuries are challenging problems. Nerve transfers are one of many options available to surgeons caring for these patients, although they do not replace tendon transfers, nerve graft, or primary repair in all patients. Distal nerve transfers for the treatment of high ulnar nerve injuries allow for a shorter reinnervation period and improved ulnar intrinsic recovery, which are critical to function of the hand. Copyright © 2016 Elsevier Inc. All rights reserved.

Chitosan conduits combined with nerve growth factor microspheres repair facial nerve defects

PubMed Central

Liu, Huawei; Wen, Weisheng; Hu, Min; Bi, Wenting; Chen, Lijie; Liu, Sanxia; Chen, Peng; Tan, Xinying

2013-01-01

Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa-line groups than in the nerve growth factor-microspheres and autologous nerve groups. physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation illustrated that the di-ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits. PMID:25206635

Optogenetic probing of nerve and muscle function after facial nerve lesion in the mouse whisker system

NASA Astrophysics Data System (ADS)

Bandi, Akhil; Vajtay, Thomas J.; Upadhyay, Aman; Yiantsos, S. Olga; Lee, Christian R.; Margolis, David J.

2018-02-01

Optogenetic modulation of neural circuits has opened new avenues into neuroscience research, allowing the control of cellular activity of genetically specified cell types. Optogenetics is still underdeveloped in the peripheral nervous system, yet there are many applications related to sensorimotor function, pain and nerve injury that would be of great benefit. We recently established a method for non-invasive, transdermal optogenetic stimulation of the facial muscles that control whisker movements in mice (Park et al., 2016, eLife, e14140)1. Here we present results comparing the effects of optogenetic stimulation of whisker movements in mice that express channelrhodopsin-2 (ChR2) selectively in either the facial motor nerve (ChAT-ChR2 mice) or muscle (Emx1-ChR2 or ACTA1-ChR2 mice). We tracked changes in nerve and muscle function before and up to 14 days after nerve transection. Optogenetic 460 nm transdermal stimulation of the distal cut nerve showed that nerve degeneration progresses rapidly over 24 hours. In contrast, the whisker movements evoked by optogenetic muscle stimulation were up-regulated after denervation, including increased maximum protraction amplitude, increased sensitivity to low-intensity stimuli, and more sustained muscle contractions (reduced adaptation). Our results indicate that peripheral optogenetic stimulation is a promising technique for probing the timecourse of functional changes of both nerve and muscle, and holds potential for restoring movement after paralysis induced by nerve damage or motoneuron degeneration.

Near-infrared signals associated with electrical stimulation of peripheral nerves

NASA Astrophysics Data System (ADS)

Fantini, Sergio; Chen, Debbie K.; Martin, Jeffrey M.; Sassaroli, Angelo; Bergethon, Peter R.

2009-02-01

We report our studies on the optical signals measured non-invasively on electrically stimulated peripheral nerves. The stimulation consists of the delivery of 0.1 ms current pulses, below the threshold for triggering any visible motion, to a peripheral nerve in human subjects (we have studied the sural nerve and the median nerve). In response to electrical stimulation, we observe an optical signal that peaks at about 100 ms post-stimulus, on a much longer time scale than the few milliseconds duration of the electrical response, or sensory nerve action potential (SNAP). While the 100 ms optical signal we measured is not a direct optical signature of neural activation, it is nevertheless indicative of a mediated response to neural activation. We argue that this may provide information useful for understanding the origin of the fast optical signal (also on a 100 ms time scale) that has been measured non-invasively in the brain in response to cerebral activation. Furthermore, the optical response to peripheral nerve activation may be developed into a diagnostic tool for peripheral neuropathies, as suggested by the delayed optical signals (average peak time: 230 ms) measured in patients with diabetic neuropathy with respect to normal subjects (average peak time: 160 ms).

The First Experience of Triple Nerve Transfer in Proximal Radial Nerve Palsy.

PubMed

Emamhadi, Mohammadreza; Andalib, Sasan

2018-01-01

Injury to distal portion of posterior cord of brachial plexus leads to palsy of radial and axillary nerves. Symptoms are usually motor deficits of the deltoid muscle; triceps brachii muscle; and extensor muscles of the wrist, thumb, and fingers. Tendon transfers, nerve grafts, and nerve transfers are options for surgical treatment of proximal radial nerve palsy to restore some motor functions. Tendon transfer is painful, requires a long immobilization, and decreases donor muscle strength; nevertheless, nerve transfer produces promising outcomes. We present a patient with proximal radial nerve palsy following a blunt injury undergoing triple nerve transfer. The patient was involved in a motorcycle accident with complete palsy of the radial and axillary nerves. After 6 months, on admission, he showed spontaneous recovery of axillary nerve palsy, but radial nerve palsy remained. We performed triple nerve transfer, fascicle of ulnar nerve to long head of the triceps branch of radial nerve, flexor digitorum superficialis branch of median nerve to extensor carpi radialis brevis branch of radial nerve, and flexor carpi radialis branch of median nerve to posterior interosseous nerve, for restoration of elbow, wrist, and finger extensions, respectively. Our experience confirmed functional elbow, wrist, and finger extensions in the patient. Triple nerve transfer restores functions of the upper limb in patients with debilitating radial nerve palsy after blunt injuries. Copyright © 2017 Elsevier Inc. All rights reserved.

Attenuated baroreflex control of sympathetic nerve activity after cardiovascular deconditioning in rats

NASA Technical Reports Server (NTRS)

Moffitt, J. A.; Foley, C. M.; Schadt, J. C.; Laughlin, M. H.; Hasser, E. M.

1998-01-01

The effect of cardiovascular deconditioning on baroreflex control of the sympathetic nervous system was evaluated after 14 days of hindlimb unloading (HU) or the control condition. Rats were chronically instrumented with catheters and sympathetic nerve recording electrodes for measurement of mean arterial pressure (MAP) and heart rate (HR) and recording of lumbar (LSNA) or renal (RSNA) sympathetic nerve activity. Experiments were conducted 24 h after surgery, with the animals in a normal posture. Baroreflex function was assessed using a logistic function that related HR and LSNA or RSNA to MAP during infusion of phenylephrine and nitroprusside. Baroreflex influence on HR was not affected by HU. Maximum baroreflex-elicited LSNA was significantly reduced in HU rats (204 +/- 11.9 vs. 342 +/- 30.6% baseline LSNA), as was maximum reflex gain (-4.0 +/- 0.6 vs. -7.8 +/- 1.3 %LSNA/mmHg). Maximum baroreflex-elicited RSNA (259 +/- 10.8 vs. 453 +/- 28.0% baseline RSNA), minimum baroreflex-elicited RSNA (-2 +/- 2.8 vs. 13 +/- 4.5% baseline RSNA), and maximum gain (-5.8 +/- 0.5 vs. -13.6 +/- 3.1 %RSNA/mmHg) were significantly decreased in HU rats. Results demonstrate that baroreflex modulation of sympathetic nervous system activity is attenuated after cardiovascular deconditioning in rodents. Data suggest that alterations in the arterial baroreflex may contribute to orthostatic intolerance after a period of bedrest or spaceflight in humans.

Reflex regulation of airway sympathetic nerves in guinea-pigs

PubMed Central

Oh, Eun Joo; Mazzone, Stuart B; Canning, Brendan J; Weinreich, Daniel

2006-01-01

Sympathetic nerves innervate the airways of most species but their reflex regulation has been essentially unstudied. Here we demonstrate sympathetic nerve-mediated reflex relaxation of airway smooth muscle measured in situ in the guinea-pig trachea. Retrograde tracing, immunohistochemistry and electrophysiological analysis identified a population of substance P-containing capsaicin-sensitive spinal afferent neurones in the upper thoracic (T1–T4) dorsal root ganglia (DRG) that innervate the airways and lung. After bilateral vagotomy, atropine pretreatment and precontraction of the trachealis with histamine, nebulized capsaicin (10–60 μm) evoked a 63 ± 7% reversal of the histamine-induced contraction of the trachealis. Either the β-adrenoceptor antagonist propranolol (2 μm, administered directly to the trachea) or bilateral sympathetic nerve denervation of the trachea essentially abolished these reflexes (10 ± 9% and 6 ± 4% relaxations, respectively), suggesting that they were mediated primarily, if not exclusively, by sympathetic adrenergic nerve activation. Cutting the upper thoracic dorsal roots carrying the central processes of airway spinal afferents also markedly blocked the relaxations (9 ± 5% relaxation). Comparable inhibitory effects were observed following intravenous pretreatment with neurokinin receptor antagonists (3 ± 7% relaxations). These reflexes were not accompanied by consistent changes in heart rate or blood pressure. By contrast, stimulating the rostral cut ends of the cervical vagus nerves also evoked a sympathetic adrenergic nerve-mediated relaxation that were accompanied by marked alterations in blood pressure. The results indicate that the capsaicin-induced reflex-mediated relaxation of airway smooth muscle following vagotomy is mediated by sequential activation of tachykinin-containing spinal afferent and sympathetic efferent nerves innervating airways. This sympathetic nerve-mediated response may serve to oppose airway

Differentiation of vasoactive renal sympathetic nerve fibres.

PubMed

Dibona, G F

2000-01-01

Activation of renal sympathetic nerves produces marked changes in renal haemodynamics, tubular ion and water transport and renin secretion. This review examines information indicating that these effects are mediated by functionally specific groups of renal sympathetic nerve fibres separately innervating the renal vessels, tubules and juxtaglomerular granular cells.

Nerve ultrasound shows subclinical peripheral nerve involvement in neurofibromatosis type 2.

PubMed

Telleman, Johan A; Stellingwerff, Menno D; Brekelmans, Geert J; Visser, Leo H

2018-02-01

Neurofibromatosis type 2 (NF2) is mainly associated with central nervous system (CNS) tumors. Peripheral nerve involvement is described in symptomatic patients, but evidence of subclinical peripheral nerve involvement is scarce. We conducted a cross-sectional pilot study in 2 asymptomatic and 3 minimally symptomatic patients with NF2 to detect subclinical peripheral nerve involvement. Patients underwent clinical examination, nerve conduction studies (NCS), and high-resolution ultrasonography (HRUS). A total of 30 schwannomas were found, divided over 20 nerve segments (33.9% of all investigated nerve segments). All patients had at least 1 schwannoma. Schwannomas were identified with HRUS in 37% of clinically unaffected nerve segments and 50% of nerve segments with normal NCS findings. HRUS shows frequent subclinical peripheral nerve involvement in NF2. Clinicians should consider peripheral nerve involvement as a cause of weakness and sensory loss in the extremities in patients with this disease. Muscle Nerve 57: 312-316, 2018. © 2017 Wiley Periodicals, Inc.

Synthesis and Biological Evaluation of 4-Sulfamoylphenyl/Sulfocoumarin Carboxamides as Selective Inhibitors of Carbonic Anhydrase Isoforms hCA II, IX, and XII.

PubMed

Angapelly, Srinivas; Angeli, Andrea; Khan, Arbaj Jabbar; Sri Ramya, P V; Supuran, Claudiu T; Arifuddin, Mohammed

2018-04-19

With the aim to develop potent and selective human carbonic anhydrase inhibitors (hCAIs), we synthesized 4-sulfamoylphenyl/sulfocoumarin benzamides (series 5 a-r and series 7 a-q) and evaluated their inhibition profiles against five isoforms of the zinc-containing human carbonic anhydrase (hCA, EC 4.2.1.1): cytosolic hCA I and II, and the transmembrane isozymes hCA IV, IX, and XII. Compounds 5 a-r were found to selectively inhibit hCA II in the nanomolar range, while being less effective against the other hCA isoforms. As noted from the literature, sulfocoumarin (1,2-benzoxathiine 2,2-dioxide) acts as a "prodrug" inhibitor and is hydrolyzed by the esterase activity of hCA to form 2-hydroxyphenylvinylsulfonic acid, which thereafter binds to the enzyme in a manner similar to that of coumarins and sulfoxocoumarins. All these sulfocoumarins (compounds 7 a-q) were found to be very weak or ineffective as inhibitors of the housekeeping off-target hCA isoforms I and II, and effectively inhibited the transmembrane tumor-associated isoforms IX and XII in the high nanomolar to micromolar ranges. Further structural modifications of these molecules could be useful for the development of effective hCA inhibitors used for the treatment of glaucoma, epilepsy, and cancer. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A rare case of recurrent vasodepressive attacks of 2-hours duration: analysis of the mechanism by muscle sympathetic nerve activity recording.

PubMed

Yatomi, A; Iguchi, A; Uemura, K; Sakamoto, N; Iwase, S; Mano, T

1989-03-01

Muscle sympathetic nerve activity was recorded in a 57-year-old male patient suffering from severe hypotensive attacks with bradycardia for 10 years. Continuous blood pressure recording demonstrated frequent drastic falls in pressure. Disappearance and reappearance of muscle sympathetic nerve activity coincided with the onset and termination of attacks. Awakening from sleep or emotional and/or cardiovascular stress seems to trigger hypotension. Cardiac pacemaker was not useful in limiting the attack, because right ventricular pacing caused abrupt falls in both blood pressure and heart rate.

Activity Based Protein Profiling Leads to Identification of Novel Protein Targets for Nerve Agent VX.

PubMed

Carmany, Dan; Walz, Andrew J; Hsu, Fu-Lian; Benton, Bernard; Burnett, David; Gibbons, Jennifer; Noort, Daan; Glaros, Trevor; Sekowski, Jennifer W

2017-04-17

Organophosphorus (OP) nerve agents continue to be a threat at home and abroad during the war against terrorism. Human exposure to nerve agents such as VX results in a cascade of toxic effects relative to the exposure level including ocular miosis, excessive secretions, convulsions, seizures, and death. The primary mechanism behind these overt symptoms is the disruption of cholinergic pathways. While much is known about the primary toxicity mechanisms of nerve agents, there remains a paucity of information regarding impacts on other pathways and systemic effects. These are important for establishing a comprehensive understanding of the toxic mechanisms of OP nerve agents. To identify novel proteins that interact with VX, and that may give insight into these other mechanisms, we used activity-based protein profiling (ABPP) employing a novel VX-probe on lysates from rat heart, liver, kidney, diaphragm, and brain tissue. By making use of a biotin linked VX-probe, proteins covalently bound by the probe were isolated and enriched using streptavidin beads. The proteins were then digested, labeled with isobarically distinct tandem mass tag (TMT) labels, and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Quantitative analysis identified 132 bound proteins, with many proteins found in multiple tissues. As with previously published ABPP OP work, monoacylglycerol lipase associated proteins and fatty acid amide hydrolase (FAAH) were shown to be targets of VX. In addition to these two and other predicted neurotransmitter-related proteins, a number of proteins involved with energy metabolism were identified. Four of these enzymes, mitochondrial isocitrate dehydrogenase 2 (IDH2), isocitrate dehydrogenase 3 (IDH3), malate dehydrogenase (MDH), and succinyl CoA (SCS) ligase, were assayed for VX inhibition. Only IDH2 NADP+ activity was shown to be inhibited directly. This result is consistent with other work reporting animals exposed to OP compounds exhibit

Electromechanical Nerve Stimulator

NASA Technical Reports Server (NTRS)

Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.

1993-01-01

Nerve stimulator applies and/or measures precisely controlled force and/or displacement to nerve so response of nerve measured. Consists of three major components connected in tandem: miniature probe with spherical tip; transducer; and actuator. Probe applies force to nerve, transducer measures force and sends feedback signal to control circuitry, and actuator positions force transducer and probe. Separate box houses control circuits and panel. Operator uses panel to select operating mode and parameters. Stimulator used in research to characterize behavior of nerve under various conditions of temperature, anesthesia, ventilation, and prior damage to nerve. Also used clinically to assess damage to nerve from disease or accident and to monitor response of nerve during surgery.

Tissue-engineered spiral nerve guidance conduit for peripheral nerve regeneration.

PubMed

Chang, Wei; Shah, Munish B; Lee, Paul; Yu, Xiaojun

2018-06-01

Recently in peripheral nerve regeneration, preclinical studies have shown that the use of nerve guidance conduits (NGCs) with multiple longitudinally channels and intra-luminal topography enhance the functional outcomes when bridging a nerve gap caused by traumatic injury. These features not only provide guidance cues for regenerating nerve, but also become the essential approaches for developing a novel NGC. In this study, a novel spiral NGC with aligned nanofibers and wrapped with an outer nanofibrous tube was first developed and investigated. Using the common rat sciatic 10-mm nerve defect model, the in vivo study showed that a novel spiral NGC (with and without inner nanofibers) increased the successful rate of nerve regeneration after 6 weeks recovery. Substantial improvements in nerve regeneration were achieved by combining the spiral NGC with inner nanofibers and outer nanofibrous tube, based on the results of walking track analysis, electrophysiology, nerve histological assessment, and gastrocnemius muscle measurement. This demonstrated that the novel spiral NGC with inner aligned nanofibers and wrapped with an outer nanofibrous tube provided a better environment for peripheral nerve regeneration than standard tubular NGCs. Results from this study will benefit for future NGC design to optimize tissue-engineering strategies for peripheral nerve regeneration. We developed a novel spiral nerve guidance conduit (NGC) with coated aligned nanofibers. The spiral structure increases surface area by 4.5 fold relative to a tubular NGC. Furthermore, the aligned nanofibers was coated on the spiral walls, providing cues for guiding neurite extension. Finally, the outside of spiral NGC was wrapped with randomly nanofibers to enhance mechanical strength that can stabilize the spiral NGC. Our nerve histological data have shown that the spiral NGC had 50% more myelinated axons than a tubular structure for nerve regeneration across a 10 mm gap in a rat sciatic nerve

Direct Administration of Nerve-Specific Contrast to Improve Nerve Sparing Radical Prostatectomy

PubMed Central

Barth, Connor W.; Gibbs, Summer L.

2017-01-01

Nerve damage remains a major morbidity following nerve sparing radical prostatectomy, significantly affecting quality of life post-surgery. Nerve-specific fluorescence guided surgery offers a potential solution by enhancing nerve visualization intraoperatively. However, the prostate is highly innervated and only the cavernous nerve structures require preservation to maintain continence and potency. Systemic administration of a nerve-specific fluorophore would lower nerve signal to background ratio (SBR) in vital nerve structures, making them difficult to distinguish from all nervous tissue in the pelvic region. A direct administration methodology to enable selective nerve highlighting for enhanced nerve SBR in a specific nerve structure has been developed herein. The direct administration methodology demonstrated equivalent nerve-specific contrast to systemic administration at optimal exposure times. However, the direct administration methodology provided a brighter fluorescent nerve signal, facilitating nerve-specific fluorescence imaging at video rate, which was not possible following systemic administration. Additionally, the direct administration methodology required a significantly lower fluorophore dose than systemic administration, that when scaled to a human dose falls within the microdosing range. Furthermore, a dual fluorophore tissue staining method was developed that alleviates fluorescence background signal from adipose tissue accumulation using a spectrally distinct adipose tissue specific fluorophore. These results validate the use of the direct administration methodology for specific nerve visualization with fluorescence image-guided surgery, which would improve vital nerve structure identification and visualization during nerve sparing radical prostatectomy. PMID:28255352

Direct Administration of Nerve-Specific Contrast to Improve Nerve Sparing Radical Prostatectomy.

PubMed

Barth, Connor W; Gibbs, Summer L

2017-01-01

Nerve damage remains a major morbidity following nerve sparing radical prostatectomy, significantly affecting quality of life post-surgery. Nerve-specific fluorescence guided surgery offers a potential solution by enhancing nerve visualization intraoperatively. However, the prostate is highly innervated and only the cavernous nerve structures require preservation to maintain continence and potency. Systemic administration of a nerve-specific fluorophore would lower nerve signal to background ratio (SBR) in vital nerve structures, making them difficult to distinguish from all nervous tissue in the pelvic region. A direct administration methodology to enable selective nerve highlighting for enhanced nerve SBR in a specific nerve structure has been developed herein. The direct administration methodology demonstrated equivalent nerve-specific contrast to systemic administration at optimal exposure times. However, the direct administration methodology provided a brighter fluorescent nerve signal, facilitating nerve-specific fluorescence imaging at video rate, which was not possible following systemic administration. Additionally, the direct administration methodology required a significantly lower fluorophore dose than systemic administration, that when scaled to a human dose falls within the microdosing range. Furthermore, a dual fluorophore tissue staining method was developed that alleviates fluorescence background signal from adipose tissue accumulation using a spectrally distinct adipose tissue specific fluorophore. These results validate the use of the direct administration methodology for specific nerve visualization with fluorescence image-guided surgery, which would improve vital nerve structure identification and visualization during nerve sparing radical prostatectomy.

Nerve regeneration in nerve grafts conditioned by vibration exposure.

PubMed

Bergman, S; Widerberg, A; Danielsen, N; Lundborg, G; Dahlin, L B

1995-01-01

Regeneration distances were studied in nerves from vibration-exposed limbs. One hind limb of anaesthetized rats was attached to a vibration exciter and exposed to vibration (80 Hz/32 m/s2) for 5 h/day for 2 or 5 days. Seven days after the latest vibration period a 10-mm long nerve graft was taken from the vibrated sciatic nerve and sutured into a corresponding defect in the con-tralateral sciatic nerve and vice versa, thereby creating two different models within the same animal: (i) regeneration from a freshly transected unvibrated nerve into a vibrated graft and (ii) regeneration from a vibrated nerve into a fresh nerve graft (vibrated recipient side). Four, 6 or 8 days postoperatively (p.o.) the distances achieved by the regenerating axons were determined using the pinch reflex test. Two days of vibration did not influence the regeneration, but 5 days of vibration reduced the initial delay period and a slight reduction of regeneration rate was observed. After 5 days of vibration an increased regeneration distance was observed in both models at day 4 p.o. and at day 6 p.o. in vibrated grafts. This study demonstrates that vibration can condition peripheral nerves and this may be caused by local changes in the peripheral nerve trunk and in the neuron itself.

The role of great auricular-facial nerve neurorrhaphy in facial nerve damage.

PubMed

Sun, Yan; Liu, Limei; Han, Yuechen; Xu, Lei; Zhang, Daogong; Wang, Haibo

2015-01-01

Facial nerve is easy to be damaged, and there are many reconstructive methods for facial nerve reconstructive, such as facial nerve end to end anastomosis, the great auricular nerve graft, the sural nerve graft, or hypoglossal-facial nerve anastomosis. However, there is still little study about great auricular-facial nerve neurorrhaphy. The aim of the present study was to identify the role of great auricular-facial nerve neurorrhaphy and the mechanism. Rat models of facial nerve cut (FC), facial nerve end to end anastomosis (FF), facial-great auricular neurorrhaphy (FG), and control (Ctrl) were established. Apex nasi amesiality observation, electrophysiology and immunofluorescence assays were employed to investigate the function and mechanism. In apex nasi amesiality observation, it was found apex nasi amesiality of FG group was partly recovered. Additionally, electrophysiology and immunofluorescence assays revealed that facial-great auricular neurorrhaphy could transfer nerve impulse and express AChR which was better than facial nerve cut and worse than facial nerve end to end anastomosis. The present study indicated that great auricular-facial nerve neurorrhaphy is a substantial solution for facial lesion repair, as it is efficiently preventing facial muscles atrophy by generating neurotransmitter like ACh.

Assessment of nerve regeneration across nerve allografts treated with tacrolimus.

PubMed

Haisheng, Han; Songjie, Zuo; Xin, Li

2008-01-01

Although regeneration of nerve allotransplant is a major concern in the clinic, there have been few papers quantitatively assessing functional recovery of animals' nerve allografts in the long term. In this study, functional recovery, histopathological study, and immunohistochemistry changes of rat nerve allograft with FK506 were investigated up to 12 weeks without slaughtering. C57 and SD rats were used for transplantation. The donor's nerve was sliced and transplanted into the recipient. The sciatic nerve was epineurally sutured with 10-0 nylon. In total, 30 models of transplantation were performed and divided into 3 groups that were either treated with FK506 or not. Functional recovery of the grafted nerve was serially assessed by the pin click test, walking track analysis and electrophysiological evaluations. A histopathological study and immunohistochemistry study were done in the all of the models. Nerve allografts treated with FK506 have no immune rejection through 12 weeks. Sensibility had similarly improved in both isografts and allografts. There has been no difference in each graft. Walk track analysis demonstrates significant recovery of motor function of the nerve graft. No histological results of difference were found up to 12 weeks in each graft. In the rodent nerve graft model, FK506 prevented nerve allograft rejection across a major histocompatibility barrier. Sensory recovery seems to be superior to motor function. Nerve isograft and allograft treated with FK506 have no significant difference in function recovery, histopathological result, and immunohistochemistry changes.

Cytokine and estrogen stimulation of endothelial cells augments activation of the prekallikrein-high molecular weight kininogen complex: Implications for hereditary angioedema.

PubMed

Joseph, Kusumam; Tholanikunnel, Baby G; Kaplan, Allen P

2017-07-01

When the prekallikrein-high molecular weight kininogen complex is bound to endothelial cells, prekallikrein is stoichiometrically converted to kallikrein because of release of heat shock protein-90 (Hsp90). Although bradykinin formation is typically initiated by factor XII autoactivation, it is also possible to activate factor XII either by kallikrein, thus formed, or by plasmin. Because attacks of hereditary angioedema can be related to infection and/or exposure to estrogen, we questioned whether estrogen or cytokine stimulation of endothelial cells could augment release of Hsp90 and prekallikrein activation. We also tested release of profibrinolytic enzymes, urokinase, and tissue plasminogen activator (TPA) as a source for plasmin formation. Cells were stimulated with agonists, and secretion of Hsp90, urokinase, and TPA was measured in the culture supernatants by ELISA. Activation of the prekallikrein-HK complex was measured by using pro-phe-arg-p-nitroanilide reflecting kallikrein formation. Hsp90 release was stimulated with optimal doses of estradiol, IL-1, and TNF-α (10 ng/mL) from 15 minutes to 120 minutes. TPA release was not augmented by any of the agonists tested but urokinase was released by IL-1, TNF-α, and thrombin (positive control), but not estrogen. Augmented activation of the prekallikrein-HK complex to generate kallikrein was seen with each agonist that releases Hsp90. Addition of 0.1% factor XII relative to prekallikrein-HK leads to rapid formation of kallikrein; factor XII alone does not autoactivate. IL-1, TNF-α, and estrogen stimulate release of Hsp90 and augment activation of the prekallikrein-HK complex to generate kallikrein and bradykinin. IL-1 and TNF-α stimulate release of urokinase, which can convert plasminogen to plasmin and represents a possible source for plasmin generation in all types of hereditary angioedema, but particularly hereditary angioedema with normal C1 inhibitor with a factor XII mutation. Both kallikrein and

Shock wave treatment improves nerve regeneration in the rat.

PubMed

Mense, Siegfried; Hoheisel, Ulrich

2013-05-01

The aims of the experiments were to: (1) determine whether low-energy shock wave treatment accelerates the recovery of muscle sensitivity and functionality after a nerve lesion; and (2) assess the effect of shock waves on the regeneration of injured nerve fibers. After compression of a muscle nerve in rats the effects of shock wave treatment on the sequelae of the lesion were tested. In non-anesthetized animals, pressure pain thresholds and exploratory activity were determined. The influence of the treatment on the distance of nerve regeneration was studied in immunohistochemical experiments. Both behavioral and immunohistochemical data show that shock wave treatment accelerates the recovery of muscle sensitivity and functionality and promotes regeneration of injured nerve fibers. Treatment with focused shock waves induces an improvement of nerve regeneration in a rodent model of nerve compression. Copyright © 2012 Wiley Periodicals, Inc.

Nanofiber Nerve Guide for Peripheral Nerve Repair and Regeneration

DTIC Science & Technology

2016-04-01

faster regeneration and functional recovery. Peripheral nerve injury is a common complication of complex tissue trauma and often results in significant...having poor regeneration overall, the areas of regenerating nerve tissue could often be found in sections of the nerve guide where luminal spaces of...conducted in this Aim also provided important insight into the NGC design parameters necessary to allow for maximum nerve tissue ingrowth and regeneration

The role of great auricular-facial nerve neurorrhaphy in facial nerve damage

PubMed Central

Sun, Yan; Liu, Limei; Han, Yuechen; Xu, Lei; Zhang, Daogong; Wang, Haibo

2015-01-01

Background: Facial nerve is easy to be damaged, and there are many reconstructive methods for facial nerve reconstructive, such as facial nerve end to end anastomosis, the great auricular nerve graft, the sural nerve graft, or hypoglossal-facial nerve anastomosis. However, there is still little study about great auricular-facial nerve neurorrhaphy. The aim of the present study was to identify the role of great auricular-facial nerve neurorrhaphy and the mechanism. Methods: Rat models of facial nerve cut (FC), facial nerve end to end anastomosis (FF), facial-great auricular neurorrhaphy (FG), and control (Ctrl) were established. Apex nasi amesiality observation, electrophysiology and immunofluorescence assays were employed to investigate the function and mechanism. Results: In apex nasi amesiality observation, it was found apex nasi amesiality of FG group was partly recovered. Additionally, electrophysiology and immunofluorescence assays revealed that facial-great auricular neurorrhaphy could transfer nerve impulse and express AChR which was better than facial nerve cut and worse than facial nerve end to end anastomosis. Conclusions: The present study indicated that great auricular-facial nerve neurorrhaphy is a substantial solution for facial lesion repair, as it is efficiently preventing facial muscles atrophy by generating neurotransmitter like ACh. PMID:26550216

Pathotyping and Phylogenetic Characterization of Newcastle Disease Viruses Isolated in Peru: Defining Two Novel Subgenotypes Within Genotype XII.

PubMed

Chumbe, Ana; Izquierdo-Lara, Ray; Tataje, Luis; Gonzalez, Rosa; Cribillero, Giovana; González, Armando E; Fernández-Díaz, Manolo; Icochea, Eliana

2017-03-01

Infections of poultry with virulent strains of avian paramyxovirus 1 (APMV-1), also known as Newcastle disease viruses (NDVs), cause Newcastle disease (ND). This highly contagious disease affects poultry and many other species of birds worldwide. In countries where the disease is prevalent, constant monitoring and characterization of isolates causing outbreaks are necessary. In this study, we report the results of pathogenicity testing and phylogenetic analyses of seven NDVs isolated from several regions of Peru between 2004 and 2015. Six viruses had intracerebral pathogenicity indices (ICPIs) of between 1.75 and 1.88, corresponding to a velogenic pathotype. The remaining virus had an ICPI of 0.00, corresponding to a lentogenic pathotype. These results were consistent with amino acid sequences at the fusion protein (F) cleavage site. All velogenic isolates had the polybasic amino acid sequence 112 RRQKR↓F 117 at the F cleavage site. Phylogenetic analyses of complete F gene sequences showed that all isolates are classified in class II of APMV-1. The velogenic viruses are classified in genotype XII, while the lentogenic virus is classified in genotype II, closely related to the LaSota vaccine strain. Moreover, tree topology, bootstrap values, and genetic distances observed within genotype XII resulted in the identification of novel subgenotypes XIIa (in South America) and XIIb (in China) and possibly two clades within genotype XIIa. All velogenic Peruvian viruses belonged to subgenotype XIIa. Overall, our results confirm the presence of genotype XII in Peru and suggest that it is the prevalent genotype currently circulating in our country. The phylogenetic characterization of these isolates helps to characterize the evolution of NDV and may help with the development of vaccines specific to our regional necessities.

Muscle sympathetic nerve responses to passive and active one-legged cycling: insights into the contributions of central command.

PubMed

Doherty, Connor J; Incognito, Anthony V; Notay, Karambir; Burns, Matthew J; Slysz, Joshua T; Seed, Jeremy D; Nardone, Massimo; Burr, Jamie F; Millar, Philip J

2018-01-01

The contribution of central command to the peripheral vasoconstrictor response during exercise has been investigated using primarily handgrip exercise. The purpose of the present study was to compare muscle sympathetic nerve activity (MSNA) responses during passive (involuntary) and active (voluntary) zero-load cycling to gain insights into the effects of central command on sympathetic outflow during dynamic exercise. Hemodynamic measurements and contralateral leg MSNA (microneurography) data were collected in 18 young healthy participants at rest and during 2 min of passive and active zero-load one-legged cycling. Arterial baroreflex control of MSNA burst occurrence and burst area were calculated separately in the time domain. Blood pressure and stroke volume increased during exercise ( P < 0.0001) but were not different between passive and active cycling ( P > 0.05). In contrast, heart rate, cardiac output, and total vascular conductance were greater during the first and second minute of active cycling ( P < 0.001). MSNA burst frequency and incidence decreased during passive and active cycling ( P < 0.0001), but no differences were detected between exercise modes ( P > 0.05). Reductions in total MSNA were attenuated during the first ( P < 0.0001) and second ( P = 0.0004) minute of active compared with passive cycling, in concert with increased MSNA burst amplitude ( P = 0.02 and P = 0.005, respectively). The sensitivity of arterial baroreflex control of MSNA burst occurrence was lower during active than passive cycling ( P = 0.01), while control of MSNA burst strength was unchanged ( P > 0.05). These results suggest that central feedforward mechanisms are involved primarily in modulating the strength, but not the occurrence, of a sympathetic burst during low-intensity dynamic leg exercise. NEW & NOTEWORTHY Muscle sympathetic nerve activity burst frequency decreased equally during passive and active cycling, but reductions in total muscle sympathetic nerve

Influences of casein hydrolysate ingestion on cerebral activity, autonomic nerve activity, and anxiety.

PubMed

Nakamura, Hirohiko; Iwamoto, Mario; Washida, Kenji; Sekine, Kazunori; Takase, Mitsunori; Park, Bum-Jin; Morikawa, Takeshi; Miyazaki, Yoshifumi

2010-01-01

This study examined the influences of the oral ingestion of casein hydrolysate from bovine milk at rest physiologically and psychologically. Eleven male university students were given a casein hydrolysate drink (H) or a maltitol drink as a control (C) in a crossover study. Just before and one hour after ingestion of each drink, the total-hemoglobin (tHb) concentrations at ten points of the prefrontal cortex to evaluate cerebral activity, and heart rate variability (HRV) to evaluate autonomic nerve activity through spectral analysis were measured as physiological indicators. The Japanese version of the State--Trait Anxiety Inventory--state anxiety (STAI-s) score was also used, as a psychological indicator. In comparison between H and C ingestion, a significant difference is observed only in tHb concentrations at one of ten points. At this point, the change in tHb concentration was lower after H ingestion compared to C ingestion. And in comparison between before and after ingestion of each drink, a significant increase in tHb concentration at two points after C ingestion, a significant increase in parasympathetic activity and decrease in sympathetic activity after H ingestion, and a significant decrease in STAI-s score in H ingestion were observed. These results suggest that ingestion of the casein hydrolysate may keep prefrontal cortex activity stable while maltitol ingestion partially increases the activity. Moreover, there is a possibility that casein hydrolysate might decrease sympathetic activity, increase parasympathetic activity, and lower anxiety. We conclude that the bovine milk casein hydrolysate may have more relaxing effects than maltitol.

Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophosphate nerve agent exposure

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

Halbrook, R.S.; Shugart, L.R.; Watson, A.P.

1992-09-01

A biomonitoring protocol, using blood cholinesterase (ChE) activity in livestock as a monitor of potential organophosphate nerve agent exposure during the planned destruction of US unitary chemical warfare agent stockpiles, is described. The experimental design included analysis of blood ChE activity in individual healthy sheep, horses, and dairy and beef cattle during a 10- to 12-month period. Castrated and sexually intact males, pregnant and lactating females, and adult and immature animals were examined through at least one reproductive cycle. The same animals were used throughout the period of observation and were not exposed to ChE-inhibiting organophosphate or carbamate compounds. Amore » framework for an effective biomonitoring protocol within a monitoring area includes establishing individual baseline blood ChE activity for a sentinel group of 6 animals on the bases of blood samples collected over a 6-month period, monthly collection of blood samples for ChE-activity determination during monitoring, and selection of adult animals as sentinels. Exposure to ChE-inhibiting compounds would be suspected when all blood ChE activity of all animals within the sentinel group are decreased greater than 20% from their own baseline value. Sentinel species selection is primarily a logistical and operational concern; however, sheep appear to be the species of choice because within-individual baseline ChE activity and among age and gender group ChE activity in sheep had the least variability, compared with data from other species. This protocol provides an effective and efficient means for detecting abnormal depressions in blood ChE activity in livestock and can serve as a valuable indicator of the extent of actual plume movement and/or deposition in the event of organophosphate nerve agent release.« less

Relationship between size and latency of action potentials in human muscle sympathetic nerve activity.

PubMed

Salmanpour, Aryan; Brown, Lyndon J; Steinback, Craig D; Usselman, Charlotte W; Goswami, Ruma; Shoemaker, J Kevin

2011-06-01

We employed a novel action potential detection and classification technique to study the relationship between the recruitment of sympathetic action potentials (i.e., neurons) and the size of integrated sympathetic bursts in human muscle sympathetic nerve activity (MSNA). Multifiber postganglionic sympathetic nerve activity from the common fibular nerve was collected using microneurography in 10 healthy subjects at rest and during activation of sympathetic outflow using lower body negative pressure (LBNP). Burst occurrence increased with LBNP. Integrated burst strength (size) varied from 0.22 ± 0.07 V at rest to 0.28 ± 0.09 V during LBNP. Sympathetic burst size (i.e., peak height) was directly related to the number of action potentials within a sympathetic burst both at baseline (r = 0.75 ± 0.13; P < 0.001) and LBNP (r = 0.75 ± 0.12; P < 0.001). Also, the amplitude of detected action potentials within sympathetic bursts was directly related to the increased burst size at both baseline (r = 0.59 ± 0.16; P < 0.001) and LBNP (r = 0.61 ± 0.12; P < 0.001). In addition, the number of detected action potentials and the number of distinct action potential clusters within a given sympathetic burst were correlated at baseline (r = 0.7 ± 0.1; P < 0.001) and during LBNP (r = 0.74 ± 0.03; P < 0.001). Furthermore, action potential latency (i.e., an inverse index of neural conduction velocity) was decreased as a function of action potential size at baseline and LBNP. LBNP did not change the number of action potentials and unique clusters per sympathetic burst. It was concluded that there exists a hierarchical pattern of recruitment of additional faster conducting neurons of larger amplitude as the sympathetic bursts become stronger (i.e., larger amplitude bursts). This fundamental pattern was evident at rest and was not altered by the level of baroreceptor unloading applied in this study.

Cranial nerve monitoring during subpial dissection in temporomesial surgery.

PubMed

Ortler, Martin; Fiegele, Thomas; Walser, Gerald; Trinka, Eugen; Eisner, Wilhelm

2011-06-01

Cranial nerves (CNs) crossing between the brainstem and skull base at the level of the tentorial hiatus may be at risk in temporomesial surgery involving subpial dissection and/or tumorous growth leading to distorted anatomy. We aimed to identify the surgical steps most likely to result in CN damage in this type of surgery. Electromyographic responses obtained with standard neuromonitoring techniques and a continuous free-running EMG were graded as either contact activity or pathological spontaneous activity (PSA) during subpial resection of temporomesial structures in 16 selective amygdalohippocampectomy cases. Integrity of peripheral motor axons was tested by transpial/transarachnoidal electrical stimulation while recording compound muscle action potentials from distal muscle(s). Continuous EMG showed pathological activity in five (31.2%) patients. Nine events with PSA (slight activity, n = 8; strong temporary activity, n = 1) were recorded. The oculomotor nerve was involved three times, the trochlear nerve twice, the facial nerve once, and all monitored nerves on three occasions. Surgical maneuvers associated with PSA were the resection of deep parts of the hippocampus and parahippocampal gyrus (CN IV, twice; CN III, once), lining with or removing cotton patties from the resection cavity (III, twice; all channels, once) and indirect exertion of tension on the intact pia/arachnoid of the uncal region while mobilizing the hippocampus and parahippocampal gyrus en bloc (all channels, once; III, once). CMAPs were observed at 0.3 mA in two patients and at 0.6 mA in one patient, and without registering the exact amount of intensity in three patients. The most dangerous steps leading to cranial nerve damage during mesial temporal lobe surgery are the final stages of the intervention while the resection is being completed in the deep posterior part and the resection cavity is being lined with patties. Distant traction may act on nerves crossing the tentorial

Characterization of Macrophage/Microglial Activation and Effect of Photobiomodulation in the Spared Nerve Injury Model of Neuropathic Pain.

PubMed

Kobiela Ketz, Ann; Byrnes, Kimberly R; Grunberg, Neil E; Kasper, Christine E; Osborne, Lisa; Pryor, Brian; Tosini, Nicholas L; Wu, Xingjia; Anders, Juanita J

2017-05-01

Neuropathic pain is common and debilitating with limited effective treatments. Macrophage/microglial activation along ascending somatosensory pathways following peripheral nerve injury facilitates neuropathic pain. However, polarization of macrophages/microglia in neuropathic pain is not well understood. Photobiomodulation treatment has been used to decrease neuropathic pain, has anti-inflammatory effects in spinal injury and wound healing models, and modulates microglial polarization in vitro. Our aim was to characterize macrophage/microglia response after peripheral nerve injury and modulate the response with photobiomodulation. Adult male Sprague-Dawley rats were randomly assigned to sham (N = 13), spared nerve injury (N = 13), or injury + photobiomodulation treatment groups (N = 7). Mechanical hypersensitivity was assessed with electronic von Frey. Photobiomodulation (980 nm) was applied to affected hind paw (output power 1 W, 20 s, 41cm above skin, power density 43.25 mW/cm 2 , dose 20 J), dorsal root ganglia (output power 4.5W, 19s, in skin contact, power density 43.25 mW/cm 2 , dose 85.5 J), and spinal cord regions (output power 1.5 W, 19s, in skin contact, power density 43.25 mW/cm 2 , dose 28.5 J) every other day from day 7-30 post-operatively. Immunohistochemistry characterized macrophage/microglial activation. Injured groups demonstrated mechanical hypersensitivity 1-30 days post-operatively. Photobiomodulation-treated animals began to recover after two treatments; at day 26, mechanical sensitivity reached baseline. Peripheral nerve injury caused region-specific macrophages/microglia activation along spinothalamic and dorsal-column medial lemniscus pathways. A pro-inflammatory microglial marker was expressed in the spinal cord of injured rats compared to photobiomodulation-treated and sham group. Photobiomodulation-treated dorsal root ganglion macrophages expressed anti-inflammatory markers. Photobiomodulation effectively reduced

Nerve Blocks

MedlinePlus

... turn off" a pain signal along a specific distribution of nerve. Imaging guidance may be used to place the needle in the most appropriate location for maximum benefit. A nerve block may allow a damaged nerve time to heal, provide temporary pain relief and help ...

Hydrogel derived from porcine decellularized nerve tissue as a promising biomaterial for repairing peripheral nerve defects.

PubMed

Lin, Tao; Liu, Sheng; Chen, Shihao; Qiu, Shuai; Rao, Zilong; Liu, Jianghui; Zhu, Shuang; Yan, Liwei; Mao, Haiquan; Zhu, Qingtang; Quan, Daping; Liu, Xiaolin

2018-06-01

Decellularized matrix hydrogels derived from tissues or organs have been used for tissue repair due to their biocompatibility, tunability, and tissue-specific extracellular matrix (ECM) components. However, the preparation of decellularized peripheral nerve matrix hydrogels and their use to repair nerve defects have not been reported. Here, we developed a hydrogel from porcine decellularized nerve matrix (pDNM-G), which was confirmed to have minimal DNA content and retain collagen and glycosaminoglycans content, thereby allowing gelatinization. The pDNM-G exhibited a nanofibrous structure similar to that of natural ECM, and a ∼280-Pa storage modulus at 10 mg/mL similar to that of native neural tissues. Western blot and liquid chromatography tandem mass spectrometry analysis revealed that the pDNM-G consisted mostly of ECM proteins and contained primary ECM-related proteins, including fibronectin and collagen I and IV). In vitro experiments showed that pDNM-G supported Schwann cell proliferation and preserved cell morphology. Additionally, in a 15-mm rat sciatic nerve defect model, pDNM-G was combined with electrospun poly(lactic-acid)-co-poly(trimethylene-carbonate)conduits to bridge the defect, which did not elicit an adverse immune response and promoted the activation of M2 macrophages associated with a constructive remodeling response. Morphological analyses and electrophysiological and functional examinations revealed that the regenerative outcomes achieved by pDNM-G were superior to those by empty conduits and closed to those using rat decellularized nerve matrix allograft scaffolds. These findings indicated that pDNM-G, with its preserved ECM composition and nanofibrous structure, represents a promising biomaterial for peripheral nerve regeneration. Decellularized nerve allografts have been widely used to treat peripheral nerve injury. However, given their limited availability and lack of bioactive factors, efforts have been made to improve the efficacy

Sleep deprivation aggravates median nerve injury-induced neuropathic pain and enhances microglial activation by suppressing melatonin secretion.

PubMed

Huang, Chun-Ta; Chiang, Rayleigh Ping-Ying; Chen, Chih-Li; Tsai, Yi-Ju

2014-09-01

Sleep deprivation is common in patients with neuropathic pain, but the effect of sleep deprivation on pathological pain remains uncertain. This study investigated whether sleep deprivation aggravates neuropathic symptoms and enhances microglial activation in the cuneate nucleus (CN) in a median nerve chronic constriction injury (CCI) model. Also, we assessed if melatonin supplements during the sleep deprived period attenuates these effects. Rats were subjected to sleep deprivation for 3 days by the disc-on-water method either before or after CCI. In the melatonin treatment group, CCI rats received melatonin supplements at doses of 37.5, 75, 150, or 300 mg/kg during sleep deprivation. Melatonin was administered at 23:00 once a day. Male Sprague-Dawley rats, weighing 180-250 g (n = 190), were used. Seven days after CCI, behavioral testing was conducted, and immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analyses of microglial activation and measurements of proinflammatory cytokines. In rats who underwent post-CCI sleep deprivation, microglia were more profoundly activated and neuropathic pain was worse than those receiving pre-CCI sleep deprivation. During the sleep deprived period, serum melatonin levels were low over the 24-h period. Administration of melatonin to CCI rats with sleep deprivation significantly attenuated activation of microglia and development of neuropathic pain, and markedly decreased concentrations of proinflammatory cytokines. Sleep deprivation makes rats more vulnerable to nerve injury-induced neuropathic pain, probably because of associated lower melatonin levels. Melatonin supplements to restore a circadian variation in melatonin concentrations during the sleep deprived period could alleviate nerve injury-induced behavioral hypersensitivity. © 2014 Associated Professional Sleep Societies, LLC.

Fibrolipomatous hamartoma of the inferior calcaneal nerve (Baxter nerve).

PubMed

Zeng, Rong; Frederick-Dyer, Katherine; Ferguson, N Lynn; Lewis, James; Fu, Yitong

2012-09-01

Fibrolipomatous hamartoma (FLH) is a rare, benign lesion of the peripheral nerves most frequently involving the median nerve and its digital branches (80 %). Pathognomonic MR features of FLH such as coaxial-cable-like appearance on axial planes and a spaghetti-like appearance on coronal planes have been described by Marom and Helms, obviating the need for diagnostic biopsy. We present a case of fibrolipomatous hamartoma of the inferior calcaneal nerve (Baxter nerve) with associated subcutaneous fat proliferation.

Effects of Asymmetric Superior Laryngeal Nerve Stimulation on Glottic Posture, Acoustics, Vibration

PubMed Central

Chhetri, Dinesh K.; Neubauer, Juergen; Bergeron, Jennifer L.; Sofer, Elazar; Peng, Kevin A.; Jamal, Nausheen

2013-01-01

Objectives Evaluate the effects of asymmetric superior laryngeal nerve stimulation on the vibratory phase, laryngeal posture, and acoustics. Study Design Basic science study using an in vivo canine model. Methods The superior laryngeal nerves were symmetrically and asymmetrically stimulated over eight activation levels to mimic laryngeal asymmetries representing various levels of superior laryngeal nerve paresis and paralysis conditions. Glottal posture change, vocal fold speed, and vibration of these 64 distinct laryngeal activation conditions were evaluated by high speed video and concurrent acoustic and aerodynamic recordings. Assessments were made at phonation onset. Results Vibratory phase was symmetric in all symmetric activation conditions but consistent phase asymmetry towards the vocal fold with higher superior laryngeal nerve activation was observed. Superior laryngeal nerve paresis and paralysis conditions had reduced vocal fold strain and fundamental frequency. Superior laryngeal nerve activation increased vocal fold closure speed, but this effect was more pronounced for the ipsilateral vocal fold. Increasing asymmetry led to aperiodic and chaotic vibration. Conclusions This study directly links vocal fold tension asymmetry with vibratory phase asymmetry; in particular the side with greater tension leads in the opening phase. The clinical observations of vocal fold lag, reduced vocal range, and aperiodic voice in superior laryngeal paresis and paralysis is also supported. PMID:23712542

The plasminogen activator system modulates sympathetic nerve function.

PubMed

Schaefer, Ulrich; Machida, Takuji; Vorlova, Sandra; Strickland, Sidney; Levi, Roberto

2006-09-04

Sympathetic neurons synthesize and release tissue plasminogen activator (t-PA). We investigated whether t-PA modulates sympathetic activity. t-PA inhibition markedly reduced contraction of the guinea pig vas deferens to electrical field stimulation (EFS) and norepinephrine (NE) exocytosis from cardiac synaptosomes. Recombinant t-PA (rt-PA) induced exocytotic and carrier-mediated NE release from cardiac synaptosomes and cultured neuroblastoma cells; this was a plasmin-independent effect but was potentiated by a fibrinogen cleavage product. Notably, hearts from t-PA-null mice released much less NE upon EFS than their wild-type (WT) controls (i.e., a 76.5% decrease; P<0.01), whereas hearts from plasminogen activator inhibitor-1 (PAI-1)-null mice released much more NE (i.e., a 275% increase; P<0.05). Furthermore, vasa deferentia from t-PA-null mice were hyporesponsive to EFS (P<0.0001) but were normalized by the addition of rt-PA. In contrast, vasa from PAI-1-null mice were much more responsive (P<0.05). Coronary NE overflow from hearts subjected to ischemia/reperfusion was much smaller in t-PA-null than in WT control mice (P<0.01). Furthermore, reperfusion arrhythmias were significantly reduced (P<0.05) in t-PA-null hearts. Thus, t-PA enhances NE release from sympathetic nerves and contributes to cardiac arrhythmias in ischemia/reperfusion. Because the risk of arrhythmias and sudden cardiac death is increased in hyperadrenergic conditions, targeting the NE-releasing effect of t-PA may have valuable therapeutic potential.

Protein corona changes mediated by surface modification of amorphous silica nanoparticles suppress acute toxicity and activation of intrinsic coagulation cascade in mice

NASA Astrophysics Data System (ADS)

Yoshida, Tokuyuki; Yoshioka, Yasuo; Morishita, Yuki; Aoyama, Michihiko; Tochigi, Saeko; Hirai, Toshiro; Tanaka, Kota; Nagano, Kazuya; Kamada, Haruhiko; Tsunoda, Shin-ichi; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Higashisaka, Kazuma; Tsutsumi, Yasuo

2015-06-01

Recently, nanomaterial-mediated biological effects have been shown to be governed by the interaction of nanomaterials with some kinds of proteins in biological fluids, and the physical characteristics of the nanomaterials determine the extent and type of their interactions with proteins. Here, we examined the relationships between the surface properties of amorphous silica nanoparticles with diameters of 70 nm (nSP70), their interactions with some proteins in biological fluids, and their toxicity in mice after intravenous administration. The surface modification of nSP70 with amino groups (nSP70-N) prevented acute lethality and abnormal activation of the coagulation cascade found in the nSP70-treated group of mice. Since our previous study showed that coagulation factor XII played a role in the nSP70-mediated abnormal activation of the coagulation cascade, we examined the interaction of nSP70 and nSP70-N with coagulation factor XII. Coagulation factor XII bonded to the surface of nSP70 to a greater extent than that observed for nSP70-N, and consequently more activation of coagulation factor XII was observed for nSP70 than for nSP70-N. Collectively, our results suggest that controlling the interaction of nSP70 with blood coagulation factor XII by modifying the surface properties would help to inhibit the nSP70-mediated abnormal activation of the blood coagulation cascade.

Mindfulness meditation lowers muscle sympathetic nerve activity and blood pressure in African-American males with chronic kidney disease.

PubMed

Park, Jeanie; Lyles, Robert H; Bauer-Wu, Susan

2014-07-01

Mindfulness meditation (MM) is a stress-reduction technique that may have real biological effects on hemodynamics but has never previously been tested in chronic kidney disease (CKD) patients. In addition, the mechanisms underlying the potential blood pressure (BP)-lowering effects of MM are unknown. We sought to determine whether MM acutely lowers BP in CKD patients, and whether these hemodynamic changes are mediated by a reduction in sympathetic nerve activity. In 15 hypertensive African-American (AA) males with CKD, we conducted a randomized, crossover study in which participants underwent 14 min of MM or 14 min of BP education (control intervention) during two separate random-order study visits. Muscle sympathetic nerve activity (MSNA), beat-to-beat arterial BP, heart rate (HR), and respiratory rate (RR) were continuously measured at baseline and during each intervention. A subset had a third study visit to undergo controlled breathing (CB) to determine whether a reduction in RR alone was sufficient in exacting hemodynamic changes. We observed a significantly greater reduction in systolic BP, diastolic BP, mean arterial pressure, and HR, as well as a significantly greater reduction in MSNA, during MM compared with the control intervention. Participants had a significantly lower RR during MM; however, in contrast to MM, CB alone did not reduce BP, HR, or MSNA. MM acutely lowers BP and HR in AA males with hypertensive CKD, and these hemodynamic effects may be mediated by a reduction in sympathetic nerve activity. RR is significantly lower during MM, but CB alone without concomitant meditation does not acutely alter hemodynamics or sympathetic activity in CKD.

Routine exposure of recurrent laryngeal nerve in thyroid surgery can prevent nerve injury.

PubMed

Shen, Chenling; Xiang, Mingliang; Wu, Hao; Ma, Yan; Chen, Li; Cheng, Lan

2013-06-15

To determine the value of dissecting the recurrent laryngeal nerve during thyroid surgery with respect to preventing recurrent laryngeal nerve injury, we retrospectively analyzed clinical data from 5 344 patients undergoing thyroidectomy. Among these cases, 548 underwent dissection of the recurrent laryngeal nerve, while 4 796 did not. There were 12 cases of recurrent laryngeal nerve injury following recurrent laryngeal nerve dissection (injury rate of 2.2%) and 512 cases of recurrent laryngeal nerve injury in those not undergoing nerve dissection (injury rate of 10.7%). This difference remained statistically significant between the two groups in terms of type of thyroid disease, type of surgery, and number of surgeries. Among the 548 cases undergoing recurrent laryngeal nerve dissection, 128 developed anatomical variations of the recurrent laryngeal nerve (incidence rate of 23.4%), but no recurrent laryngeal nerve injury was found. In addition, the incidence of recurrent laryngeal nerve injury was significantly lower in patients with the inferior parathyroid gland and middle thyroid veins used as landmarks for locating the recurrent laryngeal nerve compared with those with the entry of the recurrent laryngeal nerve into the larynx as a landmark. These findings indicate that anatomical variations of the recurrent laryngeal nerve are common, and that dissecting the recurrent laryngeal nerve during thyroid surgery is an effective means of preventing nerve injury.

Routine exposure of recurrent laryngeal nerve in thyroid surgery can prevent nerve injury★

PubMed Central

Shen, Chenling; Xiang, Mingliang; Wu, Hao; Ma, Yan; Chen, Li; Cheng, Lan

2013-01-01

To determine the value of dissecting the recurrent laryngeal nerve during thyroid surgery with respect to preventing recurrent laryngeal nerve injury, we retrospectively analyzed clinical data from 5 344 patients undergoing thyroidectomy. Among these cases, 548 underwent dissection of the recurrent laryngeal nerve, while 4 796 did not. There were 12 cases of recurrent laryngeal nerve injury following recurrent laryngeal nerve dissection (injury rate of 2.2%) and 512 cases of recurrent laryngeal nerve injury in those not undergoing nerve dissection (injury rate of 10.7%). This difference remained statistically significant between the two groups in terms of type of thyroid disease, type of surgery, and number of surgeries. Among the 548 cases undergoing recurrent laryngeal nerve dissection, 128 developed anatomical variations of the recurrent laryngeal nerve (incidence rate of 23.4%), but no recurrent laryngeal nerve injury was found. In addition, the incidence of recurrent laryngeal nerve injury was significantly lower in patients with the inferior parathyroid gland and middle thyroid veins used as landmarks for locating the recurrent laryngeal nerve compared with those with the entry of the recurrent laryngeal nerve into the larynx as a landmark. These findings indicate that anatomical variations of the recurrent laryngeal nerve are common, and that dissecting the recurrent laryngeal nerve during thyroid surgery is an effective means of preventing nerve injury. PMID:25206452

A collagen-based nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and nonhuman primates.

PubMed

Archibald, S J; Krarup, C; Shefner, J; Li, S T; Madison, R D

1991-04-22

When a peripheral nerve is severed and left untreated, the most likely result is the formation of an endbulb neuroma; this tangled mass of disorganized nerve fibers blocks functional recovery following nerve injury. Although there are several different approaches for promoting nerve repair, which have been greatly refined over recent years, the clinical results of peripheral nerve repair remain very disappointing. In this paper we compare the results of a collagen nerve guide conduit to the more standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves in rats and nonhuman primates. In rats, we tested recovery from sciatic nerve transection and repair by 1) direct microsurgical suture, 2) 4 mm autograft, or 3) entubulation repair with collagen-based nerve guide conduits. Evoked muscle action potentials (MAP) were recorded from the gastrocnemius muscle at 4 and 12 weeks following sciatic nerve transection. At 4 weeks the repair group of direct suture demonstrated a significantly greater MAP, compared to the other surgical repair groups. However, at 12 weeks all four surgical repair groups displayed similar levels of recovery of the motor response. In six adult male Macaca fascicularis monkeys the median nerve was transected 2 cm above the wrist and repaired by either a 4 mm nerve autograft or a collagen-based nerve guide conduit leaving a 4 mm gap between nerve ends. Serial studies of motor and sensory fibers were performed by recording the evoked MAP from the abductor pollicis brevis muscle (APB) and the sensory action potential (SAP) evoked by stimulation of digital nerves (digit II), respectively, up to 760 days following surgery. Evoked muscle responses returned to normal baseline levels in all cases. Statistical analysis of the motor responses, as judged by the slope of the recovery curves, indicated a significantly more rapid rate of recovery for the nerve guide repair group. The final level of recovery of the MAP

[Facial nerve neurinomas].

PubMed

Sokołowski, Jacek; Bartoszewicz, Robert; Morawski, Krzysztof; Jamróz, Barbara; Niemczyk, Kazimierz

2013-01-01

Evaluation of diagnostic, surgical technique, treatment results facial nerve neurinomas and its comparison with literature was the main purpose of this study. Seven cases of patients (2005-2011) with facial nerve schwannomas were included to retrospective analysis in the Department of Otolaryngology, Medical University of Warsaw. All patients were assessed with history of the disease, physical examination, hearing tests, computed tomography and/or magnetic resonance imaging, electronystagmography. Cases were observed in the direction of potential complications and recurrences. Neurinoma of the facial nerve occurred in the vertical segment (n=2), facial nerve geniculum (n=1) and the internal auditory canal (n=4). The symptoms observed in patients were analyzed: facial nerve paresis (n=3), hearing loss (n=2), dizziness (n=1). Magnetic resonance imaging and computed tomography allowed to confirm the presence of the tumor and to assess its staging. Schwannoma of the facial nerve has been surgically removed using the middle fossa approach (n=5) and by antromastoidectomy (n=2). Anatomical continuity of the facial nerve was achieved in 3 cases. In the twelve months after surgery, facial nerve paresis was rated at level II-III° HB. There was no recurrence of the tumor in radiological observation. Facial nerve neurinoma is a rare tumor. Currently surgical techniques allow in most cases, the radical removing of the lesion and reconstruction of the VII nerve function. The rate of recurrence is low. A tumor of the facial nerve should be considered in the differential diagnosis of nerve VII paresis. Copyright © 2013 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

Distal nerve transfer versus supraclavicular nerve grafting: comparison of elbow flexion outcome in neonatal brachial plexus palsy with C5-C7 involvement.

PubMed

Heise, Carlos O; Siqueira, Mario G; Martins, Roberto S; Foroni, Luciano H; Sterman-Neto, Hugo

2017-09-01

Ulnar and median nerve transfers to arm muscles have been used to recover elbow flexion in infants with neonatal brachial plexus palsy, but there is no direct outcome comparison with the classical supraclavicular nerve grafting approach. We retrospectively analyzed patients with C5-C7 neonatal brachial plexus palsy submitted to nerve surgery and recorded elbow flexion recovery using the active movement scale (0-7) at 12 and 24 months after surgery. We compared 13 patients submitted to supraclavicular nerve grafting with 21 patients submitted to distal ulnar or median nerve transfer to biceps motor branch. We considered elbow flexion scores of 6 or 7 as good results. The mean elbow flexion score and the proportion of good results were better using distal nerve transfers than supraclavicular grafting at 12 months (p < 0.01), but not at 24 months. Two patients with failed supraclavicular nerve grafting at 12 months showed good elbow flexion recovery after ulnar nerve transfers. Distal nerve transfers provided faster elbow flexion recovery than supraclavicular nerve grafting, but there was no significant difference in the outcome after 24 months of surgery. Patients with failed supraclavicular grafting operated early can still benefit from late distal nerve transfers. Supraclavicular nerve grafting should remain as the first line surgical treatment for children with neonatal brachial plexus palsy.

Innervation of the human cricopharyngeal muscle by the recurrent laryngeal nerve and external branch of the superior laryngeal nerve.

PubMed

Uludag, Mehmet; Aygun, Nurcihan; Isgor, Adnan

2017-06-01

The major component of the upper esophageal sphincter is the cricopharyngeal muscle (CPM). We assessed the contribution of the laryngeal nerves to motor innervation of the CPM. We performed an intraoperative electromyographic study of 27 patients. The recurrent laryngeal nerve (RLN), vagus nerve, external branch of the superior laryngeal nerve (EBSLN), and pharyngeal plexus (PP) were stimulated. Responses were evaluated by visual observation of CPM contractions and electromyographic examination via insertion of needle electrodes into the CPM. In total, 46 CPMs (24 right, 22 left) were evaluated. PP stimulation produced both positive visual contractions and electromyographic (EMG) responses in 42 CPMs (2080 ± 1583 μV). EBSLN stimulation produced visual contractions of 28 CPMs and positive EMG responses in 35 CPMs (686 ± 630 μV). Stimulation of 45 RLNs produced visible contractions of 37 CPMs and positive EMG activity in 41 CPMs (337 ± 280 μV). Stimulation of 42 vagal nerves resulted in visible contractions of 36 CPMs and positive EMG responses in 37 CPMs (292 ± 229 μV). Motor activity was noted in 32 CPMs by both RLN and EBSLN stimulation, 9 CPMs by RLN stimulation, and 3 CPMs by EBSLN stimulation; 2 CPMs exhibited no response. This is the first study to show that the EBSLN contributes to motor innervation of the human CPM. The RLN, EBSLN, or both of the nerves innervate the 90, 75, and 70 % of the CPMs ipsilaterally, respectively.

Increased renal sympathetic nerve activity leads to hypertension and renal dysfunction in offspring from diabetic mothers.

PubMed

de Almeida Chaves Rodrigues, Aline Fernanda; de Lima, Ingrid Lauren Brites; Bergamaschi, Cássia Toledo; Campos, Ruy Ribeiro; Hirata, Aparecida Emiko; Schoorlemmer, Guus Hermanus Maria; Gomes, Guiomar Nascimento

2013-01-15

The exposure of the fetus to a hyperglycemic environment promotes the development of hypertension and renal dysfunction in the offspring at adult age. We evaluated the role of renal nerves in the hypertension and renal changes seen in offspring of diabetic rats. Diabetes was induced in female Wistar rats (streptozotocin, 60 mg/kg ip) before mating. Male offspring from control and diabetic dams were studied at an age of 3 mo. Systolic blood pressure measured by tail cuff was increased in offspring of diabetic dams (146 ± 1.6 mmHg, n = 19, compared with 117 ± 1.4 mmHg, n = 18, in controls). Renal function, baseline renal sympathetic nerve activity (rSNA), and arterial baroreceptor control of rSNA were analyzed in anesthetized animals. Glomerular filtration rate, fractional sodium excretion, and urine flow were significantly reduced in offspring of diabetic dams. Two weeks after renal denervation, blood pressure and renal function in offspring from diabetic dams were similar to control, suggesting that renal nerves contribute to sodium retention in offspring from diabetic dams. Moreover, basal rSNA was increased in offspring from diabetic dams, and baroreceptor control of rSNA was impaired, with blunted responses to infusion of nitroprusside and phenylephrine. Thus, data from this study indicate that in offspring from diabetic mothers, renal nerves have a clear role in the etiology of hypertension; however, other factors may also contribute to this condition.

Bayesian Estimation of Reliability Burr Type XII Under Al-Bayyatis’ Suggest Loss Function with Numerical Solution

NASA Astrophysics Data System (ADS)

Mohammed, Amal A.; Abraheem, Sudad K.; Fezaa Al-Obedy, Nadia J.

2018-05-01

In this paper is considered with Burr type XII distribution. The maximum likelihood, Bayes methods of estimation are used for estimating the unknown scale parameter (α). Al-Bayyatis’ loss function and suggest loss function are used to find the reliability with the least loss. So the reliability function is expanded in terms of a set of power function. For this performance, the Matlab (ver.9) is used in computations and some examples are given.

Hyperchlorhidrosis caused by homozygous mutation in CA12, encoding carbonic anhydrase XII.

PubMed

Feldshtein, Maya; Elkrinawi, Suliman; Yerushalmi, Baruch; Marcus, Barak; Vullo, Daniela; Romi, Hila; Ofir, Rivka; Landau, Daniel; Sivan, Sara; Supuran, Claudiu T; Birk, Ohad S

2010-11-12

Excessive chloride secretion in sweat (hyperchlorhidrosis), leading to a positive sweat test, is most commonly indicative of cystic fibrosis yet is found also in conjunction with various metabolic, endocrine, and dermatological disorders. There is conflicting evidence regarding the existence of autosomal-recessive hyperchlorhidrosis. We now describe a consanguineous Israeli Bedouin kindred with autosomal-recessive hyperchlohidrosis whose sole symptoms are visible salt precipitates after sweating, a preponderance to hyponatremic dehydration, and poor feeding and slow weight gain at infancy. Through genome-wide linkage analysis, we demonstrate that the phenotype is due to a homozygous mutation in CA12, encoding carbonic anhydrase XII. The mutant (c.427G>A [p.Glu143Lys]) protein showed 71% activity of the wild-type enzyme for catalyzing the CO₂ hydration to bicarbonate and H(+), and it bound the clinically used sulfonamide inhibitor acetazolamide with high affinity (K(I) of 10 nM). Unlike the wild-type enzyme, which is not inhibited by chloride, bromide, or iodide (K(I)s of 73-215 mM), the mutant is inhibited in the submicromolar range by these anions (K(I)s of 0.37-0.73 mM). Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Optic Nerve Decompression

MedlinePlus

... Nerve Decompression Dacryocystorhinostomy (DCR) Disclosure Statement Printer Friendly Optic Nerve Decompression John Lee, MD Introduction Optic nerve decompression is a surgical procedure aimed at ...

Large-Scale Coronal Heating from "Cool" Activity in the Solar Magnetic Network

NASA Technical Reports Server (NTRS)

Falconer, D. A.; Moore, R. L.; Porter, J. G.; Hathaway, D. H.

1999-01-01

In Fe XII images from SOHO/EIT, the quiet solar corona shows structure on scales ranging from sub-supergranular (i.e., bright points and coronal network) to multi-supergranular (large-scale corona). In Falconer et al 1998 (Ap.J., 501, 386) we suppressed the large-scale background and found that the network-scale features are predominantly rooted in the magnetic network lanes at the boundaries of the supergranules. Taken together, the coronal network emission and bright point emission are only about 5% of the entire quiet solar coronal Fe XII emission. Here we investigate the relationship between the large-scale corona and the network as seen in three different EIT filters (He II, Fe IX-X, and Fe XII). Using the median-brightness contour, we divide the large-scale Fe XII corona into dim and bright halves, and find that the bright-half/dim half brightness ratio is about 1.5. We also find that the bright half relative to the dim half has 10 times greater total bright point Fe XII emission, 3 times greater Fe XII network emission, 2 times greater Fe IX-X network emission, 1.3 times greater He II network emission, and has 1.5 times more magnetic flux. Also, the cooler network (He II) radiates an order of magnitude more energy than the hotter coronal network (Fe IX-X, and Fe XII). From these results we infer that: 1) The heating of the network and the heating of the large-scale corona each increase roughly linearly with the underlying magnetic flux. 2) The production of network coronal bright points and heating of the coronal network each increase nonlinearly with the magnetic flux. 3) The heating of the large-scale corona is driven by widespread cooler network activity rather than by the exceptional network activity that produces the network coronal bright points and the coronal network. 4) The large-scale corona is heated by a nonthermal process since the driver of its heating is cooler than it is. This work was funded by the Solar Physics Branch of NASA's office of

A Physicochemically Optimized and Neuroconductive Biphasic Nerve Guidance Conduit for Peripheral Nerve Repair.

PubMed

Ryan, Alan J; Lackington, William A; Hibbitts, Alan J; Matheson, Austyn; Alekseeva, Tijna; Stejskalova, Anna; Roche, Phoebe; O'Brien, Fergal J

2017-12-01

Clinically available hollow nerve guidance conduits (NGCs) have had limited success in treating large peripheral nerve injuries. This study aims to develop a biphasic NGC combining a physicochemically optimized collagen outer conduit to bridge the transected nerve, and a neuroconductive hyaluronic acid-based luminal filler to support regeneration. The outer conduit is mechanically optimized by manipulating crosslinking and collagen density, allowing the engineering of a high wall permeability to mitigate the risk of neuroma formation, while also maintaining physiologically relevant stiffness and enzymatic degradation tuned to coincide with regeneration rates. Freeze-drying is used to seamlessly integrate the luminal filler into the conduit, creating a longitudinally aligned pore microarchitecture. The luminal stiffness is modulated to support Schwann cells, with laminin incorporation further enhancing bioactivity by improving cell attachment and metabolic activity. Additionally, this biphasic NGC is shown to support neurogenesis and gliogenesis of neural progenitor cells and axonal outgrowth from dorsal root ganglia. These findings highlight the paradigm that a successful NGC requires the concerted optimization of both a mechanical support phase capable of bridging a nerve defect and a neuroconductive phase with an architecture capable of supporting both Schwann cells and neurons in order to achieve functional regenerative outcome. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mathematical Model Of Nerve/Muscle Interaction

NASA Technical Reports Server (NTRS)

Hannaford, Blake

1990-01-01

Phasic Excitation/Activation (PEA) mathematical model simulates short-term nonlinear dynamics of activation and control of muscle by nerve. Includes electronic and mechanical elements. Is homeomorphic at level of its three major building blocks, which represent motoneuron, dynamics of activation of muscle, and mechanics of muscle.

Large Extremity Peripheral Nerve Repair

DTIC Science & Technology

2015-10-01

Outcomes are unsatisfactory, affecting quality of life and return to active duty. We are investigating a sutureless, light- activated technology for...on Avance® nerve graft procedure for large animal studies in Aim 3. (All PIs, Month 22) This study shows that outcomes following light- activated ...when severe injuries, complicated with limb loss, preclude the use of autograft. The demonstrated success of light- activated sealing of isograft

Resting afferent renal nerve discharge and renal inflammation: Elucidating the role of afferent and efferent renal nerves in DOCA-salt hypertension

PubMed Central

Banek, Christopher T.; Knuepfer, Mark M.; Foss, Jason D.; Fiege, Jessica K.; Asirvatham-Jeyaraj, Ninitha; Van Helden, Dusty; Shimizu, Yoji; Osborn, John W.

2016-01-01

Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity (RSNA) has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA)-salt rat model. Uninephrectomized male Sprague Dawley rats (275–300g) underwent selective afferent-selective RDNx (A-RDNx; n=10), total RDNx (T-RDNx; n=10), or Sham (n=10) and were instrumented for measurement of mean arterial pressure (MAP) and heart rate (HR) by radiotelemetry. Rats received 100mg DOCA (s.c.) and 0.9% saline for 21 days. Resting afferent renal nerve activity (ARNA) in DOCA and Vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting ARNA, expressed as a percent of peak afferent nerve activity (%Amax), was substantially increased in DOCA vs. Vehicle (35.8±4.4 vs. 15.3±2.8%Amax). The DOCA-Sham hypertension (132±12 mmHg) was attenuated by ~50% in both T-RDNx (111±8) and A-RDNx (117±5mmHg) groups. Renal inflammation induced by DOCA-salt was attenuated by T-RDNx, and unaffected by A-RDNx. These data suggest ARNA may mediate the hypertensive response to DOCA-salt, but inflammation may be mediated primarily by efferent RSNA. Also, resting ARNA is elevated in DOCA-salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension. PMID:27698066

Facial nerve mapping and monitoring in lymphatic malformation surgery.

PubMed

Chiara, Jospeh; Kinney, Greg; Slimp, Jefferson; Lee, Gi Soo; Oliaei, Sepehr; Perkins, Jonathan A

2009-10-01

Establish the efficacy of preoperative facial nerve mapping and continuous intraoperative EMG monitoring in protecting the facial nerve during resection of cervicofacial lymphatic malformations. Retrospective study in which patients were clinically followed for at least 6 months postoperatively, and long-term outcome was evaluated. Patient demographics, lesion characteristics (i.e., size, stage, location) were recorded. Operative notes revealed surgical techniques, findings, and complications. Preoperative, short-/long-term postoperative facial nerve function was standardized using the House-Brackmann Classification. Mapping was done prior to incision by percutaneously stimulating the facial nerve and its branches and recording the motor responses. Intraoperative monitoring and mapping were accomplished using a four-channel, free-running EMG. Neurophysiologists continuously monitored EMG responses and blindly analyzed intraoperative findings and final EMG interpretations for abnormalities. Seven patients collectively underwent 8 lymphatic malformation surgeries. Median age was 30 months (2-105 months). Lymphatic malformation diagnosis was recorded in 6/8 surgeries. Facial nerve function was House-Brackmann grade I in 8/8 cases preoperatively. Facial nerve was abnormally elongated in 1/8 cases. EMG monitoring recorded abnormal activity in 4/8 cases--two suggesting facial nerve irritation, and two with possible facial nerve damage. Transient or long-term facial nerve paresis occurred in 1/8 cases (House-Brackmann grade II). Preoperative facial nerve mapping combined with continuous intraoperative EMG and mapping is a successful method of identifying the facial nerve course and protecting it from injury during resection of cervicofacial lymphatic malformations involving the facial nerve.

Bradykinin activates a cross-signaling pathway between sensory and adrenergic nerve endings in the heart: a novel mechanism of ischemic norepinephrine release?

PubMed

Seyedi, N; Maruyama, R; Levi, R

1999-08-01

We had shown that bradykinin (BK) generated by cardiac sympathetic nerve endings (i.e., synaptosomes) promotes exocytotic norepinephrine (NE) release in an autocrine mode. Because the synaptosomal preparation may include sensory C-fiber endings, which BK is known to stimulate, sensory nerves could contribute to the proadrenergic effects of BK in the heart. We report that BK is a potent releaser of NE from guinea pig heart synaptosomes (EC(50) approximately 20 nM), an effect mediated by B(2) receptors, and almost completely abolished by prior C-fiber destruction or blockade of calcitonin gene-related peptide and neurokinin-1 receptors. C-fiber destruction also greatly decreased BK-induced NE release from the intact heart, whereas tyramine-induced NE release was unaffected. Furthermore, C-fiber stimulation with capsaicin and activation of calcitonin gene-related peptide and neurokinin-1 receptors initiated NE release from cardiac synaptosomes, indicating that stimulation of sensory neurons in turn activates sympathetic nerve terminals. Thus, BK is likely to release NE in the heart in part by first liberating calcitonin gene-related peptide and Substance P from sensory nerve endings; these neuropeptides then stimulate specific receptors on sympathetic terminals. This action of BK is positively modulated by cyclooxygenase products, attenuated by activation of histamine H(3) receptors, and potentiated at a lower pH. The NE-releasing action of BK is likely to be enhanced in myocardial ischemia, when protons accumulate, C fibers become activated, and the production of prostaglandins and BK increases. Because NE is a major arrhythmogenic agent, the activation of this interneuronal signaling system between sensory and adrenergic neurons may contribute to ischemic dysrhythmias and sudden cardiac death.

Spike rate of multi-unit muscle sympathetic nerve fibers following catheter-based renal nerve ablation

PubMed Central

Tank, Jens; Heusser, Karsten; Brinkmann, Julia; Schmidt, Bernhard M.; Menne, Jan; Bauersachs, Johann; Haller, Hermann; Diedrich, André; Jordan, Jens

2016-01-01

Patients with treatment-resistant arterial hypertension exhibited profound reductions in single sympathetic vasoconstrictor fiber firing rates following renal nerve ablation. In contrast, integrated multi-unit muscle sympathetic nerve activity (MSNA) changed little or not at all. We hypothesized that conventional MSNA analysis may have missed single fiber discharges, thus, obscuring sympathetic inhibition following renal denervation. We studied patients with difficult to control arterial hypertension (age 45–74 years) before, 6 (n=11), and 12 months (n=8) following renal nerve ablation. Electrocardiogram, respiration, brachial, and finger arterial blood pressure (BP), as well as the MSNA raw MSNA signal were analyzed. We detected MSNA action potential spikes using 2 stage kurtosis wavelet denoising techniques to assess mean, median, and maximum spike rates for each beat-to-beat interval. Supine heart rate and systolic BP did not change at 6 (ΔHR: −2±3 bpm; ΔSBP: 2±9 mmHg) or at 12 months (ΔHR: −1±3 mmHg, ΔSBP: −1±9 mmHg) after renal nerve ablation. Mean burst frequency and mean spike frequency at baseline were 34±3 bursts per minute and 8±1 spikes per sec. Both measurements did not change at 6 months (−1.4±3.6 bursts/minute; −0.6±1.4 spikes per sec) or at 12 months (−2.5±4.0 bursts/minute; −2.0±1.6 spikes per sec) following renal nerve ablation. After renal nerve ablation, BP decreased in 3 out of 11 patients. BP and MSNA spike frequency changes were not correlated (slope=−0.06; p=0.369). Spike rate analysis of multi-unit MSNA neurograms further suggests that profound sympathetic inhibition is not a consistent finding following renal nerve ablation. PMID:26324745

Gellan Gum-based luminal fillers for peripheral nerve regeneration: an in vivo study in the rat sciatic nerve repair model.

PubMed

Carvalho, C R; Wrobel, S; Meyer, C; Brandenberger, C; Cengiz, I F; López-Cebral, R; Silva-Correia, J; Ronchi, G; Reis, R L; Grothe, C; Oliveira, J M; Haastert-Talini, K

2018-05-01

Peripheral nerve injuries (PNI) resulting in a gap to be bridged between the transected nerve ends are commonly reconstructed with autologous nerve tissue, but there is a need for valuable alternatives. This experimental work considers the innovative use of the biomaterial Gellan Gum (GG) as a luminal filler for nerve guidance channels made from chitosan with a 5% degree of acetylation. The engineered constructs should remodel the structural support given to regenerating axons by the so-called bands of Büngner. Four different GG formulations were produced by combining varying amounts of High-Acyl GG (HA-GG) and Methacrylated GG (MA-GG). The effective porosity of the freeze-dried networks was analysed by SEM and micro-CT 3D reconstructions, while the degradation and swelling abilities were characterized in vitro for up to 30 days. The metabolic activity and viability of immortalized Schwann cells seeded onto the freeze-dried networks were also evaluated. Finally, the developed hydrogel formulations were freeze-dried within the chitosan nerve guides and implanted in a 10 mm rat sciatic nerve defect. Functional and histomorphological analyses after 3, 6, and 12 weeks in vivo revealed that although it did not result in improved nerve regeneration, the NGC25:75 formulations could provide a basis for further development of GG scaffolds as luminal fillers for hollow nerve guidance channels.

Diaphragmatic reinnervation in ventilator-dependent patients with cervical spinal cord injury and concomitant phrenic nerve lesions using simultaneous nerve transfers and implantable neurostimulators.

PubMed

Kaufman, Matthew R; Elkwood, Andrew I; Aboharb, Farid; Cece, John; Brown, David; Rezzadeh, Kameron; Jarrahy, Reza

2015-06-01

Patients who are ventilator dependent as a result of combined cervical spinal cord injury and phrenic nerve lesions are generally considered to be unsuitable candidates for diaphragmatic pacing due to loss of phrenic nerve integrity and denervation of the diaphragm. There is limited data regarding efficacy of simultaneous nerve transfers and diaphragmatic pacemakers in the treatment of this patient population. A retrospective review was conducted of 14 consecutive patients with combined lesions of the cervical spinal cord and phrenic nerves, and with complete ventilator dependence, who were treated with simultaneous microsurgical nerve transfer and implantation of diaphragmatic pacemakers. Parameters of interest included time to recovery of diaphragm electromyographic activity, average time pacing without the ventilator, and percent reduction in ventilator dependence. Recovery of diaphragm electromyographic activity was demonstrated in 13 of 14 (93%) patients. Eight of these 13 (62%) patients achieved sustainable periods (> 1 h/d) of ventilator weaning (mean = 10 h/d [n = 8]). Two patients recovered voluntary control of diaphragmatic activity and regained the capacity for spontaneous respiration. The one patient who did not exhibit diaphragmatic reinnervation remains within 12 months of initial treatment. Surgical intervention resulted in a 25% reduction (p < 0.05) in ventilator dependency. We have demonstrated that simultaneous nerve transfers and pacemaker implantation can result in reinnervation of the diaphragm and lead to successful ventilator weaning. Our favorable outcomes support consideration of this surgical method for appropriate patients who would otherwise have no alternative therapy to achieve sustained periods of ventilator independence. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Long-term outcome of accessory nerve to suprascapular nerve transfer in obstetric brachial plexus lesion: functional, morphological, and electrophysiological results.

PubMed

Gmeiner, Matthias; Topakian, Raffi; Göschl, Manuel; Wurm, Sarah; Holzinger, Anita; van Ouwerkerk, Willem J R; Holl, Kurt

2015-09-01

An accessory to suprascapular nerve (XIN-SSN) transfer is considered in patients with obstetric brachial plexus lesion who fail to recover active shoulder external rotation. The aim of this study was to evaluate the quality of extraplexal suprascapular nerve neurotization and to perform a detailed analysis of the infraspinatus muscle (IM) and shoulder external rotation. A XIN-SSN transfer was performed in 14 patients between 2000 and 2007. Patients had been operated at the age of 3.7 ± 2.8 years. Follow-up examinations were conducted up to 8.5 ± 2.5 years. Magnetic resonance imaging was performed to investigate muscle trophism. Fatty muscle degeneration of the IM was classified according to the Goutallier classification. We conducted nerve conduction velocity studies of the suprascapular nerve and needle electromyography of the IM to assess pathologic spontaneous activity and interference patterns. Active glenohumeral shoulder external rotation and global shoulder function were evaluated using the Mallet score. Postoperatively, growth of the IM increased equally on the affected and unaffected sides, although significant differences of muscle thickness persisted over time. There was only grade 1 or 2 fatty degeneration pre- and postoperatively. Electromyography of the IM revealed a full interference pattern in all except one patient, and there was no pathological spontaneous activity. Glenohumeral external rotation as well as global shoulder function increased significantly. Our results indicate that the anastomosis after XIN-SSN transfer is functional and that successful reinnervation of the infraspinatus muscle may enable true glenohumeral active external rotation.

The Role of Hypothalamic mTORC1 Signaling in Insulin Regulation of Food Intake, Body Weight, and Sympathetic Nerve Activity in Male Mice

PubMed Central

Muta, Kenjiro; Morgan, Donald A.

2015-01-01

Insulin action in the brain particularly the hypothalamus is critically involved in the regulation of several physiological processes, including energy homeostasis and sympathetic nerve activity, but the underlying mechanisms are poorly understood. The mechanistic target of rapamycin complex 1 (mTORC1) is implicated in the control of diverse cellular functions, including sensing nutrients and energy status. Here, we examined the role of hypothalamic mTORC1 in mediating the anorectic, weight-reducing, and sympathetic effects of central insulin action. In a mouse hypothalamic cell line (GT1–7), insulin treatment increased mTORC1 activity in a time-dependent manner. In addition, intracerebroventricular (ICV) administration of insulin to mice activated mTORC1 pathway in the hypothalamic arcuate nucleus, a key site of central action of insulin. Interestingly, inhibition of hypothalamic mTORC1 with rapamycin reversed the food intake- and body weight-lowering effects of ICV insulin. Rapamycin also abolished the ability of ICV insulin to cause lumbar sympathetic nerve activation. In GT1–7 cells, we found that insulin activation of mTORC1 pathway requires phosphatidylinositol 3-kinase (PI3K). Consistent with this, genetic disruption of PI3K in mice abolished insulin stimulation of hypothalamic mTORC1 signaling as well as the lumbar sympathetic nerve activation evoked by insulin. These results demonstrate the importance of mTORC1 pathway in the hypothalamus in mediating the action of insulin to regulate energy homeostasis and sympathetic nerve traffic. Our data also highlight the key role of PI3K as a link between insulin receptor and mTORC1 signaling in the hypothalamus. PMID:25574706

Lyman-alpha observations of Comet Kohoutek 1973 XII with Copernicus

NASA Technical Reports Server (NTRS)

Drake, J. F.; Jenkins, E. B.; Bertaux, J. L.; Festou, M.; Keller, H. U.

1976-01-01

Comet Kohoutek 1973 XII was observed with a telescope-spectrometer on the Copernicus satellite on six occasions over a 1-month period starting on January 29, 1974. Positive detection of the cometary Ly-alpha emission profile was obtained on January 29 and February 2. Earlier observations of the geocoronal Ly-alpha emission profile allowed an instrumental intensity calibration and confirmation of the computed instrumental profile for an extended source at the Ly-alpha wavelength. After allowing for broadening by the instrument, a hydrogen-outflow velocity of about 10.6 km/s is derived from the width of the Ly-alpha emission on January 29. The intensity calibration combined with an appropriate cometary model led to cometary water-production rates for January 29 and February 2. Only upper limits were obtained for Ly-alpha on and after February 14. Searches for OH and D led to negative results.

In vivo microdialysis and electroencephalographic activity in freely moving guinea pigs exposed to organophosphorus nerve agents sarin and VX: analysis of acetylcholine and glutamate.

PubMed

O'Donnell, John C; McDonough, John H; Shih, Tsung-Ming

2011-12-01

Organophosphorus nerve agents such as sarin (GB) and VX irreversibly inhibit acetylcholinesterase, causing a buildup of acetylcholine (ACh) in synapses and neuromuscular junctions, which leads to excess bronchial secretions, convulsions, seizures, coma, and death. Understanding the unique toxic characteristics of different nerve agents is vital in the effort to develop broad spectrum medical countermeasures. To this end, we employed a repeated measure multivariate design with striatal microdialysis collection and high-performance liquid chromatography analysis to measure changes in concentrations of several neurotransmitters (ACh, glutamate, aspartate, GABA) in the same samples during acute exposure to GB or VX in freely moving guinea pigs. Concurrent with microdialysis collection, we used cortical electrodes to monitor brain seizure activity. This robust double multivariate design provides greater fidelity when comparing data while also reducing the required number of subjects. No correlation between nerve agents' propensity for causing seizure and seizure-related lethality was observed. The GB seizure group experienced more rapid and severe cholinergic toxicity and lethality than that of the VX seizure group. Seizures generated from GB and VX exposure resulted in further elevation of ACh level and then a gradual return to baseline. Glutamate levels increased in the GB, but not in the VX, seizure group. There were no consistent changes in either aspartate or GABA as a result of either nerve agent. These observations reinforce findings with other nerve agents that seizure activity per se contributes to the elevated levels of brain ACh observed after nerve agent exposure.

Radial nerve palsy

PubMed Central

Bumbasirevic, Marko; Palibrk, Tomislav; Lesic, Aleksandar; Atkinson, Henry DE

2016-01-01

As a result of its proximity to the humeral shaft, as well as its long and tortuous course, the radial nerve is the most frequently injured major nerve in the upper limb, with its close proximity to the bone making it vulnerable when fractures occur. Injury is most frequently sustained during humeral fracture and gunshot injuries, but iatrogenic injuries are not unusual following surgical treatment of various other pathologies. Treatment is usually non-operative, but surgery is sometimes necessary, using a variety of often imaginative procedures. Because radial nerve injuries are the least debilitating of the upper limb nerve injuries, results are usually satisfactory. Conservative treatment certainly has a role, and one of the most important aspects of this treatment is to maintain a full passive range of motion in all the affected joints. Surgical treatment is indicated in cases when nerve transection is obvious, as in open injuries or when there is no clinical improvement after a period of conservative treatment. Different techniques are used including direct suture or nerve grafting, vascularised nerve grafts, direct nerve transfer, tendon transfer, functional muscle transfer or the promising, newer treatment of biological therapy. Cite this article: Bumbasirevic M, Palibrk T, Lesic A, Atkinson HDE. Radial nerve palsy. EFORT Open Rev 2016;1:286-294. DOI: 10.1302/2058-5241.1.000028. PMID:28461960

Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits.

PubMed

Prior, Larissa J; Eikelis, Nina; Armitage, James A; Davern, Pamela J; Burke, Sandra L; Montani, Jean-Pierre; Barzel, Benjamin; Head, Geoffrey A

2010-04-01

The activation of the sympathetic nervous system through the central actions of the adipokine leptin has been suggested as a major mechanism by which obesity contributes to the development of hypertension. However, direct evidence for elevated sympathetic activity in obesity has been limited to muscle. The present study examined the renal sympathetic nerve activity and cardiovascular effects of a high-fat diet (HFD), as well as the changes in the sensitivity to intracerebroventricular leptin. New Zealand white rabbits fed a 13.5% HFD for 4 weeks showed modest weight gain but a 2- to 3-fold greater accumulation of visceral fat compared with control rabbits. Mean arterial pressure, heart rate, and plasma norepinephrine concentration increased by 8%, 26%, and 87%, respectively (P<0.05), after 3 weeks of HFD. Renal sympathetic nerve activity was 48% higher (P<0.05) in HFD compared with control diet rabbits and was correlated to plasma leptin (r=0.87; P<0.01). Intracerebroventricular leptin administration (5 to 100 microg) increased mean arterial pressure similarly in both groups, but renal sympathetic nerve activity increased more in HFD-fed rabbits. By contrast, intracerebroventricular leptin produced less neurons expressing c-Fos in HFD compared with control rabbits in regions important for appetite and sympathetic actions of leptin (arcuate: -54%, paraventricular: -69%, and dorsomedial hypothalamus: -65%). These results suggest that visceral fat accumulation through consumption of a HFD leads to marked sympathetic activation, which is related to increased responsiveness to central sympathoexcitatory effects of leptin. The paradoxical reduction in hypothalamic neuronal activation by leptin suggests a marked "selective leptin resistance" in these animals.

Rehabilitation, Using Guided Cerebral Plasticity, of a Brachial Plexus Injury Treated with Intercostal and Phrenic Nerve Transfers.

PubMed

Dahlin, Lars B; Andersson, Gert; Backman, Clas; Svensson, Hampus; Björkman, Anders

2017-01-01

Recovery after surgical reconstruction of a brachial plexus injury using nerve grafting and nerve transfer procedures is a function of peripheral nerve regeneration and cerebral reorganization. A 15-year-old boy, with traumatic avulsion of nerve roots C5-C7 and a non-rupture of C8-T1, was operated 3 weeks after the injury with nerve transfers: (a) terminal part of the accessory nerve to the suprascapular nerve, (b) the second and third intercostal nerves to the axillary nerve, and (c) the fourth to sixth intercostal nerves to the musculocutaneous nerve. A second operation-free contralateral gracilis muscle transfer directly innervated by the phrenic nerve-was done after 2 years due to insufficient recovery of the biceps muscle function. One year later, electromyography showed activation of the biceps muscle essentially with coughing through the intercostal nerves, and of the transferred gracilis muscle by deep breathing through the phrenic nerve. Voluntary flexion of the elbow elicited clear activity in the biceps/gracilis muscles with decreasing activity in intercostal muscles distal to the transferred intercostal nerves (i.e., corresponding to eighth intercostal), indicating cerebral plasticity, where neural control of elbow flexion is gradually separated from control of breathing. To restore voluntary elbow function after nerve transfers, the rehabilitation of patients operated with intercostal nerve transfers should concentrate on transferring coughing function, while patients with phrenic nerve transfers should focus on transferring deep breathing function.

Nerve lesioning with direct current

NASA Astrophysics Data System (ADS)

Ravid, E. Natalie; Shi Gan, Liu; Todd, Kathryn; Prochazka, Arthur

2011-02-01

Spastic hypertonus (muscle over-activity due to exaggerated stretch reflexes) often develops in people with stroke, cerebral palsy, multiple sclerosis and spinal cord injury. Lesioning of nerves, e.g. with phenol or botulinum toxin is widely performed to reduce spastic hypertonus. We have explored the use of direct electrical current (DC) to lesion peripheral nerves. In a series of animal experiments, DC reduced muscle force by controlled amounts and the reduction could last several months. We conclude that in some cases controlled DC lesioning may provide an effective alternative to the less controllable molecular treatments available today.

Electrophysiology of Cranial Nerve Testing: Trigeminal and Facial Nerves.

PubMed

Muzyka, Iryna M; Estephan, Bachir

2018-01-01

The clinical examination of the trigeminal and facial nerves provides significant diagnostic value, especially in the localization of lesions in disorders affecting the central and/or peripheral nervous system. The electrodiagnostic evaluation of these nerves and their pathways adds further accuracy and reliability to the diagnostic investigation and the localization process, especially when different testing methods are combined based on the clinical presentation and the electrophysiological findings. The diagnostic uniqueness of the trigeminal and facial nerves is their connectivity and their coparticipation in reflexes commonly used in clinical practice, namely the blink and corneal reflexes. The other reflexes used in the diagnostic process and lesion localization are very nerve specific and add more diagnostic yield to the workup of certain disorders of the nervous system. This article provides a review of commonly used electrodiagnostic studies and techniques in the evaluation and lesion localization of cranial nerves V and VII.

Early transcutaneous electrical nerve stimulation reduces hyperalgesia and decreases activation of spinal glial cells in mice with neuropathic pain.

PubMed

Matsuo, Hideaki; Uchida, Kenzo; Nakajima, Hideaki; Guerrero, Alexander Rodriguez; Watanabe, Shuji; Takeura, Naoto; Sugita, Daisuke; Shimada, Seiichiro; Nakatsuka, Terumasa; Baba, Hisatoshi

2014-09-01

Although transcutaneous electrical nerve stimulation (TENS) is widely used for the treatment of neuropathic pain, its effectiveness and mechanism of action in reducing neuropathic pain remain uncertain. We investigated the effects of early TENS (starting from the day after surgery) in mice with neuropathic pain, on hyperalgesia, glial cell activation, pain transmission neuron sensitization, expression of proinflammatory cytokines, and opioid receptors in the spinal dorsal horn. Following nerve injury, TENS and behavioral tests were performed every day. Immunohistochemical, immunoblot, and flow cytometric analysis of the lumbar spinal cord were performed after 8 days. Early TENS reduced mechanical and thermal hyperalgesia and decreased the activation of microglia and astrocytes (P<0.05). In contrast, the application of TENS at 1 week (TENS-1w) or 2 weeks (TENS-2w) after injury was ineffective in reducing hyperalgesia (mechanical and thermal) or activation of microglia and astrocytes. Early TENS decreased p-p38 within microglia (P<0.05), the expression levels of protein kinase C (PKC-γ), and phosphorylated anti-phospho-cyclic AMP response element-binding protein (p-CREB) in the superficial spinal dorsal horn neurons (P<0.05), mitogen-activated protein (MAP) kinases, and proinflammatory cytokines, and increased the expression levels of opioid receptors (P<0.05). The results suggested that the application of early TENS relieved hyperalgesia in our mouse model of neuropathic pain by inhibiting glial activation, MAP kinase activation, PKC-γ, and p-CREB expression, and proinflammatory cytokines expression, as well as maintenance of spinal opioid receptors. The findings indicate that TENS treatment is more effective when applied as early after nerve injury as possible. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Skin application of urea-containing cream affected cutaneous arterial sympathetic nerve activity, blood flow, and water evaporation.

PubMed

Horii, Yuko; Tanida, Mamoru; Shen, Jiao; Fujisaki, Yosiyuki; Fuyuki, Risa; Hashimoto, Kazuko; Niijima, Akira; Nakashima, Toshihiro; Nagai, Katsuya

2011-02-01

We observed that olfactory stimulation with scent of grapefruit oil elevated the activities of sympathetic nerves, and increased the plasma glycerol concentration and blood pressure. In contrast, olfactory stimulation with scent of lavender oil had opposite effects in rats. These suggest that changes in autonomic activities cause physiological functions via histaminergic H1 and H3 receptor. Moreover, it has been reported that somatic sensory stimulation affected autonomic neurotransmission. To examine effects of skin application of urea-containing cream on cutaneous arterial sympathetic nerve activity (CASNA), blood flow, and transepidermal water loss (TEWL). The activity of CASNA was determined by electrophysiological method, and cutaneous blood flow was determined using laser flowmeter in urethane-anesthetized rats, TEWL was measured using VapoMeter in the back skin of HWY hairless rats. CASNA was markedly and significantly inhibited by skin application of 10% urea-containing cream, whereas cutaneous blood flow was significantly elevated via histaminergic H3-receptor. In conscious hairless rats, TEWL was significantly decreased 24 h after application of 10% urea-containing cream to the back skin. These findings suggest that skin application of 10% urea-containing cream increases the cutaneous blood flow and water retaining ability, and that histaminergic H3-receptors may mediate these effects. © 2010 John Wiley & Sons A/S.

Miconazole enhances nerve regeneration and functional recovery after sciatic nerve crush injury.

PubMed

Lin, Tao; Qiu, Shuai; Yan, Liwei; Zhu, Shuang; Zheng, Canbin; Zhu, Qingtang; Liu, Xiaolin

2018-05-01

Improving axonal outgrowth and remyelination is crucial for peripheral nerve regeneration. Miconazole appears to enhance remyelination in the central nervous system. In this study we assess the effect of miconazole on axonal regeneration using a sciatic nerve crush injury model in rats. Fifty Sprague-Dawley rats were divided into control and miconazole groups. Nerve regeneration and myelination were determined using histological and electrophysiological assessment. Evaluation of sensory and motor recovery was performed using the pinprick assay and sciatic functional index. The Cell Counting Kit-8 assay and Western blotting were used to assess the proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole promoted axonal regrowth, increased myelinated nerve fibers, improved sensory recovery and walking behavior, enhanced stimulated amplitude and nerve conduction velocity, and elevated proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole was beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Muscle Nerve 57: 821-828, 2018. © 2017 Wiley Periodicals, Inc.

Transplantation of embryonic stem cells improves nerve repair and functional recovery after severe sciatic nerve axotomy in rats.

PubMed

Cui, Lin; Jiang, Jun; Wei, Ling; Zhou, Xin; Fraser, Jamie L; Snider, B Joy; Yu, Shan Ping

2008-05-01

Extensive research has focused on transplantation of pluripotent stem cells for the treatment of central nervous system disorders, the therapeutic potential of stem cell therapy for injured peripheral nerves is largely unknown. We used a rat sciatic nerve transection model to test the ability of implanted embryonic stem (ES) cell-derived neural progenitor cells (ES-NPCs) in promoting repair of a severely injured peripheral nerve. Mouse ES cells were neurally induced in vitro; enhanced expression and/or secretion of growth factors were detected in differentiating ES cells. One hour after removal of a 1-cm segment of the left sciatic nerve, ES-NPCs were implanted into the gap between the nerve stumps with the surrounding epineurium as a natural conduit. The transplantation resulted in substantial axonal regrowth and nerve repair, which were not seen in culture medium controls. One to 3 months after axotomy, co-immunostaining with the mouse neural cell membrane specific antibody M2/M6 and the Schwann cell marker S100 suggested that transplanted ES-NPCs had survived and differentiated into myelinating cells. Regenerated axons were myelinated and showed a uniform connection between proximal and distal stumps. Nerve stumps had near normal diameter with longitudinally oriented, densely packed Schwann cell-like phenotype. Fluoro-Gold retrogradely labeled neurons were found in the spinal cord (T12-13) and DRG (L4-L6), suggesting reconnection of axons across the transection. Electrophysiological recordings showed functional activity recovered across the injury gap. These data suggest that transplanted neurally induced ES cells differentiate into myelin-forming cells and provide a potential therapy for severely injured peripheral nerves.

Modern management of epilepsy: Vagus nerve stimulation.

PubMed

Ben-Menachem, E

1996-12-01

Vagus nerve stimulation (VNS) was first tried as a treatment for seizure patients in 1988. The idea to stimulate the vagus nerve and disrupt or prevent seizures was proposed by Jacob Zabarra. He observed a consistent finding among several animal studies which indicated that stimulation of the vagus nerve could alter the brain wave patterns of the animals under study. His hypothesis formed the basis for the development of the vagus nerve stimulator, an implantable device similar to a pacemaker, which is implanted in the left chest and attached to the left vagus nerve via a stimulating lead. Once implanted, the stimulator is programmed by a physician to deliver regular stimulation 24 hours a day regardless of seizure activity. Patients can also activate extra 'on-demand' stimulation with a handheld magnet. Clinical studies have demonstrated VNS therapy to be a safe and effective mode of treatment when added to the existing regimen of severe, refractory patients with epilepsy. Efficacy ranges from seizure free to no response with the majority of patients (> 50%) reporting at least a 50% improvement in number of seizures after 1.5 years of treatment. The side-effect profile is unique and mostly includes stimulation-related sensations in the neck and throat. The mechanism of action for VNS is not clearly understood although two theories have emerged. First, the direct connection theory hypothesizes that the anticonvulsant action of VNS is caused by a threshold raising effect of the connections to the nucleus of the solitary tract and on to other structures. The second is the concept that chronic stimulation of the vagus nerve increases the amount of inhibitory neurotransmitters and decreases the amount of excitatory neurotransmitters. Additional research into the optimal use of VNS is ongoing. Animal and clinical research have produced some interesting new data suggesting there are numerous ways to improve the clinical performance of vagus nerve stimulation as a

Optic Nerve Disorders

MedlinePlus

The optic nerve is a bundle of more than 1 million nerve fibers that carry visual messages. You have one connecting ... retina) to your brain. Damage to an optic nerve can cause vision loss. The type of vision ...

Axillary nerve injury.

PubMed

Perlmutter, G S

1999-11-01

Axillary nerve injury remains the most common peripheral nerve injury to affect the shoulder. It most often is seen after glenohumeral joint dislocation, proximal humerus fracture, or a direct blow to the deltoid muscle. Compression neuropathy has been reported to occur in the quadrilateral space syndrome, although the true pathophysiology of this disorder remains unclear. The axillary nerve is vulnerable during any operative procedure involving the inferior aspect of the shoulder and iatrogenic injury remains a serious complication of shoulder surgery. During the acute phase of injury, the shoulder should be rested, and when clinically indicated, a patient should undergo an extensive rehabilitation program emphasizing range of motion and strengthening of the shoulder girdle muscles. If no axillary nerve recovery is observed by 3 to 6 months after injury, surgical exploration may be indicated, especially if the mechanism of injury is consistent with nerve rupture. Patients who sustain injury to the axillary nerve have a variable prognosis for nerve recovery although return of function of the involved shoulder typically is good to excellent, depending on associated ligamentous or bony injury.

Effect of laminin-binding BDNF on induction of recurrent laryngeal nerve regeneration by miR-222 activation of mTOR signal pathway.

PubMed

Xie, Jin; Jin, Bin; Li, Da-Wei; Shen, Bin; Gong, Ning; Zhang, Tian-Zhen; Dong, Pin

2015-01-01

Recurrent laryngeal nerve injury is a common severe complication in neck surgery, which can cause varying degrees of vocal fold paralysis and respiratory tract problems. In present study, the effects of laminin-binding brain derived neurotrophic factor (LBD-BDNF) on recurrent laryngeal nerve regeneration were explored and its possible mechanism was investigated. LBD-BDNF or NAT-BDNF (BDNF without LBD binding) treatment was performed in laryngeal nerve injured rabbits for sixteen weeks. The laryngeal nerve was removed, and histological examination as well as laryngeal electromyography was employed to evaluate its morphology and function of conduction. PC12 cells were cultured to investigate the mechanisms underlying the effects of LBD-BDNF. Neurite outgrowth, proliferation and migration were determined in nerve cells. The expression of miRNAs and protein of mTOR was quantified by real-time PCR and western blotting respectively. In vivo experiments, LBD-BDNF significantly improved the histological structure and function of recurrent laryngeal nerve compared with NAT-BDNF. LBD-BDNF also markedly promoted neurite outgrowth, proliferation and migration in PC12 cells in vitro experiments. The levels of miR-222 and p-mTOR were up-regulated by LBD-BDNF treatment in both in vivo and in vitro experiments. miR-222 inhibitor attenuated the expression of phosphorylated mTOR and miR-222 mimic enhanced its expression in PC12 cells. In addition, the improved nerve conduction by LBD-BDNF was canceled by miR-222 inhibitor, and the mTOR inhibitor reversed the effects of miR-222 inhibitor on LBD-BDNF treated cells. The present study revealed that LBD-BDNF promoted the recurrent laryngeal nerve regeneration in laryngeal nerve injured rabbits. The underlying mechanism was closely related to activation of p-mTOR by miR-222.

Effect of laminin-binding BDNF on induction of recurrent laryngeal nerve regeneration by miR-222 activation of mTOR signal pathway

PubMed Central

Xie, Jin; Jin, Bin; Li, Da-Wei; Shen, Bin; Gong, Ning; Zhang, Tian-Zhen; Dong, Pin

2015-01-01

Background and Aim: Recurrent laryngeal nerve injury is a common severe complication in neck surgery, which can cause varying degrees of vocal fold paralysis and respiratory tract problems. In present study, the effects of laminin-binding brain derived neurotrophic factor (LBD-BDNF) on recurrent laryngeal nerve regeneration were explored and its possible mechanism was investigated. Methods: LBD-BDNF or NAT-BDNF (BDNF without LBD binding) treatment was performed in laryngeal nerve injured rabbits for sixteen weeks. The laryngeal nerve was removed, and histological examination as well as laryngeal electromyography was employed to evaluate its morphology and function of conduction. PC12 cells were cultured to investigate the mechanisms underlying the effects of LBD-BDNF. Neurite outgrowth, proliferation and migration were determined in nerve cells. The expression of miRNAs and protein of mTOR was quantified by real-time PCR and western blotting respectively. Results: In vivo experiments, LBD-BDNF significantly improved the histological structure and function of recurrent laryngeal nerve compared with NAT-BDNF. LBD-BDNF also markedly promoted neurite outgrowth, proliferation and migration in PC12 cells in vitro experiments. The levels of miR-222 and p-mTOR were up-regulated by LBD-BDNF treatment in both in vivo and in vitro experiments. miR-222 inhibitor attenuated the expression of phosphorylated mTOR and miR-222 mimic enhanced its expression in PC12 cells. In addition, the improved nerve conduction by LBD-BDNF was canceled by miR-222 inhibitor, and the mTOR inhibitor reversed the effects of miR-222 inhibitor on LBD-BDNF treated cells. Conclusions: The present study revealed that LBD-BDNF promoted the recurrent laryngeal nerve regeneration in laryngeal nerve injured rabbits. The underlying mechanism was closely related to activation of p-mTOR by miR-222. PMID:26279751

Permanent nerve damage from inferior alveolar nerve blocks: a current update.

PubMed

Pogrel, M Anthony

2012-10-01

Permanent nerve involvement has been reported following inferior alveolar nerve blocks. This study provides an update on cases reported to one unit in the preceding six years. Lidocaine was associated with 25 percent of cases, articaine with 33 percent of cases, and prilocaine with 34 percent of cases. It does appear that inferior alveolar nerve blocks can cause permanent nerve damage with any local anesthetic, but the incidences may vary.

The electrophysiology of thyroid surgery: electrophysiologic and muscular responses with stimulation of the vagus nerve, recurrent laryngeal nerve, and external branch of the superior laryngeal nerve.

PubMed

Liddy, Whitney; Barber, Samuel R; Cinquepalmi, Matteo; Lin, Brian M; Patricio, Stephanie; Kyriazidis, Natalia; Bellotti, Carlo; Kamani, Dipti; Mahamad, Sadhana; Dralle, Henning; Schneider, Rick; Dionigi, Gianlorenzo; Barczynski, Marcin; Wu, Che-Wei; Chiang, Feng Yu; Randolph, Gregory

2017-03-01

Correlation of physiologically important electromyographic (EMG) waveforms with demonstrable muscle activation is important for the reliable interpretation of evoked waveforms during intraoperative neural monitoring (IONM) of the vagus nerve, recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve (EBSLN) in thyroid surgery. Retrospective chart review. Data were reviewed retrospectively for thyroid surgery patients with laryngeal nerve IONM from January to December, 2015. EMG responses to monopolar stimulation of the vagus/RLN and EBSLN were recorded in bilateral vocalis, cricothyroid (CTM), and strap muscles using endotracheal tube-based surface and intramuscular hook electrodes, respectively. Target muscles for vagal/RLN and EBSLN stimulation were the ipsilateral vocalis and CTM, respectively. All other recording channels were nontarget muscles. Fifty surgical sides were identified in 37 subjects. All target muscle mean amplitudes were significantly higher than in nontarget muscles. With vagal/RLN stimulation, target ipsilateral vocalis mean amplitude was 1,095.7 μV (mean difference range = -814.1 to -1,078 μV, P < .0001). For EBSLN stimulation, target ipsilateral CTM mean amplitude was 6,379.3 μV (mean difference range = -6,222.6 to -6,362.3 μV, P < .0001). Target muscle large-amplitude EMG responses correlated with meaningful visual or palpable muscular responses, whereas nontarget EMG responses showed no meaningful muscle activation. Target and nontarget laryngeal muscles are differentiated based on divergence of EMG response directly correlating with presence or absence of visual and palpable muscle activation. Low-amplitude EMG waveforms in nontarget muscles with neural stimulation can be explained by the concept of far-field artifactual waveforms and do not correspond to a true muscular response. The surgeon should be aware of these nonphysiologic waveforms when interpreting and applying IONM during thyroid surgery. 4

The vestibulocochlear nerve (VIII).

PubMed

Benoudiba, F; Toulgoat, F; Sarrazin, J-L

2013-10-01

The vestibulocochlear nerve (8th cranial nerve) is a sensory nerve. It is made up of two nerves, the cochlear, which transmits sound and the vestibular which controls balance. It is an intracranial nerve which runs from the sensory receptors in the internal ear to the brain stem nuclei and finally to the auditory areas: the post-central gyrus and superior temporal auditory cortex. The most common lesions responsible for damage to VIII are vestibular Schwannomas. This report reviews the anatomy and various investigations of the nerve. Copyright © 2013. Published by Elsevier Masson SAS.

Sensation, mechanoreceptor, and nerve fiber function after nerve regeneration.

PubMed

Krarup, Christian; Rosén, Birgitta; Boeckstyns, Michel; Ibsen Sørensen, Allan; Lundborg, Göran; Moldovan, Mihai; Archibald, Simon J

2017-12-01

Sensation is essential for recovery after peripheral nerve injury. However, the relationship between sensory modalities and function of regenerated fibers is uncertain. We have investigated the relationships between touch threshold, tactile gnosis, and mechanoreceptor and sensory fiber function after nerve regeneration. Twenty-one median or ulnar nerve lesions were repaired by a collagen nerve conduit or direct suture. Quantitative sensory hand function and sensory conduction studies by near-nerve technique, including tactile stimulation of mechanoreceptors, were followed for 2 years, and results were compared to noninjured hands. At both repair methods, touch thresholds at the finger tips recovered to 81 ± 3% and tactile gnosis only to 20 ± 4% (p < 0.001) of control. The sensory nerve action potentials (SNAPs) remained dispersed and areas recovered to 23 ± 2% and the amplitudes only to 7 ± 1% (P < 0.001). The areas of SNAPs after tactile stimulation recovered to 61 ± 11% and remained slowed. Touch sensation correlated with SNAP areas (p < 0.005) and was negatively related to the prolongation of tactile latencies (p < 0.01); tactile gnosis was not related to electrophysiological parameters. The recovered function of regenerated peripheral nerve fibers and reinnervated mechanoreceptors may differentially influence recovery of sensory modalities. Touch was affected by the number and function of regenerated fibers and mechanoreceptors. In contrast, tactile gnosis depends on the input and plasticity of the central nervous system (CNS), which may explain the absence of a direct relation between electrophysiological parameters and poor recovery. Dispersed maturation of sensory nerve fibers with desynchronized inputs to the CNS also contributes to the poor recovery of tactile gnosis. Ann Neurol 2017. Ann Neurol 2017;82:940-950. © 2017 American Neurological Association.

Non-recurrent laryngeal nerve with a coexisting contralateral nerve demonstrating extralaryngeal branching.

PubMed

Constable, James D; Bathala, Srinivasalu; Ahmed, Jacob J; McGlashan, Julian A

2017-03-17

Non-recurrence and extralaryngeal branching are 2 of the more frequently encountered anomalies of the recurrent laryngeal nerve. If not anticipated intraoperatively, these abnormalities can put the nerve at risk, with subsequent vocal cord palsy. It is therefore important to report on and understand these abnormalities. We present a unique case of a non-recurrent laryngeal nerve with a coexisting contralateral nerve demonstrating extralaryngeal branching. This case allows us to demonstrate the importance of arteria lusoria in head and neck surgery, and to conclude that non-recurrence and extralaryngeal branching can occur separately within individual nerves in the same patient. The case also highlights the importance of a systematic intraoperative approach to the identification of every recurrent laryngeal nerve, especially in bilateral procedures having already exposed an anomalous nerve on one side. 2017 BMJ Publishing Group Ltd.

[Glaucoma and optic nerve drusen: Limitations of optic nerve head OCT].

PubMed

Poli, M; Colange, J; Goutagny, B; Sellem, E

2017-09-01

Optic nerve head drusen are congenital calcium deposits located in the prelaminar section of the optic nerve head. Their association with visual field defects has been classically described, but the diagnosis of glaucoma is not easy in these cases of altered optic nerve head anatomy. We describe the case of a 67-year-old man with optic nerve head drusen complicated by glaucoma, which was confirmed by visual field and OCT examination of the peripapillary retinal nerve fiber layer (RNFL), but the measurement of the minimum distance between the Bruch membrane opening and the internal limiting membrane (minimum rim width, BMO-MRW) by OCT was normal. OCT of the BMO-MRW is a new diagnostic tool for glaucoma. Superficial optic nerve head drusen, which are found between the internal limiting membrane and the Bruch's membrane opening, overestimate the value of this parameter. BMO-MRW measurement is not adapted to cases of optic nerve head drusen and can cause false-negative results for this parameter, and the diagnosis of glaucoma in this case should be based on other parameters such as the presence of a fascicular defect in the retinal nerve fibers, RNFL or macular ganglion cell complex thinning, as well as visual field data. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Astrocytes as gate-keepers in optic nerve regeneration--a mini-review.

PubMed

García, Dana M; Koke, Joseph R

2009-02-01

Animals that develop without extra-embryonic membranes (anamniotes--fish, amphibians) have impressive regenerative capacity, even to the extent of replacing entire limbs. In contrast, animals that develop within extra-embryonic membranes (amniotes--reptiles, birds, mammals) have limited capacity for regeneration as adults, particularly in the central nervous system (CNS). Much is known about the process of nerve development in fish and mammals and about regeneration after lesions in the CNS in fish and mammals. Because the retina of the eye and optic nerve are functionally part of the brain and are accessible in fish, frogs, and mice, optic nerve lesion and regeneration (ONR) has been extensively used as a model system for study of CNS nerve regeneration. When the optic nerve of a mouse is severed, the axons leading into the brain degenerate. Initially, the cut end of the axons on the proximal, eye-side of the injury sprout neurites which begin to grow into the lesion. Simultaneously, astrocytes of the optic nerve become activated to initiate wound repair as a first step in reestablishing the structural integrity of the optic nerve. This activation appears to initiate a cascade of molecular signals resulting in apoptotic cell death of the retinal ganglion cells axons of which make up the neural component of the optic nerve; regeneration fails and the injury is permanent. Evidence specifically implicating astrocytes comes from studies showing selective poisoning of astrocytes at the optic nerve lesion, along with activation of a gene whose product blocks apoptosis in retinal ganglion cells, creates conditions favorable to neurites sprouting from the cut proximal stump, growing through the lesion and into the distal portion of the injured nerve, eventually reaching appropriate targets in the brain. In anamniotes, astrocytes ostensibly present no such obstacle since optic nerve regeneration occurs without intervention; however, no systematic study of glial involvement

Immediate versus delayed primary nerve repair in the rabbit sciatic nerve

PubMed Central

Piskin, Ahmet; Altunkaynak, Berrin Zühal; Çιtlak, Atilla; Sezgin, Hicabi; Yazιcι, Ozgür; Kaplan, Süleyman

2013-01-01

It is well known that peripheral nerve injury should be treated immediately in the clinic, but in some instances, repair can be delayed. This study investigated the effects of immediate versus delayed (3 days after injury) neurorrhaphy on repair of transected sciatic nerve in New Zealand rabbits using stereological, histomorphological and biomechanical methods. At 8 weeks after immediate and delayed neurorrhaphy, axon number and area in the sciatic nerve, myelin sheath and epineurium thickness, Schwann cell morphology, and the mechanical property of nerve fibers did not differ obviously. These results indicate that delayed neurorrhaphy do not produce any deleterious effect on sciatic nerve repair. PMID:25206663

Exposure to a high-fat diet during development alters leptin and ghrelin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits.

PubMed

Prior, Larissa J; Davern, Pamela J; Burke, Sandra L; Lim, Kyungjoon; Armitage, James A; Head, Geoffrey A

2014-02-01

Exposure to maternal obesity or a maternal diet rich in fat during development may have adverse outcomes in offspring, such as the development of obesity and hypertension. The present study examined the effect of a maternal high-fat diet (m-HFD) on offspring blood pressure and renal sympathetic nerve activity, responses to stress, and sensitivity to central administration of leptin and ghrelin. Offspring of New Zealand white rabbits fed a 13% HFD were slightly heavier than offspring from mothers fed a 4% maternal normal fat diet (P<0.05) but had 64% greater fat pad mass (P=0.015). Mean arterial pressure, heart rate, and renal sympathetic nerve activity at 4 months of age were 7%, 7%, and 24% greater, respectively (P<0.001), in m-HFD compared with maternal normal fat diet rabbits, and the renal sympathetic nerve activity response to airjet stress was enhanced in the m-HFD group. m-HFD offspring had markedly elevated pressor and renal sympathetic nerve activity responses to intracerebroventricular leptin (5-100 µg) and enhanced sympathetic responses to intracerebroventricular ghrelin (1-5 nmol). In contrast, there was resistance to the anorexic effects of intracerebroventricular leptin and less neuronal activation as detected by Fos immunohistochemistry in the arcuate (-57%; P<0.001) and paraventricular (-37%; P<0.05) nuclei of the hypothalamus in m-HFD offspring compared with maternal normal fat diet rabbits. We conclude that offspring from mothers consuming an HFD exhibit an adverse cardiovascular profile in adulthood because of altered central hypothalamic sensitivity to leptin and ghrelin.

The neglected cranial nerve: nervus terminalis (cranial nerve N).

PubMed

Vilensky, Joel A

2014-01-01

The nervus terminalis (NT; terminal nerve) was clearly identified as an additional cranial nerve in humans more than a century ago yet remains mostly undescribed in modern anatomy textbooks. The nerve is referred to as the nervus terminalis because in species initially examined its fibers were seen entering the brain in the region of the lamina terminalis. It has also been referred to as cranial nerve 0, but because there is no Roman symbol for zero, an N for the Latin word nulla is a better numerical designation. This nerve is very distinct in human fetuses and infants but also has been repeatedly identified in adult human brains. The NT fibers are unmyelinated and emanate from ganglia. The fibers pass through the cribriform plate medial to those of the olfactory nerve fila. The fibers end in the nasal mucosa and probably arise from autonomic/neuromodulatory as well as sensory neurons. The NT has been demonstrated to release luteinizing-releasing luteinizing hormone and is therefore thought to play a role in reproductive behavior. Based on the available evidence, the NT appears to be functional in adult humans and should be taught in medical schools and incorporated into anatomy/neuroanatomy textbooks. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Engineering a multimodal nerve conduit for repair of injured peripheral nerve

NASA Astrophysics Data System (ADS)

Quigley, A. F.; Bulluss, K. J.; Kyratzis, I. L. B.; Gilmore, K.; Mysore, T.; Schirmer, K. S. U.; Kennedy, E. L.; O'Shea, M.; Truong, Y. B.; Edwards, S. L.; Peeters, G.; Herwig, P.; Razal, J. M.; Campbell, T. E.; Lowes, K. N.; Higgins, M. J.; Moulton, S. E.; Murphy, M. A.; Cook, M. J.; Clark, G. M.; Wallace, G. G.; Kapsa, R. M. I.

2013-02-01

Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate

Exercise training to reduce sympathetic nerve activity in heart failure patients. A systematic review and meta-analysis.

PubMed

Saavedra, María Javiera; Romero, Fernando; Roa, Jorge; Rodríguez-Núñez, Iván

To determine the effects of exercise training on sympathetic nerve activity in heart failure patients. A systematic review was performed. An electronic search of MEDLINE, ProQuest, SciELO, SPORTDiscus, Rehabilitation and Sport Medicine Source, Cumulative Index to Nursing and Allied Health Literature, Tripdatabase, Science Direct and PEDrO was performed from their inception to February 2017. Clinical trials and quasi-experimental studies were considered for primary article selection. The studies should include patients diagnosed with chronic heart failure that performed exercise training for at least 4 weeks. Sympathetic nerve activity should be measured by microneurography before and after the intervention. The Cochrane Collaboration's Risk of Bias Tool was used to evaluate risk of bias, and the quality of evidence was rated following the GRADE approach. Standardized mean differences (SMD) were calculated for control and experimental groups. Meta-analysis was performed using the random effects model. Five trials were included. Overall, the trials had moderate risk of bias. The experimental group indicated a significant decrease in the number of bursts per minute (SMD -2.48; 95% CI -3.55 to -1.41) when compared to the control group. Meanwhile, a significant decrease was also observed in the prevalence of bursts per 100 beats in the experimental group when compared to the control group (SMD -2.66; 95% CI -3.64 to -1.69). Exercise training could be effective in reducing sympathetic nerve activity in patients with heart failure. The quality of evidence across the studies was moderate. Future studies are necessary to confirm these results. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Magnetic reconnection driven by Gekko XII lasers with a Helmholtz capacitor-coil target

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

Pei, X. X.; University of Chinese Academy of Sciences, Beijing 100049; Zhong, J. Y., E-mail: jyzhong@bnu.edu.cn, E-mail: gzhao@bao.ac.cn

2016-03-15

We demonstrate a novel plasma device for magnetic reconnection, driven by Gekko XII lasers irradiating a double-turn Helmholtz capacitor-coil target. Optical probing revealed an accumulated plasma plume near the magnetic reconnection outflow. The background electron density and magnetic field were measured to be approximately 10{sup 18 }cm{sup −3} and 60 T by using Nomarski interferometry and the Faraday effect, respectively. In contrast with experiments on magnetic reconnection constructed by the Biermann battery effect, which produced high beta values, our beta value was much lower than one, which greatly extends the parameter regime of laser-driven magnetic reconnection and reveals its potential in astrophysicalmore » plasma applications.« less

Synovial sarcoma of nerve.

PubMed

Scheithauer, Bernd W; Amrami, Kimberly K; Folpe, Andrew L; Silva, Ana I; Edgar, Mark A; Woodruff, James M; Levi, Allan D; Spinner, Robert J

2011-04-01

Tumors of peripheral nerve are largely neuroectodermal in nature and derived from 2 elements of nerve, Schwann or perineurial cells. In contrast, mesenchymal tumors affecting peripheral nerve are rare and are derived mainly from epineurial connective tissue. The spectrum of the latter is broad and includes lipoma, vascular neoplasms, hematopoietic tumors, and even meningioma. Of malignant peripheral nerve neoplasms, the vast majority are primary peripheral nerve sheath tumors. Malignancies of mesenchymal type are much less common. To date, only 12 cases of synovial sarcoma of nerve have been described. Whereas in the past, parallels were drawn between synovial sarcoma and malignant glandular schwannoma, an uncommon form of malignant peripheral nerve sheath tumor, molecular genetics have since clarified the distinction. Herein, we report 10 additional examples of molecularly confirmed synovial sarcoma, all arising within minor or major nerves. Affecting 7 female and 3 male patients, 4 tumors occurred in pediatric patients. Clinically and radiologically, most lesions were initially thought to be benign nerve sheath tumors. On reinterpretation of imaging, they were considered indeterminate in nature with some features suspicious for malignancy. Synovial sarcoma of nerve, albeit rare, seems to behave in a manner similar to its more common, soft tissue counterpart. Those affecting nerve have a variable prognosis. Definitive recommendations regarding surgery and adjuvant therapies await additional reports and long-term follow-up. The literature is reviewed and a meta-analysis is performed with respect to clinicopathologic features versus outcome. Copyright © 2011. Published by Elsevier Inc.

[Which changes occur in nerve grafts harvested with a nerve stripper? Morphological studies].

PubMed

Koller, R; Frey, M; Rab, M; Deutinger, M; Freilinger, G

1995-03-01

A histological and morphometric study was undertaken in order to evaluate the alterations in sural nerves harvested for nerve grafting using a nerve stripper. In 19 nerves biopsies were taken from the proximal and/or the distal end of the stripped nerve graft. Cross sections were examined for alterations of the perineurium and the myelin sheaths. In four nerves alterations within the perineurium were found, which affected 37% of the endoneural cross-sectional area on the average. In all specimens, the perineurial sheath was seen to be intact. The results of the present study suggest that harvesting of a nerve graft using a stripper does not cause major injuries to the graft and therefore successful neurotization of the graft should not be impaired.

Superficial or deep implantation of motor nerve after denervation: an experimental study--superficial or deep implantation of motor nerve.

PubMed

Askar, Ibrahím; Sabuncuoglu, Bízden Tavíl

2002-01-01

manner in both experimental groups. However, they were more dense in the superficial implantation group than the deep implantation group. It was concluded that superficial implantation has a more powerful contractile capacity than that of deep implantation. We believe that this might arise from the high activity of glycolytic enzymes in peripheral muscle fibers of gastrocnemius muscle, decrease in insufficient intramuscular guidance apparatus, and intramuscular microneuroma formation at the insufficient neuromuscular junction since the motor nerve had less route to muscle fibers. Copyright 2002 Wiley-Liss, Inc.

Chitosan-film enhanced chitosan nerve guides for long-distance regeneration of peripheral nerves.

PubMed

Meyer, Cora; Stenberg, Lena; Gonzalez-Perez, Francisco; Wrobel, Sandra; Ronchi, Giulia; Udina, Esther; Suganuma, Seigo; Geuna, Stefano; Navarro, Xavier; Dahlin, Lars B; Grothe, Claudia; Haastert-Talini, Kirsten

2016-01-01

Biosynthetic nerve grafts are developed in order to complement or replace autologous nerve grafts for peripheral nerve reconstruction. Artificial nerve guides currently approved for clinical use are not widely applied in reconstructive surgery as they still have limitations especially when it comes to critical distance repair. Here we report a comprehensive analysis of fine-tuned chitosan nerve guides (CNGs) enhanced by introduction of a longitudinal chitosan film to reconstruct critical length 15 mm sciatic nerve defects in adult healthy Wistar or diabetic Goto-Kakizaki rats. Short and long term investigations demonstrated that the CNGs enhanced by the guiding structure of the introduced chitosan film significantly improved functional and morphological results of nerve regeneration in comparison to simple hollow CNGs. Importantly, this was detectable both in healthy and in diabetic rats (short term) and the regeneration outcome almost reached the outcome after autologous nerve grafting (long term). Hollow CNGs provide properties likely leading to a wider clinical acceptance than other artificial nerve guides and their performance can be increased by simple introduction of a chitosan film with the same advantageous properties. Therefore, the chitosan film enhanced CNGs represent a new generation medical device for peripheral nerve reconstruction. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Incidence of Concurrent Peroneal Nerve Injury in Multiligament Knee Injuries and Outcomes after Knee Reconstruction.

PubMed

Worley, John R; Brimmo, Olubusola; Nuelle, Clayton W; Cook, James L; Stannard, James P

2018-06-13

The purpose of this study was to determine incidence of concurrent peroneal nerve injury and to compare outcomes in patients with and without peroneal nerve injury after surgical treatment for multiligament knee injuries (MLKIs). A retrospective study of 357 MLKIs was conducted. Patients with two or more knee ligaments requiring surgical reconstruction were included. Mean follow-up was 35 months (0-117). Incidence of concurrent peroneal nerve injury was noted and patients with and without nerve injury were evaluated for outcomes. Concurrent peroneal nerve injury occurred in 68 patients (19%). In patients with nerve injury, 45 (73%) returned to full duty at work; 193 (81%) patients without nerve injury returned to full duty ( p  = 0.06). In patients with nerve injury, 37 (60%) returned to their previous level of activity; 148 (62%) patients without nerve injury returned to their previous level of activity ( p  = 0.41). At final follow-up, there were no significant differences in level of pain (mean visual analog scale 1.6 vs. 2; p  = 0.17), Lysholm score (mean 88.6 vs. 88.8; p  = 0.94), or International Knee Documentation Committee score (mean 46.2 vs. 47.8; p  = 0.67) for patients with or without peroneal nerve injury, respectively. Postoperative range of motion (ROM) (mean 121 degrees) was significantly lower ( p  = 0.02) for patients with nerve injury compared with patients without nerve injury (mean 127 degrees). Concurrent peroneal nerve injury occurred in 19% of patients in this large cohort suffering MLKIs. After knee reconstruction surgery, patients with concurrent peroneal nerve injuries had significantly lower knee ROM and trended toward a lower rate of return to work. However, outcomes with respect to activity level, pain, and function were not significantly different between the two groups. This study contributes to our understanding of patient outcomes in patients with concurrent MLKI and peroneal nerve injury, with a focus on

Enhanced peripheral nerve regeneration through asymmetrically porous nerve guide conduit with nerve growth factor gradient.

PubMed

Oh, Se Heang; Kang, Jun Goo; Kim, Tae Ho; Namgung, Uk; Song, Kyu Sang; Jeon, Byeong Hwa; Lee, Jin Ho

2018-01-01

In this study, we fabricated a nerve guide conduit (NGC) with nerve growth factor (NGF) gradient along the longitudinal direction by rolling a porous polycaprolactone membrane with NGF concentration gradient. The NGF immobilized on the membrane was continuously released for up to 35 days, and the released amount of the NGF from the membrane gradually increased from the proximal to distal NGF ends, which may allow a neurotrophic factor gradient in the tubular NGC for a sufficient period. From the in vitro cell culture experiment, it was observed that the PC12 cells sense the NGF concentration gradient on the membrane for the cell proliferation and differentiation. From the in vivo animal experiment using a long gap (20 mm) sciatic nerve defect model of rats, the NGC with NGF concentration gradient allowed more rapid nerve regeneration through the NGC than the NGC itself and NGC immobilized with uniformly distributed NGF. The NGC with NGF concentration gradient seems to be a promising strategy for the peripheral nerve regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 52-64, 2018. © 2017 Wiley Periodicals, Inc.

A structure-activity analysis of the variation in oxime efficacy against nerve agents

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

Maxwell, Donald M.; Koplovitz, Irwin; Worek, Franz

2008-09-01

A structure-activity analysis was used to evaluate the variation in oxime efficacy of 2-PAM, obidoxime, HI-6 and ICD585 against nerve agents. In vivo oxime protection and in vitro oxime reactivation were used as indicators of oxime efficacy against VX, sarin, VR and cyclosarin. Analysis of in vivo oxime protection was conducted with oxime protective ratios (PR) from guinea pigs receiving oxime and atropine therapy after sc administration of nerve agent. Analysis of in vitro reactivation was conducted with second-order rate contants (k{sub r2}) for oxime reactivation of agent-inhibited acetylcholinesterase (AChE) from guinea pig erythrocytes. In vivo oxime PR and inmore » vitro k{sub r2} decreased as the volume of the alkylmethylphosphonate moiety of nerve agents increased from VX to cyclosarin. This effect was greater with 2-PAM and obidoxime (> 14-fold decrease in PR) than with HI-6 and ICD585 (< 3.7-fold decrease in PR). The decrease in oxime PR and k{sub r2} as the volume of the agent moiety conjugated to AChE increased was consistent with a steric hindrance mechanism. Linear regression of log (PR-1) against log (k{sub r2} {center_dot} [oxime dose]) produced two offset parallel regression lines that delineated a significant difference between the coupling of oxime reactivation and oxime protection for HI-6 and ICD585 compared to 2-PAM and obidoxime. HI-6 and ICD585 appeared to be 6.8-fold more effective than 2-PAM and obidoxime at coupling oxime reactivation to oxime protection, which suggested that the isonicotinamide group that is common to both of these oximes, but absent from 2-PAM and obidoxime, is important for oxime efficacy.« less

The search of the target of promotion: Phenylbenzoate esterase activities in hen peripheral nerve

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

Moretto, A.; Nicolli, A.; Lotti, M.

2007-03-15

Certain esterase inhibitors, such as carbamates, phosphinates and sulfonyl halides, do not cause neuropathy as some organophosphates, but they may exacerbate chemical or traumatic insults to axons. This phenomenon is called promotion of axonopathies. Given the biochemical and toxicological characteristics of these compounds, the hypothesis was made that the target of promotion is a phenyl valerate (PV) esterase similar to neuropathy target esterase (NTE), the target of organophosphate induced delayed polyneuropathy. However, attempts to identify a PV esterase in hen peripheral nerve have been, so far, unsuccessful. We tested several esters, other than PV, as substrates of esterases from crudemore » homogenate of the hen peripheral nerve. The ideal substrate should be poorly hydrolysed by NTE but extensively by enzyme(s) that are insensitive to non-promoters, such as mipafox, and sensitive to promoters, such as phenyl methane sulfonyl fluoride (PMSF). When phenyl benzoate (PB) was used as substrate, about 65% of total activity was resistant to the non-promoter mipafox (up to 0.5 mM, 20 min, pH 8.0), that inhibits NTE and other esterases. More than 90% of this resistant activity was sensitive to the classical promoter PMSF (1 mM, 20 min, pH 8.0) with an IC{sub 50} of about 0.08 mM (20 min, pH 8.0). On the contrary, the non-promoter p-toluene sulfonyl fluoride caused only about 10% inhibition at 0.5 mM. Several esterase inhibitors including, paraoxon, phenyl benzyl carbamate, di-n-butyl dichlorovinyl phosphate and di-isopropyl fluorophosphate, were tested both in vitro and in vivo for inhibition of this PB activity. Mipafox-resistant PMSF-sensitive PB esterase activity(ies) was inhibited by promoters but not by non promoters and neuropathic compounds.« less

Dynamic interactions between arterial pressure and sympathetic nerve activity: role of arterial baroreceptors.

PubMed

Julien, Claude; Chapuis, Bruno; Cheng, Yong; Barrès, Christian

2003-10-01

The role of arterial baroreceptors in controlling arterial pressure (AP) variability through changes in sympathetic nerve activity was examined in conscious rats. AP and renal sympathetic nerve activity (RSNA) were measured continuously during 1-h periods in freely behaving rats that had been subjected to sinoaortic baroreceptor denervation (SAD) or a sham operation 2 wk before study (n = 10 in each group). Fast Fourier transform analysis revealed that chronic SAD did not alter high-frequency (0.75-5 Hz) respiratory-related oscillations of mean AP (MAP) and RSNA, decreased by approximately 50% spectral power of both variables in the midfrequency band (MF, 0.27-0.74 Hz) containing the so-called Mayer waves, and induced an eightfold increase in MAP power without altering RSNA power in the low-frequency band (0.005-0.27 Hz). In both groups of rats, coherence between RSNA and MAP was maximal in the MF band and was usually weak at lower frequencies. In SAD rats, the transfer function from RSNA to MAP showed the characteristics of a second-order low-pass filter containing a fixed time delay ( approximately 0.5 s). These results indicate that arterial baroreceptors are not involved in production of respiratory-related oscillations of RSNA but play a major role in the genesis of synchronous oscillations of MAP and RSNA at the frequency of Mayer waves. The weak coupling between slow fluctuations of RSNA and MAP in sham-operated and SAD rats points to the interference of noise sources unrelated to RSNA affecting MAP and of noise sources unrelated to MAP affecting RSNA.

Reinnervation of Urethral and Anal Sphincters With Femoral Motor Nerve to Pudendal Nerve Transfer

PubMed Central

Ruggieri, Michael R.; Braverman, Alan S.; Bernal, Raymond M.; Lamarre, Neil S.; Brown, Justin M.; Barbe, Mary F.

2012-01-01

Aims Lower motor neuron damage to sacral roots or nerves can result in incontinence and a flaccid urinary bladder. We showed bladder reinnervation after transfer of coccygeal to sacral ventral roots, and genitofemoral nerves (L1, 2 origin) to pelvic nerves. This study assesses the feasibility of urethral and anal sphincter reinnervation using transfer of motor branches of the femoral nerve (L2–4 origin) to pudendal nerves (S1, 2 origin) that innervate the urethral and anal sphincters in a canine model. Methods Sacral ventral roots were selected by their ability to stimulate bladder, urethral sphincter, and anal sphincter contraction and transected. Bilaterally, branches of the femoral nerve, specifically, nervus saphenous pars muscularis [Evans HE. Miller’s anatomy of the dog. Philadelphia: W.B. Saunders; 1993], were transferred and end-to-end anastomosed to transected pudendal nerve branches in the perineum, then enclosed in unipolar nerve cuff electrodes with leads to implanted RF micro-stimulators. Results Nerve stimulation induced increased anal and urethral sphincter pressures in five of six transferred nerves. Retrograde neurotracing from the bladder, urethral sphincter, and anal sphincter using fluorogold, fast blue, and fluororuby, demonstrated urethral and anal sphincter labeled neurons in L2–4 cord segments (but not S1–3) in nerve transfer canines, consistent with rein-nervation by the transferred femoral nerve motor branches. Controls had labeled neurons only in S1–3 segments. Postmortem DiI and DiO labeling confirmed axonal regrowth across the nerve repair site. Conclusions These results show spinal cord reinnervation of urethral and anal sphincter targets after sacral ventral root transection and femoral nerve transfer (NT) to the denervated pudendal nerve. These surgical procedures may allow patients to regain continence. PMID:21953679

Controlled nerve growth factor release from multi-ply alginate/chitosan-based nerve conduits.

PubMed

Pfister, Lukas A; Alther, Eva; Papaloïzos, Michaël; Merkle, Hans P; Gander, Bruno

2008-06-01

The delivery kinetics of growth factors has been suggested to play an important role in the regeneration of peripheral nerves following axotomy. In this context, we designed a nerve conduit (NC) with adjustable release kinetics of nerve growth factor (NGF). A multi-ply system was designed where NC consisting of a polyelectrolyte alginate/chitosan complex was coated with layers of poly(lactide-co-glycolide) (PLGA) to control the release of embedded NGF. Prior to assessing the in vitro NGF release from NC, various release test media, with and without stabilizers for NGF, were evaluated to ensure adequate quantification of NGF by ELISA. Citrate (pH 5.0) and acetate (pH 5.5) buffered saline solutions containing 0.05% Tween 20 yielded the most reliable results for ELISA active NGF. The in vitro release experiments revealed that the best results in terms of reproducibility and release control were achieved when the NGF was embedded between two PLGA layers and the ends of the NC tightly sealed by the PLGA coatings. The release kinetics could be efficiently adjusted by accommodating NGF at different radial locations within the NC. A sustained release of bioactive NGF in the low nanogram per day range was obtained for at least 15days. In conclusion, the developed multi-ply NGF loaded NC is considered a suitable candidate for future implantation studies to gain insight into the relationship between local growth factor availability and nerve regeneration.

Histochemical discrimination of fibers in regenerating rat infraorbital nerve

NASA Technical Reports Server (NTRS)

Wilke, R. A.; Riley, D. A.; Sanger, J. R.

1992-01-01

In rat dorsal root ganglia, histochemical staining of carbonic anhydrase (CA) and cholinesterase (CE) yields a reciprocal pattern of activity: Sensory processes are CA positive and CE negative, whereas motor processes are CA negative and CE positive. In rat infraorbital nerve (a sensory peripheral nerve), we saw extensive CA staining of nearly 100% of the myelinated axons. Although CE reactivity in myelinated axons was extremely rare, we did observe CE staining of unmyelinated autonomic fibers. Four weeks after transection of infraorbital nerves, CA-stained longitudinal sections of the proximal stump demonstrated 3 distinct morphological zones. A fraction of the viable axons retained CA activity to within 2 mm of the distal extent of the stump, and the stain is capable of resolving growth sprouts being regenerated from these fibers. Staining of unmyelinated autonomic fibers in serial sections shows that CE activity was not retained as far distally as is the CA sensory staining.

Nerve-dependent factors regulating transcript levels of glycogen phosphorylase in skeletal muscle.

PubMed

Matthews, C C; Carlsen, R C; Froman, B; Tait, R; Gorin, F

1998-06-01

1. Muscle glycogen phosphorylase (MGP), the rate-limiting enzyme for glycogen metabolism in skeletal muscle, is neurally regulated. Steady-state transcript levels of the skeletal muscle isozyme of MGP decrease significantly following muscle denervation and after prolonged muscle inactivity with an intact motor nerve. These data suggest that muscle activity has an important influence on MGP gene expression. The evidence to this point, however, does not preclude the possibility that MGP is also regulated by motor neuron-derived trophic factors. This study attempts to distinguish between regulation provided by nerve-evoked muscle contractile activity and that provided by the delivery of neurotrophic factors. 2. Steady-state MGP transcript levels were determined in rat tibialis anterior (TA) muscles following controlled interventions aimed at separating the contributions of contractile activity from axonally transported trophic factors. The innervated TA was rendered inactive by daily epineural injections of tetrodotoxin (TTX) into the sciatic nerve. Sustained inhibition of axonal transport was accomplished by applying one of three different concentrations of the antimicrotubule agent, vinblastine (VIN), to the proximal sciatic nerve for 1 hr. The axonal transport of acetylcholinesterase (AChE) was assessed 7, 14, and 28 days after the single application of VIN. 3. MGP transcript levels normalized to total RNA were reduced by 67% in rat TA, 7 days after nerve section. Daily injection of 2 microg TTX into the sciatic nerve for 7 days eliminated muscle contractile activity and reduced MGP transcript levels by 60%. 4. A single, 1-hr application of 0.10% (w/v) VIN to the sciatic nerve reduced axonal transport but did not alter MGP transcript levels in the associated TA, 7 days after treatment. Application of 0.10% VIN to the sciatic nerve also did not affect IA sensory or motor nerve conduction velocities or TA contractile function. 5. Treatment of the sciatic nerve with 0

Laparoscopic anatomy of the autonomic nerves of the pelvis and the concept of nerve-sparing surgery by direct visualization of autonomic nerve bundles.

PubMed

Lemos, Nucelio; Souza, Caroline; Marques, Renato Moretti; Kamergorodsky, Gil; Schor, Eduardo; Girão, Manoel J B C

2015-11-01

To demonstrate the laparoscopic neuroanatomy of the autonomic nerves of the pelvis using the laparoscopic neuronavigation technique, as well as the technique for a nerve-sparing radical endometriosis surgery. Step-by-step explanation of the technique using videos and pictures (educational video) to demonstrate the anatomy of the intrapelvic bundles of the autonomic nerve system innervating the bladder, rectum, and pelvic floor. Tertiary referral center. One 37-year-old woman with an infiltrative endometriotic nodule on the anterior third of the left uterosacral ligament and one 34-year-old woman with rectovaginal endometriosis. Exposure and preservation by direct visualization of the hypogastric nerve and the inferior hypogastric plexus. Visual control and identification of the autonomic nerve branches of the posterior pelvis. Exposure and preservation of the hypogastric nerve and the superficial part of the left hypogastric nerve were achieved on the first patient. Nerve roots S2, S3, and S4 were identified on the second patient, allowing for the exposure and preservation of the pelvic splanchnic nerves and the deep portion inferior hypogastric plexus. Radical surgery for endometriosis can induce urinary dysfunction in 2.4%-17.5% of patients owing to lesion of the autonomic nerves. The surgeon's knowledge of the anatomy of these nerves is the main factor for preserving postoperative urinary function. The following nerves are the intrapelvic part of the autonomic nervous system: the hypogastric nerves, which derive from the superior hypogastric plexus and carry the sympathetic signals to the internal urethral and anal sphincters as well as to the pelvic visceral proprioception; and the pelvic splanchnic nerves, which arise from S2 to S4 and carry nociceptive and parasympathetic signals to the bladder, rectum, and the sigmoid and left colons. The hypogastric and pelvic splanchnic nerves merge into the pararectal fossae to form the inferior hypogastric plexus. Most

Afferent Nerve Regulation of Bladder Function in Health and Disease

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2012-01-01

The afferent innervation of the urinary bladder consists primarily of small myelinated (Aδ) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent neurons synthesize several putative neurotransmitters, including neuropeptides, glutamic acid, aspartic acid, and nitric oxide. The afferent neurons also express various types of receptors and ion channels, including transient receptor potential channels, purinergic, muscarinic, endothelin, neurotrophic factor, and estrogen receptors. Patch-clamp recordings in dissociated bladder afferent neurons and recordings of bladder afferent nerve activity have revealed that activation of many of these receptors enhances neuronal excitability. Afferent nerves can respond to chemicals present in urine as well as chemicals released in the bladder wall from nerves, smooth muscle, inflammatory cells, and epithelial cells lining the bladder lumen. Pathological conditions alter the chemical and electrical properties of bladder afferent pathways, leading to urinary urgency, increased voiding frequency, nocturia, urinary incontinence, and pain. Neurotrophic factors have been implicated in the pathophysiological mechanisms underlying the sensitization of bladder afferent nerves. Neurotoxins such as capsaicin, resiniferatoxin, and botulinum neurotoxin that target sensory nerves are useful in treating disorders of the lower urinary tract. PMID:19655106

Electrophysiology of Cranial Nerve Testing: Cranial Nerves IX and X.

PubMed

Martinez, Alberto R M; Martins, Melina P; Moreira, Ana Lucila; Martins, Carlos R; Kimaid, Paulo A T; França, Marcondes C

2018-01-01

The cranial nerves IX and X emerge from medulla oblongata and have motor, sensory, and parasympathetic functions. Some of these are amenable to neurophysiological assessment. It is often hard to separate the individual contribution of each nerve; in fact, some of the techniques are indeed a composite functional measure of both nerves. The main methods are the evaluation of the swallowing function (combined IX and X), laryngeal electromyogram (predominant motor vagal function), and heart rate variability (predominant parasympathetic vagal function). This review describes, therefore, the techniques that best evaluate the major symptoms presented in IX and X cranial nerve disturbance: dysphagia, dysphonia, and autonomic parasympathetic dysfunction.

4-Functionalized 1,3-diarylpyrazoles bearing 6-aminosulfonylbenzothiazole moiety as potent inhibitors of carbonic anhydrase isoforms hCA I, II, IX and XII.

PubMed

SitaRam; Ceruso, Mariangela; Khloya, Poonam; Supuran, Claudiu T; Sharma, Pawan K

2014-12-15

A series of 24 novel heterocyclic compounds-functionalized at position 4 with aldehyde (5a-5f), carboxylic acid (6a-6f), nitrile (7a-7f) and oxime (8a-8f) functional groups-bearing 6-aminosulfonybenzothiazole moiety at position 1 of pyrazole has been synthesized and investigated for the inhibition of four isoforms of the α-class carbonic anhydrases (CAs, EC 4.2.1.1), comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (transmembrane, tumor associated isozymes). Against the human isozyme hCA I, compounds 6a-6f showed medium-weak inhibitory potential with Ki values in the range of 157-690nM with 6a showing better potential than the standard drug acetazolamide (AZA). Against hCA II, all the compounds showed excellent to moderate inhibition with Ki values of compounds 5a, 5d, 5f, 6a-6f, 8d and 8f lower than 12nM (Ki of AZA). Against hCA IX, all the compounds showed moderate inhibition with the exception of 6e which showed nearly 9 fold a better profile compared to AZA, whereas against hCA XII, four compounds 6e, 7a, 7b and 7d showed Ki in the same order as that of AZA. Carboxylic acid 6e was found to be an excellent inhibitor of both hCA IX and XII, with Ki values of 2.8nM and 5.5nM, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

Phrenic nerve transfer to the musculocutaneous nerve for the repair of brachial plexus injury: electrophysiological characteristics

PubMed Central

Liu, Ying; Xu, Xun-cheng; Zou, Yi; Li, Su-rong; Zhang, Bin; Wang, Yue

2015-01-01

Phrenic nerve transfer is a major dynamic treatment used to repair brachial plexus root avulsion. We analyzed 72 relevant articles on phrenic nerve transfer to repair injured brachial plexus that were indexed by Science Citation Index. The keywords searched were brachial plexus injury, phrenic nerve, repair, surgery, protection, nerve transfer, and nerve graft. In addition, we performed neurophysiological analysis of the preoperative condition and prognosis of 10 patients undergoing ipsilateral phrenic nerve transfer to the musculocutaneous nerve in our hospital from 2008 to 201 3 and observed the electromyograms of the biceps brachii and motor conduction function of the musculocutaneous nerve. Clinically, approximately 28% of patients had brachial plexus injury combined with phrenic nerve injury, and injured phrenic nerve cannot be used as a nerve graft. After phrenic nerve transfer to the musculocutaneous nerve, the regenerated potentials first appeared at 3 months. Recovery of motor unit action potential occurred 6 months later and became more apparent at 12 months. The percent of patients recovering ‘excellent’ and ‘good’ muscle strength in the biceps brachii was 80% after 18 months. At 12 months after surgery, motor nerve conduction potential appeared in the musculocutaneous nerve in seven cases. These data suggest that preoperative evaluation of phrenic nerve function may help identify the most appropriate nerve graft in patients with an injured brachial plexus. The functional recovery of a transplanted nerve can be dynamically observed after the surgery. PMID:25883637

Phrenic nerve transfer to the musculocutaneous nerve for the repair of brachial plexus injury: electrophysiological characteristics.

PubMed

Liu, Ying; Xu, Xun-Cheng; Zou, Yi; Li, Su-Rong; Zhang, Bin; Wang, Yue

2015-02-01

Phrenic nerve transfer is a major dynamic treatment used to repair brachial plexus root avulsion. We analyzed 72 relevant articles on phrenic nerve transfer to repair injured brachial plexus that were indexed by Science Citation Index. The keywords searched were brachial plexus injury, phrenic nerve, repair, surgery, protection, nerve transfer, and nerve graft. In addition, we performed neurophysiological analysis of the preoperative condition and prognosis of 10 patients undergoing ipsilateral phrenic nerve transfer to the musculocutaneous nerve in our hospital from 2008 to 201 3 and observed the electromyograms of the biceps brachii and motor conduction function of the musculocutaneous nerve. Clinically, approximately 28% of patients had brachial plexus injury combined with phrenic nerve injury, and injured phrenic nerve cannot be used as a nerve graft. After phrenic nerve transfer to the musculocutaneous nerve, the regenerated potentials first appeared at 3 months. Recovery of motor unit action potential occurred 6 months later and became more apparent at 12 months. The percent of patients recovering 'excellent' and 'good' muscle strength in the biceps brachii was 80% after 18 months. At 12 months after surgery, motor nerve conduction potential appeared in the musculocutaneous nerve in seven cases. These data suggest that preoperative evaluation of phrenic nerve function may help identify the most appropriate nerve graft in patients with an injured brachial plexus. The functional recovery of a transplanted nerve can be dynamically observed after the surgery.

Sciatic Nerve Intrafascicular Lidocaine Injection-induced Peripheral Neuropathic Pain: Alleviation by Systemic Minocycline Administration.

PubMed

Cheng, Kuang-I; Wang, Hung-Chen; Wu, Yi-Chia; Tseng, Kuang-Yi; Chuang, Yi-Ta; Chou, Chao-Wen; Chen, Ping-Luen; Chang, Lin-Li; Lai, Chung-Sheng

2016-06-01

Peripheral nerve block guidance with a nerve stimulator or echo may not prevent intrafascicular injury. This study investigated whether intrafascicular lidocaine induces peripheral neuropathic pain and whether this pain can be alleviated by minocycline administration. A total of 168 male Sprague-Dawley rats were included. In experiment 1, 2% lidocaine (0.1 mL) was injected into the left sciatic nerve. Hindpaw responses to thermal and mechanical stimuli, and sodium channel and activating transcription factor (ATF-3) expression in dorsal root ganglion (DRG) and glial cells in the spinal dorsal horn (SDH), were measured on days 4, 7, 14, 21, and 28. On the basis of the results in experiment 1, rats in experiment 2 were divided into sham, extraneural, intrafascicular, peri-injury minocycline, and postinjury minocycline groups. Behavioral responses, macrophage recruitment, expression changes of myelin basic protein and Schwann cells in the sciatic nerve, dysregulated expression of ATF-3 in the DRG, and activated glial cells in L5 SDH were assessed on days 7 and 14. Intrafascicular lidocaine induced mechanical allodynia, downregulated Nav1.8, increased ATF-3 expression in the DRG, and activated glial cells in the SDH. Increased expression of macrophages, Schwann cells, and myelin basic protein was found in the sciatic nerve. Minocycline attenuated intrafascicular lidocaine-induced neuropathic pain and nerve damage significantly. Peri-injury minocycline was better than postinjury minocycline administration in alleviating mechanical behaviors, mitigating macrophage recruitment into the sciatic nerve, and suppressing activated microglial cells in the spinal cord. Systemic minocycline administration alleviates intrafascicular lidocaine injection-induced peripheral nerve damage.

Development of a nerve conduction technique for the recurrent laryngeal nerve.

PubMed

J Kim, Sang; G Lee, Dae; Kwon, Jeong-Yi

2014-12-01

To develop a reliable and safe laryngeal nerve conduction technique and to obtain consistent parameters as normal reference values. A prospective single-arm study. A nerve conduction test was performed on the contralateral normal side in 42 patients with unilateral vocal fold palsy. The recording was performed in the intact thyroarytenoid muscle using a monopolar needle. The electrical stimulation using a 37-mm monopolar needle was applied 3 cm below the lower margin of the cricoid cartilage, just lateral to the trachea and medial to the carotid artery, and its intensity was gradually increased until the amplitude of the electrical response reached the maximum level. The latency of the evoked muscle response was acquired at the first evoked waveform deflection from the baseline. The average latency of the recurrent laryngeal nerves was 1.98 ± 0.26 ms. The latencies showed normal distribution according to the quantile-quantile plot and Kolmogorov-Smirnov test (P = .098). There was no significant difference in latencies between the right and left recurrent laryngeal nerves. Anthropometric factors including height and weight did not show any correlation with the latencies. We developed a reliable and safe laryngeal nerve conduction technique and obtained normal reference values for the recurrent laryngeal nerve conduction study. This laryngeal nerve conduction study can be an additional tool for detecting recurrent laryngeal nerve injury if it is performed in combination with the conventional laryngeal electromyography. 4. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Imaging of radicals following injury or acute stress in peripheral nerves with activatable fluorescent probes.

PubMed

Zhou, Haiying; Yan, Ying; Ee, Xueping; Hunter, Daniel A; Akers, Walter J; Wood, Matthew D; Berezin, Mikhail Y

2016-12-01

Peripheral nerve injury evokes a complex cascade of chemical reactions including generation of molecular radicals. Conversely, the reactions within nerve induced by stress are difficult to directly detect or measure to establish causality. Monitoring these reactions in vivo would enable deeper understanding of the nature of the injury and healing processes. Here, we utilized near-infrared fluorescence molecular probes delivered via intra-neural injection technique to enable live, in vivo imaging of tissue response associated with nerve injury and stress. These initially quenched fluorescent probes featured specific sensitivity to hydroxyl radicals and become fluorescent upon encountering reactive oxygen species (ROS). Intraneurally delivered probes demonstrated rapid activation in injured rat sciatic nerve but minimal activation in normal, uninjured nerve. In addition, these probes reported activation within sciatic nerves of living rats after a stress caused by a pinprick stimulus to the abdomen. This imaging approach was more sensitive to detecting changes within nerves due to the induced stress than other techniques to evaluate cellular and molecular changes. Specifically, neither histological analysis of the sciatic nerves, nor the expression of pain and stress associated genes in dorsal root ganglia could provide statistically significant differences between the control and stressed groups. Overall, the results demonstrate a novel imaging approach to measure ROS in addition to the impact of ROS within nerve in live animals. Copyright © 2016 Elsevier Inc. All rights reserved.

Afferent renal denervation impairs baroreflex control of efferent renal sympathetic nerve activity.

PubMed

Kopp, Ulla C; Jones, Susan Y; DiBona, Gerald F

2008-12-01

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which decreases ERSNA to prevent sodium retention. High-sodium diet enhances ARNA, suggesting an important role for ARNA in suppressing ERSNA during excess sodium intake. Mean arterial pressure (MAP) is elevated in afferent renal denervated by dorsal rhizotomy (DRX) rats fed high-sodium diet. We examined whether the increased MAP in DRX is due to impaired arterial baroreflex function. In DRX and sham DRX rats fed high-sodium diet, arterial baroreflex function was determined in conscious rats by intravenous nitroprusside and phenylephrine or calculation of transfer function gain from arterial pressure to ERSNA (spontaneous baroreflex sensitivity). Increasing MAP did not suppress ERSNA to the same extent in DRX as in sham DRX, -60 +/- 4 vs. -77 +/- 6%. Maximum gain, -4.22 +/- 0.45 vs. -6.04 +/- 0.90% DeltaERSNA/mmHg, and the maximum value of instantaneous gain, -4.19 +/- 0.45 vs. -6.04 +/- 0.81% DeltaERSNA/mmHg, were less in DRX than in sham DRX. Likewise, transfer function gain was lower in DRX than in sham DRX, 3.9 +/- 0.2 vs. 6.1 +/- 0.5 NU/mmHg. Air jet stress produced greater increases in ERSNA in DRX than in sham DRX, 35,000 +/- 4,900 vs. 20,900 +/- 3,410%.s (area under the curve). Likewise, the ERSNA responses to thermal cutaneous stimulation were greater in DRX than in sham DRX. These studies suggest impaired arterial baroreflex suppression of ERSNA in DRX fed high-sodium diet. There were no differences in arterial baroreflex function in DRX and sham DRX fed normal-sodium diet. Impaired arterial baroreflex function contributes to increased ERSNA, which would eventually lead to sodium retention and increased MAP in DRX rats fed high-sodium diet.

Central command does not suppress baroreflex control of cardiac sympathetic nerve activity at the onset of spontaneous motor activity in the decerebrate cat.

PubMed

Matsukawa, Kanji; Ishii, Kei; Asahara, Ryota; Idesako, Mitsuhiro

2016-10-01

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in animals. We have examined whether baroreflex control of cardiac sympathetic nerve activity (CSNA) and/or cardiovagal baroreflex sensitivity are altered at the onset of spontaneously occurring motor behavior, which was monitored with tibial nerve activity in paralyzed, decerebrate cats. CSNA exhibited a peak increase (126 ± 17%) immediately after exercise onset, followed by increases in HR and mean arterial pressure (MAP). With development of the pressor response, CSNA and HR decreased near baseline, although spontaneous motor activity was not terminated. Atropine methyl nitrate (0.1-0.2 mg/kg iv) with little central influence delayed the initial increase in HR but did not alter the response magnitudes of HR and CSNA, while atropine augmented the pressor response. The baroreflex-induced decreases in CSNA and HR elicited by brief occlusion of the abdominal aorta were challenged at the onset of spontaneous motor activity. Spontaneous motor activity blunted the baroreflex reduction in HR by aortic occlusion but did not alter the baroreflex inhibition of CSNA. Similarly, atropine abolished the baroreflex reduction in HR but did not influence the baroreflex inhibition of CSNA. Thus it is likely that central command increases CSNA and decreases cardiac vagal outflow at the onset of spontaneous motor activity while preserving baroreflex control of CSNA. Accordingly, central command must attenuate cardiovagal baroreflex sensitivity against an excess rise in MAP as estimated from the effect of muscarinic blockade. Copyright © 2016 the American Physiological Society.

An update-tissue engineered nerve grafts for the repair of peripheral nerve injuries.

PubMed

Patel, Nitesh P; Lyon, Kristopher A; Huang, Jason H

2018-05-01

Peripheral nerve injuries (PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts (ANGs), nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts (TENGs). Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems (DDS), co-administration of platelet-rich plasma (PRP), and pretreatment with chondroitinase ABC (Ch-ABC). Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix (ECM) deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia (DRG) neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.

Nerve Entrapment Syndromes at the Wrist and Elbow by Sonography.

PubMed

Klauser, Andrea S; Buzzegoli, Tommaso; Taljanovic, Mihra S; Strobl, Sylvia; Rauch, Stefan; Teh, James; Wanschitz, Julia; Löscher, Wolfgang; Martinoli, Carlo

2018-07-01

Nerve entrapment syndromes of the upper extremity are associated with structural abnormalities or by an intrinsic abnormality of the nerve. Nerve entrapment syndromes generally have a typical clinical presentation, and findings on physical examination and in conjunction with electrodiagnostic studies imaging is used to evaluate the cause, severity, and etiology of the entrapment. With the development of high-frequency linear array transducers (12-24 MHz), ultrasound (US) is incomparable in terms of spatial resolution to depict morphological aspects and changes in nerves. US can identify the abnormalities causing entrapment, such as fibrous bands, ganglia, anomalous muscles, and osseous deformities, with the advantage of dynamic assessment under active and passive examination. US is a unique diagnostic modality that allows superb visualization of both large and small peripheral terminal nerve branches of the upper extremity and enables the correct diagnosis of various nerve entrapment syndromes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Silk fibroin enhances peripheral nerve regeneration by improving vascularization within nerve conduits.

PubMed

Wang, Chunyang; Jia, Yachao; Yang, Weichao; Zhang, Cheng; Zhang, Kuihua; Chai, Yimin

2018-07-01

Silk fibroin (SF)-based nerve conduits have been widely used to bridge peripheral nerve defects. Our previous study showed that nerve regeneration in a SF-blended poly (l-lactide-co-ɛ-caprolactone) [P(LLA-CL)] nerve conduit is better than that in a P(LLA-CL) conduit. However, the involved mechanisms remain unclarified. Because angiogenesis within a nerve conduit plays an important role in nerve regeneration, vascularization of SF/P(LLA-CL) and P(LLA-CL) conduits was compared both in vitro and in vivo. In the present study, we observed that SF/P(LLA-CL) nanofibers significantly promoted fibroblast proliferation, and vascular endothelial growth factor secreted by fibroblasts seeded in SF/P(LLA-CL) nanofibers was more than seven-fold higher than that in P(LLA-CL) nanofibers. Conditioned medium of fibroblasts in the SF/P(LLA-CL) group stimulated more human umbilical vein endothelial cells (HUVEC) to form capillary-like networks and promoted faster HUVEC migration. The two kinds of nerve conduits were used to bridge 10-mm-length nerve defects in rats. At 3 weeks of reparation, the blood vessel area in the SF/P(LLA-CL) group was significantly larger than that in the P(LLA-CL) group. More regenerated axons and Schwann cells were also observed in the SF/P(LLA-CL) group, which was consistent with the results of blood vessels. Collectively, our data revealed that the SF/P(LLA-CL) nerve conduit enhances peripheral nerve regeneration by improving angiogenesis within the conduit. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2070-2077, 2018. © 2018 Wiley Periodicals, Inc.

Human muscle sympathetic nerve activity and plasma noradrenaline kinetics in space

NASA Technical Reports Server (NTRS)

Ertl, Andrew C.; Diedrich, Andre; Biaggioni, Italo; Levine, Benjamin D.; Robertson, Rose Marie; Cox, James F.; Zuckerman, Julie H.; Pawelczyk, James A.; Ray, Chester A.; Buckey, Jay C Jr;

Pre-differentiation of mesenchymal stromal cells in combination with a microstructured nerve guide supports peripheral nerve regeneration in the rat sciatic nerve model.

PubMed

Boecker, Arne Hendrik; van Neerven, Sabien Geraldine Antonia; Scheffel, Juliane; Tank, Julian; Altinova, Haktan; Seidensticker, Katrin; Deumens, Ronald; Tolba, Rene; Weis, Joachim; Brook, Gary Anthony; Pallua, Norbert; Bozkurt, Ahmet

2016-02-01

Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration-supporting function, often in comparison to autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides Ansselin et al. (1998). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefitted from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labelled sensory neurons and the axon density within the implant were elevated in the cell-seeded scaffold group with pre-differentiated mesenchymal stromal cells. However, a pre-differentiation had no influence on functional recovery. An additional cell seeding of the Perimaix nerve guide with mesenchymal stromal cells led to an extent of functional recovery, independent of the differentiation status, similar to autologous nerve transplantation. These findings encourage further investigations on pre-differentiated mesenchymal stromal cells as a cellular support for peripheral nerve regeneration. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Motor nerve transplantation.

PubMed

Gray, W P; Keohane, C; Kirwan, W O

1997-10-01

The motor nerve transplantation (MNT) technique is used to transfer an intact nerve into a denervated muscle by harvesting a neurovascular pedicle of muscle containing motor endplates from the motor endplate zone of a donor muscle and implanting it into a denervated muscle. Thirty-six adult New Zealand White rabbits underwent reinnervation of the left long peroneal (LP) muscle (fast twitch) with a motor nerve graft from the soleus muscle (slow twitch). The right LP muscle served as a control. Reinnervation was assessed using microstimulatory single-fiber electromyography (SFEMG), alterations in muscle fiber typing and grouping, and isometric response curves. Neurofilament antibody was used for axon staining. The neurofilament studies provided direct evidence of nerve growth from the motor nerve graft into the adjacent denervated muscle. Median motor endplate jitter was 13 microsec preoperatively, and 26 microsec at 2 months, 29.5 microsec at 4 months, and 14 microsec at 6 months postoperatively (p < 0.001). Isometric tetanic tension studies showed a progressive functional recovery in the reinnervated muscle over 6 months. There was no histological evidence of aberrant reinnervation from any source outside the nerve pedicle. Isometric twitch responses and adenosine triphosphatase studies confirmed the conversion of the reinnervated LP muscle to a slow-type muscle. Acetylcholinesterase studies confirmed the presence of functioning motor endplates beneath the insertion of the motor nerve graft. It is concluded that the MNT technique achieves motor reinnervation by growth of new nerve fibers across the pedicle graft into the recipient muscle.

Extralaryngeal division of the recurrent laryngeal nerve: a new description for the inferior laryngeal nerve.

PubMed

Yalcin, Bulent; Tunali, Selcuk; Ozan, Hasan

2008-05-01

Extralaryngeal division of the recurrent laryngeal nerve was contradictory in the literature. We aimed to investigate extralaryngeal division of the nerve, and also propose a new description for the inferior laryngeal nerve. Sixty specimens (120 sides) were examined for this project, including 41 men and 19 women cadavers between the ages of 40 and 89 years at death. In one right side, terminal segment of the nerve gave off many small branches surrounding the inferior thyroid artery then reaching the larynx, trachea, thyroid gland and esophagus. In eight sides, terminal segment of the nerve had no extralaryngeal division and entered the larynx as a single trunk. In 110 sides, the nerve had extralaryngeal division. One hundred and three nerves had two laryngeal and one to three extralaryngeal branches. Two types were described in this group. In type I (66 nerves), both branches arose from the same level of nerve. Type I had two subtypes: type Ia, the origin of the branches was just below the inferior constrictor muscle; type Ib, the origin of the branches was 15-35 mm below the muscle. In type II (37 nerves), the laryngeal branches arose just 3-5 mm above the extralaryngeal branches. We observed that the laryngeal and extralaryngeal branches arose generally from the same point of the recurrent laryngeal nerve. The inferior laryngeal nerve is thus very short, or even nonexistent. Therefore, we suggest that if the term "superior laryngeal nerve" is a given, standard, and accepted term, then the term "inferior laryngeal nerve" should also be accepted instead of the term "recurrent laryngeal nerve."

Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury.

PubMed

Oñate, Maritza; Catenaccio, Alejandra; Martínez, Gabriela; Armentano, Donna; Parsons, Geoffrey; Kerr, Bredford; Hetz, Claudio; Court, Felipe A

2016-02-24

Although protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models of spinal cord injury and neurodegeneration, the contribution of this pathway to peripheral nerve damage remains poorly explored. Here we targeted the unfolded protein response (UPR), an adaptive reaction against ER stress, in mouse models of sciatic nerve injury and found that ablation of the transcription factor XBP1, but not ATF4, significantly delay locomotor recovery. XBP1 deficiency led to decreased macrophage recruitment, a reduction in myelin removal and axonal regeneration. Conversely, overexpression of XBP1s in the nervous system in transgenic mice enhanced locomotor recovery after sciatic nerve crush, associated to an improvement in key pro-regenerative events. To assess the therapeutic potential of UPR manipulation to axonal regeneration, we locally delivered XBP1s or an shRNA targeting this transcription factor to sensory neurons of the dorsal root ganglia using a gene therapy approach and found an enhancement or reduction of axonal regeneration in vivo, respectively. Our results demonstrate a functional role of specific components of the ER proteostasis network in the cellular changes associated to regeneration and functional recovery after peripheral nerve injury.

42 CFR 88.1 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... sites in the respiratory system and intrathoracic organs. (xi) Mesothelioma. (xii) Malignant neoplasms of the peripheral nerves and autonomic nervous system, and other connective and soft tissue. (xiii... disorder means a chronic or recurrent disorder of the musculoskeletal system caused by heavy lifting or...

Intraoperative cranial nerve monitoring.

PubMed

Harper, C Michel

2004-03-01

The purpose of intraoperative monitoring is to preserve function and prevent injury to the nervous system at a time when clinical examination is not possible. Cranial nerves are delicate structures and are susceptible to damage by mechanical trauma or ischemia during intracranial and extracranial surgery. A number of reliable electrodiagnostic techniques, including nerve conduction studies, electromyography, and the recording of evoked potentials have been adapted to the study of cranial nerve function during surgery. A growing body of evidence supports the utility of intraoperative monitoring of cranial nerve nerves during selected surgical procedures.

Tendon Transfers Part II: Transfers for Ulnar Nerve Palsy and Median Nerve Palsy

PubMed Central

Sammer, Douglas M.; Chung, Kevin C.

2009-01-01

Objectives After reading this article (part II of II), the participant should be able to: 1. Describe the anatomy and function of the median and ulnar nerves in the forearm and hand. 2. Describe the clinical deficits associated with injury to each nerve. 3. Describe the indications, benefits, and drawbacks for various tendon transfer procedures used to treat median and ulnar nerve palsy.4. Describe the treatment of combined nerve injuries. 5. Describe postoperative care and possible complications associated with these tendon transfer procedures. Summary This article discusses the use of tendon transfer procedures for treatment of median and ulnar nerve palsy as well as combined nerve palsies. Postoperative management and potential complications are also discussed. PMID:19730287

Microsurgical reconstruction of large nerve defects using autologous nerve grafts.

PubMed

Daoutis, N K; Gerostathopoulos, N E; Efstathopoulos, D G; Misitizis, D P; Bouchlis, G N; Anagnostou, S K

1994-01-01

Between 1986 and 1993, 643 patients with peripheral nerve trauma were treated in our clinic. Primary neurorraphy was performed in 431 of these patients and nerve grafting in 212 patients. We present the functional results after nerve grafting in 93 patients with large nerve defects who were followed for more than 2 years. Evaluation of function was based on the Medical Research Council (MRC) classification for motor and sensory recovery. Factors affecting functional outcome, such as age of the patient, denervation time, length of the defect, and level of the injury were noted. Good results according to the MRC classification were obtained in the majority of cases, although function remained less than that of the uninjured side.

Use of Nerve Conduction Velocity to Assess Peripheral Nerve Health in Aging Mice

PubMed Central

Walsh, Michael E.; Sloane, Lauren B.; Fischer, Kathleen E.; Austad, Steven N.; Richardson, Arlan

2015-01-01

Nerve conduction velocity (NCV), the speed at which electrical signals propagate along peripheral nerves, is used in the clinic to evaluate nerve function in humans. A decline in peripheral nerve function is associated with a number of age-related pathologies. While several studies have shown that NCV declines with age in humans, there is little information on the effect of age on NCV in peripheral nerves in mice. In this study, we evaluated NCV in male and female C57Bl/6 mice ranging from 4 to 32 months of age. We observed a decline in NCV in both male and female mice after 20 months of age. Sex differences were detected in sensory NCV as well as the rate of decline during aging in motor nerves; female mice had slower sensory NCV and a slower age-related decline in motor nerves compared with male mice. We also tested the effect of dietary restriction on NCV in 30-month-old female mice. Dietary restriction prevented the age-related decline in sciatic NCV but not other nerves. Because NCV is clinically relevant to the assessment of nerve function, we recommend that NCV be used to evaluate healthspan in assessing genetic and pharmacological interventions that increase the life span of mice. PMID:25477428

A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity

PubMed Central

Hilzendeger, Aline M.; Morgan, Donald A.; Brooks, Leonard; Dellsperger, David; Liu, Xuebo; Grobe, Justin L.; Rahmouni, Kamal; Sigmund, Curt D.

2012-01-01

The sympathetic nervous system, leptin, and renin-angiotensin system (RAS) have been implicated in obesity-associated hypertension. There is increasing evidence for the presence of both leptin and angiotensin II receptors in several key brain cardiovascular and metabolic control regions. We tested the hypothesis that the brain RAS plays a facilitatory role in the sympathetic nerve responses to leptin. In rats, intracerebroventricular (ICV) administration of losartan (5 μg) selectively inhibited increases in renal and brown adipose tissue (BAT) sympathetic nerve activity (SNA) produced by leptin (10 μg ICV) but did not reduce the SNA responses to corticotrophin-releasing factor (CRF) or the melanocortin receptor agonist MTII. In mice with deletion of angiotensin II type-1a receptors (AT1aR−/−), increases in renal and BAT SNA induced by leptin (2 μg ICV) were impaired whereas SNA responses to MTII were preserved. Decreases in food intake and body weight with ICV leptin did not differ in AT1aR−/− vs. AT1aR+/+ mice. ICV leptin in rats increased AT1aR and angiotensin-converting enzyme (ACE) mRNA in the subfornical organ and AT1aR mRNA in the arcuate nucleus, suggesting leptin-induced upregulation of the brain RAS in specific brain regions. To evaluate the role of de novo production of brain angiotensin II in SNA responses to leptin, we treated rats with captopril (12.5 μg ICV). Captopril attenuated leptin effects on renal and BAT SNA. In conclusion, these studies provide evidence that the brain RAS selectively facilitates renal and BAT sympathetic nerve responses to leptin while sparing effects on food intake. PMID:22610169

A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity.

PubMed

Hilzendeger, Aline M; Morgan, Donald A; Brooks, Leonard; Dellsperger, David; Liu, Xuebo; Grobe, Justin L; Rahmouni, Kamal; Sigmund, Curt D; Mark, Allyn L

2012-07-15

The sympathetic nervous system, leptin, and renin-angiotensin system (RAS) have been implicated in obesity-associated hypertension. There is increasing evidence for the presence of both leptin and angiotensin II receptors in several key brain cardiovascular and metabolic control regions. We tested the hypothesis that the brain RAS plays a facilitatory role in the sympathetic nerve responses to leptin. In rats, intracerebroventricular (ICV) administration of losartan (5 μg) selectively inhibited increases in renal and brown adipose tissue (BAT) sympathetic nerve activity (SNA) produced by leptin (10 μg ICV) but did not reduce the SNA responses to corticotrophin-releasing factor (CRF) or the melanocortin receptor agonist MTII. In mice with deletion of angiotensin II type-1a receptors (AT(1a)R(-/-)), increases in renal and BAT SNA induced by leptin (2 μg ICV) were impaired whereas SNA responses to MTII were preserved. Decreases in food intake and body weight with ICV leptin did not differ in AT(1a)R(-/-) vs. AT(1a)R(+/+) mice. ICV leptin in rats increased AT(1a)R and angiotensin-converting enzyme (ACE) mRNA in the subfornical organ and AT(1a)R mRNA in the arcuate nucleus, suggesting leptin-induced upregulation of the brain RAS in specific brain regions. To evaluate the role of de novo production of brain angiotensin II in SNA responses to leptin, we treated rats with captopril (12.5 μg ICV). Captopril attenuated leptin effects on renal and BAT SNA. In conclusion, these studies provide evidence that the brain RAS selectively facilitates renal and BAT sympathetic nerve responses to leptin while sparing effects on food intake.

A silk sericin/silicone nerve guidance conduit promotes regeneration of a transected sciatic nerve.

PubMed

Xie, Hongjian; Yang, Wen; Chen, Jianghai; Zhang, Jinxiang; Lu, Xiaochen; Zhao, Xiaobo; Huang, Kun; Li, Huili; Chang, Panpan; Wang, Zheng; Wang, Lin

2015-10-28

Peripheral nerve gap defects lead to significant loss of sensory or motor function. Tissue engineering has become an important alternative to nerve repair. Sericin, a major component of silk, is a natural protein whose value in tissue engineering has just begun to be explored. Here, the first time use of sericin in vivo is reported as a long-term implant for peripheral nerve regeneration. A sericin nerve guidance conduit is designed and fabricated. This conduit is highly porous with mechanical strength matching peripheral nerve tissue. It supports Schwann cell proliferation and is capable of up-regulating the transcription of glial cell derived neurotrophic factor and nerve growth factor in Schwann cells. The sericin conduit wrapped with a silicone conduit (sericin/silicone double conduits) is used for bridging repair of a 5 mm gap in a rat sciatic nerve transection model. The sericin/silicone double conduits achieve functional recovery comparable to that of autologous nerve grafting as evidenced by drastically improved nerve function and morphology. Importantly, this improvement is mainly attributed to the sericin conduit as the silicone conduit alone only produces marginal functional recovery. This sericin/silicone-double-conduit strategy offers an efficient and valuable alternative to autologous nerve grafting for repairing damaged peripheral nerve. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transfer of obturator nerve for femoral nerve injury: an experiment study in rats.

PubMed

Meng, Depeng; Zhou, Jun; Lin, Yaofa; Xie, Zheng; Chen, Huihao; Yu, Ronghua; Lin, Haodong; Hou, Chunlin

2018-07-01

Quadriceps palsy is mainly caused by proximal lesions in the femoral nerve. The obturator nerve has been previously used to repair the femoral nerve, although only a few reports have described the procedure, and the outcomes have varied. In the present study, we aimed to confirm the feasibility and effectiveness of this treatment in a rodent model using the randomized control method. Sixty Sprague-Dawley rats were randomized into two groups: the experimental group, wherein rats underwent femoral neurectomy and obturator nerve transfer to the femoral nerve motor branch; and the control group, wherein rats underwent femoral neurectomy without nerve transfer. Functional outcomes were measured using the BBB score, muscle mass, and histological assessment. At 12 and 16 weeks postoperatively, the rats in the experimental group exhibited recovery to a stronger stretch force of the knee and higher BBB score, as compared to the control group (p < 0.05). The muscle mass and myofiber cross-sectional area of the quadriceps were heavier and larger than those in the control group (p < 0.05). A regenerated nerve with myelinated and unmyelinated fibers was observed in the experimental group. No significant differences were observed between groups at 8 weeks postoperatively (p > 0.05). Obturator nerve transfer for repairing femoral nerve injury was feasible and effective in a rat model, and can hence be considered as an option for the treatment of femoral nerve injury.

Visual abnormalities associated with enhanced optic nerve myelination.

PubMed

Yu, Minzhong; Narayanan, S Priyadarshini; Wang, Feng; Morse, Emily; Macklin, Wendy B; Peachey, Neal S

2011-02-16

Expression of the constitutively active serine/threonine kinase Akt in oligodendrocytes results in enhanced myelination in the CNS. Here, we have examined the effects of this Akt overexpression on optic nerve structure and on optic nerve function, assessed using the visual evoked potential (VEP). Transgenic mice have been generated with the Plp promoter driving expression of a modified form of Akt, in which aspartic acids are substituted for Thr308 and Ser473. These Plp-Akt-DD (Akt-DD) mice, and littermate controls, were studied at different ages. Optic nerves were examined anatomically at 2 and 6 months of age. At 2 months of age, optic nerves were substantially thicker in Akt-DD mice, reflecting an increase in myelination of optic nerve axons. By electron microscopy, myelin thickness was increased in Akt-DD optic nerve, with extended paranodal domains having excess paranodal loops, and the density of nodes of Ranvier was reduced, relative to control mice. We recorded VEPs in response to strobe flash ganzfeld stimuli presented after overnight dark- and light-adapted conditions at ages ranging from 1 to 10 months. It was possible to record a clear VEP from Akt-DD mice at all ages examined. At 1 month of age, VEP implicit times were somewhat shorter in Akt-DD transgenic mice than in control animals. Beyond 6months of age, VEP latencies were consistently delayed in Akt-DD transgenic mice. These abnormalities did not reflect an alteration in retinal function as there were no significant differences between ERGs obtained from control or Akt-DD transgenic mice. In young mice, the somewhat faster responses may reflect improved transmission due to increased myelination of optic nerve axons. In older mice, where the Akt-DD optic nerve is markedly thicker than control, it is remarkable that optic nerves continue to function. Copyright © 2010 Elsevier B.V. All rights reserved.

Morphological differences in skeletal muscle atrophy of rats with motor nerve and/or sensory nerve injury★

PubMed Central

Zhao, Lei; Lv, Guangming; Jiang, Shengyang; Yan, Zhiqiang; Sun, Junming; Wang, Ling; Jiang, Donglin

2012-01-01

Skeletal muscle atrophy occurs after denervation. The present study dissected the rat left ventral root and dorsal root at L4-6 or the sciatic nerve to establish a model of simple motor nerve injury, sensory nerve injury or mixed nerve injury. Results showed that with prolonged denervation time, rats with simple motor nerve injury, sensory nerve injury or mixed nerve injury exhibited abnormal behavior, reduced wet weight of the left gastrocnemius muscle, decreased diameter and cross-sectional area and altered ultrastructure of muscle cells, as well as decreased cross-sectional area and increased gray scale of the gastrocnemius muscle motor end plate. Moreover, at the same time point, the pathological changes were most severe in mixed nerve injury, followed by simple motor nerve injury, and the changes in simple sensory nerve injury were the mildest. These findings indicate that normal skeletal muscle morphology is maintained by intact innervation. Motor nerve injury resulted in larger damage to skeletal muscle and more severe atrophy than sensory nerve injury. Thus, reconstruction of motor nerves should be considered first in the clinical treatment of skeletal muscle atrophy caused by denervation. PMID:25337102

Measurement of wavefront aberrations in cortex and peripheral nerve using a two-photon excitation guidestar

NASA Astrophysics Data System (ADS)

Futia, Gregory L.; Fontaine, Arjun; McCullough, Connor; Ozbay, Baris N.; George, Nickolas M.; Caldwell, John; Restrepo, Diego; Weir, Richard; Gibson, Emily A.

2018-02-01

Neural-machine interfaces using optogenetics are of interest due to their minimal invasiveness and potential for parallel read in and read out of activity. One possible biological target for such an interface is the peripheral nerve, where axonlevel imaging or stimulation could greatly improve interfacing with artificial limbs or enable neuron/fascicle level neuromodulation in the vagus nerve. Two-photon imaging has been successful in imaging brain activity using genetically encoded calcium or voltage indicators, but in the peripheral nerve, this is severely limited by scattering and aberrations from myelin. We employ a Shack-Hartman wavefront sensor and two-photon excitation guidestar to quantify optical scattering and aberrations in peripheral nerves and cortex. The sciatic and vagus nerves, and cortex from a ChAT-Cre ChR-eYFP transgenic mouse were excised and imaged directly. In peripheral nerves, defocus was the strongest aberration followed by astigmatism and coma. Peripheral nerve had orders of magnitude higher aberration compared with cortex. These results point to the potential of adaptive optics for increasing the depth of two-photon access into peripheral nerves.

The Effects of Phrenic Nerve Degeneration by Axotomy and Crush on the Electrical Activities of Diaphragm Muscles of Rats.

PubMed

Alkiş, Mehmet Eşref; Kavak, Servet; Sayır, Fuat; Him, Aydin

2016-03-01

The aim of this study was to investigate the effect of axotomy and crush-related degeneration on the electrical activities of diaphragm muscle strips of experimental rats. In the present study, twenty-one male Wistar-albino rats were used and divided into three groups. The animals in the first group were not crushed or axotomized and served as controls. Phrenic nerves of the rats in the second and third groups were crushed or axotomized in the diaphragm muscle. Resting membrane potential (RMP) was decreased significantly in both crush and axotomy of diaphragm muscle strips of experimental rats (p < 0.05). Depolarization time (T DEP) and half-repolarization (1/2 RT) time were significantly prolonged in crush and axotomy rats (p < 0.05). Crushing or axotomizing the phrenic nerves may produce electrical activities in the diaphragm muscle of the rat by depolarization time and half-repolarization time prolonged in crush and axotomy rats.

Temperature-controlled optical stimulation of the rat prostate cavernous nerves

NASA Astrophysics Data System (ADS)

Tozburun, Serhat; Hutchens, Thomas C.; McClain, Michael A.; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

2013-06-01

Optical nerve stimulation (ONS) may be useful as a diagnostic tool for intraoperative identification and preservation of the prostate cavernous nerves (CN), responsible for erectile function, during prostate cancer surgery. Successful ONS requires elevating the nerve temperature to within a narrow range (˜42 to 47°C) for nerve activation without thermal damage to the nerve. This preliminary study explores a prototype temperature-controlled optical nerve stimulation (TC-ONS) system for maintaining a constant (±1°C) nerve temperature during short-term ONS of the rat prostate CNs. A 150-mW, 1455-nm diode laser was operated in continuous-wave mode, with and without temperature control, during stimulation of the rat CNs for 15 to 30 s through a fiber optic probe with a 1-mm-diameter spot. A microcontroller opened and closed an in-line mechanical shutter in response to an infrared sensor, with a predetermined temperature set point. With TC-ONS, higher laser power settings were used to rapidly and safely elevate the CNs to a temperature necessary for a fast intracavernous pressure response, while also preventing excessive temperatures that would otherwise cause thermal damage to the nerve. With further development, TC-ONS may provide a rapid, stable, and safe method for intraoperative identification and preservation of the prostate CNs.

The impact of hydroquinone on acetylcholine esterase and certain human carbonic anhydrase isoenzymes (hCA I, II, IX, and XII).

PubMed

Scozzafava, Andrea; Kalın, Pınar; Supuran, Claudiu T; Gülçin, İlhami; Alwasel, Saleh H

2015-12-01

Carbonic anhydrases (CAs) are widespread and the most studied members of a great family of metalloenzymes in higher vertebrates including humans. CAs were investigated for their inhibition of all of the catalytically active mammalian isozymes of the Zn(2+)-containing CA, (CA, EC 4.2.1.1). On the other hand, acetylcholinesterase (AChE. EC 3.1.1.7), a serine protease, is responsible for ACh hydrolysis and plays a fundamental role in impulse transmission by terminating the action of the neurotransmitter ACh at the cholinergic synapses and neuromuscular junction. In the present study, the inhibition effect of the hydroquinone (benzene-1,4-diol) on AChE activity was evaluated and effectively inhibited AChE with Ki of 1.22 nM. Also, hydroquinone strongly inhibited some human cytosolic CA isoenzymes (hCA I and II) and tumour-associated transmembrane isoforms (hCA IX, and XII), with Kis in the range between micromolar (415.81 μM) and nanomolar (706.79 nM). The best inhibition was observed in cytosolic CA II.

Dilation of the oropharynx via selective stimulation of the hypoglossal nerve

NASA Astrophysics Data System (ADS)

Huang, Jingtao; Sahin, Mesut; Durand, Dominique M.

2005-12-01

The functional effects of selective hypoglossal nerve (HG) stimulation with a multi-contact peripheral nerve electrode were assessed using images of the upper airways and the tongue in anesthetized beagles. A biphasic pulse train of 50 Hz frequency and 2 s duration was applied through each one of the tripolar contact sets of the nerve electrode while the pharyngeal images were acquired into a computer. The stimulation current was limited to 20% above the activation threshold for maximum selectivity. The images showed that various contact sets could generate several different activation patterns of the tongue muscles resulting in medial and/or lateral dilation and closing of the airways at the tongue root. Some of these patterns translated into an increase in the oropharyngeal size while others did not have any effect. The pharyngeal sizes were not statistically different during stimulation either between the two different positions of the head (30° and 60°), or when the lateral contacts were compared with the medial ones. The contacts that had the least effect generated an average of 53 ± 15% pharyngeal dilation relative to the best contacts, indicating that the results are marginally sensitive to the contact position around the HG nerve trunk. These results suggest that selective HG nerve stimulation can be a useful technique to produce multiple tongue activation patterns that can dilate the pharynx. This may in turn increase the size of the patient population who can benefit from HG nerve stimulation as a treatment method for obstructive sleep apnea.

Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

PubMed Central

Tiradentes, R.V.; Pires, J.G.P.; Silva, N.F.; Ramage, A.G.; Santuzzi, C.H.; Futuro, H.A.

2014-01-01

Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central. PMID:25003632

Recent advances in nerve tissue engineering.

PubMed

Zhang, Bill G X; Quigley, Anita F; Myers, Damian E; Wallace, Gordon G; Kapsa, Robert M I; Choong, Peter F M

2014-04-01

Nerve injury secondary to trauma, neurological disease or tumor excision presents a challenge for surgical reconstruction. Current practice for nerve repair involves autologous nerve transplantation, which is associated with significant donor-site morbidity and other complications. Previously artificial nerve conduits made from polycaprolactone, polyglycolic acid and collagen were approved by the FDA (USA) for nerve repair. More recently, there have been significant advances in nerve conduit design that better address the requirements of nerve regrowth. Innovations in materials science, nanotechnology, and biology open the way for the synthesis of new generation nerve repair conduits that address issues currently faced in nerve repair and regeneration. This review discusses recent innovations in this area, including the use of nanotechnology to improve the design of nerve conduits and to enhance nerve regeneration.

Ulnar nerve damage (image)

MedlinePlus

The ulnar nerve originates from the brachial plexus and travels down arm. The nerve is commonly injured at the elbow because of elbow fracture or dislocation. The ulnar nerve is near the surface of the body where ...

Chondromyxoid fibroma of the mastoid facial nerve canal mimicking a facial nerve schwannoma.

PubMed

Thompson, Andrew L; Bharatha, Aditya; Aviv, Richard I; Nedzelski, Julian; Chen, Joseph; Bilbao, Juan M; Wong, John; Saad, Reda; Symons, Sean P

2009-07-01

Chondromyxoid fibroma of the skull base is a rare entity. Involvement of the temporal bone is particularly rare. We present an unusual case of progressive facial nerve paralysis with imaging and clinical findings most suggestive of a facial nerve schwannoma. The lesion was tubular in appearance, expanded the mastoid facial nerve canal, protruded out of the stylomastoid foramen, and enhanced homogeneously. The only unusual imaging feature was minor calcification within the tumor. Surgery revealed an irregular, cystic lesion. Pathology diagnosed a chondromyxoid fibroma involving the mastoid portion of the facial nerve canal, destroying the facial nerve.

Hypoglossal-facial-jump-anastomosis without an interposition nerve graft.

PubMed

Beutner, Dirk; Luers, Jan C; Grosheva, Maria

2013-10-01

The hypoglossal-facial-anastomosis is the most often applied procedure for the reanimation of a long lasting peripheral facial nerve paralysis. The use of an interposition graft and its end-to-side anastomosis to the hypoglossal nerve allows the preservation of the tongue function and also requires two anastomosis sites and a free second donor nerve. We describe the modified technique of the hypoglossal-facial-jump-anastomosis without an interposition and present the first results. Retrospective case study. We performed the facial nerve reconstruction in five patients. The indication for the surgery was a long-standing facial paralysis with preserved portion distal to geniculate ganglion, absent voluntary activity in the needle facial electromyography, and an intact bilateral hypoglossal nerve. Following mastoidectomy, the facial nerve was mobilized in the fallopian canal down to its bifurcation in the parotid gland and cut in its tympanic portion distal to the lesion. Then, a tensionless end-to-side suture to the hypoglossal nerve was performed. The facial function was monitored up to 16 months postoperatively. The reconstruction technique succeeded in all patients: The facial function improved within the average time period of 10 months to the House-Brackmann score 3. This modified technique of the hypoglossal-facial reanimation is a valid method with good clinical results, especially in cases of a preserved intramastoidal facial nerve. Level 4. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury

PubMed Central

Oñate, Maritza; Catenaccio, Alejandra; Martínez, Gabriela; Armentano, Donna; Parsons, Geoffrey; Kerr, Bredford; Hetz, Claudio; Court, Felipe A.

2016-01-01

Although protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models of spinal cord injury and neurodegeneration, the contribution of this pathway to peripheral nerve damage remains poorly explored. Here we targeted the unfolded protein response (UPR), an adaptive reaction against ER stress, in mouse models of sciatic nerve injury and found that ablation of the transcription factor XBP1, but not ATF4, significantly delay locomotor recovery. XBP1 deficiency led to decreased macrophage recruitment, a reduction in myelin removal and axonal regeneration. Conversely, overexpression of XBP1s in the nervous system in transgenic mice enhanced locomotor recovery after sciatic nerve crush, associated to an improvement in key pro-regenerative events. To assess the therapeutic potential of UPR manipulation to axonal regeneration, we locally delivered XBP1s or an shRNA targeting this transcription factor to sensory neurons of the dorsal root ganglia using a gene therapy approach and found an enhancement or reduction of axonal regeneration in vivo, respectively. Our results demonstrate a functional role of specific components of the ER proteostasis network in the cellular changes associated to regeneration and functional recovery after peripheral nerve injury. PMID:26906090

Femoral nerve damage (image)

MedlinePlus

The femoral nerve is located in the leg and supplies the muscles that assist help straighten the leg. It supplies sensation ... leg. One risk of damage to the femoral nerve is pelvic fracture. Symptoms of femoral nerve damage ...

TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase

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

Piao, L.-H.; Fujita, Tsugumi; Jiang, C.-Y.

2009-02-20

We examined the effects of local anesthetics lidocaine and procaine on glutamatergic spontaneous excitatory transmission in substantia gelatinosa (SG) neurons in adult rat spinal cord slices with whole-cell patch-clamp techniques. Bath-applied lidocaine (1-5 mM) dose-dependently and reversibly increased the frequency but not the amplitude of spontaneous excitatory postsynaptic current (sEPSC) in SG neurons. Lidocaine activity was unaffected by the Na{sup +}-channel blocker, tetrodotoxin, and the TRPV1 antagonist, capsazepine, but was inhibited by the TRP antagonist, ruthenium red. In the same neuron, the TRPA1 agonist, allyl isothiocyanate, and lidocaine both increased sEPSC frequency. In contrast, procaine did not produce presynaptic enhancement.more » These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of L-glutamate.« less

Normal and sonographic anatomy of selected peripheral nerves. Part III: Peripheral nerves of the lower limb.

PubMed

Kowalska, Berta; Sudoł-Szopińska, Iwona

2012-06-01

The ultrasonographic examination is currently increasingly used in imaging peripheral nerves, serving to supplement the physical examination, electromyography and magnetic resonance imaging. As in the case of other USG imaging studies, the examination of peripheral nerves is non-invasive and well-tolerated by patients. The typical ultrasonographic picture of peripheral nerves as well as the examination technique have been discussed in part I of this article series, following the example of the median nerve. Part II of the series presented the normal anatomy and the technique for examining the peripheral nerves of the upper limb. This part of the article series focuses on the anatomy and technique for examining twelve normal peripheral nerves of the lower extremity: the iliohypogastric and ilioinguinal nerves, the lateral cutaneous nerve of the thigh, the pudendal, sciatic, tibial, sural, medial plantar, lateral plantar, common peroneal, deep peroneal and superficial peroneal nerves. It includes diagrams showing the proper positioning of the sonographic probe, plus USG images of the successively discussed nerves and their surrounding structures. The ultrasonographic appearance of the peripheral nerves in the lower limb is identical to the nerves in the upper limb. However, when imaging the lower extremity, convex probes are more often utilized, to capture deeply-seated nerves. The examination technique, similarly to that used in visualizing the nerves of upper extremity, consists of locating the nerve at a characteristic anatomic reference point and tracking it using the "elevator technique". All 3 parts of the article series should serve as an introduction to a discussion of peripheral nerve pathologies, which will be presented in subsequent issues of the "Journal of Ultrasonography".

Normal and sonographic anatomy of selected peripheral nerves. Part III: Peripheral nerves of the lower limb

PubMed Central

Sudoł-Szopińska, Iwona

2012-01-01

The ultrasonographic examination is currently increasingly used in imaging peripheral nerves, serving to supplement the physical examination, electromyography and magnetic resonance imaging. As in the case of other USG imaging studies, the examination of peripheral nerves is non-invasive and well-tolerated by patients. The typical ultrasonographic picture of peripheral nerves as well as the examination technique have been discussed in part I of this article series, following the example of the median nerve. Part II of the series presented the normal anatomy and the technique for examining the peripheral nerves of the upper limb. This part of the article series focuses on the anatomy and technique for examining twelve normal peripheral nerves of the lower extremity: the iliohypogastric and ilioinguinal nerves, the lateral cutaneous nerve of the thigh, the pudendal, sciatic, tibial, sural, medial plantar, lateral plantar, common peroneal, deep peroneal and superficial peroneal nerves. It includes diagrams showing the proper positioning of the sonographic probe, plus USG images of the successively discussed nerves and their surrounding structures. The ultrasonographic appearance of the peripheral nerves in the lower limb is identical to the nerves in the upper limb. However, when imaging the lower extremity, convex probes are more often utilized, to capture deeply-seated nerves. The examination technique, similarly to that used in visualizing the nerves of upper extremity, consists of locating the nerve at a characteristic anatomic reference point and tracking it using the “elevator technique”. All 3 parts of the article series should serve as an introduction to a discussion of peripheral nerve pathologies, which will be presented in subsequent issues of the “Journal of Ultrasonography”. PMID:26674560

Sound-induced facial synkinesis following facial nerve paralysis.

PubMed

Ma, Ming-San; van der Hoeven, Johannes H; Nicolai, Jean-Philippe A; Meek, Marcel F

2009-08-01

Facial synkinesis (or synkinesia) (FS) occurs frequently after paresis or paralysis of the facial nerve and is in most cases due to aberrant regeneration of (branches of) the facial nerve. Patients suffer from inappropriate and involuntary synchronous facial muscle contractions. Here we describe two cases of sound-induced facial synkinesis (SFS) after facial nerve injury. As far as we know, this phenomenon has not been described in the English literature before. Patient A presented with right hemifacial palsy after lesion of the facial nerve due to skull base fracture. He reported involuntary muscle activity at the right corner of the mouth, specifically on hearing ringing keys. Patient B suffered from left hemifacial palsy following otitis media and developed involuntary muscle contraction in the facial musculature specifically on hearing clapping hands or a trumpet sound. Both patients were evaluated by means of video, audio and EMG analysis. Possible mechanisms in the pathophysiology of SFS are postulated and therapeutic options are discussed.

Neuroprotective effects of (-)-epigallocatechin-3-gallate (EGCG) against peripheral nerve transection-induced apoptosis.

PubMed

Kian, Kosar; Khalatbary, Ali Reza; Ahmadvand, Hassan; Karimpour Malekshah, Abbasali; Shams, Zahra

2018-01-02

Recent studies revealed the neuroprotective effects of epigallocatechin-3-gallate (EGCG) on a variety of neural injury models. The purpose of this study was to determine the neuroprotective effects of EGCG following sciatic nerve transection (SNT). Rats were randomly divided into four groups each as follows: Sham-operated group, SNT group, and Pre-EGCG (50-mg/kg, i.p., 30 minutes before nerve transection and followed for 3 days) and Post-EGCG (50-mg/kg, i.p., 1 hour after nerve transection and followed for 3 days) groups. Spinal cord segments of the sciatic nerve and related dorsal root ganglions were removed four weeks after nerve transection for the assessment of malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities, immunohistochemistry of caspase-3, cyclooxygenase-2 (COX-2), S100beta (S100B), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). MDA levels were significantly decreased, and SOD and CAT activities were significantly increased in EGCG-treated rats after nerve transection. Attenuated caspase-3 and COX-2 expression, and TUNEL reaction could be significantly detected in the EGCG-treated rats after nerve transection. Also, EGCG significantly increased S100B expression. We propose that EGCG may be effective in the protection of neuronal cells against retrograde apoptosis and may enhance neuronal survival time following nerve transection.

The re-innervation of the tongue and salivary glands after lingual nerve repair by stretch, sural nerve graft or frozen muscle graft.

PubMed

Smith, K G; Robinson, P P

1995-12-01

The lingual nerve is sometimes injured during the surgical removal of impacted third molar teeth and may require repair. Removal of the damaged section of nerve prior to repair leaves a gap between the nerve ends, and we have investigated methods of closing the gap. THe characteristics of regenerated fibers in the chorda tympani have been recorded in cats 24 weeks after the removal of a segment of lingual nerve and repair of the defect by three methods. The nerve gap was closed either by stretching the nerve ends together and repairing under tension, or by the insertion of a sural nerve graft or freeze-thawed muscle graft. The properties of gustatory, thermosensitive, and mechanosensitive units and the return of the vasomotor and secretomotor responses were investigated by electrophysiological techniques and the data from each of the repair groups compared with those obtained from a series of normal control animals. After each method of repair, the integrated whole-nerve activity recorded from the chorda tympani during gustatory or thermal stimulation of the tongue was reduced when compared with controls, but there was little significant difference between the repair groups. Recordings made from single units in the chorda tympani revealed that conduction velocities were faster after stretch repair than after sural nerve graft or frozen muscle graft. In addition, 48% of the units had developed into principally gustatory units after stretch repair, indicating a better level of recovery than in the graft groups, which contained 33% and 32%, respectively. The secretomotor responses were also significantly greater after stretch repair than in either of the graft groups or the controls, but there was no difference in the vasomotor responses. These results reveal that repair of a short gap in the lingual nerve by stretching the ends together is followed by better overall recovery than after grafting, but where a graft is used, a similar level of recovery results from use

Phrenic and intercostal nerves with rhythmic discharge can promote early nerve regeneration after brachial plexus repair in rats.

PubMed

Rui, Jing; Xu, Ya-Li; Zhao, Xin; Li, Ji-Feng; Gu, Yu-Dong; Lao, Jie

2018-05-01

Exogenous discharge can positively promote nerve repair. We, therefore, hypothesized that endogenous discharges may have similar effects. The phrenic nerve and intercostal nerve, controlled by the respiratory center, can emit regular nerve impulses; therefore these endogenous automatically discharging nerves might promote nerve regeneration. Action potential discharge patterns were examined in the diaphragm, external intercostal and latissimus dorsi muscles of rats. The phrenic and intercostal nerves showed rhythmic clusters of discharge, which were consistent with breathing frequency. From the first to the third intercostal nerves, spontaneous discharge amplitude was gradually increased. There was no obvious rhythmic discharge in the thoracodorsal nerve. Four animal groups were performed in rats as the musculocutaneous nerve cut and repaired was bland control. The other three groups were followed by a side-to-side anastomosis with the phrenic nerve, intercostal nerve and thoracodorsal nerve. Compound muscle action potentials in the biceps muscle innervated by the musculocutaneous nerve were recorded with electrodes. The tetanic forces of ipsilateral and contralateral biceps muscles were detected by a force displacement transducer. Wet muscle weight recovery rate was measured and pathological changes were observed using hematoxylin-eosin staining. The number of nerve fibers was observed using toluidine blue staining and changes in nerve ultrastructure were observed using transmission electron microscopy. The compound muscle action potential amplitude was significantly higher at 1 month after surgery in phrenic and intercostal nerve groups compared with the thoracodorsal nerve and blank control groups. The recovery rate of tetanic tension and wet weight of the right biceps were significantly lower at 2 months after surgery in the phrenic nerve, intercostal nerve, and thoracodorsal nerve groups compared with the negative control group. The number of myelinated axons

Synaptic activation of putative sensory neurons by hexamethonium-sensitive nerve pathways in mouse colon.

PubMed

Hibberd, Timothy J; Travis, Lee; Wiklendt, Lukasz; Costa, Marcello; Brookes, Simon J H; Hu, Hongzhen; Keating, Damien J; Spencer, Nick J

2018-01-01

The gastrointestinal tract contains its own independent population of sensory neurons within the gut wall. These sensory neurons have been referred to as intrinsic primary afferent neurons (IPANs) and can be identified by immunoreactivity to calcitonin gene-related peptide (CGRP) in mice. A common feature of IPANs is a paucity of fast synaptic inputs observed during sharp microelectrode recordings. Whether this is observed using different recording techniques is of particular interest for understanding the physiology of these neurons and neural circuit modeling. Here, we imaged spontaneous and evoked activation of myenteric neurons in isolated whole preparations of mouse colon and correlated recordings with CGRP and nitric oxide synthase (NOS) immunoreactivity, post hoc. Calcium indicator fluo 4 was used for this purpose. Calcium responses were recorded in nerve cell bodies located 5-10 mm oral to transmural electrical nerve stimuli. A total of 618 recorded neurons were classified for CGRP or NOS immunoreactivity. Aboral electrical stimulation evoked short-latency calcium transients in the majority of myenteric neurons, including ~90% of CGRP-immunoreactive Dogiel type II neurons. Activation of Dogiel type II neurons had a time course consistent with fast synaptic transmission and was always abolished by hexamethonium (300 μM) and by low-calcium Krebs solution. The nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium iodide (during synaptic blockade) directly activated Dogiel type II neurons. The present study suggests that murine colonic Dogiel type II neurons receive prominent fast excitatory synaptic inputs from hexamethonium-sensitive neural pathways. NEW & NOTEWORTHY Myenteric neurons in isolated mouse colon were recorded using calcium imaging and then neurochemically defined. Short-latency calcium transients were detected in >90% of calcitonin gene-related peptide-immunoreactive neurons to electrical stimulation of hexamethonium-sensitive pathways

Electrophysiological Assessment of a Peptide Amphiphile Nanofiber Nerve Graft for Facial Nerve Repair.

PubMed

Greene, Jacqueline J; McClendon, Mark T; Stephanopoulos, Nicholas; Álvarez, Zaida; Stupp, Samuel I; Richter, Claus-Peter

2018-04-27

Facial nerve injury can cause severe long-term physical and psychological morbidity. There are limited repair options for an acutely transected facial nerve not amenable to primary neurorrhaphy. We hypothesize that a peptide amphiphile nanofiber neurograft may provide the nanostructure necessary to guide organized neural regeneration. Five experimental groups were compared, animals with 1) an intact nerve, 2) following resection of a nerve segment, and following resection and immediate repair with either a 3) autograft (using the resected nerve segment), 4) neurograft, or 5) empty conduit. The buccal branch of the rat facial nerve was directly stimulated with charge balanced biphasic electrical current pulses at different current amplitudes while nerve compound action potentials (nCAPs) and electromygraphic (EMG) responses were recorded. After 8 weeks, the proximal buccal branch was surgically re-exposed and electrically evoked nCAPs were recorded for groups 1-5. As expected, the intact nerves required significantly lower current amplitudes to evoke an nCAP than those repaired with the neurograft and autograft nerves. For other electrophysiologic parameters such as latency and maximum nCAP, there was no significant difference between the intact, autograft and neurograft groups. The resected group had variable responses to electrical stimulation, and the empty tube group was electrically silent. Immunohistochemical analysis and TEM confirmed myelinated neural regeneration. This study demonstrates that the neuroregenerative capability of peptide amphiphile nanofiber neurografts is similar to the current clinical gold standard method of repair and holds potential as an off-the-shelf solution for facial reanimation and potentially peripheral nerve repair. This article is protected by copyright. All rights reserved.

Comparative analysis of transverse intrafascicular multichannel, longitudinal intrafascicular and multipolar cuff electrodes for the selective stimulation of nerve fascicles

NASA Astrophysics Data System (ADS)

Badia, Jordi; Boretius, Tim; Andreu, David; Azevedo-Coste, Christine; Stieglitz, Thomas; Navarro, Xavier

2011-06-01

The selection of a suitable nerve electrode for neuroprosthetic applications implies a trade-off between invasiveness and selectivity, wherein the ultimate goal is achieving the highest selectivity for a high number of nerve fascicles by the least invasiveness and potential damage to the nerve. The transverse intrafascicular multichannel electrode (TIME) is intended to be transversally inserted into the peripheral nerve and to be useful to selectively activate subsets of axons in different fascicles within the same nerve. We present a comparative study of TIME, LIFE and multipolar cuff electrodes for the selective stimulation of small nerves. The electrodes were implanted on the rat sciatic nerve, and the activation of gastrocnemius, plantar and tibialis anterior muscles was recorded by EMG signals. Thus, the study allowed us to ascertain the selectivity of stimulation at the interfascicular and also at the intrafascicular level. The results of this study indicate that (1) intrafascicular electrodes (LIFE and TIME) provide excitation circumscribed to the implanted fascicle, whereas extraneural electrodes (cuffs) predominantly excite nerve fascicles located superficially; (2) the minimum threshold for muscle activation with TIME and LIFE was significantly lower than with cuff electrodes; (3) TIME allowed us to selectively activate the three tested muscles when stimulating through different active sites of one device, both at inter- and intrafascicular levels, whereas selective activation using multipolar cuff (with a longitudinal tripolar stimulation configuration) was only possible for two muscles, at the interfascicular level, and LIFE did not activate selectively more than one muscle in the implanted nerve fascicle.

Effect of noxious electrical stimulation of the peroneal nerve on stretch reflex activity of the hamstring muscle in rats: possible implications of neuronal mechanisms in the development of tight hamstrings in lumbar disc herniation.

PubMed

Hirayama, Jiro; Yamagata, Masatsune; Takahashi, Kazuhisa; Moriya, Hideshige

2005-05-01

The effect of noxious electrical stimulation of the peroneal nerve on the stretch reflex electromyogram activity of the hamstring muscle (semitendinous) was studied. To verify the following hypothetical mechanisms underlying tight hamstrings in lumbar disc herniation: stretch reflex muscle activity of hamstrings is increased by painful inputs from an injured spinal nerve root and the increased stretch reflex muscle activity is maintained by central sensitization. It is reported that stretch reflex activity of the trunk muscles is induced by noxious stimulation of the sciatic nerve and maintained by central sensitization. In spinalized rats (transected spinal cord), the peroneal nerve was stimulated electrically as a conditioning stimulus. Stretch reflex electromyogram activity of the semitendinous muscle was recorded before and after the conditioning stimulus. Even after electrical stimulation was terminated, an increased stretch reflex activity of the hamstring muscle was observed. It is likely that a central sensitization mechanism at the spinal cord level was involved in the increased reflex activity. Central sensitization may play a part in the neuronal mechanisms of tight hamstrings in lumbar disc herniation.

[Immediate recurrent laryngeal nerve reconstruction in the treatment of thyroid cancer invading the recurrent laryngeal nerve].

PubMed

Feng, Yun; Yang, Dazhang; Liu, Dandan; Chen, Jian; Bi, Qingling; Luo, Keqiang

2014-08-01

To explore the application of immediate recurrent laryngeal nerve reconstruction in the treatment of thyroid cancer invading the recurrent laryngeal nerve. Ten patients with thyroid cancer invading unilateral recurrent laryngeal nerve underwent radical surgery and immediate recurrent laryngeal nerve reconstruction. The reconstructive surgical approach included recurrent laryngeal nerve decompression surgery, end-to-end anastomosis of the recurrent laryngeal nerve, anastomosis of ansa cervicalis nerve to the recurrent laryngeal nerve, and nerve-muscle pedicle (NMP) technique. Among the ten patients, one underwent nerve decompression, one underwent end-to-end anastomosis of the recurrent laryngeal nerve, seven had anastomosis of ansa cervicalis to recurrent laryngeal nerve, and one case had anastomosis of ansa cervicalis to recurrent laryngeal nerve combined with nerve-muscle pedicle (NMP) technique. The effect of surgery was evaluated by videolaryngoscopy, maximum phonation time (MPT), phonation efficiency index (PEI) and voice assessment. T-test was used in the statistical analysis. All of the 10 patients had no complications including tumor recurrence and hypoparathyroidism after the surgery. Their hoarseness symptoms were improved, and the patients returned to normal or near-normal voice. Postoperative videolaryngoscopy showed that paralyzed vocal cord returned to normal muscle tone and volume, and the vocal cord vibration and mucosal wave were symmetric and the patients got good glottal closure. The pre- and post-operative maximum phone times of the patients were (4.52 ± 0.89) s and (11.91 ± 1.87) s, respectively (P < 0.01). The pre- and post-operative phonation efficiency indices were (1.37 ± 0.43) s/L and (4.02 ± 1.33) s/L, respectively (P < 0.05). In patients with thyroid cancer invading unilateral recurrent laryngeal nerve, immediate recurrent laryngeal nerve reconstruction following radical surgery of thyroid cancer can effectively achieve recovery in

THE EFFECTS OF POLARIZATION UPON THE STEEL WIRE-NITRIC ACID MODEL OF NERVE ACTIVITY

PubMed Central

Bishop, George H.

1927-01-01

The active process in a short length of steel wire passivated by 65 per cent nitric acid has been observed under the influence of a polarizing current, and the form of the potential recorded by the cathode ray oscillograph. In the passive wire, 80 per cent of the total potential drop takes place at the anode, 20 per cent at the cathode. The change from active to passive states, as measured by the potential change, is very abrupt compared to the duration of activity and the potential curve at a point on the wire is probably almost rectangular. The duration of the refractory state is decreased at the anode and increased at the cathode, as in nerve. This fact is against the idea that reactivity after passivation results from a partial reduction of an oxide layer. Soft iron wire passivated by anodal polarization repassivates after activation in acid of a dilution that fails to passivate it initially. It soon becomes rhythmic with a very short refractory phase, and then reacts continuously. Such a wire exhibits a very sharp alternation between a dark brown oxide coat during activity, and a bright clean surface during passivation. A passive steel wire in nitric acid shows many of the characteristics of an inert electrode such as platinum, and it may be inferred that, superposed upon the primary passivation potential, there exists an electrode or oxidation-reduction potential equilibrium between the effects of the various constituents of the solution. It is suggested that the phenomena of nerve-like reactivity in this system may involve an alternation between two protective coatings of the steel wire. During activity, the surface becomes mechanically coated with a brown oxide. If this coating does not adhere, due to gas convection or to rapid solution of the oxide, passivation does not result. Under sufficiently intense oxidizing conditions, a second oxide coat may form in the interstices of the first, and cover the surface as the first coating dissolves off. This

THE EFFECTS OF POLARIZATION UPON THE STEEL WIRE-NITRIC ACID MODEL OF NERVE ACTIVITY.

PubMed

Bishop, G H

1927-11-20

The active process in a short length of steel wire passivated by 65 per cent nitric acid has been observed under the influence of a polarizing current, and the form of the potential recorded by the cathode ray oscillograph. In the passive wire, 80 per cent of the total potential drop takes place at the anode, 20 per cent at the cathode. The change from active to passive states, as measured by the potential change, is very abrupt compared to the duration of activity and the potential curve at a point on the wire is probably almost rectangular. The duration of the refractory state is decreased at the anode and increased at the cathode, as in nerve. This fact is against the idea that reactivity after passivation results from a partial reduction of an oxide layer. Soft iron wire passivated by anodal polarization repassivates after activation in acid of a dilution that fails to passivate it initially. It soon becomes rhythmic with a very short refractory phase, and then reacts continuously. Such a wire exhibits a very sharp alternation between a dark brown oxide coat during activity, and a bright clean surface during passivation. A passive steel wire in nitric acid shows many of the characteristics of an inert electrode such as platinum, and it may be inferred that, superposed upon the primary passivation potential, there exists an electrode or oxidation-reduction potential equilibrium between the effects of the various constituents of the solution. It is suggested that the phenomena of nerve-like reactivity in this system may involve an alternation between two protective coatings of the steel wire. During activity, the surface becomes mechanically coated with a brown oxide. If this coating does not adhere, due to gas convection or to rapid solution of the oxide, passivation does not result. Under sufficiently intense oxidizing conditions, a second oxide coat may form in the interstices of the first, and cover the surface as the first coating dissolves off. This

The ovine fetal endocrine reflex responses to haemorrhage are not mediated by cardiac nerves

PubMed Central

Wood, Charles E

2002-01-01

This study was designed to test the hypothesis that cardiac receptors tonically inhibit the secretion of renin, arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) in late-gestation fetal sheep. Eight chronically catheterised fetal sheep between 122 and 134 days gestation were subjected to injection or infusion of saline or 4 % procaine into the pericardial space. Fetal blood pressure and heart rate were monitored and fetal blood samples were drawn to measure the response to these injections. Injection of procaine into the pericardial space effectively blocked cardiac nerves, as evidenced by a reduction in the variability of fetal heart rate and by the blockade of reflex reductions in fetal heart rate after intravenous injection of phenylephrine (an α-adrenergic agonist which raises blood pressure). Injection of saline had no discernable effects on any of the measured variables. A single injection of procaine, followed by a slow infusion, produced a transient blockade of cardiac nerves. Multiple injections of procaine produced a sustained blockade of cardiac nerves and a sustained rise in fetal plasma renin activity and ACTH. In none of the experiments did procaine significantly alter fetal plasma AVP concentrations. In 11 fetuses between 121 and 134 days gestation, we combined the cardiac nerve blockade with slow haemorrhage to test the cardiac nerves as mediators of the endocrine response to haemorrhage in utero. Cardiac nerve blockade exaggerated the fetal blood gas response to haemorrhage somewhat but did not significantly alter the magnitude of the ACTH, AVP, or plasma renin activity response to haemorrhage. We conclude that cardiac nerves in the late-gestation fetal sheep have minor influences on plasma renin activity and ACTH in normovolaemic fetuses, but that changes in cardiac nerve activity do not mediate the endocrine responsiveness to haemorrhage. PMID:12042365

High-voltage-activated calcium current subtypes in mouse DRG neurons adapt in a subpopulation-specific manner after nerve injury.

PubMed

Murali, Swetha S; Napier, Ian A; Mohammadi, Sarasa A; Alewood, Paul F; Lewis, Richard J; Christie, MacDonald J

2015-03-01

Changes in ion channel function and expression are characteristic of neuropathic pain. Voltage-gated calcium channels (VGCCs) are integral for neurotransmission and membrane excitability, but relatively little is known about changes in their expression after nerve injury. In this study, we investigate whether peripheral nerve ligation is followed by changes in the density and proportion of high-voltage-activated (HVA) VGCC current subtypes in dorsal root ganglion (DRG) neurons, the contribution of presynaptic N-type calcium channels in evoked excitatory postsynaptic currents (EPSCs) recorded from dorsal horn neurons in the spinal cord, and the changes in expression of mRNA encoding VGCC subunits in DRG neurons. Using C57BL/6 mice [8- to 11-wk-old males (n = 91)] for partial sciatic nerve ligation or sham surgery, we performed whole cell patch-clamp recordings on isolated DRG neurons and dorsal horn neurons and measured the expression of all VGCC subunits with RT-PCR in DRG neurons. After nerve injury, the density of P/Q-type current was reduced overall in DRG neurons. There was an increase in the percentage of N-type and a decrease in that of P/Q-type current in medium- to large-diameter neurons. No changes were found in the contribution of presynaptic N-type calcium channels in evoked EPSCs recorded from dorsal horn neurons. The α2δ-1 subunit was upregulated by 1.7-fold and γ-3, γ-2, and β-4 subunits were all downregulated 1.7-fold in injured neurons compared with sham-operated neurons. This comprehensive characterization of HVA VGCC subtypes in mouse DRG neurons after nerve injury revealed changes in N- and P/Q-type current proportions only in medium- to large-diameter neurons. Copyright © 2015 the American Physiological Society.

A device for emulating cuff recordings of action potentials propagating along peripheral nerves.

PubMed

Rieger, Robert; Schuettler, Martin; Chuang, Sheng-Chih

2014-09-01

This paper describes a device that emulates propagation of action potentials along a peripheral nerve, suitable for reproducible testing of bio-potential recording systems using nerve cuff electrodes. The system is a microcontroller-based stand-alone instrument which uses established nerve and electrode models to represent neural activity of real nerves recorded with a nerve cuff interface, taking into consideration electrode impedance, voltages picked up by the electrodes, and action potential propagation characteristics. The system emulates different scenarios including compound action potentials with selectable propagation velocities and naturally occurring nerve traffic from different velocity fiber populations. Measured results from a prototype implementation are reported and compared with in vitro recordings from Xenopus Laevis frog sciatic nerve, demonstrating that the electrophysiological setting is represented to a satisfactory degree, useful for the development, optimization and characterization of future recording systems.

Deep Temporal Nerve Transfer for Facial Reanimation: Anatomic Dissections and Surgical Case Report.

PubMed

Mahan, Mark A; Sivakumar, Walavan; Weingarten, David; Brown, Justin M

2017-09-08

Facial nerve palsy is a disabling condition that may arise from a variety of injuries or insults and may occur at any point along the nerve or its intracerebral origin. To examine the use of the deep temporal branches of the motor division of the trigeminal nerve for neural reconstruction of the temporal branches of the facial nerve for restoration of active blink and periorbital facial expression. Formalin-fixed human cadaver hemifaces were dissected to identify landmarks for the deep temporal branches and the tension-free coaptation lengths. This technique was then utilized in 1 patient with a history of facial palsy due to a brainstem cavernoma. Sixteen hemifaces were dissected. The middle deep temporal nerve could be consistently identified on the deep side of the temporalis, within 9 to 12 mm posterior to the jugal point of the zygoma. From a lateral approach through the temporalis, the middle deep temporal nerve could be directly coapted to facial temporal branches in all specimens. Our patient has recovered active and independent upper facial muscle contraction, providing the first case report of a distinct distal nerve transfer for upper facial function. The middle deep temporal branches can be readily identified and utilized for facial reanimation. This technique provided a successful reanimation of upper facial muscles with independent activation. Utilizing multiple sources for neurotization of the facial muscles, different potions of the face can be selectively reanimated to reduce the risk of synkinesis and improved control. Copyright © 2017 by the Congress of Neurological Surgeons

Reconstruction of the Abdominal Vagus Nerve Using Sural Nerve Grafts in Canine Models

PubMed Central

Luo, Fen; Wang, Zhiming; Wang, Yin

2013-01-01

Background Recently, vagus nerve preservation or reconstruction of vagus has received increasing attention. The present study aimed to investigate the feasibility of reconstructing the severed vagal trunk using an autologous sural nerve graft. Methods Ten adult Beagle dogs were randomly assigned to two groups of five, the nerve grafting group (TG) and the vagal resection group (VG). The gastric secretion and emptying functions in both groups were assessed using Hollander insulin and acetaminophen tests before surgery and three months after surgery. All dogs underwent laparotomy under general anesthesia. In TG group, latency and conduction velocity of the action potential in a vagal trunk were measured, and then nerves of 4 cm long were cut from the abdominal anterior and posterior vagal trunks. Two segments of autologous sural nerve were collected for performing end-to-end anastomoses with the cut ends of vagal trunk (8–0 nylon suture, 3 sutures for each anastomosis). Dogs in VG group only underwent partial resections of the anterior and posterior vagal trunks. Laparotomy was performed in dogs of TG group, and latency and conduction velocity of the action potential in their vagal trunks were measured. The grafted nerve segment was removed, and stained with anti-neurofilament protein and toluidine blue. Results Latency of the action potential in the vagal trunk was longer after surgery than before surgery in TG group, while the conduction velocity was lower after surgery. The gastric secretion and emptying functions were weaker after surgery in dogs of both groups, but in TG group they were significantly better than in VG group. Anti-neurofilament protein staining and toluidine blue staining showed there were nerve fibers crossing the anastomosis of the vagus and sural nerves in dogs of TG group. Conclusion Reconstruction of the vagus nerve using the sural nerve is technically feasible. PMID:23555604

Electrophysiology of Extraocular Cranial Nerves: Oculomotor, Trochlear, and Abducens Nerve.

PubMed

Hariharan, Praveen; Balzer, Jeffery R; Anetakis, Katherine; Crammond, Donald J; Thirumala, Parthasarathy D

2018-01-01

The utility of extraocular cranial nerve electrophysiologic recordings lies primarily in the operating room during skull base surgeries. Surgical manipulation during skull base surgeries poses a risk of injury to multiple cranial nerves, including those innervating extraocular muscles. Because tumors distort normal anatomic relationships, it becomes particularly challenging to identify cranial nerve structures. Studies have reported the benefits of using intraoperative spontaneous electromyographic recordings and compound muscle action potentials evoked by electrical stimulation in preventing postoperative neurologic deficits. Apart from surgical applications, electromyography of extraocular muscles has also been used to guide botulinum toxin injections in patients with strabismus and as an adjuvant diagnostic test in myasthenia gravis. In this article, we briefly review the rationale, current available techniques to monitor extraocular cranial nerves, technical difficulties, clinical and surgical applications, as well as future directions for research.

Fish oil supplementation prevents diabetes-induced nerve conduction velocity and neuroanatomical changes in rats.

PubMed

Gerbi, A; Maixent, J M; Ansaldi, J L; Pierlovisi, M; Coste, T; Pelissier, J F; Vague, P; Raccah, D

1999-01-01

Diabetic neuropathy has been associated with a decrease in nerve conduction velocity, Na,K-ATPase activity and characteristic histological damage of the sciatic nerve. The aim of this study was to evaluate the potential effect of a dietary supplementation with fish oil [(n-3) fatty acids] on the sciatic nerve of diabetic rats. Diabetes was induced by intravenous streptozotocin injection. Diabetic animals (n = 20) were fed a nonpurified diet supplemented with either olive oil (DO) or fish oil (DM), and control animals (n = 10) were fed a nonpurified diet supplemented with olive oil at a daily dose of 0.5 g/kg by gavage for 8 wk. Nerves were characterized by their conduction velocity, morphometric analysis and membrane Na, K-ATPase activity. Nerve conduction velocity, as well as Na,K-ATPase activity, was improved by fish oil treatment. A correlation was found between these two variables (R = 0.999, P < 0.05). Moreover, a preventive effect of fish oil was observed on nerve histological damage [endoneurial edema, axonal degeneration (by 10-15%) with demyelination]. Moreover, the normal bimodal distribution of the internal diameter of myelinated fibers was absent in the DO group and was restored in the DM group. These data suggest that fish oil therapy may be effective in the prevention of diabetic neuropathy.