Hypoglossal nerve palsy in infectious mononucleosis.

PubMed

DeSimone, P A; Snyder, D

1978-08-01

Involvement of the central nervous system is a rare complication of infectious mononucleosis. Isolated cranial nerve palsy is the least reported neurologic complication. We report a second case of hypoglossal nerve palsy associated with infectious mononucleosis, and review 20 other reported cases of cranial nerve palsies. Any cranial nerve may be involved. The onset of the palsy usually follows the diagnosis and clinical presentation of infectious mononucleosis. The prognosis for a complete recovery is excellent, although recovery may be protracted. The use of steroids does not appear to be etiologic, nor beneficial or deleterious in treatment.

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.

Nervous kidney. Interaction between renal sympathetic nerves and the renin-angiotensin system in the control of renal function.

PubMed

DiBona, G F

2000-12-01

Increases in renal sympathetic nerve activity regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. Because increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between the renal sympathetic nerves and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, for example, the direct (by specific innervation) and indirect (by angiotensin II) contributions of increased renal sympathetic nerve activity to the regulation of renal function. The effects of increased renal sympathetic nerve activity on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with ACE inhibitors or angiotensin II-type AT(1)-receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated after renal denervation. These interactions can also be extrarenal, for example, in the central nervous system, wherein renal sympathetic nerve activity and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, whose permeable blood-brain barrier permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II-type AT(1)-receptor antagonists into the ventricular system or microinjected into the rostral ventrolateral medulla are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (eg, congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and renal sympathetic nerve activity are involved in influencing the neural control of renal function.

Complaints to the Norwegian System of Patient Injury Compensation 2001-14 following nerve blockade.

PubMed

Kongsgaard, Ulf E; Fischer, Kristine; Pedersen, Tor Erlend; Bukholm, Ida Rashida Khan; Warncke, Torhild

2016-12-01

There has been a steady increase in cases reported to the Norwegian System of Patient Injury Compensation (NPE). We wished to look into what might characterise those cases of central and peripheral nerve blockade for anaesthesia that led to compensation claims. Cases with codes for central and peripheral blockade within the field of anaesthesiology were retrieved from the NPE database for the period 2001 – 14. The cases were evaluated on the basis of variables including sex, age, type of anaesthesia, diagnosis, type of injury, site of injury, damages received, and written descriptions of treatment and injury. The expert reports were anonymised and reviewed in detail. A total of 339 patient compensation claims relating to nerve blockade were identified, of which 149 concerned spinal anaesthesia, 142 epidural anaesthesia, 21 combined spinal and epidural anaesthesia and 27 peripheral nerve blockade. The group consisted of 236 women and 103 men, and the average age was 46 years. The 339 cases comprised 0.8 % of all cases reported to the NPE in this period. A total of 107 claims resulted in compensation. Eighty-two million Norwegian kroner were paid out in total. Peripheral and central nerve blockade accounts for only a small proportion of cases handled by the NPE. Only one in three applicants had their claim upheld, but when claims were upheld, the injuries were often severe and led to substantial pay-outs.

Axonal Elongation into Peripheral Nervous System ``Bridges'' after Central Nervous System Injury in Adult Rats

NASA Astrophysics Data System (ADS)

David, Samuel; Aguayo, Albert J.

1981-11-01

The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as ``bridges'' between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millimeters. The regenerative potential of these central neurons seems to be expressed when the central nervous system glial environment is changed to that of the peripheral nervous system.

Nerve conduction studies are safe in patients with central venous catheters.

PubMed

London, Zachary N; Mundwiler, Andrew; Oral, Hakan; Gallagher, Gary W

2017-08-01

It is unknown if central venous catheters bypass the skin's electrical resistance and engender a risk of nerve conduction study-induced cardiac arrhythmia. The objective of this study is to determine if nerve conduction studies affect cardiac conduction and rhythm in patients with central venous catheters. Under continuous 12-lead electrocardiogram monitoring, subjects with and without central venous catheters underwent a series of upper extremity nerve conduction studies. A cardiologist reviewed the electrocardiogram tracings for evidence of cardiac conduction abnormality or arrhythmia. Ten control subjects and 10 subjects with central venous catheters underwent the nerve conduction study protocol. No malignant arrhythmias or conduction abnormalities were noted in either group. Nerve conduction studies of the upper extremities, including both proximal stimulation and repetitive stimulation, do not appear to confer increased risk of cardiac conduction abnormality in those patients with central venous catheters who are not critically ill or have a prior history of arrhythmia. Muscle Nerve 56: 321-323, 2017. © 2016 Wiley Periodicals, Inc.

Magnetic resonance imaging of optic nerve

PubMed Central

Gala, Foram

2015-01-01

Optic nerves are the second pair of cranial nerves and are unique as they represent an extension of the central nervous system. Apart from clinical and ophthalmoscopic evaluation, imaging, especially magnetic resonance imaging (MRI), plays an important role in the complete evaluation of optic nerve and the entire visual pathway. In this pictorial essay, the authors describe segmental anatomy of the optic nerve and review the imaging findings of various conditions affecting the optic nerves. MRI allows excellent depiction of the intricate anatomy of optic nerves due to its excellent soft tissue contrast without exposure to ionizing radiation, better delineation of the entire visual pathway, and accurate evaluation of associated intracranial pathologies. PMID:26752822

Sensory neuropathy may cause central neuronal reorganization but does not respecify perceptual quality or localization of sensation.

PubMed

Ginanneschi, Federica; Mondelli, Mauro; Rossi, Alessandro

2012-10-01

Functional reorganization in the somatosensory network after peripheral nerve lesions has been suspected to modify the clinical expression of symptoms. However, no conclusive evidence exists to support this notion. We addressed this question by investigating the topographic distribution of the subjective sensory report in various chronic human mononeuropathies. We report the clinical results of 86 patients who were diagnosed with meralgia paresthetica, 86 patients with ulnar neuropathy at the elbow, and 203 patients with carpal tunnel syndrome. In the carpal tunnel syndrome group, 10% of the patients exhibited a spread of sensory symptoms beyond the innervation territory of the median nerve. As previously reported, this spread was contingent upon an indirect compressive lesion of the ulnar nerve at the wrist. In all of the patients who were affected with meralgia paresthetica or ulnar neuropathy at the elbow, the peripheral referral of sensation was always within the anatomic distribution of the affected nerve. In human neuropathies, the projected sensory symptoms are restricted to the innervation territories of the affected nerves, with no extraterritorial spread. Thus, the somatosensory localization function remains accurate, despite the central reorganization that presumably occurs after nerve injury. We conclude that reorganization of the sensory connections within the central nervous system after peripheral nerve injury in humans is a clinically silent adaptive phenomenon.

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.

Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia

PubMed Central

Pavlov, Valentin A.; Ochani, Mahendar; Gallowitsch-Puerta, Margot; Ochani, Kanta; Huston, Jared M.; Czura, Christopher J.; Al-Abed, Yousef; Tracey, Kevin J.

2006-01-01

TNF has a critical mediator role in inflammation and is an important therapeutic target. We recently discovered that TNF production is regulated by neural signals through the vagus nerve. Activation of this “cholinergic antiinflammatory pathway” inhibits the production of TNF and other cytokines and protects animals from the inflammatory damage caused by endotoxemia and severe sepsis. Here, we describe a role for central muscarinic acetylcholine receptors in the activation of the cholinergic antiinflammatory pathway. Central muscarinic cholinergic activation by muscarine, the M1 receptor agonist McN-A-343, and the M2 receptor antagonist methoctramine inhibited serum TNF levels significantly during endotoxemia. Centrally administered methoctramine stimulated vagus-nerve activity measured by changes in instantaneous heart-rate variability. Blockade of peripheral muscarinic receptors did not abolish antiinflammatory signaling through the vagus nerve, indicating that peripheral muscarinic receptors on immune cells are not required for the cytokine-regulating activities of the cholinergic antiinflammatory pathway. The role of central muscarinic receptors in activating the cholinergic antiinflammatory pathway is of interest for the use of centrally acting muscarinic cholinergic enhancers as antiinflammatory agents. PMID:16549778

Inflammation and the nervous system: the connection in the cornea in patients with infectious keratitis.

PubMed

Cruzat, Andrea; Witkin, Deborah; Baniasadi, Neda; Zheng, Lixin; Ciolino, Joseph B; Jurkunas, Ula V; Chodosh, James; Pavan-Langston, Deborah; Dana, Reza; Hamrah, Pedram

2011-07-11

To study the density and morphologic characteristics of epithelial dendritic cells, as correlated to subbasal corneal nerve alterations in acute infectious keratitis (IK) by in vivo confocal microscopy (IVCM). IVCM of the central cornea was performed prospectively in 53 eyes with acute bacterial (n = 23), fungal (n = 13), and Acanthamoeba (n = 17) keratitis, and in 20 normal eyes, by using laser in vivo confocal microscopy. Density and morphology of dendritic-shaped cells (DCs) of the central cornea, corneal nerve density, nerve numbers, branching, and tortuosity were assessed and correlated. It should be noted that due to the "in vivo" nature of the study, the exact identity of these DCs cannot be specified, as they could be monocytes or tissue macrophages, but most likely dendritic cells. IVCM revealed the presence of central corneal DCs in all patients and controls. The mean DC density was significantly higher in patients with bacterial (441.1 ± 320.5 cells/mm(2); P < 0.0001), fungal (608.9 ± 812.5 cells/mm(2); P < 0.0001), and Acanthamoeba keratitis (1000.2 ± 1090.3 cells/mm(2); P < 0.0001) compared with controls (49.3 ± 39.6 cells/mm(2)). DCs had an increased size and dendrites in patients with IK. Corneal nerves were significantly reduced in eyes with IK compared with controls across all subgroups, including nerve density (674.2 ± 976.1 vs. 3913.9 ± 507.4 μm/frame), total nerve numbers (2.7 ± 3.9 vs. 20.2 ± 3.3), main trunks (1.5 ± 2.2 vs. 6.9 ± 1.1), and branching (1.2 ± 2.0 vs. 13.5 ± 3.1; P < 0.0001). A strong association between the diminishment of corneal nerves and the increase of DC density was observed (r = -0.44; P < 0.0005). IVCM reveals an increased density and morphologic changes of central epithelial DCs in infectious keratitis. There is a strong and significant correlation between the increase in DC numbers and the decreased subbasal corneal nerves, suggesting a potential interaction between the immune and nervous system in the cornea.

Role of the Sympathetic Nervous System and Its Modulation in Renal Hypertension

PubMed Central

Sata, Yusuke; Head, Geoffrey A.; Denton, Kate; May, Clive N.; Schlaich, Markus P.

2018-01-01

The kidneys are densely innervated with renal efferent and afferent nerves to communicate with the central nervous system. Innervation of major structural components of the kidneys, such as blood vessels, tubules, the pelvis, and glomeruli, forms a bidirectional neural network to relay sensory and sympathetic signals to and from the brain. Renal efferent nerves regulate renal blood flow, glomerular filtration rate, tubular reabsorption of sodium and water, as well as release of renin and prostaglandins, all of which contribute to cardiovascular and renal regulation. Renal afferent nerves complete the feedback loop via central autonomic nuclei where the signals are integrated and modulate central sympathetic outflow; thus both types of nerves form integral parts of the self-regulated renorenal reflex loop. Renal sympathetic nerve activity (RSNA) is commonly increased in pathophysiological conditions such as hypertension and chronic- and end-stage renal disease. Increased RSNA raises blood pressure and can contribute to the deterioration of renal function. Attempts have been made to eliminate or interfere with this important link between the brain and the kidneys as a neuromodulatory treatment for these conditions. Catheter-based renal sympathetic denervation has been successfully applied in patients with resistant hypertension and was associated with significant falls in blood pressure and renal protection in most studies performed. The focus of this review is the neural contribution to the control of renal and cardiovascular hemodynamics and renal function in the setting of hypertension and chronic kidney disease, as well as the specific roles of renal efferent and afferent nerves in this scenario and their utility as a therapeutic target. PMID:29651418

Role of the Sympathetic Nervous System and Its Modulation in Renal Hypertension.

PubMed

Sata, Yusuke; Head, Geoffrey A; Denton, Kate; May, Clive N; Schlaich, Markus P

2018-01-01

The kidneys are densely innervated with renal efferent and afferent nerves to communicate with the central nervous system. Innervation of major structural components of the kidneys, such as blood vessels, tubules, the pelvis, and glomeruli, forms a bidirectional neural network to relay sensory and sympathetic signals to and from the brain. Renal efferent nerves regulate renal blood flow, glomerular filtration rate, tubular reabsorption of sodium and water, as well as release of renin and prostaglandins, all of which contribute to cardiovascular and renal regulation. Renal afferent nerves complete the feedback loop via central autonomic nuclei where the signals are integrated and modulate central sympathetic outflow; thus both types of nerves form integral parts of the self-regulated renorenal reflex loop. Renal sympathetic nerve activity (RSNA) is commonly increased in pathophysiological conditions such as hypertension and chronic- and end-stage renal disease. Increased RSNA raises blood pressure and can contribute to the deterioration of renal function. Attempts have been made to eliminate or interfere with this important link between the brain and the kidneys as a neuromodulatory treatment for these conditions. Catheter-based renal sympathetic denervation has been successfully applied in patients with resistant hypertension and was associated with significant falls in blood pressure and renal protection in most studies performed. The focus of this review is the neural contribution to the control of renal and cardiovascular hemodynamics and renal function in the setting of hypertension and chronic kidney disease, as well as the specific roles of renal efferent and afferent nerves in this scenario and their utility as a therapeutic target.

Cranial nerve vascular compression syndromes of the trigeminal, facial and vago-glossopharyngeal nerves: comparative anatomical study of the central myelin portion and transitional zone; correlations with incidences of corresponding hyperactive dysfunctional syndromes.

PubMed

Guclu, Bulent; Sindou, Marc; Meyronet, David; Streichenberger, Nathalie; Simon, Emile; Mertens, Patrick

2011-12-01

The aim of this study was to evaluate the anatomy of the central myelin portion and the central myelin-peripheral myelin transitional zone of the trigeminal, facial, glossopharyngeal and vagus nerves from fresh cadavers. The aim was also to investigate the relationship between the length and volume of the central myelin portion of these nerves with the incidences of the corresponding cranial dysfunctional syndromes caused by their compression to provide some more insights for a better understanding of mechanisms. The trigeminal, facial, glossopharyngeal and vagus nerves from six fresh cadavers were examined. The length of these nerves from the brainstem to the foramen that they exit were measured. Longitudinal sections were stained and photographed to make measurements. The diameters of the nerves where they exit/enter from/to brainstem, the diameters where the transitional zone begins, the distances to the most distal part of transitional zone from brainstem and depths of the transitional zones were measured. Most importantly, the volume of the central myelin portion of the nerves was calculated. Correlation between length and volume of the central myelin portion of these nerves and the incidences of the corresponding hyperactive dysfunctional syndromes as reported in the literature were studied. The distance of the most distal part of the transitional zone from the brainstem was 4.19  ±  0.81 mm for the trigeminal nerve, 2.86  ±  1.19 mm for the facial nerve, 1.51  ±  0.39 mm for the glossopharyngeal nerve, and 1.63  ±  1.15 mm for the vagus nerve. The volume of central myelin portion was 24.54  ±  9.82 mm(3) in trigeminal nerve; 4.43  ±  2.55 mm(3) in facial nerve; 1.55  ±  1.08 mm(3) in glossopharyngeal nerve; 2.56  ±  1.32 mm(3) in vagus nerve. Correlations (p  < 0.001) have been found between the length or volume of central myelin portions of the trigeminal, facial, glossopharyngeal and vagus nerves and incidences of the corresponding diseases. At present it is rather well-established that primary trigeminal neuralgia, hemifacial spasm and vago-glossopharyngeal neuralgia have as one of the main causes a vascular compression. The strong correlations found between the lengths and volumes of the central myelin portions of the nerves and the incidences of the corresponding diseases is a plea for the role played by this anatomical region in the mechanism of these diseases.

Central and peripheral components of short latency vestibular responses in the chicken

NASA Technical Reports Server (NTRS)

Nazareth, A. M.; Jones, T. A.

1998-01-01

Far-field recordings of short latency vestibular responses to pulsed cranial translation are composed of a series of positive and negative peaks occurring within 10 ms following stimulus onset. In the bird, these vestibular evoked potentials (VsEPs) can be recorded noninvasively and have been shown in the chicken and quail to depend strictly upon the activation of the vestibular component of the eighth nerve. The utility of the VsEP in the study of vestibular systems is dependent upon a clear understanding of the neural sources of response components. The primary aim of the current research in the chicken was to critically test the hypotheses that 1) responses are generated by both peripheral and central neurons and 2) peaks P1 and N1 originate from first order vestibular neurons, whereas later waves primarily depend on activity in higher order neurons. The principal strategy used here was to surgically isolate the eighth nerve as it enters the brainstem. Interruption of primary afferents of the eighth nerve in the brainstem substantially reduced or eliminated peaks beyond P2, whereas P1 and N1 were generally spared. Surgical sections that spared vestibular pathways had little effect on responses. The degree of change in response components beyond N1 was correlated with the extent of damage to central vestibular relays. These findings support the conclusion that responses are produced by both peripheral and central elements of the vestibular system. Further, response peaks later than N1 appear to be dependent upon central relays, whereas P1 and N1 reflect activity of the peripheral nerve. These findings clarify the roles of peripheral and central neurons in the generation of vestibular evoked potentials and provide the basis for a more useful and detailed interpretation of data from vestibular response testing.

Phrenic Nerve Stimulation: Technology and Clinical Applications.

PubMed

Abdunnur, Shane V; Kim, Daniel H

2015-01-01

Phrenic nerve stimulation is a technique used to reanimate the diaphragm of patients with central nervous system etiologies of respiratory insufficiency. Current clinical indications include congenital central hypoventilation syndrome, spinal cord injury above C4, brain stem injury, and idiopathic severe sleep apnea. Presurgical evaluation ensures proper patient selection by validating the intact circuit from the phrenic nerve through alveolar oxygenation. The procedure involves placing leads around the phrenic nerves bilaterally and attaching these leads to radio receivers in a subcutaneous pocket. The rate and amplitude of the current is adjusted via an external radio transmitter. After implantation, each patient progresses through a conditioning phase that strengthens the diaphragm and progressively provides independence from the mechanical ventilator. Studies indicate that patients and families experience an improved quality of life and are satisfied with the results. Phrenic nerve stimulation provides a safe and effective means for reanimating the diaphragm for certain patients with respiratory insufficiency, providing independence from mechanical ventilation. © 2016 S. Karger AG, Basel.

Renal neural mechanisms in salt-sensitive hypertension.

PubMed

DiBona, G F

1995-01-01

Genetic forms of salt (NaCl)-sensitive hypertension are characterized by increased renal sympathetic nerve activity responses to environmental stimuli. The increases in renal sympathetic nerve activity produce marked changes in renal function with renal vasoconstriction and sodium and water retention which can contribute to the initiation, development and maintenance of hypertension. In genetic forms of NaCl-sensitive hypertension, increased dietary NaCl intake produces alterations in norepinephrine kinetics with decreased concentrations of norepinephrine in regions of the anterior hypothalamus which are critical for the regulation of peripheral sympathetic nerve activity. This local central decrease in tonic alpha 2 adrenoceptor sympathoinhibitory input leads to increased peripheral (renal) sympathetic nerve activity and hypertension. Similarly, with increased dietary NaCl intake, patients with NaCl-sensitive hypertension develop increased arterial pressure, renal vasoconstriction, increased glomerular capillary pressure and increased urinary albumin excretion. Thus, increased dietary NaCl intake can, via central nervous system actions, produce increases in renal sympathetic nerve activity whose renal functional effects contribute to the pathophysiology of hypertension.

Evolution of and perspectives on therapeutic approaches to nerve agent poisoning.

PubMed

Masson, Patrick

2011-09-25

After more than 70 years of considerable efforts, research on medical defense against nerve agents has come to a standstill. Major progress in medical countermeasures was achieved between the 50s and 70s with the development of anticholinergic drugs and carbamate-based pretreatment, the introduction of pyridinium oximes as antidotes, and benzodiazepines in emergency treatments. These drugs ensure good protection of the peripheral nervous system and mitigate the acute effects of exposure to lethal doses of nerve agents. However, pyridostigmine and cholinesterase reactivators currently used in the armed forces do not protect/reactivate central acetylcholinesterases. Moreover, other drugs used are not sufficiently effective in protecting the central nervous system against seizures, irreversible brain damages and long-term sequelae of nerve agent poisoning.New developments of medical counter-measures focus on: (a) detoxification of organophosphorus molecules before they react with acetylcholinesterase and other physiological targets by administration of stoichiometric or catalytic scavengers; (b) protection and reactivation of central acetylcholinesterases, and (c) improvement of neuroprotection following delayed therapy.Future developments will aim at treatment of acute and long-term effects of low level exposure to nerve agents, research on alternative routes for optimizing drug delivery, and therapies. Though gene therapy for in situ generation of bioscavengers, and cell therapy based on neural progenitor engraftment for neuronal regeneration have been successfully explored, more studies are needed before practical medical applications can be made of these new approaches. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Influence of oculomotor nerve afferents on central endings of primary trigeminal fibers.

PubMed

Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E; Draicchio, F

1987-12-01

Painful fibers running in the third nerve and originating from the ophthalmic trigeminal area send their central projections at level of substantia gelatinosa of nucleus caudalis trigemini. The central endings of these fibers form axoaxonic synapses with trigeminal fibers entering the brain stem through the trigeminal root. The effect of electrical stimulation of the third nerve central stump on the central endings of trigeminal afferent fibers consists in an increased excitability, possibly resulting in a presynaptic inhibition. This inhibitory influence is due to both direct and indirect connections of the third nerve afferent fibers with the trigeminal ones.

Severe brachial plexopathy after an ultrasound-guided single-injection nerve block for total shoulder arthroplasty in a patient with multiple sclerosis.

PubMed

Koff, Matthew D; Cohen, Jeffrey A; McIntyre, John J; Carr, Charles F; Sites, Brian D

2008-02-01

DESPITE the known benefits of regional anesthesia for patients undergoing joint arthroplasty, the performance of peripheral nerve blocks in patients with multiple sclerosis (MS) remains controversial. MS has traditionally been described as an isolated disease of the central nervous system, without involvement of the peripheral nerves, and peripheral nerve blockade has been suggested to be safe. However, careful review of the literature suggests that MS may also be associated with involvement of the peripheral nervous system, challenging traditional teachings. There is a paucity of evidence with regard to safety in using peripheral nerve regional anesthesia in these patients. This makes it difficult to provide adequate "informed consent" to these patients. This case report describes a patient with MS who sustained a severe brachial plexopathy after a total shoulder arthroplasty during combined general anesthesia and interscalene nerve block.

Comparative Discussion on Psychophysiological Effect of Self-administered Facial Massage by Treatment Method

NASA Astrophysics Data System (ADS)

Nozawa, Akio; Takei, Yuya

The aim of study was to quantitatively evaluate the effects of self-administered facial massage, which was done by hand or facial roller. In this study, the psychophysiological effects of facial massage were evaluated. The central nerves system and the autonomic nervous system were administered to evaluate physiological system. The central nerves system was assessed by Electroencephalogram (EEG). The autonomic nervous system were assessed by peripheral skin temperature(PST) and heart rate variability (HRV) with spectral analysis. In the spectral analysis of HRV, the high-frequency components (HF) were evaluated. State-Trait Anxiety Inventory (STAI), Profile of Mood Status (POMS) and subjective sensory amount with Visual Analog Scale (VAS) were administered to evaluate psychological status. These results suggest that kept brain activity and had strong effects on stress alleviation.

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.

Central sensitization does not identify patients with carpal tunnel syndrome who are likely to achieve short-term success with physical therapy.

PubMed

Fernández-de-Las-Peñas, César; Cleland, Joshua A; Ortega-Santiago, Ricardo; de-la-Llave-Rincon, Ana Isabel; Martínez-Perez, Almudena; Pareja, Juan A

2010-11-01

The aim of the current study was to identify whether hyperexcitability of the central nervous system is a prognostic factor for individuals with carpal tunnel syndrome (CTS) likely to experience rapid and clinical self-reported improvement following a physical therapy program including soft tissue mobilization and nerve slider neurodynamic interventions. Women presenting with clinical and electrophysiological findings of CTS were involved in a prospective single-arm trial. Participants underwent a standardized examination and then a physical therapy session. The physical therapy sessions included both soft tissue mobilization directed at the anatomical sites of potential median nerve entrapment and a passive nerve slider neurodynamic technique targeted to the median nerve. Pressure pain thresholds (PPT) over the median, radial and ulnar nerves, C5-C6 zygapophyseal joint, carpal tunnel and tibialis anterior muscle were assessed bilaterally. Additionally, thermal detection and pain thresholds were measured over the carpal tunnel and thenar eminence bilaterally to evaluate central nervous system excitability. Subjects were classified as responders (having achieved a successful outcome) or non-responders based on self-perceived recovery. Variables were entered into a stepwise logistic regression model to determine the most accurate variables for determining prognosis. Data from 72 women were included in the analysis, of which 35 experienced a successful outcome (48.6%). Three variables including PPT over the C5-C6 joint affected side <137 kPa, HPT carpal tunnel affected side <39.6º and general health >66 points were identified. If 2 out of 3 variables were present (LR + 14.8), the likelihood of success increased from 48.6 to 93.3%. We identified 3 factors that may be associated with a rapid clinical response to both soft tissue mobilization and nerve slider neurodynamic techniques targeted to the median nerve in women presenting with CTS. Our results support that widespread central sensitization may not be present in women with CTS who are likely to achieve a successful outcome with physical therapy. Future studies are now necessary to validate these findings.

Interfacing with the nervous system: a review of current bioelectric technologies.

PubMed

Sahyouni, Ronald; Mahmoodi, Amin; Chen, Jefferson W; Chang, David T; Moshtaghi, Omid; Djalilian, Hamid R; Lin, Harrison W

2017-10-23

The aim of this study is to discuss the state of the art with regard to established or promising bioelectric therapies meant to alter or control neurologic function. We present recent reports on bioelectric technologies that interface with the nervous system at three potential sites-(1) the end organ, (2) the peripheral nervous system, and (3) the central nervous system-while exploring practical and clinical considerations. A literature search was executed on PubMed, IEEE, and Web of Science databases. A review of the current literature was conducted to examine functional and histomorphological effects of neuroprosthetic interfaces with a focus on end-organ, peripheral, and central nervous system interfaces. Innovations in bioelectric technologies are providing increasing selectivity in stimulating distinct nerve fiber populations in order to activate discrete muscles. Significant advances in electrode array design focus on increasing selectivity, stability, and functionality of implantable neuroprosthetics. The application of neuroprosthetics to paretic nerves or even directly stimulating or recording from the central nervous system holds great potential in advancing the field of nerve and tissue bioelectric engineering and contributing to clinical care. Although current physiotherapeutic and surgical treatments seek to restore function, structure, or comfort, they bear significant limitations in enabling cosmetic or functional recovery. Instead, the introduction of bioelectric technology may play a role in the restoration of function in patients with neurologic deficits.

Recovery of function, peripheral sensitization and sensory neurone activation by novel pathways following axonal injury in Aplysia californica.

PubMed

Dulin, M F; Steffensen, I; Morris, C E; Walters, E T

1995-10-01

Recovery of behavioural and sensory function was examined following unilateral pedal nerve crush in Aplysia californica. Nerve crush that transected all axons connecting the tail to the central nervous system (CNS) eliminated the ipsilateral tail-evoked siphon reflex, whose sensory input travels in the crushed tail nerve (p9). The first reliable signs of recovery of this reflex were observed within 1 week, and most animals displayed tail-evoked siphon responses within 2 weeks. Wide-dynamic-range mechanosensory neurons with somata in the ventrocaudal (VC) cluster of the ipsilateral pleural ganglion exhibited a few receptive fields (RFs) on the tail 3 weeks after unilateral pedal nerve crush, indicating that the RFs had either regenerated or been reconnected to the central somata. These RFs were smaller and sensitized compared with corresponding RFs on the contralateral, uncrushed side. Centrally conducted axon responses of VC sensory neurones to electrical stimulation distal to the nerve crush site did not reappear until at least 10 days after the crush. Because the crush site was much closer to the CNS than to the tail, the failure of axon responses to be restored earlier than the behavioural responses indicates that early stages of reflex recovery are not due to regeneration of VC sensory neurone axons into the tail. Following nerve crush, VC sensory neurones often could be activated by stimulating central connectives or peripheral nerves that do not normally contain the sensory neurone's axons. These results suggest that recovery of behavioral function after nerve injury involves complex mechanisms, including regenerative growth of axotomized VC sensory neurones, sensitization of regenerating RFs and sprouting of VC sensory neurone fibres within the CNS. Furthermore, the rapidity of behavioural recovery indicates that its initial phases are mediated by additional mechanisms, perhaps centripetal regeneration of unidentified sensory neurones having peripheral somata, or transient reconnection of proximal and distal stumps of axotomized VC cells.

Peripheral nerve conduits: technology update

PubMed Central

Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

2014-01-01

Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

Inflammation and the Nervous System: The Connection in the Cornea in Patients with Infectious Keratitis

PubMed Central

Cruzat, Andrea; Witkin, Deborah; Baniasadi, Neda; Zheng, Lixin; Ciolino, Joseph B.; Jurkunas, Ula V.; Chodosh, James; Pavan-Langston, Deborah; Dana, Reza

2011-01-01

Purpose. To study the density and morphologic characteristics of epithelial dendritic cells, as correlated to subbasal corneal nerve alterations in acute infectious keratitis (IK) by in vivo confocal microscopy (IVCM). Methods. IVCM of the central cornea was performed prospectively in 53 eyes with acute bacterial (n = 23), fungal (n = 13), and Acanthamoeba (n = 17) keratitis, and in 20 normal eyes, by using laser in vivo confocal microscopy. Density and morphology of dendritic-shaped cells (DCs) of the central cornea, corneal nerve density, nerve numbers, branching, and tortuosity were assessed and correlated. It should be noted that due to the “in vivo” nature of the study, the exact identity of these DCs cannot be specified, as they could be monocytes or tissue macrophages, but most likely dendritic cells. Results. IVCM revealed the presence of central corneal DCs in all patients and controls. The mean DC density was significantly higher in patients with bacterial (441.1 ± 320.5 cells/mm2; P < 0.0001), fungal (608.9 ± 812.5 cells/mm2; P < 0.0001), and Acanthamoeba keratitis (1000.2 ± 1090.3 cells/mm2; P < 0.0001) compared with controls (49.3 ± 39.6 cells/mm2). DCs had an increased size and dendrites in patients with IK. Corneal nerves were significantly reduced in eyes with IK compared with controls across all subgroups, including nerve density (674.2 ± 976.1 vs. 3913.9 ± 507.4 μm/frame), total nerve numbers (2.7 ± 3.9 vs. 20.2 ± 3.3), main trunks (1.5 ± 2.2 vs. 6.9 ± 1.1), and branching (1.2 ± 2.0 vs. 13.5 ± 3.1; P < 0.0001). A strong association between the diminishment of corneal nerves and the increase of DC density was observed (r = −0.44; P < 0.0005). Conclusions. IVCM reveals an increased density and morphologic changes of central epithelial DCs in infectious keratitis. There is a strong and significant correlation between the increase in DC numbers and the decreased subbasal corneal nerves, suggesting a potential interaction between the immune and nervous system in the cornea. PMID:21460259

An Injectable, Self-Healing Hydrogel to Repair the Central Nervous System.

PubMed

Tseng, Ting-Chen; Tao, Lei; Hsieh, Fu-Yu; Wei, Yen; Chiu, Ing-Ming; Hsu, Shan-hui

2015-06-17

An injectable, self-healing hydrogel (≈1.5 kPa) is developed for healing nerve-system deficits. Neurosphere-like progenitors proliferate in the hydrogel and differentiate into neuron-like cells. In the zebrafish injury model, the central nervous system function is partially rescued by injection of the hydrogel and significantly rescued by injection of the neurosphere-laden hydrogel. The self-healing hydrogel may thus potentially repair the central nervous system. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparative morphology of serotonergic-like immunoreactive elements in the central nervous system of kinorhynchs (Kinorhyncha, Cyclorhagida).

PubMed

Herranz, María; Pardos, Fernando; Boyle, Michael J

2013-03-01

Cycloneuralian taxa exhibit similar organ system architectures, providing informative characters of metazoan evolution, yet very few modern comparative descriptions of cellular and molecular homologies within and among those taxa are available. We immunolabeled and characterized elements of the serotonergic nervous system in the kinorhynchs Echinoderes spinifurca, Antygomonas paulae, and Zelinkaderes brightae using confocal laser scanning microscopy. Fluorescent markers targeting DNA were combined with observations of auto-fluorescent structures to guide interpretations of the internal and external anatomy in each species. Results show a common pattern of the central nervous system with a circumenteric brain divided into ring-shaped anterior and posterior neuronal somata and a central neuropil connected to a multi-stringed, longitudinal ventral nerve cord. Structural similarities and differences in the nervous systems of these species were observed and described, stressing the incomplete ring nature of the anterior region of the kinorhynch brain, the functional relationship between the brain and the movable introvert, and the number and arrangement of nerve strings and somata of the ventral nerve cord. The ventral cord ends in two ventrolateral cell bodies in E. spinifurca, and forms a terminal loop associated with a midterminal spine in A. paulae and Z. brightae. The possible functional and phylogenetic significance of these features and arrangements are discussed. Copyright © 2012 Wiley Periodicals, Inc.

The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system.

PubMed

van Riel, Debby; Verdijk, Rob; Kuiken, Thijs

2015-01-01

The olfactory nerve consists mainly of olfactory receptor neurons and directly connects the nasal cavity with the central nervous system (CNS). Each olfactory receptor neuron projects a dendrite into the nasal cavity on the apical side, and on the basal side extends its axon through the cribriform plate into the olfactory bulb of the brain. Viruses that can use the olfactory nerve as a shortcut into the CNS include influenza A virus, herpesviruses, poliovirus, paramyxoviruses, vesicular stomatitis virus, rabies virus, parainfluenza virus, adenoviruses, Japanese encephalitis virus, West Nile virus, chikungunya virus, La Crosse virus, mouse hepatitis virus, and bunyaviruses. However, mechanisms of transport via the olfactory nerve and subsequent spread through the CNS are poorly understood. Proposed mechanisms are either infection of olfactory receptor neurons themselves or diffusion through channels formed by olfactory ensheathing cells. Subsequent virus spread through the CNS could occur by multiple mechanisms, including trans-synaptic transport and microfusion. Viral infection of the CNS can lead to damage from infection of nerve cells per se, from the immune response, or from a combination of both. Clinical consequences range from nervous dysfunction in the absence of histopathological changes to severe meningoencephalitis and neurodegenerative disease. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Role of Neuroactive Steroids in the Peripheral Nervous System

PubMed Central

Melcangi, Roberto Cosimo; Giatti, Silvia; Pesaresi, Marzia; Calabrese, Donato; Mitro, Nico; Caruso, Donatella; Garcia-Segura, Luis Miguel

2011-01-01

Several reviews have so far pointed out on the relevant physiological and pharmacological role exerted by neuroactive steroids in the central nervous system. In the present review we summarize observations indicating that synthesis and metabolism of neuroactive steroids also occur in the peripheral nerves. Interestingly, peripheral nervous system is also a target of their action. Indeed, as here reported neuroactive steroids are physiological regulators of peripheral nerve functions and they may also represent interesting therapeutic tools for different types of peripheral neuropathy. PMID:22654839

The (pro)renin receptor and body fluid homeostasis

PubMed Central

Cao, Theresa

2013-01-01

The renin-angiotensin system (RAS) has long been established as one of the major mechanisms of hypertension through the increased levels of angiotensin (ANG) II and its resulting effect on the sympathetic nerve activity, arterial vasoconstriction, water reabsorption, and retention, etc. In the central nervous system, RAS activation affects body fluid homeostasis through increases in sympathetic nerve activity, water intake, food intake, and arginine vasopressin secretion. Previous studies, however, have shown that ANG II can be made in the brain, and it could possibly be through a new component called the (pro)renin receptor. This review intends to summarize the central and peripheral effects of the PRR on body fluid homeostasis. PMID:23678024

Air Force Health Study. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Volume 1

DTIC Science & Technology

1991-03-01

found to be significantly associated with coordination and a central nervous system index, but cranial nerve function and peripheral nerve status...AD-A237 516 Air Force Health Study A An Epidemiologic In vestigation of Health Effects in Air Force Personnel Following Exposure to Herbicides SAIC...Smeda SCIENCE APPLICATIONS EPIDEMIOLOGY RESEARCH DIVISION INTERNATIONAL CORPORATION ARMSTRONG LABORATORY 8400 Westpark Drive HUMAN SYSTEMS DIVISION

In Search of an Effective in vivo Reactivator for Organophosphorus Nerve Agent-Inhibited Acetylcholinesterase in the Central Nervous System

DTIC Science & Technology

2012-01-01

monoisonitrosoacetone (MINA) crossed BBB, provided some degree of CNS AChE reactivation, enhanced survival, and mitigated the seizure activity following nerve agent...tissues (brain regions, diaphragm, heart, skeletal muscle) were collected. AChE activity was measured using the Ellman assay. In GB exposure, pro...therapy. Protecting and/or restoring AChE activity in the brain is a major goal in the treatment of nerve agent intoxication. Our long-term goal is to

Direct Conversion of Human Fibroblasts into Schwann Cells that Facilitate Regeneration of Injured Peripheral Nerve In Vivo

PubMed Central

Sowa, Yoshihiro; Kishida, Tsunao; Tomita, Koichi; Yamamoto, Kenta; Numajiri, Toshiaki

2017-01-01

Abstract Schwann cells (SCs) play pivotal roles in the maintenance and regeneration of the peripheral nervous system. Although transplantation of SCs enhances repair of experimentally damaged peripheral and central nerve tissues, it is difficult to prepare a sufficient number of functional SCs for transplantation therapy without causing adverse events for the donor. Here, we generated functional SCs by somatic cell reprogramming procedures and demonstrated their capability to promote peripheral nerve regeneration. Normal human fibroblasts were phenotypically converted into SCs by transducing SOX10 and Krox20 genes followed by culturing for 10 days resulting in approximately 43% directly converted Schwann cells (dSCs). The dSCs expressed SC‐specific proteins, secreted neurotrophic factors, and induced neuronal cells to extend neurites. The dSCs also displayed myelin‐forming capability both in vitro and in vivo. Moreover, transplantation of the dSCs into the transected sciatic nerve in mice resulted in significantly accelerated regeneration of the nerve and in improved motor function at a level comparable to that with transplantation of the SCs obtained from a peripheral nerve. The dSCs induced by our procedure may be applicable for novel regeneration therapy for not only peripheral nerve injury but also for central nerve damage and for neurodegenerative disorders related to SC dysfunction. Stem Cells Translational Medicine 2017;6:1207–1216 PMID:28186702

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.

A case of primary hypothyroidism causing central nervous system atherosclerosis in a dog.

PubMed

Blois, Shauna L; Poma, Roberto; Stalker, Margaret J; Allen, Dana G

2008-08-01

A 2-year-old, castrated male, Australian shepherd was presented with a history of chronic mild ataxia, obesity, and lethargy. The dog was treated with levothyroxine, but the ataxia worsened. Cranial nerve abnormalities developed and the dog was euthanized. Postmortem examination revealed marked thyroid gland atrophy and widespread, severe central nervous system atherosclerosis.

Discovering the structure of nerve tissue: Part 3: From Jan Evangelista Purkyně to Ludwig Mauthner.

PubMed

Chvátal, Alexandr

2017-01-01

The previous works of Purkyně, Valentin, and Remak showed that the central and peripheral nervous systems contained not only nerve fibers but also cellular elements. The use of microscopes and new fixation techniques enabled them to accurately obtain data on the structure of nerve tissue and consequently in many European universities microscopes started to become widely used in histological and morphological studies. The present review summarizes important discoveries concerning the structure of neural tissue, mostly from vertebrates, during the period from 1838 to 1865. This review describes the discoveries of famous as well as less well-known scholars of the time, who contributed significantly to current understandings about the structure of neural tissue. The period is characterized by the first descriptions of different types of nerve cells and the first attempts of a cytoarchitectonic description of the spinal cord and brain. During the same time, the concept of a neuroglial tissue was introduced, first as a tissue for "gluing" nerve fibers, cells, and blood capillaries into one unit, but later some glial cells were described for the first time. Questions arose as to whether or not cells in ganglia and the central nervous system had the same morphological and functional properties, and whether nerve fibers and cell bodies were interconnected. Microscopic techniques started to be used for the examination of physiological as well as pathological nerve tissues. The overall state of knowledge was just a step away from the emergence of the concept of neurons and glial cells.

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.

Neurons of self-defence: neuronal innervation of the exocrine defence glands in stick insects.

PubMed

Stolz, Konrad; von Bredow, Christoph-Rüdiger; von Bredow, Yvette M; Lakes-Harlan, Reinhard; Trenczek, Tina E; Strauß, Johannes

2015-01-01

Stick insects (Phasmatodea) use repellent chemical substances (allomones) for defence which are released from so-called defence glands in the prothorax. These glands differ in size between species, and are under neuronal control from the CNS. The detailed neural innervation and possible differences between species are not studied so far. Using axonal tracing, the neuronal innervation is investigated comparing four species. The aim is to document the complexity of defence gland innervation in peripheral nerves and central motoneurons in stick insects. In the species studied here, the defence gland is innervated by the intersegmental nerve complex (ISN) which is formed by three nerves from the prothoracic (T1) and suboesophageal ganglion (SOG), as well as a distinct suboesophageal nerve (Nervus anterior of the suboesophageal ganglion). In Carausius morosus and Sipyloidea sipylus, axonal tracing confirmed an innervation of the defence glands by this N. anterior SOG as well as N. anterior T1 and N. posterior SOG from the intersegmental nerve complex. In Peruphasma schultei, which has rather large defence glands, only the innervation by the N. anterior SOG was documented by axonal tracing. In the central nervous system of all species, 3-4 neuron types are identified by axonal tracing which send axons in the N. anterior SOG likely innervating the defence gland as well as adjacent muscles. These neurons are mainly suboesophageal neurons with one intersegmental neuron located in the prothoracic ganglion. The neuron types are conserved in the species studied, but the combination of neuron types is not identical. In addition, the central nervous system in S. sipylus contains one suboesophageal and one prothoracic neuron type with axons in the intersegmental nerve complex contacting the defence gland. Axonal tracing shows a very complex innervation pattern of the defence glands of Phasmatodea which contains different neurons in different nerves from two adjacent body segments. The gland size correlates to the size of a neuron soma in the suboesophageal ganglion, which likely controls gland contraction. In P. schultei, the innervation pattern appears simplified to the anterior suboesophageal nerve. Hence, some evolutionary changes are notable in a conserved neuronal network.

Distribution of serine/threonine kinase SAD-B in mouse peripheral nerve synapse.

PubMed

Hagiwara, Akari; Harada, Kenu; Hida, Yamato; Kitajima, Isao; Ohtsuka, Toshihisa

2011-05-11

The serine/threonine kinase SAD regulates neural functions such as axon/dendrite polarization and neurotransmitter release. In the vertebrate central nervous system, SAD-B, a homolog of Caenorhabditis elegans SAD-1, is associated with synaptic vesicles and the active zone cytomatrix in nerve terminals. However, the distribution of SAD-B in the peripheral nervous system remains elusive. Here, we show that SAD-B is specifically localized to neuromuscular junctions. Although the active zone protein bassoon showed a punctated signal indicating its localization to motor end plates, SAD-B shows relatively diffuse localization indicating its association with both the active zone and synaptic vesicles. Therefore, SAD kinase may regulate neurotransmitter release from motor end plates in a similar manner to its regulation of neurotransmitter release in the central nervous system.

On the morphology of the central nervous system in larval stages of Carcinus maenas L. (Decapoda, Brachyura)

NASA Astrophysics Data System (ADS)

Harzsch, S.; Dawirs, R. R.

1993-02-01

We investigated the morphology of the central nervous system throughout the larval development of Carcinus maenas. For that purpose single larvae were reared in the laboratory from hatching through metamorphosis. Complete series of whole mout semithin sections were obtained from individuals of all successive larval stages and analysed with a light microscope. Morphological feature and spatial arrangement of discernable neural cell clusters, fibre tracts and neuropile are described and compared with the adult pattern. We found that most of the morphological features characterizing the adult nervous system are already present in the zoea-1. Nevertheless, there are marked differences with respect to the arrangement of nerve cell bodies, organization of cerebral neuropile, and disposition of ganglia in the ventral nerve cord. It appears that complexity of the central nervous neuropile is selectively altered during postmetamorphotic development, probably reflecting adaptive changes of sensory-motor integration in response to behavioural maturation. In contrast, during larval development there was little change in the overall structural organization of the central nervous system despite some considerable growth. However, the transition from zoea-4 to megalopa brings about multiple fundamental changes in larval morphology and behavioural pattern. Since central nervous integration should properly adapt to the altered behavioural repertoire of the megalopa, it seems necessary to ask in which respect synaptic rearrangement might characterize development of the central nervous system.

Rare Primary Central Nervous System Tumors

PubMed Central

Kubicky, Charlotte Dai; Sahgal, Arjun; Chang, Eric L.; Lo, Simon S.

2014-01-01

There are close to 70,000 new cases of primary central nervous system tumors diagnosed annually in the United States. Meningiomas, gliomas, nerve sheath tumors and pituitary tumors account for 85% of them. There is abundant literature on these commonly occurring tumors but data from the literature on infrequently encountered tumors such as atypical teratoid/rhabdoid tumor, choroid plexus carcinoma, ganglioglioma, hemangiopericytoma, and pleomorphic xanthoastrocytoma are limited. This review provides an overview of the clinicopathologic and therapeutic aspects of these rare primary central nervous system tumors. PMID:25276324

Role of insulin signaling impairment, adiponectin and dyslipidemia in peripheral and central neuropathy in mice.

PubMed

Anderson, Nicholas J; King, Matthew R; Delbruck, Lina; Jolivalt, Corinne G

2014-06-01

One of the tissues or organs affected by diabetes is the nervous system, predominantly the peripheral system (peripheral polyneuropathy and/or painful peripheral neuropathy) but also the central system with impaired learning, memory and mental flexibility. The aim of this study was to test the hypothesis that the pre-diabetic or diabetic condition caused by a high-fat diet (HFD) can damage both the peripheral and central nervous systems. Groups of C57BL6 and Swiss Webster mice were fed a diet containing 60% fat for 8 months and compared to control and streptozotocin (STZ)-induced diabetic groups that were fed a standard diet containing 10% fat. Aspects of peripheral nerve function (conduction velocity, thermal sensitivity) and central nervous system function (learning ability, memory) were measured at assorted times during the study. Both strains of mice on HFD developed impaired glucose tolerance, indicative of insulin resistance, but only the C57BL6 mice showed statistically significant hyperglycemia. STZ-diabetic C57BL6 mice developed learning deficits in the Barnes maze after 8 weeks of diabetes, whereas neither C57BL6 nor Swiss Webster mice fed a HFD showed signs of defects at that time point. By 6 months on HFD, Swiss Webster mice developed learning and memory deficits in the Barnes maze test, whereas their peripheral nervous system remained normal. In contrast, C57BL6 mice fed the HFD developed peripheral nerve dysfunction, as indicated by nerve conduction slowing and thermal hyperalgesia, but showed normal learning and memory functions. Our data indicate that STZ-induced diabetes or a HFD can damage both peripheral and central nervous systems, but learning deficits develop more rapidly in insulin-deficient than in insulin-resistant conditions and only in Swiss Webster mice. In addition to insulin impairment, dyslipidemia or adiponectinemia might determine the neuropathy phenotype. © 2014. Published by The Company of Biologists Ltd.

Brain plasticity after implanted peroneal nerve electrical stimulation to improve gait in chronic stroke patients: Two case reports.

PubMed

Thibaut, Aurore; Moissenet, Florent; Di Perri, Carol; Schreiber, Céline; Remacle, Angélique; Kolanowski, Elisabeth; Chantraine, Frédéric; Bernard, Claire; Hustinx, Roland; Tshibanda, Jean-Flory; Filipetti, Paul; Laureys, Steven; Gosseries, Olivia

2017-01-01

Recent studies have shown that stimulation of the peroneal nerve using an implantable 4-channel peroneal nerve stimulator could improve gait in stroke patients. To assess structural cortical and regional cerebral metabolism changes associated with an implanted peroneal nerve electrical stimulator to correct foot drop related to a central nervous system lesion. Two stroke patients presenting a foot drop related to a central nervous system lesion were implanted with an implanted peroneal nerve electrical stimulator. Both patients underwent clinical evaluations before implantation and one year after the activation of the stimulator. Structural magnetic resonance imaging (MRI) and [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) were acquired before and one year after the activation of the stimulator. Foot drop was corrected for both patients after the implantation of the stimulator. After one year of treatment, patient 1 improved in three major clinical tests, while patient 2 only improved in one test. Prior to treatment, FDG-PET showed a significant hypometabolism in premotor, primary and supplementary motor areas in both patients as compared to controls, with patient 2 presenting more widespread hypometabolism. One year after the activation of the stimulator, both patients showed significantly less hypometabolism in the damaged motor cortex. No difference was observed on the structural MRI. Clinical improvement of gait under peroneal nerve electrical stimulation in chronic stroke patients presenting foot drop was paralleled to metabolic changes in the damaged motor cortex.

Cnidarian Nerve Nets and Neuromuscular Efficiency.

PubMed

Satterlie, Richard A

2015-12-01

Cnidarians are considered "nerve net animals" even though their nervous systems include various forms of condensation and centralization. Yet, their broad, two-dimensional muscle sheets are innervated by diffuse nerve nets. Do the motor nerve nets represent a primitive organization of multicellular nervous systems, do they represent a consequence of radial symmetry, or do they offer an efficient way to innervate a broad, two-dimensional muscle sheet, in which excitation of the muscle sheet can come from multiple sites of initiation? Regarding the primitive nature of cnidarian nervous systems, distinct neuronal systems exhibit some adaptations that are well known in higher animals, such as the use of oversized neurons with increased speed of conduction, and condensation of neurites into nerve-like tracts. A comparison of neural control of two-dimensional muscle sheets in a mollusc and jellyfish suggests that a possible primitive feature of cnidarian neurons may be a lack of regional specialization into conducting and transmitting regions. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Comparison of three neurotropic viruses reveals differences in viral dissemination to the central nervous system

PubMed Central

Luethy, Lauren N.; Erickson, Andrea K; Jesudhasan, Palmy R.; Ikizler, Mine; Dermody, Terence S.; Pfeiffer, Julie K.

2015-01-01

Neurotropic viruses initiate infection in peripheral tissues prior to entry into the central nervous system (CNS). However, mechanisms of dissemination are not completely understood. We used genetically marked viruses to compare dissemination of poliovirus, yellow fever virus 17D (YFV-17D), and reovirus type 3 Dearing in mice from a hind limb intramuscular inoculation site to the sciatic nerve, spinal cord, and brain. While YFV-17D likely entered the CNS via blood, poliovirus and reovirus likely entered the CNS by transport through the sciatic nerve to the spinal cord. We found that dissemination was inefficient in adult immune-competent mice for all three viruses, particularly reovirus. Dissemination of all viruses was more efficient in immune-deficient mice. Although poliovirus and reovirus both accessed the CNS by transit through the sciatic nerve, stimulation of neuronal transport by muscle damage enhanced dissemination only of poliovirus. Our results suggest that these viruses access the CNS using different pathways. PMID:26479325

A study of tapping by the unaffected finger of patients presenting with central and peripheral nerve damage.

PubMed

Zhang, Lingli; Han, Xiuying; Li, Peihong; Liu, Yang; Zhu, Yulian; Zou, Jun; Yu, Zhusheng

2015-01-01

Whether the unaffected function of the hand of patients presenting with nerve injury is affected remains inconclusive. We aimed to evaluate whether there are differences in finger tapping following central or peripheral nerve injury compared with the unaffected hand and the ipsilateral hand of a healthy subject. Thirty right brain stroke patients with hemiplegia, 30 left arm peripheral nerve injury cases, and 60 healthy people were selected. We tested finger tapping of the right hands, and each subject performed the test twice. Finger tapping following peripheral nerve injury as compared with the unaffected hand and the dominant hand of a healthy person was markedly higher than was found for central nerve injury (P < 0.05). Finger tapping of the male peripheral group's unaffected hand and the control group's dominant hand was significantly higher than the central group (P < 0.001). However, finger tapping of the female control group's dominant hand was significantly higher than the central group's unaffected hand (P < 0.01, P = 0.002), the peripheral group's unaffected hand (P < 0.05, P = 0.034). The unaffected function of the hand of patients with central and peripheral nerve injury was different as compared with the ipsilateral hand of healthy individuals. The rehabilitation therapist should intensify the practice of normal upper limb fine activities and coordination of the patient.

A case of primary hypothyroidism causing central nervous system atherosclerosis in a dog

PubMed Central

Blois, Shauna L.; Poma, Roberto; Stalker, Margaret J.; Allen, Dana G.

2008-01-01

A 2-year-old, castrated male, Australian shepherd was presented with a history of chronic mild ataxia, obesity, and lethargy. The dog was treated with levothyroxine, but the ataxia worsened. Cranial nerve abnormalities developed and the dog was euthanized. Postmortem examination revealed marked thyroid gland atrophy and widespread, severe central nervous system atherosclerosis. PMID:18978973

Maintenance of Mouse Gustatory Terminal Field Organization Is Disrupted following Selective Removal of Peripheral Sodium Salt Taste Activity at Adulthood

PubMed Central

Sun, Chengsan

2017-01-01

Neural activity plays a critical role in the development of central circuits in sensory systems. However, the maintenance of these circuits at adulthood is usually not dependent on sensory-elicited neural activity. Recent work in the mouse gustatory system showed that selectively deleting the primary transduction channel for sodium taste, the epithelial sodium channel (ENaC), throughout development dramatically impacted the organization of the central terminal fields of three nerves that carry taste information to the nucleus of the solitary tract. More specifically, deleting ENaCs during development prevented the normal maturation of the fields. The present study was designed to extend these findings by testing the hypothesis that the loss of sodium taste activity impacts the maintenance of the normal adult terminal field organization in male and female mice. To do this, we used an inducible Cre-dependent genetic recombination strategy to delete ENaC function after terminal field maturation occurred. We found that removal of sodium taste neural activity at adulthood resulted in significant reorganization of mature gustatory afferent terminal fields in the nucleus of the solitary tract. Specifically, the chorda tympani and greater superficial petrosal nerve terminal fields were 1.4× and 1.6× larger than age-matched controls, respectively. By contrast, the glossopharyngeal nerve, which is not highly sensitive to sodium taste stimulation, did not undergo terminal field reorganization. These surprising results suggest that gustatory nerve terminal fields remain plastic well into adulthood, which likely impacts central coding of taste information and taste-related behaviors with altered taste experience. SIGNIFICANCE STATEMENT Neural activity plays a major role in the development of sensory circuits in the mammalian brain. However, the importance of sensory-driven activity in maintaining these circuits at adulthood, especially in subcortical structures, appears to be much less. Here, we tested whether the loss of sodium taste activity in adult mice impacts the maintenance of how taste nerves project to the first central relay. We found that specific loss of sodium-elicited taste activity at adulthood produced dramatic and selective reorganization of terminal fields in the brainstem. This demonstrates, for the first time, that taste-elicited activity is necessary for the normal maintenance of central gustatory circuits at adulthood and highlights a level of plasticity not seen in other sensory system subcortical circuits. PMID:28676575

Anteroposterior patterning in hemichordates and the origins of the chordate nervous system

NASA Technical Reports Server (NTRS)

Lowe, Christopher J.; Wu, Mike; Salic, Adrian; Evans, Louise; Lander, Eric; Stange-Thomann, Nicole; Gruber, Christian E.; Gerhart, John; Kirschner, Marc

2003-01-01

The chordate central nervous system has been hypothesized to originate from either a dorsal centralized, or a ventral centralized, or a noncentralized nervous system of a deuterostome ancestor. In an effort to resolve these issues, we examined the hemichordate Saccoglossus kowalevskii and studied the expression of orthologs of genes that are involved in patterning the chordate central nervous system. All 22 orthologs studied are expressed in the ectoderm in an anteroposterior arrangement nearly identical to that found in chordates. Domain topography is conserved between hemichordates and chordates despite the fact that hemichordates have a diffuse nerve net, whereas chordates have a centralized system. We propose that the deuterostome ancestor may have had a diffuse nervous system, which was later centralized during the evolution of the chordate lineage.

Central nervous system integration of sensorimotor signals in oral and pharyngeal structures: oropharyngeal kinematics response to recurrent laryngeal nerve lesion.

PubMed

Gould, Francois D H; Ohlemacher, Jocelyn; Lammers, Andrew R; Gross, Andrew; Ballester, Ashley; Fraley, Luke; German, Rebecca Z

2016-03-01

Safe, efficient liquid feeding in infant mammals requires the central coordination of oropharyngeal structures innervated by multiple cranial and spinal nerves. The importance of laryngeal sensation and central sensorimotor integration in this system is poorly understood. Recurrent laryngeal nerve lesion (RLN) results in increased aspiration, though the mechanism for this is unclear. This study aimed to determine the effect of unilateral RLN lesion on the motor coordination of infant liquid feeding. We hypothesized that 1) RLN lesion results in modified swallow kinematics, 2) postlesion oropharyngeal kinematics of unsafe swallows differ from those of safe swallows, and 3) nonswallowing phases of the feeding cycle show changed kinematics postlesion. We implanted radio opaque markers in infant pigs and filmed them pre- and postlesion with high-speed videofluoroscopy. Markers locations were digitized, and swallows were assessed for airway protection. RLN lesion resulted in modified kinematics of the tongue relative to the epiglottis in safe swallows. In lesioned animals, safe swallow kinematics differed from unsafe swallows. Unsafe swallow postlesion kinematics resembled prelesion safe swallows. The movement of the tongue was reduced in oral transport postlesion. Between different regions of the tongue, response to lesion was similar, and relative timing within the tongue was unchanged. RLN lesion has a pervasive effect on infant feeding kinematics, related to the efficiency of airway protection. The timing of tongue and hyolaryngeal kinematics in swallows is a crucial locus for swallow disruption. Laryngeal sensation is essential for the central coordination in feeding of oropharyngeal structures receiving motor inputs from different cranial nerves. Copyright © 2016 the American Physiological Society.

Central Projections of Antennal and Labial Palp Sensory Neurons in the Migratory Armyworm Mythimna separata

PubMed Central

Ma, Bai-Wei; Zhao, Xin-Cheng; Berg, Bente G.; Xie, Gui-Ying; Tang, Qing-Bo; Wang, Gui-Rong

2017-01-01

The oriental armyworm, Mythimna separata (Walker), is a polyphagous, migratory pest relying on olfactory cues to find mates, locate nectar, and guide long-distance flight behavior. In the present study, a combination of neuroanatomical techniques were utilized on this species, including backfills, confocal microscopy, and three-dimensional reconstructions, to trace the central projections of sensory neurons from the antenna and the labial pit organ, respectively. As previously shown, the axons of the labial sensory neurons project via the ipsilateral labial nerve and terminate in three main areas of the central nervous system: (1) the labial-palp pit organ glomerulus of each antennal lobe, (2) the gnathal ganglion, and (3) the prothoracic ganglion of the ventral nerve cord. Similarly, the antennal sensory axons project to multiple areas of the central nervous system. The ipsilateral antennal nerve targets mainly the antennal lobe, the antennal mechanosensory and motor center, and the prothoracic and mesothoracic ganglia. Specific staining experiments including dye application to each of the three antennal segments indicate that the antennal lobe receives input from flagellar olfactory neurons exclusively, while the antennal mechanosensory and motor center is innervated by mechanosensory neurons from the whole antenna, comprising the flagellum, pedicle, and scape. The terminals in the mechanosensory and motor center are organized in segregated zones relating to the origin of neurons. The flagellar mechanosensory axons target anterior zones, while the pedicular and scapal axons terminate in posterior zones. In the ventral nerve cord, the processes from the antennal sensory neurons terminate in the motor area of the thoracic ganglia, suggesting a close connection with motor neurons. Taken together, the numerous neuropils innervated by axons both from the antenna and labial palp indicate the multiple roles these sensory organs serve in insect behavior. PMID:29209176

Sustained 12 Month Benefit of Phrenic Nerve Stimulation for Central Sleep Apnea.

PubMed

Costanzo, Maria Rosa; Ponikowski, Piotr; Javaheri, Shahrokh; Augostini, Ralph; Goldberg, Lee R; Holcomb, Richard; Kao, Andrew; Khayat, Rami N; Oldenburg, Olaf; Stellbrink, Christoph; Abraham, William T

2018-06-01

Transvenous phrenic nerve stimulation improved sleep metrics and quality of life after 6 months versus control in the remedē System Pivotal Trial. This analysis explored the effectiveness of phrenic nerve stimulation in patients with central sleep apnea after 12 months of therapy. Reproducibility of treatment effect was assessed in the former control group in whom the implanted device was initially inactive for the sixth month and subsequently activated when the randomized control assessments were complete. Patients with moderate-to-severe central sleep apnea implanted with the remedē System were randomized to therapy activation at 1 month (treatment) or after 6 months (control). Sleep indices were assessed from baseline to 12 months in the treatment group and from 6 to 12 months in former controls. In the treatment group, a ≥50% reduction in apnea-hypopnea index occurred in 60% of patients at 6 months (95% confidence interval [CI] 47% to 64%) and 67% (95% CI 53% to 78%) at 12 months. After 6 months of therapy, 55% of former controls (95% CI 43% to 67%) achieved ≥50%reduction in apnea-hypopnea index. Patient Global Assessment was markedly ormoderately improved at 6 and 12 months in 60% of treatment patients.Improvements persisted at 12 months. A serious adverse event within 12 months occurred in 13 patients (9%). Phrenic nerve stimulation produced sustained improvements in sleep indices and quality of life to at least 12 months in patients with central sleep apnea. The similar improvement of former controls after 6 months of active therapy confirms benefits are reproducible and reliable. Copyright © 2018 Respicardia, Inc. Published by Elsevier Inc. All rights reserved.

Direct Conversion of Human Fibroblasts into Schwann Cells that Facilitate Regeneration of Injured Peripheral Nerve In Vivo.

PubMed

Sowa, Yoshihiro; Kishida, Tsunao; Tomita, Koichi; Yamamoto, Kenta; Numajiri, Toshiaki; Mazda, Osam

2017-04-01

Schwann cells (SCs) play pivotal roles in the maintenance and regeneration of the peripheral nervous system. Although transplantation of SCs enhances repair of experimentally damaged peripheral and central nerve tissues, it is difficult to prepare a sufficient number of functional SCs for transplantation therapy without causing adverse events for the donor. Here, we generated functional SCs by somatic cell reprogramming procedures and demonstrated their capability to promote peripheral nerve regeneration. Normal human fibroblasts were phenotypically converted into SCs by transducing SOX10 and Krox20 genes followed by culturing for 10 days resulting in approximately 43% directly converted Schwann cells (dSCs). The dSCs expressed SC-specific proteins, secreted neurotrophic factors, and induced neuronal cells to extend neurites. The dSCs also displayed myelin-forming capability both in vitro and in vivo. Moreover, transplantation of the dSCs into the transected sciatic nerve in mice resulted in significantly accelerated regeneration of the nerve and in improved motor function at a level comparable to that with transplantation of the SCs obtained from a peripheral nerve. The dSCs induced by our procedure may be applicable for novel regeneration therapy for not only peripheral nerve injury but also for central nerve damage and for neurodegenerative disorders related to SC dysfunction. Stem Cells Translational Medicine 2017;6:1207-1216. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

[The relationship between ophthalmic nerve lesion in glaucoma and ocular and systemic haemodynamic disturbance].

PubMed

Liu, L; Yuan, S; Yang, W

1999-04-01

To explore the relationship between the optic nerve lesion in glaucoma and ocular and systemic haemodynamic disturbance. The color Doppler imaging was used to study blood velocity in the ophthalmic, the central retinal and the short posterior ciliary arteries in 34 patients with primary open angle glaucoma, 31 patients with low tension glaucoma and 90 healthy controls. The peak systolic velocity(PSV), the end diastolic velocity (EDV) and resistive index (RI) in each artery were measured, moreover the nailfold microcirculation and blood viscosity in each patient were examined. Compared with the control group, the PSV and EDV of the central retinal arteries were significantly lower while the RI of the central retinal arteries was significantly higher in both POAG and LTG patients. The RI of the short posterior ciliary arteries however was significantly higher in POAG. Nailfold microcirculation shows that some important parameters, including flow pattern, loop surrounding, morphological weighted value, total weighted value and capillary deformity rate in the two glaucoma groups were higher, whereas the flow velocity was lower than in the control group. The plasm viscosity and the whole blood viscosity (low spear) were higher than normal. According to our measurements, the nailfold microcirculation and blood viscosity was worse at the end stage of glaucoma than at early stage. The correlative analysis between measurement results of color doppler imaging and microcirculation and heamorrheology showed that nailfold microcirculation morphological weighted value was negatively correlated with the EDV of the central retinal artery and positively correlated with the RI of the central retinal artery in LTG patients. The abnormity of ocular haemodynamics and systemic microcirculation and blood viscosity is one important factor of optic nerve damage in glaucoma.

Sequential involvement of the nervous system in subacute combined degeneration.

PubMed

Minn, Yang-Ki; Kim, Seung-Min; Kim, Se-Hoon; Kwon, Ki-Han; Sunwoo, Il-Nam

2012-03-01

Subacute combined degeneration (SCD) involves progressive degeneration of the spinal cord, optic nerve, and peripheral nerves. Vitamin B12 (VB12) is a co-factor in myelin synthesis. Because each cell that constitutes the myelin component in the central nervous system and peripheral nervous system is different, it is improbable that these cells undergo simultaneous degeneration. However, the sequence of degeneration in SCD has not been established. In this study, we analysed medical records and electrophysiological data of patients who showed neurological symptoms and whose serum VB12 levels were lower than 200 pg/mL. We enrolled 49 patients in this study. Their mean VB12 level was 68.3 pg/mL. Somatosensory evoked potential (SEP) study showed abnormal findings in 38 patients. Of the 40 patients who underwent visual evoked potential (VEP) study, 14 showed abnormal responses. Eighteen patients showed abnormal findings on a nerve conduction study (NCS). In this study, abnormal posterior tibial nerve SEPs only were seen in 16 patients, median nerve SEPs only were seen in 3 patients, abnormal VEPs only in two, and abnormal NCS responses in one patient. No patient complained of cognitive symptoms. In SCD, degeneration appears to progress in the following order: lower spinal cord, cervical spinal cord, peripheral nerve/optic nerve, and finally, the brain.

Central nervous system transplantation benefited by low-level laser irradiation

NASA Astrophysics Data System (ADS)

Rochkind, S.; Lubart, Rachel; Wollman, Yoram; Simantov, Rabi; Nissan, Moshe; Barr-Nea, Lilian

1990-06-01

Effect of low-level laser irradiation on the central nervous system transplantation is reported. Ernbryonal brain allografts were transplanted into the brain of 20 adult rats and peripheral nerve graft transplanted into the severely injured spinal cord of 16 dogs. The operated wound of 10 rats and 8 dogs were exposed daily for 21 days to lowpower laser irradiation CW HeNe laser (35 mW, 632.8 run, energy density of 30 J/cm2 at each point for rats and 70 J/cm2 at each point for dogs). This study shows that (i) the low-level laser irradiation prevents extensive glial scar formation (a limiting factor in CNS regeneration) between embryonal transplants and host brain; (ii) Dogs made paraplegic by spinal cord injury were able to walk 3-6 months later. Recovery of these dogs was effected by the implantation of a fragment of autologous sciatic nerve at the site of injury and subsequently exposing the dogs to low-level laser irradiation. The effect of laser irradiation on the embryonal nerve cells grown in tissue culture was also observed. We found that low-level laser irradiation induced intensive migration of neurites outward of the aggregates 15-22 The results of the present study and our previous investigations suggest that low-level laser irradiation is a novel tool for treatment of peripheral and central nervous system injuries.

Acute Effect of Pore-Forming Clostridium perfringens ε-Toxin on Compound Action Potentials of Optic Nerve of Mouse.

PubMed

Cases, Mercè; Llobet, Artur; Terni, Beatrice; Gómez de Aranda, Inmaculada; Blanch, Marta; Doohan, Briain; Revill, Alexander; Brown, Angus M; Blasi, Juan; Solsona, Carles

2017-01-01

ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood-brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system. We also investigated the effect of the toxin on compound action potentials (CAPs) in isolated mice optic nerves. When nerves were stimulated at 100 Hz during 200 ms, the decrease of the amplitude and the area of the CAPs was attenuated in the presence of ε-toxin. The computational modelling of myelinated fibers of mouse optic nerve revealed that the experimental results can be mimicked by an increase of the conductance of myelin and agrees with the pore forming activity of the toxin which binds to myelin and could drill it by making pores. The intimate ultrastructure of myelin was not modified during the periods of time investigated. In summary, the acute action of the toxin produces a subtle functional impact on the propagation of the nerve action potential in myelinated fibers of the central nervous system with an eventual desynchronization of the information. These results may agree with the hypothesis that the toxin could be an environmental trigger of multiple sclerosis (MS).

Acute Effect of Pore-Forming Clostridium perfringens ε-Toxin on Compound Action Potentials of Optic Nerve of Mouse

PubMed Central

Terni, Beatrice; Gómez de Aranda, Inmaculada; Blanch, Marta; Brown, Angus M.

2017-01-01

ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood–brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system. We also investigated the effect of the toxin on compound action potentials (CAPs) in isolated mice optic nerves. When nerves were stimulated at 100 Hz during 200 ms, the decrease of the amplitude and the area of the CAPs was attenuated in the presence of ε-toxin. The computational modelling of myelinated fibers of mouse optic nerve revealed that the experimental results can be mimicked by an increase of the conductance of myelin and agrees with the pore forming activity of the toxin which binds to myelin and could drill it by making pores. The intimate ultrastructure of myelin was not modified during the periods of time investigated. In summary, the acute action of the toxin produces a subtle functional impact on the propagation of the nerve action potential in myelinated fibers of the central nervous system with an eventual desynchronization of the information. These results may agree with the hypothesis that the toxin could be an environmental trigger of multiple sclerosis (MS). PMID:28798954

Connexin32 expression in central and peripheral nervous systems

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

Deschenes, S.M.; Scherer, S.S.; Fischbeck, K.H.

1994-09-01

Mutations have been identified in the gap junction gene, connexin32 (Cx32), in patients affected with the X-linked form of the demyelinating neuropathy, Charcot-Marie-Tooth disease (CMTX). Gap junctions composed of Cx32 are present and developmentally regulated in a wide variety of tissues. In peripheral nerve, our immunohistochemical analysis localized Cx32 to the noncompacted myelin of the paranodal regions and the Schmidt-Lantermann incisures, where previous studies describe gap junctions. In contrast to the location of Cx32 in peripheral nerve and the usual restriction of clinical manifestations to the peripheral nervous system (PNS) (abstract by Paulson describes an exception), preliminary studies show thatmore » Cx32 is present in the compacted myelin of the central nervous system (CNS), as demonstrated by radial staining through the myelin sheath of oligodendrocytes in rat spinal cord. Analysis of Cx32 expression in various regions of rat CNS during development shows that the amount of Cx32 mRNA and protein increases as myelination increases, a pattern observed for other myelin genes. Studies in the PNS provide additional evidence that Cx32 and myelin genes are coordinately regulated at the transcriptional level; Cx32 and peripheral myelin gene PMP-22 mRNAs are expressed in parallel following transient or permanent nerve injury. Differences in post-translational regulation of Cx32 in the CNS and PNS may be indicated by the presence of a faster migrating form of Cs32 in cerebrum versus peripheral nerve. Studies are currently underway to determine the unique role of Cx32 in peripheral nerve.« less

Controversies related to electromagnetic field exposure on peripheral nerves.

PubMed

Say, Ferhat; Altunkaynak, Berrin Zuhal; Coşkun, Sina; Deniz, Ömür Gülsüm; Yıldız, Çağrı; Altun, Gamze; Kaplan, Arife Ahsen; Kaya, Sefa Ersan; Pişkin, Ahmet

2016-09-01

Electromagnetic field (EMF) is a pervasive environmental presence in modern society. In recent years, mobile phone usage has increased rapidly throughout the world. As mobile phones are generally held close to the head while talking, studies have mostly focused on the central and peripheral nervous system. There is a need for further research to ascertain the real effect of EMF exposure on the nervous system. Several studies have clearly demonstrated that EMF emitted by cell phones could affect the systems of the body as well as functions. However, the adverse effects of EMF emitted by mobile phones on the peripheral nerves are still controversial. Therefore, this review summarizes current knowledge on the possible positive or negative effects of electromagnetic field on peripheral nerves. Copyright © 2015 Elsevier B.V. All rights reserved.

Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury.

PubMed

Brosius Lutz, Amanda; Chung, Won-Suk; Sloan, Steven A; Carson, Glenn A; Zhou, Lu; Lovelett, Emilie; Posada, Sean; Zuchero, J Bradley; Barres, Ben A

2017-09-19

Ineffective myelin debris clearance is a major factor contributing to the poor regenerative ability of the central nervous system. In stark contrast, rapid clearance of myelin debris from the injured peripheral nervous system (PNS) is one of the keys to this system's remarkable regenerative capacity, but the molecular mechanisms driving PNS myelin clearance are incompletely understood. We set out to discover new pathways of PNS myelin clearance to identify novel strategies for activating myelin clearance in the injured central nervous system, where myelin debris is not cleared efficiently. Here we show that Schwann cells, the myelinating glia of the PNS, collaborate with hematogenous macrophages to clear myelin debris using TAM (Tyro3, Axl, Mer) receptor-mediated phagocytosis as well as autophagy. In a mouse model of PNS nerve crush injury, Schwann cells up-regulate TAM phagocytic receptors Axl and Mertk following PNS injury, and Schwann cells lacking both of these phagocytic receptors exhibit significantly impaired myelin phagocytosis both in vitro and in vivo. Autophagy-deficient Schwann cells also display reductions in myelin clearance after mouse nerve crush injury, as has been recently shown following nerve transection. These findings add a mechanism, Axl/Mertk-mediated myelin clearance, to the repertoire of cellular machinery used to clear myelin in the injured PNS. Given recent evidence that astrocytes express Axl and Mertk and have previously unrecognized phagocytic potential, this pathway may be a promising avenue for activating myelin clearance after CNS injury.

Development and Maturation of the Neuromuscular Junciton in Cell Culture Under Conditions of Simulated Zero-gravity

NASA Technical Reports Server (NTRS)

Gruener, R.

1985-01-01

Alterations in gravitational conditions which alter the normal development and interactions of nerve and muscle cells grown in culture is examined. Clinostat conditions, similating Og, which produce changes in cell morphology and growth patterns is studied. Data show that rotation of cocultures of nerve and muscle cells results in morphologic changes which are predicted to significantly alter the functional interactions between the elements of a prototypic synapse. It is further predicted that similar alterations may occur in central synapses which may therefore affect the development of the central nervous system when subjected to altered gravitational conditions.

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

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

PubMed

Huang, Jie; Ni, Zhongge; Finch, Philip

2017-09-01

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

Potential Roles of Dental Pulp Stem Cells in Neural Regeneration and Repair

PubMed Central

Luo, Lihua; Wang, Xiaoyan; Key, Brian; Lee, Bae Hoon

2018-01-01

This review summarizes current advances in dental pulp stem cells (DPSCs) and their potential applications in the nervous diseases. Injured adult mammalian nervous system has a limited regenerative capacity due to an insufficient pool of precursor cells in both central and peripheral nervous systems. Nerve growth is also constrained by inhibitory factors (associated with central myelin) and barrier tissues (glial scarring). Stem cells, possessing the capacity of self-renewal and multicellular differentiation, promise new therapeutic strategies for overcoming these impediments to neural regeneration. Dental pulp stem cells (DPSCs) derive from a cranial neural crest lineage, retain a remarkable potential for neuronal differentiation, and additionally express multiple factors that are suitable for neuronal and axonal regeneration. DPSCs can also express immunomodulatory factors that stimulate formation of blood vessels and enhance regeneration and repair of injured nerve. These unique properties together with their ready accessibility make DPSCs an attractive cell source for tissue engineering in injured and diseased nervous systems. In this review, we interrogate the neuronal differentiation potential as well as the neuroprotective, neurotrophic, angiogenic, and immunomodulatory properties of DPSCs and its application in the injured nervous system. Taken together, DPSCs are an ideal stem cell resource for therapeutic approaches to neural repair and regeneration in nerve diseases. PMID:29853908

Sequential Involvement of the Nervous System in Subacute Combined Degeneration

PubMed Central

Minn, Yang-Ki; Kim, Seung-Min; Kim, Se-Hoon; Kwon, Ki-Han

2012-01-01

Purpose Subacute combined degeneration (SCD) involves progressive degeneration of the spinal cord, optic nerve, and peripheral nerves. Vitamin B12 (VB12) is a co-factor in myelin synthesis. Because each cell that constitutes the myelin component in the central nervous system and peripheral nervous system is different, it is improbable that these cells undergo simultaneous degeneration. However, the sequence of degeneration in SCD has not been established. Materials and Methods In this study, we analysed medical records and electrophysiological data of patients who showed neurological symptoms and whose serum VB12 levels were lower than 200 pg/mL. Results We enrolled 49 patients in this study. Their mean VB12 level was 68.3 pg/mL. Somatosensory evoked potential (SEP) study showed abnormal findings in 38 patients. Of the 40 patients who underwent visual evoked potential (VEP) study, 14 showed abnormal responses. Eighteen patients showed abnormal findings on a nerve conduction study (NCS). In this study, abnormal posterior tibial nerve SEPs only were seen in 16 patients, median nerve SEPs only were seen in 3 patients, abnormal VEPs only in two, and abnormal NCS responses in one patient. No patient complained of cognitive symptoms. Conclusion In SCD, degeneration appears to progress in the following order: lower spinal cord, cervical spinal cord, peripheral nerve/optic nerve, and finally, the brain. PMID:22318813

Unique Asymmetric Protrusion of Nerve Cord in the Amphioxus, Branchiostoma belcheri

NASA Astrophysics Data System (ADS)

Nozaki, Masumi; Terakado, Kiyoshi; Kubokawa, Kaoru

The amphioxus is the only surviving prevertebrate segmented chordate. In this animal Hatschek's pit has long been regarded as a putative homologue of the adenohypophysis because of the presence of secretory granules and immunoreactive cells to vertebrate gonadotrophic hormone in this organ. We found that the nerve cord extends a protrusion to the pit along the right side of the notochord. Furthermore, secretory granules were found not only in the pit but also in the protrusion of the nerve cord. These results suggest that Hatschek's pit and the nerve protrusion are homologous to the adenohypophysis and neurohypophysis, respectively. We believe that this is an evidence for the presence of the neuroendocrine link between the central nervous system and Hatschek's pit in the amphioxus.

Cholinergic, serotoninergic and peptidergic components of the nervous system of Discocotyle sagittata (Monogenea:Polyopisthocotylea).

PubMed

Cable, J; Marks, N J; Halton, D W; Shaw, C; Johnston, C F; Tinsley, R C; Gannicott, A M

1996-12-01

Cholinergic, serotoninergic (5-HT) and peptidergic neuronal pathways have been demonstrated in both central and peripheral nervous systems of adult Discocotyle sagittata, using enzyme histochemistry and indirect immunocytochemistry in conjunction with confocal scanning laser microscopy. Antisera to 2 native flatworm neuropeptides, neuropeptide F and the FMRFamide-related peptide (FaRP), GNFFRFamide, were employed to detect peptide immunoreactivity. The CNS is composed of paired cerebral ganglia and connecting dorsal commissure, together with several paired longitudinal nerve cords. The main longitudinal nerve cords (lateral, ventral and dorsal) are interconnected at intervals by a series of annular cross-connectives, producing a ladder-like arrangement typical of the platyhelminth nervous system. At the level of the haptor, the ventral cords provide nerve roots which innervate each of the 9 clamps. Cholinergic and peptidergic neuronal organisation was similar, but distinct from that of the serotoninergic components. The PNS and reproductive system are predominantly innervated by peptidergic neurones.

[Anorexia nervosa and nervus peronaeus lesions].

PubMed

Weber, Peter; Rost, Barbara

2009-09-01

Anorexia nervosa could be associated with numerous medical complications. In addition, malnutrition can cause different problems of central nervous system, whereas reports on periphere nerve lesions are rare. We report a case of a 14 8/12 years old girl suffering from anorexia nervosa since five months, who presented with peroneal nerve palsy. In association to anorexia nervosa the prognosis of this mononeuropathy seems to be good. Anorectic patients with neurological complications need an interdisciplinary medical treatment.

Maintenance of Mouse Gustatory Terminal Field Organization Is Disrupted following Selective Removal of Peripheral Sodium Salt Taste Activity at Adulthood.

PubMed

Skyberg, Rolf; Sun, Chengsan; Hill, David L

2017-08-09

Neural activity plays a critical role in the development of central circuits in sensory systems. However, the maintenance of these circuits at adulthood is usually not dependent on sensory-elicited neural activity. Recent work in the mouse gustatory system showed that selectively deleting the primary transduction channel for sodium taste, the epithelial sodium channel (ENaC), throughout development dramatically impacted the organization of the central terminal fields of three nerves that carry taste information to the nucleus of the solitary tract. More specifically, deleting ENaCs during development prevented the normal maturation of the fields. The present study was designed to extend these findings by testing the hypothesis that the loss of sodium taste activity impacts the maintenance of the normal adult terminal field organization in male and female mice. To do this, we used an inducible Cre-dependent genetic recombination strategy to delete ENaC function after terminal field maturation occurred. We found that removal of sodium taste neural activity at adulthood resulted in significant reorganization of mature gustatory afferent terminal fields in the nucleus of the solitary tract. Specifically, the chorda tympani and greater superficial petrosal nerve terminal fields were 1.4× and 1.6× larger than age-matched controls, respectively. By contrast, the glossopharyngeal nerve, which is not highly sensitive to sodium taste stimulation, did not undergo terminal field reorganization. These surprising results suggest that gustatory nerve terminal fields remain plastic well into adulthood, which likely impacts central coding of taste information and taste-related behaviors with altered taste experience. SIGNIFICANCE STATEMENT Neural activity plays a major role in the development of sensory circuits in the mammalian brain. However, the importance of sensory-driven activity in maintaining these circuits at adulthood, especially in subcortical structures, appears to be much less. Here, we tested whether the loss of sodium taste activity in adult mice impacts the maintenance of how taste nerves project to the first central relay. We found that specific loss of sodium-elicited taste activity at adulthood produced dramatic and selective reorganization of terminal fields in the brainstem. This demonstrates, for the first time, that taste-elicited activity is necessary for the normal maintenance of central gustatory circuits at adulthood and highlights a level of plasticity not seen in other sensory system subcortical circuits. Copyright © 2017 the authors 0270-6474/17/377619-12$15.00/0.

Primary olfactory projections and the nervus terminalis in the African lungfish: implications for the phylogeny of cranial nerves.

PubMed

von Bartheld, C S; Claas, B; Münz, H; Meyer, D L

1988-08-01

Primary olfactory and central projections of the nervus terminalis were investigated by injections of horseradish peroxidase into the olfactory epithelium in the African lungfish. In addition, gonadotropin-releasing hormone (GnRH) immunoreactivity of the nervus terminalis system was investigated. The primary olfactory projections are restricted to the olfactory bulb located at the rostral pole of the telencephalon; they do not extend into caudal parts of the telencephalon. A vomeronasal nerve and an accessory olfactory bulb could not be identified. The nervus terminalis courses through the dorsomedial telencephalon. Major targets include the nucleus of the anterior commissure and the nucleus praeopticus pars superior. some fibers cross to the contralateral side. A few fibers reach the diencephalon and mesencephalon. No label is present in the "posterior root of the nervus terminalis" (= "Pinkus's nerve" or "nervus praeopticus"). GnRH immunoreactivity is lacking in the "anterior root of the nervus terminalis," whereas it is abundant in nervus praeopticus (Pinkus's nerve). These findings may suggest that the nervus terminalis system originally consisted of two distinct cranial nerves, which have fused-in evolution-in most vertebrates. Theories of cranial nerve phylogeny are discussed in the light of the assumed "binerval origin" of the nervus terminalis system.

Pain. Part 2a: Trigeminal Anatomy Related to Pain.

PubMed

Renton, Tara; Egbuniwe, Obi

2015-04-01

In order to understand the underlying principles of orofacial pain it is important to understand the corresponding anatomy and mechanisms. Paper 1 of this series explains the central nervous and peripheral nervous systems relating to pain. The trigeminal nerve is the 'great protector' of the most important region of our body. It is the largest sensory nerve of the body and over half of the sensory cortex is responsive to any stimulation within this system. This nerve is the main sensory system of the branchial arches and underpins the protection of the brain, sight, smell, airway, hearing and taste, underpinning our very existence. The brain reaction to pain within the trigeminal system has a significant and larger reaction to the threat of, and actual, pain compared with other sensory nerves. We are physiologically wired to run when threatened with pain in the trigeminal region and it is a 'miracle' that patients volunteer to sit in a dental chair and undergo dental treatment. Clinical Relevance: This paper aims to provide the dental and medical teams with a review of the trigeminal anatomy of pain and the principles of pain assessment.

Sox10 Expression in Goldfish Retina and Optic Nerve Head in Controls and after the Application of Two Different Lesion Paradigms

PubMed Central

Parrilla, Marta; León-Lobera, Fernando; Lillo, Concepción; Arévalo, Rosario; Aijón, José; Lara, Juan Manuel; Velasco, Almudena

2016-01-01

The mammalian central nervous system (CNS) is unable to regenerate. In contrast, the CNS of fish, including the visual system, is able to regenerate after damage. Moreover, the fish visual system grows continuously throughout the life of the animal, and it is therefore an excellent model to analyze processes of myelination and re-myelination after an injury. Here we analyze Sox10+ oligodendrocytes in the goldfish retina and optic nerve in controls and after two kinds of injuries: cryolesion of the peripheral growing zone and crushing of the optic nerve. We also analyze changes in a major component of myelin, myelin basic protein (MBP), as a marker for myelinated axons. Our results show that Sox10+ oligodendrocytes are located in the retinal nerve fiber layer and along the whole length of the optic nerve. MBP was found to occupy a similar location, although its loose appearance in the retina differed from the highly organized MBP+ axon bundles in the optic nerve. After optic nerve crushing, the number of Sox10+ cells decreased in the crushed area and in the optic nerve head. Consistent with this, myelination was highly reduced in both areas. In contrast, after cryolesion we did not find changes in the Sox10+ population, although we did detect some MBP- degenerating areas. We show that these modifications in Sox10+ oligodendrocytes are consistent with their role in oligodendrocyte identity, maintenance and survival, and we propose the optic nerve head as an excellent area for research aimed at better understanding of de- and remyelination processes. PMID:27149509

Bridging Grafts and Transient Nerve Growth Factor Infusions Promote Long-Term Central Nervous System Neuronal Rescue and Partial Functional Recovery

NASA Astrophysics Data System (ADS)

Tuszynski, Mark H.; Gage, Fred H.

1995-05-01

Grafts of favorable axonal growth substrates were combined with transient nerve growth factor (NGF) infusions to promote morphological and functional recovery in the adult rat brain after lesions of the septohippocampal projection. Long-term septal cholinergic neuronal rescue and partial hippocampal reinnervation were achieved, resulting in partial functional recovery on a simple task assessing habituation but not on a more complex task assessing spatial reference memory. Control animals that received transient NGF infusions without axonal-growth-promoting grafts lacked behavioral recovery but also showed long-term septal neuronal rescue. These findings indicate that (i) partial recovery from central nervous system injury can be induced by both preventing host neuronal loss and promoting host axonal regrowth and (ii) long-term neuronal loss can be prevented with transient NGF infusions.

Surgically induced neuropathic pain: understanding the perioperative process.

PubMed

Borsook, David; Kussman, Barry D; George, Edward; Becerra, Lino R; Burke, Dennis W

2013-03-01

Nerve damage takes place during surgery. As a consequence, significant numbers (10%-40%) of patients experience chronic neuropathic pain termed surgically induced neuropathic pain (SNPP). The initiating surgery and nerve damage set off a cascade of events that includes both pain and an inflammatory response, resulting in "peripheral and central sensitization," with the latter resulting from repeated barrages of neural activity from nociceptors. In affected patients, these initial events produce chemical, structural, and functional changes in the peripheral and central nervous systems (CNS). The maladaptive changes in damaged nerves lead to peripheral manifestations of the neuropathic state-allodynia, sensory loss, shooting pains, etc, that can manifest long after the effects of the surgical injury have resolved. The CNS manifestations that occur are termed "centralization of pain" and affect sensory, emotional, and other (eg, cognitive) systems as well as contributing to some of the manifestations of the chronic pain syndrome (eg, depression). Currently there are no objective measures of nociception and pain in the perioperative period. As such, intermittent or continuous pain may take place during and after surgery. New technologies including direct measures of specific brain function of nociception and new insights into preoperative evaluation of patients including genetic predisposition, appear to provide initial opportunities for decreasing the burden of SNPP, until treatments with high efficacy and low adverse effects that either prevent or treat pain are discovered.

Potential Involvement of Draxin in the Axonal Projection of Cranial Nerves, Especially Cranial Nerve X, in the Chick Hindbrain

PubMed Central

Zhang, Sanbing; Cui, Huixian; Wang, Lei; Kang, Lin; Huang, Guannan; Du, Juan; Li, Sha; Tanaka, Hideaki; Su, Yuhong

2016-01-01

The appropriate projection of axons within the nervous system is a crucial component of the establishment of neural circuitry. Draxin is a repulsive axon guidance protein. Draxin has important functions in the guidance of three commissures in the central nervous system and in the migration of neural crest cells and dI3 interneurons in the chick spinal cord. Here, we report that the distribution of the draxin protein and the location of 23C10-positive areas have a strong temporal and spatial correlation. The overexpression of draxin, especially transmembrane draxin, caused 23C10-positive axon bundles to misproject in the dorsal hindbrain. In addition, the overexpression of transmembrane draxin caused abnormal formation of the ganglion crest of the IX and X cranial nerves, misprojection of some anti-human natural killer-1 (HNK-1)-stained structures in the dorsal roof of the hindbrain, and a simultaneous reduction in the efferent nerves of some motoneuron axons inside the hindbrain. Our data reveal that draxin might be involved in the fascicular projection of cranial nerves in the hindbrain. PMID:27199282

Sciatic nerve regeneration in rats subjected to ketogenic diet.

PubMed

Liśkiewicz, Arkadiusz; Właszczuk, Adam; Gendosz, Daria; Larysz-Brysz, Magdalena; Kapustka, Bartosz; Łączyński, Mariusz; Lewin-Kowalik, Joanna; Jędrzejowska-Szypułka, Halina

2016-01-01

Ketogenic diet (KD) is a high-fat-content diet with insufficiency of carbohydrates that induces ketogenesis. Besides its anticonvulsant properties, many studies have shown its neuroprotective effect in central nervous system, but its influence on peripheral nervous system has not been studied yet. We examined the influence of KD on regeneration of peripheral nerves in adult rats. Fifty one rats were divided into three experimental (n = 15) and one control (n = 6) groups. Right sciatic nerve was crushed and animals were kept on standard (ST group) or ketogenic diet, the latter was introduced 3 weeks before (KDB group) or on the day of surgery (KDA group). Functional (CatWalk) tests were performed once a week, and morphometric (fiber density, axon diameter, and myelin thickness) analysis of the nerves was made after 6 weeks. Body weight and blood ketone bodies level were estimated at the beginning and the end of experiment. Functional analysis showed no differences between groups. Morphometric evaluation showed most similarities to the healthy (uncrushed) nerves in KDB group. Nerves in ST group differed mostly from all other groups. Ketone bodies were elevated in both KD groups, while post-surgery animals' body weight was lower as compared to ST group. Regeneration of sciatic nerves was improved in KD - preconditioned rats. These results suggest a neuroprotective effect of KD on peripheral nerves.

Sustained reduction in blood pressure from electrical activation of the baroreflex is mediated via the central pathway of unmyelinated baroreceptors.

PubMed

Turner, Michael J; Kawada, Toru; Shimizu, Shuji; Sugimachi, Masaru

2014-06-13

This study aims to identify the contribution of myelinated (A-fiber) and unmyelinated (C-fiber) baroreceptor central pathways to the baroreflex control of sympathetic nerve activity and arterial pressure. Two binary white noise stimulation protocols were used to electrically stimulate the aortic depressor nerve and activate reflex responses from either A-fiber (3 V, 20-100 Hz) or C-fiber (20 V, 0-10 Hz) baroreceptor in anesthetized Sprague-Dawley rats (n=10). Transfer function analysis was performed between stimulation and sympathetic nerve activity (central arc), sympathetic nerve activity and arterial pressure (peripheral arc), and stimulation and arterial pressure (Stim-AP arc). The central arc transfer function from nerve stimulation to splanchnic sympathetic nerve activity displayed derivative characteristics for both stimulation protocols. However, the modeled steady-state gain (0.28 ± 0.04 vs. 4.01 ± 0.2%·Hz(-1), P<0.001) and coherence at 0.01 Hz (0.44 ± 0.05 vs. 0.81 ± 0.03, P<0.05) were significantly lower for A-fiber stimulation compared with C-fiber stimulation. The slope of the dynamic gain was higher for A-fiber stimulation (14.82 ± 1.02 vs. 7.21 ± 0.79 dB·decade(-1), P<0.001). The steady-state gain of the Stim-AP arc was also significantly lower for A-fiber stimulation compared with C-fiber stimulation (0.23 ± 0.05 vs. 3.05 ± 0.31 mmHg·Hz(-1), P<0.001). These data indicate that the A-fiber central pathway contributes to high frequency arterial pressure regulation and the C-fiber central pathway provides more sustained changes in sympathetic nerve activity and arterial pressure. A sustained reduction in arterial pressure from electrical stimulation of arterial baroreceptor afferents is likely mediated through the C-fiber central pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

Development of pretreatment compounds against nerve-gas agents. Annual report (Final), 16 May 88-30 Sep 90

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

Carroll, F.I.; Abraham, P.

1990-09-30

The U. S. Army Medical Research and Development Command is interested in research directed toward the development of countermeasures to chemical warfare (CW) agents such as the nerve gas poison soman. Soman and other nerve gas poisons are extremely potent cholinesterase inhibitors. This inhibition leads to a buildup of excess acetylcholine resulting in over-stimulation of both the peripheral and central nervous system and can lead to death. Standard therapy for organophosphate nerve agent poisoning is based on co-administration of an anticholinergic agent such as atropine to antagonize the effects of accumulated acetylcholine and a cholinesterase reactivator such as 2-PAM tomore » dephosphorylate the inhibited enzyme. However, since many problems remain in the treatment of organophosphate nerve agent poisoning, there is considerable interest and need to develop new pretreatment and treatment drugs, particularly for soman poisoning.« less

Stem cell and peripheral nerve injury and repair.

PubMed

Dong, Ming-min; Yi, Tian-hua

2010-10-01

Peripheral motor nerve injuries are a significant source of morbidity. Neural stem cells (NSCs), a group of relatively primitive cells, possess self-renewal ability and multidifferentiation potential. NSCs may be successfully separated from the human embryo and central nervous system (CNS) and differentiated into mature neurons and gliacytes by in vitro induction or transplantation into the body and may be differentiated into Schwann-like cells under specific conditions. It has been demonstrated that the ability of peripheral nerves to regenerate is mainly attributable to Schwann cells. NSC transplantation can promote peripheral nerve regeneration and provide a new means for treatment of peripheral nerve injury. In recent years, the study of NSCs has become a focus of many laboratories, but the biological characteristics and differentiation regulation mechanisms are not fully clear. In this article, we provide a brief review of NSC characteristics, cultivation, oriented differentiation, and clinical application. © Thieme Medical Publishers.

Local blood flow in peripheral nerves and their ganglia: Resurrecting key ideas around its measurement and significance.

PubMed

Zochodne, Douglas W

2018-06-01

Over 3 decades ago, seminal work by Phillip Low and colleagues established exquisite physiology around the measurement of nerve blood flow (NBF). Although not widely explored recently, its connection to the clinic has awaited human methodology. While human studies have not achieved a convincing level of rigour, newer imaging technologies are offering early information. The peripheral nerve trunk has parallel blood flow compartments that include epineurial flow dominated by arteriovenous shunts and downstream endoneurial blood flow (EBF). NBF and EBF have lower values than central nervous system blood flow, lack autoregulation yet have sympathetic and peptidergic neurovascular control. Contrary to expectation, injury to nerves is often associated with rises in NBF rather than ischemia, a finding of biological interest corroborated by human studies. Despite its potential importance, quantitative human measurements of EBF and NBF are not yet available. However, with development, careful NBF analysis may present new insights into nerve disorders. Muscle Nerve 57: 884-895, 2018. © 2017 Wiley Periodicals, Inc.

Anterograde transneuronal viral tract tracing reveals central sensory circuits from brown fat and sensory denervation alters its thermogenic responses.

PubMed

Vaughan, Cheryl H; Bartness, Timothy J

2012-05-01

Brown adipose tissue (BAT) thermogenic activity and growth are controlled by its sympathetic nervous system (SNS) innervation, but nerve fibers containing sensory-associated neuropeptides [substance P, calcitonin gene-related peptide (CGRP)] also suggest sensory innervation. The central nervous system (CNS) projections of BAT afferents are unknown. Therefore, we used the H129 strain of the herpes simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer used to delineate sensory nerve circuits, to define these projections. HSV-1 was injected into interscapular BAT (IBAT) of Siberian hamsters and HSV-1 immunoreactivity (ir) was assessed 24, 48, 72, 96, and 114 h postinjection. The 96- and 114-h groups had the most HSV-1-ir neurons with marked infections in the hypothalamic paraventricular nucleus, periaqueductal gray, olivary areas, parabrachial nuclei, raphe nuclei, and reticular areas. These sites also are involved in sympathetic outflow to BAT suggesting possible BAT sensory-SNS thermogenesis feedback circuits. We tested the functional contribution of IBAT sensory innervation on thermogenic responses to an acute (24 h) cold exposure test by injecting the specific sensory nerve toxin capsaicin directly into IBAT pads and then measuring core (T(c)) and IBAT (T(IBAT)) temperature responses. CGRP content was significantly decreased in capsaicin-treated IBAT demonstrating successful sensory nerve destruction. T(IBAT) and T(c) were significantly decreased in capsaicin-treated hamsters compared with the saline controls at 2 h of cold exposure. Thus the central sensory circuits from IBAT have been delineated for the first time, and impairment of sensory feedback from BAT appears necessary for the appropriate, initial thermogenic response to acute cold exposure.

STP Position Paper: Recommended Practices for Sampling and Processing the Nervous System (Brain, Spinal Cord, Nerve, and Eye) during Nonclinical General Toxicity Studies

EPA Science Inventory

The Society of Toxicologic Pathology charged a Nervous System Sampling Working Group with devising recommended practices to routinely screen the central and peripheral nervous systems in Good Laboratory Practice-type nonclinical general toxicity studies. Brains should be trimmed ...

Utility of the hyperventilation test in the evaluation of the dizzy patient.

PubMed

Califano, Luigi; Mazzone, Salvatore; Salafia, Francesca

2013-10-01

The aim of the review is to value the incidence, patterns and temporal characteristics of hyperventilation-induced nystagmus (HVIN) in patients suffering from vestibular diseases, as well as its contribution to the differential diagnosis between vestibular neuritis and schwannoma of the eighth cranial nerve and its behavior in some central vestibular diseases. The hyperventilation test seems to be more useful than other bedside tests in detecting schwannoma of the eighth cranial nerve in the case of sudden monolateral hypacusia. The presence of an excitatory pattern of HVIN in vestibular schwannoma that has undergone to stereotactic surgery reveals that this therapy produces demyelinization in neural fibers. The hyperventilation test is easy to perform, well tolerated and able to reveal latent vestibular asymmetries; it acts both at peripheral and central vestibular levels through metabolic mechanisms or, more rarely, through changes in cerebrospinal fluid pressure. It can provide patterns of oculomotor responses suggesting the execution of gadolinium-enhanced MRI, upon the suspicion of schwannoma of the eighth cranial nerve or of a central disease. In our opinion, the presence of HVIN always needs to be viewed within the more general context of a complete examination of auditory and vestibular systems.

Corneal Re-innervation and Sensation Recovery in Patients with Herpes Zoster Ophthalmicus: An In Vivo and Ex Vivo Study of Corneal Nerves

PubMed Central

Cruzat, Andrea; Hamrah, Pedram; Cavalcanti, Bernardo M.; Zheng, Lixin; Colby, Kathryn; Pavan-Langston, Deborah

2016-01-01

Purpose To study corneal reinnervation and sensation recovery in Herpes zoster Ophthalmicus (HZO). Methods Two patients with HZO were studied over time with serial corneal esthesiometry and laser in vivo confocal microscopy (IVCM). A Boston keratoprosthesis (B-KPro) type 1 was implanted and the explanted corneal tissues were examined by immunofluorescence histochemistry for βIII-tubulin to stain for corneal nerves. Results The initial central corneal IVCM performed in each patient, showed a complete lack of the subbasal nerve plexus, which was in accordance with severe loss of sensation (0 of 6 cm) measured by esthesiometry. When IVCM was repeated 2 years later prior to undergoing surgery, Case 1 showed a persistent lack of central subbasal nerves and sensation (0 of 6). In contrast, Case 2 showed regeneration of the central subbasal nerves (4,786 µm/mm2) with partial recovery of corneal sensation (2.5 of 6 cm). Immunostaining of the explanted corneal button in Case 1 showed no corneal nerves while Case 2, showed central and peripheral corneal nerves. Eight months after surgery, IVCM was again repeated in the donor tissue around the B-KPro in both patients, to study innervation of the corneal transplant. Case 1 showed no nerves, while Case 2 showed new nerves growing from the periphery into the corneal graft. Conclusions We demonstrate that regaining corneal innervation and function is possible in patients with HZO as shown by corneal sensation, IVCM, and ex-vivo immunostaining, indicating zoster neural damage is not always permanent and it may recover over an extended period of time. PMID:26989956

Inflammation in the Pathogenesis of Lyme Neuroborreliosis

PubMed Central

Ramesh, Geeta; Didier, Peter J.; England, John D.; Santana-Gould, Lenay; Doyle-Meyers, Lara A.; Martin, Dale S.; Jacobs, Mary B.; Philipp, Mario T.

2016-01-01

Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, affects both peripheral and central nervous systems. We assessed a causal role for inflammation in Lyme neuroborreliosis pathogenesis by evaluating the induced inflammatory changes in the central nervous system, spinal nerves, and dorsal root ganglia (DRG) of rhesus macaques that were inoculated intrathecally with live B. burgdorferi and either treated with dexamethasone or meloxicam (anti-inflammatory drugs) or left untreated. ELISA of cerebrospinal fluid showed significantly elevated levels of IL-6, IL-8, chemokine ligand 2, and CXCL13 and pleocytosis in all infected animals, except dexamethasone-treated animals. Cerebrospinal fluid and central nervous system tissues of infected animals were culture positive for B. burgdorferi regardless of treatment. B. burgdorferi antigen was detected in the DRG and dorsal roots by immunofluorescence staining and confocal microscopy. Histopathology revealed leptomeningitis, vasculitis, and focal inflammation in the central nervous system; necrotizing focal myelitis in the cervical spinal cord; radiculitis; neuritis and demyelination in the spinal roots; and inflammation with neurodegeneration in the DRG that was concomitant with significant neuronal and satellite glial cell apoptosis. These changes were absent in the dexamethasone-treated animals. Electromyography revealed persistent abnormalities in F-wave chronodispersion in nerve roots of a few infected animals; which were absent in dexamethasone-treated animals. These results suggest that inflammation has a causal role in the pathogenesis of acute Lyme neuroborreliosis. PMID:25892509

Real time imaging of peripheral nerve vasculature using optical coherence angiography

NASA Astrophysics Data System (ADS)

Vasudevan, Srikanth; Kumsa, Doe; Takmakov, Pavel; Welle, Cristin G.; Hammer, Daniel X.

2016-03-01

The peripheral nervous system (PNS) carries bidirectional information between the central nervous system and distal organs. PNS stimulation has been widely used in medical devices for therapeutic indications, such as bladder control and seizure cessation. Investigational uses of PNS stimulation include providing sensory feedback for improved control of prosthetic limbs. While nerve safety has been well documented for stimulation parameters used in marketed devices, novel PNS stimulation devices may require alternative stimulation paradigms to achieve maximum therapeutic benefit. Improved testing paradigms to assess the safety of stimulation will expedite the development process for novel PNS stimulation devices. The objective of this research is to assess peripheral nerve vascular changes in real-time with optical coherence angiography (OCA). A 1300-nm OCA system was used to image vasculature changes in the rat sciatic nerve in the region around a surface contacting single electrode. Nerves and vasculature were imaged without stimulation for 180 minutes to quantify resting blood vessel diameter. Walking track analysis was used to assess motor function before and 6 days following experiments. There was no significant change in vessel diameter between baseline and other time points in all animals. Motor function tests indicated the experiments did not impair functionality. We also evaluated the capabilities to image the nerve during electrical stimulation in a pilot study. Combining OCA with established nerve assessment methods can be used to study the effects of electrical stimulation safety on neural and vascular tissue in the periphery.

Corneal subbasal nerve fiber regeneration in myopic patients after laser in situ keratomileusis★

PubMed Central

Deng, Shijing; Wang, Mengmeng; Zhang, Fengju; Sun, Xuguang; Hou, Wenbo; Guo, Ning

2012-01-01

A total of 26 myopic patients (52 eyes) underwent laser in situ keratomileusis. In vivo confocal microscopy revealed that most of the regenerated corneal subbasal nerve fibers in the corneal flap originated from the stump of corneal subbasal nerve fibers outside the ablation zone and extended towards the center of the cornea in all patients. Meanwhile, new fibers were also found to directly regenerate from deep in the stroma in some cases. Approximately 94% of regenerated corneal subbasal nerve fibers (73/78 eyes) regrew vertically into the peripheral central 6-mm circle area 1 month after surgery, 78% (28/36 eyes) grew into the central 3–6 mm area at 2 months, and 23% into the central 3-mm circle area at 3 months. In addition, there was no significant difference in corneal subbasal nerve fiber regenerative capacity between the basic fibroblast growth factor group and the 20% (v/v) deproteinized extract of calf blood group. The majority of corneal subbasal nerve fiber regeneration occurred from the stump of corneal subbasal nerve fibers outside the corneal flap, and the remaining growth occurred deep within the stroma. PMID:25657693

Trigeminal Neuralgia, Glossopharyngeal Neuralgia, and Myofascial Pain Dysfunction Syndrome: An Update.

PubMed

Khan, Mohammad; Nishi, Shamima Easmin; Hassan, Siti Nazihahasma; Islam, Md Asiful; Gan, Siew Hua

2017-01-01

Neuropathic pain is a common phenomenon that affects millions of people worldwide. Maxillofacial structures consist of various tissues that receive frequent stimulation during food digestion. The unique functions (masticatory process and facial expression) of the maxillofacial structure require the exquisite organization of both the peripheral and central nervous systems. Neuralgia is painful paroxysmal disorder of the head-neck region characterized by some commonly shared features such as the unilateral pain, transience and recurrence of attacks, and superficial and shock-like pain at a trigger point. These types of pain can be experienced after nerve injury or as a part of diseases that affect peripheral and central nerve function, or they can be psychological. Since the trigeminal and glossopharyngeal nerves innervate the oral structure, trigeminal and glossopharyngeal neuralgia are the most common syndromes following myofascial pain dysfunction syndrome. Nevertheless, misdiagnoses are common. The aim of this review is to discuss the currently available diagnostic procedures and treatment options for trigeminal neuralgia, glossopharyngeal neuralgia, and myofascial pain dysfunction syndrome.

Trigeminal Neuralgia, Glossopharyngeal Neuralgia, and Myofascial Pain Dysfunction Syndrome: An Update

PubMed Central

Nishi, Shamima Easmin; Hassan, Siti Nazihahasma

2017-01-01

Neuropathic pain is a common phenomenon that affects millions of people worldwide. Maxillofacial structures consist of various tissues that receive frequent stimulation during food digestion. The unique functions (masticatory process and facial expression) of the maxillofacial structure require the exquisite organization of both the peripheral and central nervous systems. Neuralgia is painful paroxysmal disorder of the head-neck region characterized by some commonly shared features such as the unilateral pain, transience and recurrence of attacks, and superficial and shock-like pain at a trigger point. These types of pain can be experienced after nerve injury or as a part of diseases that affect peripheral and central nerve function, or they can be psychological. Since the trigeminal and glossopharyngeal nerves innervate the oral structure, trigeminal and glossopharyngeal neuralgia are the most common syndromes following myofascial pain dysfunction syndrome. Nevertheless, misdiagnoses are common. The aim of this review is to discuss the currently available diagnostic procedures and treatment options for trigeminal neuralgia, glossopharyngeal neuralgia, and myofascial pain dysfunction syndrome. PMID:28827979

The nerve supply of the lumbar intervertebral disc.

PubMed

Edgar, M A

2007-09-01

The anatomical studies, basic to our understanding of lumbar spine innervation through the sinu-vertebral nerves, are reviewed. Research in the 1980s suggested that pain sensation was conducted in part via the sympathetic system. These sensory pathways have now been clarified using sophisticated experimental and histochemical techniques confirming a dual pattern. One route enters the adjacent dorsal root segmentally, whereas the other supply is non-segmental ascending through the paravertebral sympathetic chain with re-entry through the thoracolumbar white rami communicantes. Sensory nerve endings in the degenerative lumbar disc penetrate deep into the disrupted nucleus pulposus, insensitive in the normal lumbar spine. Complex as well as free nerve endings would appear to contribute to pain transmission. The nature and mechanism of discogenic pain is still speculative but there is growing evidence to support a 'visceral pain' hypothesis, unique in the muscloskeletal system. This mechanism is open to 'peripheral sensitisation' and possibly 'central sensitisation' as a potential cause of chronic back pain.

Sympatho-renal axis in chronic disease.

PubMed

Sobotka, Paul A; Mahfoud, Felix; Schlaich, Markus P; Hoppe, Uta C; Böhm, Michael; Krum, Henry

2011-12-01

Essential hypertension, insulin resistance, heart failure, congestion, diuretic resistance, and functional renal disease are all characterized by excessive central sympathetic drive. The contribution of the kidney's somatic afferent nerves, as an underlying cause of elevated central sympathetic drive, and the consequences of excessive efferent sympathetic signals to the kidney itself, as well as other organs, identify the renal sympathetic nerves as a uniquely logical therapeutic target for diseases linked by excessive central sympathetic drive. Clinical studies of renal denervation in patients with resistant hypertension using an endovascular radiofrequency ablation methodology have exposed the sympathetic link between these conditions. Renal denervation could be expected to simultaneously affect blood pressure, insulin resistance, sleep disorders, congestion in heart failure, cardiorenal syndrome and diuretic resistance. The striking epidemiologic evidence for coexistence of these disorders suggests common causal pathways. Chronic activation of the sympathetic nervous system has been associated with components of the metabolic syndrome, such as blood pressure elevation, obesity, dyslipidemia, and impaired fasting glucose with hyperinsulinemia. Over 50% of patients with essential hypertension are hyperinsulinemic, regardless of whether they are untreated or in a stable program of treatment. Insulin resistance is related to sympathetic drive via a bidirectional mechanism. In this manuscript, we review the data that suggests that selective impairment of renal somatic afferent and sympathetic efferent nerves in patients with resistant hypertension both reduces markers of central sympathetic drive and favorably impacts diseases linked through central sympathetics-insulin resistance, heart failure, congestion, diuretic resistance, and cardiorenal disorders.

Prevalence of myelinated retinal nerve fibres in adult Indians: the Central India Eye and Medical Study.

PubMed

Nangia, Vinay; Jonas, Jost B; Khare, Anshu; Bhate, Karishma; Agarwal, Shubhra; Panda-Jonas, Songhomitra

2014-05-01

To determine the prevalence of myelinated retinal nerve fibers in the adult Indian population. The Central India Eye and Medical Study performed in rural Central India included 4711 participants aged 30+ years. The participants underwent a detailed ophthalmic and medical examination. Readable fundus photographs were available for 8645 eyes of 4485 (95.2%) subjects. Myelinated retinal nerve fibers were detected in 52 eyes (46 subjects) with a prevalence rate of 0.58±0.08 per 100 eyes [95% confidence interval (CI): 0.42, 0.74] and 1.03±0.15 per 100 subjects (95%CI: 0.73, 1.32). Prevalence of myelinated retinal nerve fibers was significantly associated hyperopic refractive error (p=0.008; OR: 1.31; 95%CI: 1.07, 1.59). It was not significantly associated with age (p=0.11), best corrected visual acuity (logMAR; p=0.33), intraocular pressure (p=0.09), amount of nuclear cataract (p=0.93), optic disc area (p=0.60), presence of glaucomatous optic nerve atrophy (p=0.62), and early age-related macular degeneration (p=0.53). Myelinated retinal nerve fibers are present in about 10 out of 1000 adult Indians in rural Central India, with a higher prevalence in hyperopic eyes. Prevalence of myelinated retinal nerve fibers was not associated with age, visual acuity, glaucoma and macular degeneration. © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

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.

Virus signaling and apoptosis in the central nervous system infection.

PubMed

Perkins, Dana

2005-09-01

Viruses target the central nervous system (CNS) incidentally, due to complications of systemic infection, or specifically, by ascending via the axons of peripheral and cranial nerves. In the CNS, viruses cause acute disease (viz. encephalitis), latent infections or neurodegenerative pathology. Causation of acute disease or immune-mediated pathology, and virus involvement in the etiology of chronic neurodegenerative diseases depends, at least in part, on the ability to commander signaling pathways. Better understanding of these virus-host cell interactions will help identify molecular targets for the development of improved therapeutic strategies.

Encoding of the cough reflex in anesthetized guinea pigs

PubMed Central

Mori, Nanako

2011-01-01

We have previously described the physiological and morphological properties of the cough receptors and their sites of termination in the airways and centrally in the nucleus tractus solitarius (nTS). In the present study, we have addressed the hypothesis that the primary central synapses of the cough receptors subserve an essential role in the encoding of cough. We found that cough requires sustained, high-frequency (≥8-Hz) afferent nerve activation. We also found evidence for processes that both facilitate (summation, sensitization) and inhibit the initiation of cough. Sensitization of cough occurs with repetitive subthreshold activation of the cough receptors or by coincident activation of C-fibers and/or nTS neurokinin receptor activation. Desensitization of cough evoked by repetitive and/or continuous afferent nerve activation has a rapid onset (<60 s) and does not differentiate between tussive stimuli, suggesting a central nervous system-dependent process. The cough reflex can also be actively inhibited upon activation of other airway afferent nerve subtypes, including slowly adapting receptors and pulmonary C-fibers. The sensitization and desensitization of cough are likely attributable to the prominent, primary, and unique role of N-methyl-d-aspartate receptor-dependent signaling at the central synapses of the cough receptors. These attributes may have direct relevance to the presentation of cough in disease and for the effectiveness of antitussive therapies. PMID:20926760

Non-invasive peripheral nerve stimulation via focused ultrasound in vivo

NASA Astrophysics Data System (ADS)

Downs, Matthew E.; Lee, Stephen A.; Yang, Georgiana; Kim, Seaok; Wang, Qi; Konofagou, Elisa E.

2018-02-01

Focused ultrasound (FUS) has been employed on a wide range of clinical applications to safely and non-invasively achieve desired effects that have previously required invasive and lengthy procedures with conventional methods. Conventional electrical neuromodulation therapies that are applied to the peripheral nervous system (PNS) are invasive and/or non-specific. Recently, focused ultrasound has demonstrated the ability to modulate the central nervous system and ex vivo peripheral neurons. Here, for the first time, noninvasive stimulation of the sciatic nerve eliciting a physiological response in vivo is demonstrated with FUS. FUS was applied on the sciatic nerve in mice with simultaneous electromyography (EMG) on the tibialis anterior muscle. EMG signals were detected during or directly after ultrasound stimulation along with observable muscle contraction of the hind limb. Transecting the sciatic nerve downstream of FUS stimulation eliminated EMG activity during FUS stimulation. Peak-to-peak EMG response amplitudes and latency were found to be comparable to conventional electrical stimulation methods. Histology along with behavioral and thermal testing did not indicate damage to the nerve or surrounding regions. The findings presented herein demonstrate that FUS can serve as a targeted, safe and non-invasive alternative to conventional peripheral nervous system stimulation to treat peripheral neuropathic diseases in the clinic.

The thoracic muscular system and its innervation in third instar Calliphora vicina Larvae. II. Projection patterns of the nerves associated with the pro- and mesothorax and the pharyngeal complex.

PubMed

Schoofs, Andreas; Hanslik, Ulrike; Niederegger, Senta; Heinzel, Hans-Georg; Spiess, Roland

2010-08-01

We describe the anatomy of the nerves that project from the central nervous system (CNS) to the pro- and mesothoracic segments and the cephalopharyngeal skeleton (CPS) for third instar Calliphora larvae. Due to the complex branching pattern we introduce a nomenclature that labels side branches of first and second order. Two fine nerves that were not yet described are briefly introduced. One paired nerve projects to the ventral arms (VAs) of the CPS. The second, an unpaired nerve, projects to the ventral surface of the cibarial part of the esophagus (ES). Both nerves were tentatively labeled after the structures they innervate. The antennal nerve (AN) innervates the olfactory dorsal organ (DO). It contains motor pathways that project through the frontal connectives (FC) to the frontal nerve (FN) and innervate the cibarial dilator muscles (CDM) which mediate food ingestion. The maxillary nerve (MN) innervates the sensory terminal organ (TO), ventral organ (VO), and labial organ (LO) and comprises the motor pathways to the mouth hook (MH) elevator, MH depressor, and the labial retractor (LR) which opens the mouth cavity. An anastomosis of unknown function exists between the AN and MN. The prothoracic accessory nerve (PaN) innervates a dorsal protractor muscle of the CPS and sends side branches to the aorta and the bolwig organ (BO) (stemmata). In its further course, this nerve merges with the prothoracic nerve (PN). The architecture of the PN is extremely complex. It innervates a set of accessory pharyngeal muscles attached to the CPS and the body wall musculature of the prothorax. Several anastomoses exist between side branches of this nerve which were shown to contain motor pathways. The mesothoracic nerve (MeN) innervates a MH accessor and the longitudinal and transversal body wall muscles of the second segment. J. Morphol. 271:969-979, 2010. (c) 2010 Wiley-Liss, Inc.

Nerve injuries of the upper extremity and hand

PubMed Central

Dahlin, Lars B.; Wiberg, Mikael

2017-01-01

A nerve injury has a profound impact on the patient’s daily life due to the impaired sensory and motor function, impaired dexterity, sensitivity to cold as well as eventual pain problems. To perform an appropriate treatment of nerve injuries, a correct diagnosis must be made, where the injury is properly classified, leading to an optimal surgical approach and technique, where timing of surgery is also important for the outcome. Knowledge about the nerve regeneration process, where delicate processes occur in neurons, non-neuronal cells (i.e. Schwann cells) and other cells in the peripheral as well as the central nervous systems, is crucial for the treating surgeon. The surgical decision to perform nerve repair and/or reconstruction depends on the type of injury, the condition of the wound as well as the vascularity of the wound. To reconnect injured nerve ends, various techniques can be used, which include both epineurial and fascicular nerve repair, and if a nerve defect is caused by the injury, a nerve reconstruction procedure has to be performed, including bridging the defect using nerve-grafts or nerve transfer techniques. The patients must be evaluated properly and regularly after the surgical procedure and appropriate rehabilitation programmes are useful to improve the final outcome. Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160071. Originally published online at www.efortopenreviews.org PMID:28630754

Is the term "fasciculus opticus cerebralis" more justifiable than the term "optic nerve"?

PubMed

Vojniković, Bojo; Bajek, Snjezana; Bajek, Goran; Strenja-Linić, Ines; Grubesić, Aron

2013-04-01

The terminology of the optic nerve had already been changed three times, since 1895 until 1955 when the term "nervus opticus" was introduced in the "Terminologia Anatomica". Following our study we claim that, from the aspect of phylogenetic evolution of binocular vision development as well as optical embryogenesis where opticus is evidently presented as a product of diencephalic structures, the addition of the term "nervus" to opticus is not adequate and justified. From the clinical aspect the term "nervus opticus" is also inadequate, both as a "nerve" that has no functional regenerative properties, unlike other cranial nerves, as well as from a pedagogical and didactical aspect of educating future physicians. We suggest that the term "Fasciculus Opticus Cerebralis" should be used as it much better explains the origin as well as its affiliation to the central nervous system.

Lost in the jungle: new hurdles for optic nerve axon regeneration.

PubMed

Pernet, Vincent; Schwab, Martin E

2014-07-01

The poor regenerative capacity of injured central nervous system (CNS) axons leads to permanent neurological deficits after brain, spinal cord, or optic nerve lesions. In the optic nerve, recent studies showed that stimulation of the cytokine or mammalian target of rapamycin (mTOR) signaling pathways potently enhances sprouting and regeneration of injured retinal ganglion cell axons in adult mice, but does not allow the majority of axons to reach their main cerebral targets. New analyses have revealed axon navigation defects in the optic nerve and at the optic chiasm under conditions of strong growth stimulation. We propose that a balanced growth stimulatory treatment will have to be combined with guidance factors and suppression of local growth inhibitory factors to obtain the full regeneration of long CNS axonal tracts. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Restoration of quinine-stimulated Fos-immunoreactive neurons in the central nucleus of the amygdala and gustatory cortex following reinnervation or cross-reinnervation of the lingual taste nerves in rats.

PubMed

King, Camille Tessitore; Garcea, Mircea; Spector, Alan C

2014-08-01

Remarkably, when lingual gustatory nerves are surgically rerouted to inappropriate taste fields in the tongue, some taste functions recover. We previously demonstrated that quinine-stimulated oromotor rejection reflexes and neural activity (assessed by Fos immunoreactivity) in subregions of hindbrain gustatory nuclei were restored if the posterior tongue, which contains receptor cells that respond strongly to bitter compounds, was cross-reinnervated by the chorda tympani nerve. Such functional recovery was not seen if instead, the anterior tongue, where receptor cells are less responsive to bitter compounds, was cross-reinnervated by the glossopharyngeal nerve, even though this nerve typically responds robustly to bitter substances. Thus, recovery depended more on the taste field being reinnervated than on the nerve itself. Here, the distribution of quinine-stimulated Fos-immunoreactive neurons in two taste-associated forebrain areas was examined in these same rats. In the central nucleus of the amygdala (CeA), a rostrocaudal gradient characterized the normal quinine-stimulated Fos response, with the greatest number of labeled cells situated rostrally. Quinine-stimulated neurons were found throughout the gustatory cortex, but a "hot spot" was observed in its anterior-posterior center in subregions approximating the dysgranular/agranular layers. Fos neurons here and in the rostral CeA were highly correlated with quinine-elicited gapes. Denervation of the posterior tongue eliminated, and its reinnervation by either nerve restored, numbers of quinine-stimulated labeled cells in the rostralmost CeA and in the subregion approximating the dysgranular gustatory cortex. These results underscore the remarkable plasticity of the gustatory system and also help clarify the functional anatomy of neural circuits activated by bitter taste stimulation. © 2014 Wiley Periodicals, Inc.

Prions spread via the autonomic nervous system from the gut to the central nervous system in cattle incubating bovine spongiform encephalopathy.

PubMed

Hoffmann, Christine; Ziegler, Ute; Buschmann, Anne; Weber, Artur; Kupfer, Leila; Oelschlegel, Anja; Hammerschmidt, Baerbel; Groschup, Martin H

2007-03-01

To elucidate the still-unknown pathogenesis of bovine spongiform encephalopathy (BSE), an oral BSE challenge and sequential kill study was carried out on 56 calves. Relevant tissues belonging to the peripheral and central nervous system, as well as to the lymphoreticular tract, from necropsied animals were analysed by highly sensitive immunohistochemistry and immunoblotting techniques to reveal the presence of BSE-associated pathological prion protein (PrPSc) depositions. Our results demonstrate two routes involving the autonomic nervous system through which BSE prions spread by anterograde pathways from the gastrointestinal tract (GIT) to the central nervous system (CNS): (i) via the coeliac and mesenteric ganglion complex, splanchnic nerves and the lumbal/caudal thoracic spinal cord (representing the sympathetic GIT innervation); and (ii) via the Nervus vagus (parasympathetic GIT innervation). The dorsal root ganglia seem to be subsequently affected, so it is likely that BSE prion invasion of the non-autonomic peripheral nervous system (e.g. sciatic nerve) is a secondary retrograde event following prion replication in the CNS. Moreover, BSE-associated PrPSc was already detected in the brainstem of an animal 24 months post-infection, which is 8 months earlier than reported previously. These findings are important for the understanding of BSE pathogenesis and for the development of new diagnostic strategies for this infectious disease.

Surgically-Induced Neuropathic Pain (SNPP): Understanding the Perioperative Process

PubMed Central

Borsook, David; Kussman, Barry D.; George, Edward; Becerra, Lino R.; Burke, Dennis W.

2012-01-01

Objective Nerve damage takes place during surgery. As a consequence, significant numbers (10–40%) of patients experience chronic neuropathic pain termed surgically induced neuropathic pain (SNPP). Background The initiating surgery and nerve damage set off a cascade of events that includes both pain and an inflammatory response, resulting in ‘peripheral’ and ‘central sensitization’, with the latter resulting from repeated barrages of neural activity from nociceptors. In affected patients these initial events produce chemical, structural and functional changes in the peripheral (PNS) and central nervous (CNS) systems. The maladaptive changes in damaged nerves lead to peripheral manifestations of the neuropathic state – allodynia, sensory loss, shooting pains etc., that can manifest long after the effects of the surgical injury have resolved. The CNS manifestations that occur are termed ‘centralization of pain’ and affect sensory, emotional and other (e.g., cognitive) systems as well as contributing to some of the manifestations of the chronic pain syndrome (e.g., depression). Conclusions Currently there are no objective measures of pain in the peri-operative period. As such intermittent pain or continuous may take place during and after surgery. New technologies including direct measures of specific brain function of nociception and new insights into preoperative evaluation of patients including genetic predisposition appear to provide initial opportunities for decreasing the burden of SNPP until treatments with high efficacy and low side effects that either prevent or treat pain are discovered. PMID:23059501

Potential Involvement of Draxin in the Axonal Projection of Cranial Nerves, Especially Cranial Nerve X, in the Chick Hindbrain.

PubMed

Zhang, Sanbing; Cui, Huixian; Wang, Lei; Kang, Lin; Huang, Guannan; Du, Juan; Li, Sha; Tanaka, Hideaki; Su, Yuhong

2016-07-01

The appropriate projection of axons within the nervous system is a crucial component of the establishment of neural circuitry. Draxin is a repulsive axon guidance protein. Draxin has important functions in the guidance of three commissures in the central nervous system and in the migration of neural crest cells and dI3 interneurons in the chick spinal cord. Here, we report that the distribution of the draxin protein and the location of 23C10-positive areas have a strong temporal and spatial correlation. The overexpression of draxin, especially transmembrane draxin, caused 23C10-positive axon bundles to misproject in the dorsal hindbrain. In addition, the overexpression of transmembrane draxin caused abnormal formation of the ganglion crest of the IX and X cranial nerves, misprojection of some anti-human natural killer-1 (HNK-1)-stained structures in the dorsal roof of the hindbrain, and a simultaneous reduction in the efferent nerves of some motoneuron axons inside the hindbrain. Our data reveal that draxin might be involved in the fascicular projection of cranial nerves in the hindbrain. © 2016 The Histochemical Society.

Electroneurographic findings in patients with solvent induced central nervous system dysfunction.

PubMed Central

Orbaek, P; Rosén, I; Svensson, K

1988-01-01

The function of the peripheral nervous system was examined in a group of 32 men aged 30-65 (mean 49) with diagnosed solvent induced chronic toxic encephalopathy. The subjects were examined at the time of diagnosis and 26 were re-examined after a follow up period of 22-72 months (mean 40) and compared with a group of 50 unexposed male workers aged 27-64 (mean 42) with appropriate adjustment for age. All subjects were carefully scrutinised for alcohol abuse and other neurological diseases. The results of motor fibre neurography disclosed no difference between the groups. Nevertheless, a significant decrease in motor conduction velocity was found in the patients at follow up. Sensory fibre neurography showed signs of slight axonal degeneration with significantly decreased sensory nerve action potential amplitudes in the median and sural nerves; these amplitudes increased during follow up. The duration of sensory nerve action potentials was longer in the exposed group for the median and the sural nerves. The percentage of late components was significantly higher in the median nerve. The warm-cold sensitivity in the exposed group also indicated a slight sensory dysfunction with statistically significant wider detection limits. PMID:2840109

[Functional anatomy of the cochlear nerve and the central auditory system].

PubMed

Simon, E; Perrot, X; Mertens, P

2009-04-01

The auditory pathways are a system of afferent fibers (through the cochlear nerve) and efferent fibers (through the vestibular nerve), which are not limited to a simple information transmitting system but create a veritable integration of the sound stimulus at the different levels, by analyzing its three fundamental elements: frequency (pitch), intensity, and spatial localization of the sound source. From the cochlea to the primary auditory cortex, the auditory fibers are organized anatomically in relation to the characteristic frequency of the sound signal that they transmit (tonotopy). Coding the intensity of the sound signal is based on temporal recruitment (the number of action potentials) and spatial recruitment (the number of inner hair cells recruited near the cell of the frequency that is characteristic of the stimulus). Because of binaural hearing, commissural pathways at each level of the auditory system and integration of the phase shift and the difference in intensity between signals coming from both ears, spatial localization of the sound source is possible. Finally, through the efferent fibers in the vestibular nerve, higher centers exercise control over the activity of the cochlea and adjust the peripheral hearing organ to external sound conditions, thus protecting the auditory system or increasing sensitivity by the attention given to the signal.

[Impact of hypoglycemic episodes on nerves conduction and auditory and visual evoked potentials in children with type 1 diabetes].

PubMed

Wysocka-Mincewicz, Marta; Trippenbach-Dulska, Hanna; Emeryk-Szajewska, Barbara; Zakrzewska-Pniewska, Beata; Kochanek, Krzysztof; Pańkowska, Ewa

2007-01-01

Hypoglycemia is an acute disturbance of energy, especially impacting the central nervous system, but direct influence on peripheral nervous function is not detected. The aim of the study was to establish the influence of hypoglycemic moderate and severe episodes on the function of peripheral nerves, hearing and visual pathway. 97 children with type 1 diabetes (mean age 15.4+/-2.16 years, mean duration of diabetes 8.11+/-2.9 years, mean HbA1c 8,58+/-1.06%), at least 10 years old and with at least 3 years duration of diabetes, were included to study. Nerve conduction studies, visual (VEP) and auditory (ABR) evoked potentials were performed with standard surface stimulating and recording techniques. Moderate hypoglycemic episodes were defined as events of low glycemia requiring help of another person but without loss of consciousness and/or convulsions but recurrent frequently in at least one year. Severe hypoglycemia was defined as events with loss of consciousness and/or convulsions. Univariate ANOVA tests of significance or H Kruskal-Wallis test were used, depending on normality of distribution. The subgroups with a history of hypoglycemic episodes had significant delay in all conduction parameters in the sural nerve (amplitude p<0.05, sensory latency p<0.05, and velocity p<0.005) and in motor potential amplitude of tibial nerve (p<0.005). In ABR wave III latency and interval I-III in subgroups with episodes of hypoglycemia (p<0,05) were significantly prolonged. In analyses of VEP parameters no differences were detected. The study showed influence of hypoglycemic episodes on function of all sural nerve parameters and tibial motor amplitude, and in ABR on wave III and interval I-III. Frequent moderate hypoglycemic episodes were strong risk factors for damage of the peripheral and central nervous systems, comparable with impact of several severe hypoglycemias.

Gross anatomy of central nervous system in firefly, Pteroptyx tener (Coleoptera: Lampyridae)

NASA Astrophysics Data System (ADS)

Hudawiyah, Nur; Wahida, O. Nurul; Norela, S.

2015-09-01

This paper describes for the first time the organization and fine structure of the central nervous system (CNS) in the fireflies, Pteroptyx tener (Coleoptera: Lampyridae). The morphology of the CNS was examined by using Carl Zeiss AxioScope A1 photomicroscope with iSolution Lite software. Some specific structural features such as the localization of protocerebrum, deutocerebrum and tritocerebrum in the brain region were analyzed. Other than that, the nerve cord and its peripheral structure were also analyzed. This study suggests that, there is a very obvious difference between male and female central nervous system which illustrates that they may differ in function in controlling physiological and behavioral activities.

Brainstem abnormalities and vestibular nerve enhancement in acute neuroborreliosis.

PubMed

Farshad-Amacker, Nadja A; Scheffel, Hans; Frauenfelder, Thomas; Alkadhi, Hatem

2013-12-21

Borreliosis is a widely distributed disease. Neuroborreliosis may present with unspecific symptoms and signs and often remains difficult to diagnose in patients with central nervous system symptoms, particularly if the pathognomonic erythema chronica migrans does not develop or is missed. Thus, vigilance is mandatory in cases with atypical presentation of the disease and with potentially severe consequences if not recognized early. We present a patient with neuroborreliosis demonstrating brain stem and vestibular nerve abnormalities on magnetic resonance imaging. A 28-year-old Caucasian female presented with headaches, neck stiffness, weight loss, nausea, tremor, and gait disturbance. Magnetic resonance imaging showed T2-weighted hyperintense signal alterations in the pons and in the vestibular nerves as well as bilateral post-contrast enhancement of the vestibular nerves. Serologic testing of the cerebrospinal fluid revealed the diagnosis of neuroborreliosis. Patients infected with neuroborreliosis may present with unspecific neurologic symptoms and magnetic resonance imaging as a noninvasive imaging tool showing signal abnormalities in the brain stem and nerve root enhancement may help in establishing the diagnosis.

Regeneration-associated genes on optic nerve regeneration in fish retina.

PubMed

Ogai, Kazuhiro; Nishitani, Maki; Kuwana, Ayaka; Mawatari, Kazuhiro; Koriyama, Yoshiki; Sugitani, Kayo; Nakashima, Hiroshi; Kato, Satoru

2014-01-01

It has been well documented that fish central nervous system, including retina and optic nerve, can regenerate and recover its function after nerve injury. Within a few decades, a number of regeneration-associated genes (RAGs) have been identified in fish retina following optic nerve injury (ONI). RAGs can be classified into two groups: cell survival- and axonal outgrowth-related genes. In fish retina after ONI, cell survival-related genes were upregulated in 1-6 days after ONI, which corresponds to the preparation stage for cell survival and axonal sprouting. Subsequently, axonal outgrowth-related genes were upregulated in 1-6 weeks after ONI, which corresponds to the axonal regrowth stage. Recently, we've found a novel type of RAGs, dedifferentiation-related genes, that are upregulated in overlapping time between cell survival and axonal regrowth (3-10 days after ONI). In this chapter we summarize these three types of RAGs that promote optic nerve regeneration in the fish retina after ONI.

Current progress in use of adipose derived stem cells in peripheral nerve regeneration

PubMed Central

Zack-Williams, Shomari DL; Butler, Peter E; Kalaskar, Deepak M

2015-01-01

Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental models have been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells (ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury (PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair. PMID:25621105

Vagus-brain communication in atherosclerosis-related inflammation: a neuroimmunomodulation perspective of CAD.

PubMed

Gidron, Yori; Kupper, Nina; Kwaijtaal, Martijn; Winter, Jobst; Denollet, Johan

2007-12-01

The current understanding of the pathophysiology of atherosclerosis leading to coronary artery disease (CAD) emphasizes the role of inflammatory mediators. Given the bidirectional communication between the immune and central nervous systems, an important question is whether the brain can be "informed" about and modulate CAD-related inflammation. A candidate communicator and modulator is the vagus nerve. Until now, the vagus nerve has received attention in cardiology mainly due to its role in the parasympathetic cardiovascular response. However, the vagus nerve can also "inform" the brain about peripheral inflammation since its paraganglia have receptors for interleukin-1. Furthermore, its efferent branch has a local anti-inflammatory effect. These effects have not been considered in research on the vagus nerve in CAD or in vagus nerve stimulation trials in CAD. In addition, various behavioural interventions, including relaxation, may influence CAD prognosis by affecting vagal activity. Based on this converging evidence, we propose a neuroimmunomodulation approach to atherogenesis. In this model, the vagus nerve "informs" the brain about CAD-related cytokines; in turn, activation of the vagus (via vagus nerve stimulation, vagomimetic drugs or relaxation) induces an anti-inflammatory response that can slow down the chronic process of atherogenesis.

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

Optic Nerve Head Biomechanics in Aging and Disease

PubMed Central

Downs, J. Crawford

2015-01-01

This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression. PMID:25819451

Phase 1/2 Study of LOXO-195 in Patients With Previously Treated NTRK Fusion Cancers

ClinicalTrials.gov

2018-05-30

Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms; Sarcoma; Colorectal Neoplasms; Salivary Gland Neoplasms; Biliary Tract Neoplasms; Brain Neoplasm, Primary; Melanoma; Glioblastoma; Bile Duct Neoplasms; Astrocytoma; Head and Neck Squamous Cell Carcinoma; Pontine Glioma; Pancreatic Neoplasms; Ovarian Neoplasms; Carcinoma, Renal Cell; Cholangiocarcinoma; Skin Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Intestinal Neoplasms; Thyroid Cancer; GIST; Malignant Peripheral Nerve Sheath Tumors; Breast Secretory Carcinoma; Uterine Neoplasms; Fibrosarcoma; Infantile Fibrosarcoma; Congenital Mesoblastic Nephroma; Central Nervous System Neoplasms

[Participation of septum on the increase of plasma cortisol level induced by stimulation of the greater splanchnic nerve of cats].

PubMed

Zhou, Y Q; Zhu, X M; Zhu, Z T; Guo, J K; Hu, L M; Zhou, W J

1995-06-01

Experimens were performed on 36 cats, showing that stimulation of the central end of the left major splanchnic nerve induced an increase of the plasma cortisol level. The centripetal effect was abolished by lesioning the septal nuclei, just as the same as injection of propranolol into the nuclei; but phentolamine had no such preventive action. All the findings show that it is the noradrenergic beta-receptor system of the septal nuclei that exerts a considerable effect on cortisol secretion.

Studies on the pathogenesis of fixed rabies virus in rats*

PubMed Central

Baer, G. M.; Shanthaveerappa, T. R.; Bourne, G. H.

1965-01-01

Investigations were made on the spread of fixed rabies virus after its inoculation into the rear foot-pads of rats. The presence of rabies virus in the central nervous system was first detected in the lumbar segment of the spinal cord. Removal of the sciatic nerve or of its fasciculus, either before or soon after challenge, drastically lowered mortality, thus giving evidence of a rapid neural spread of the infection. Neither the perineural structures nor the axons appeared to be involved. Although the presence of virus in the sciatic nerves was first demonstrated by the development of neutralizing antibodies in the serum of rats ”immunized” by multiple injections of nerve material from rats killed 48 hours after challenge, resection of nerves had to be carried out long before that time to be effective in preventing viral progression. ImagesFIG. 1FIG. 2-5 PMID:5295402

Central nervous system involvement in eosinophilic granulomatosis with polyangiitis (Churg-Strauss): Report of 26 patients and review of the literature.

PubMed

André, Raphaël; Cottin, Vincent; Saraux, Jean-Luc; Blaison, Gilles; Bienvenu, Boris; Cathebras, Pascal; Dhote, Robin; Foucher, Aurélie; Gil, Helder; Lapoirie, Joëlle; Launay, David; Loustau, Valentine; Maurier, François; Pertuiset, Edouard; Zénone, Thierry; Seebach, Jörg; Costedoat-Chalumeau, Nathalie; Puéchal, Xavier; Mouthon, Luc; Guillevin, Loïc; Terrier, Benjamin

2017-09-01

Although peripheral nervous system involvement is common in eosinophilic granulomatosis with polyangiitis (EGPA), central nervous system (CNS) manifestations are poorly described. This study aimed to describe CNS involvement in EGPA. This retrospective, observational, multicenter study included patients with EGPA and CNS involvement affecting cranial nerves, brain and/or spinal cord. We also undertook a systematic literature review. We analyzed 26 personal cases and 62 previously reported cases. At EGPA diagnosis, asthma was noted in 97%, eosinophilia in 98%, peripheral neuropathy in 55% and cardiac involvement in 41%. 38/71 (54%) were ANCA-positive, with a perinuclear-labeling pattern and/or anti-MPO specificity. CNS was involved in 86% at EGPA diagnosis, preceded EGPA in 2%, and occurred during follow-up in 12% after a median of 24months. Main neurological manifestations were ischemic cerebrovascular lesions in 46 (52%), intracerebral hemorrhage and/or subarachnoid hemorrhage in 21 (24%), loss of visual acuity in 28 (33%) (15 with optic neuritis, 9 with central retinal artery occlusion, 4 with cortical blindness), and cranial nerves palsies in 18 (21%), with 25 patients having ≥1 of these clinical CNS manifestations. Among the 81 patients with assessable neurological responses, 43% had complete responses without sequelae, 43% had partial responses with long-term sequelae and 14% refractory disease. After a mean follow-up of 36months, 11 patients died including 5 from intracerebral hemorrhages. EGPA-related CNS manifestations form 4 distinct neurological pictures: ischemic lesions, intracerebral hemorrhages, cranial nerve palsies and loss of visual acuity. Such manifestation should prompt practitioners to consider EGPA in such conditions. Long-term neurological sequelae were common, and intracerebral hemorrhages had the worst prognostic impact. Copyright © 2017 Elsevier B.V. All rights reserved.

Crosstalk between p38, Hsp25 and Akt in spinal motor neurons after sciatic nerve injury

NASA Technical Reports Server (NTRS)

Murashov, A. K.; Ul Haq, I.; Hill, C.; Park, E.; Smith, M.; Wang, X.; Wang, X.; Goldberg, D. J.; Wolgemuth, D. J.

2001-01-01

The p38 stress-activated protein kinase pathway is involved in regulation of phosphorylation of Hsp25, which in turn regulates actin filament dynamic in non-neuronal cells. We report that p38, Hsp25 and Akt signaling pathways were specifically activated in spinal motor neurons after sciatic nerve axotomy. The activation of the p38 kinase was required for induction of Hsp25 expression. Furthermore, Hsp25 formed a complex with Akt, a member of PI-3 kinase pathway that prevents neuronal cell death. Together, our observations implicate Hsp25 as a central player in a complex system of signaling that may both promote regeneration of nerve fibers and prevent neuronal cell death in the injured spinal cord.

Neural control of the kidney: functionally specific renal sympathetic nerve fibers.

PubMed

DiBona, G F

2000-11-01

The sympathetic nervous system provides differentiated regulation of the functions of various organs. This differentiated regulation occurs via mechanisms that operate at multiple sites within the classic reflex arc: peripherally at the level of afferent input stimuli to various reflex pathways, centrally at the level of interconnections between various central neuron pools, and peripherally at the level of efferent fibers targeted to various effectors within the organ. In the kidney, increased renal sympathetic nerve activity regulates the functions of the intrarenal effectors: the tubules, the blood vessels, and the juxtaglomerular granular cells. This enables a physiologically appropriate coordination between the circulatory, filtration, reabsorptive, excretory, and renin secretory contributions to overall renal function. Anatomically, each of these effectors has a dual pattern of innervation consisting of a specific and selective innervation by unmyelinated slowly conducting C-type renal sympathetic nerve fibers in addition to an innervation that is shared among all the effectors. This arrangement permits the maximum flexibility in the coordination of physiologically appropriate responses of the tubules, the blood vessels, and the juxtaglomerular granular cells to a variety of homeostatic requirements.

Functionally specific renal sympathetic nerve fibers: role in cardiovascular regulation.

PubMed

DiBona, G F

2001-06-01

The sympathetic nervous system provides differentiated regulation of the functions of various organs. This differentiated regulation occurs through mechanisms that operate at multiple sites within the classic reflex arc: peripherally at the level of afferent input stimuli to various reflex pathways, centrally at the level of interconnections between various central neuron pools, and peripherally at the level of efferent fibers targeted to various effectors within the organ. In the kidney, increased renal sympathetic nerve activity regulates the functions of the intrarenal effectors: the tubules, the blood vessels, and the juxtaglomerular granular cells. This enables a physiologically appropriate coordination between the circulatory, filtration, reabsorptive, excretory, and renin secretory contributions to overall renal function. Anatomically, each of these effectors has a dual pattern of innervation consisting of a specific and selective innervation by unmyelinated slowly conducting C-type renal sympathetic nerve fibers and an innervation that is shared among all the effectors. This arrangement facilitates maximum flexibility in the coordination of the tubules, the blood vessels, and the juxtaglomerular granular cells so as to produce physiologically appropriate responses to a variety of homeostatic requirements.

Extrinsic nerves are not involved in branchial 5-HT dynamics or pulsatile urea excretion in Gulf toadfish, Opsanus beta.

PubMed

Cartolano, Maria C; Amador, Molly H B; Tzaneva, Velislava; Milsom, William K; McDonald, M Danielle

2017-12-01

Gulf toadfish (Opsanus beta) can switch from continuously excreting ammonia as their primary nitrogenous waste to excreting predominantly urea in distinct pulses. Previous studies have shown that the neurotransmitter serotonin (5-HT) is involved in controlling this process, but it is unknown if 5-HT availability is under central nervous control or if the 5-HT signal originates from a peripheral source. Following up on a previous study, cranial nerves IX (glossopharyngeal) and X (vagus) were sectioned to further characterize their role in controlling pulsatile urea excretion and 5-HT release within the gill. In contrast to an earlier study, nerve sectioning did not result in a change in urea pulse frequency. Total urea excretion, average pulse size, total nitrogen excretion, and percent ureotely were reduced the first day post-surgery in nerve-sectioned fish but recovered by 72h post-surgery. Nerve sectioning also had no effect on toadfish urea transporter (tUT), 5-HT transporter (SERT), or 5-HT 2A receptor mRNA expression or 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) abundance in the gill, all of which were found consistently across the three gill arches except 5-HIAA, which was undetectable in the first gill arch. Our findings indicate that the central nervous system does not directly control pulsatile urea excretion or local changes in gill 5-HT and 5-HIAA abundance. Copyright © 2017 Elsevier Inc. All rights reserved.

Pan-brachial plexus neuropraxia following lightning: A rare case report.

PubMed

Patnaik, Ashis; Mahapatra, Ashok Kumar; Jha, Menka

2015-01-01

Neurological complications following lightning are rare and occur in form of temporary neurological deficits of central origin. Involvement of peripheral nervous system is extremely rare and only a few cases have been described in the literature. Isolated unilateral pan-brachial plexus neuropraxia has never been reported in the literature. Steroids have long been used for treatment of neuropraxia. However, their use in lightning neural injury is unique and requires special mention. We report a rare case of lightning-induced unilateral complete flaccid paralysis along with sensory loss in a young patient. Lightning typically causes central nervous involvement in various types of motor and sensory deficit. Surprisingly, the nerve conduction study showed the involvement of peripheral nervous system involvement. Steroids were administered and there was significant improvement in neurological functions within a short span of days. Patients' functions in the affected limb were normal in one month. Our case was interesting since it is the first such case in the literature where lightning has caused such a rare instance of unilateral pan-brachial plexus lesion. Such cases when seen, raises the possibility of more common central nervous system pathology rather than peripheral involvement. However, such lesions can be purely benign forms of peripheral nerve neuropraxia, which can be managed by steroid treatment without leaving any long-term neurological deficits.

The respiratory system.

PubMed

Zifko, U; Chen, R

1996-10-01

Neurological disorders frequently contribute to respiratory failure in critically ill patients. They may be the primary reason for the initiation of mechanical ventilation, or may develop later as a secondary complication. Disorders of the central nervous system leading to respiratory failure include metabolic encephalopathies, acute stroke, lesions of the motor cortex and brain-stem respiratory centres, and their descending pathways. Guillan-Barré syndrome, critical illness polyneuropathy and acute quadriplegic myopathy are the more common neuromuscular causes of respiratory failure. Clinical observations and pulmonary function tests are important in monitoring respiratory function. Respiratory electrophysiological studies are useful in the investigation and monitoring of respiratory failure. Transcortical and cervical magnetic stimulation can assess the central respiratory drive, and may be useful in determining the prognosis in ventilated patients, with cervical cord dysfunction. It is also helpful in the assessment of failure to wean, which is often caused by a combination of central and peripheral nervous system disorders. Phrenic nerve conduction studies and needle electromyography of the diaphragm and chest wall muscles are useful to characterize neuropathies and myopathies affecting the diaphragm. Repetitive phrenic nerve stimulation can assess neuromuscular transmission defects. It is important to identify patients at risk of respiratory failure. They should be carefully monitored and mechanical ventilation should be initiated before the development of severe hypoxaemia.

Seasonal meningoencephalitis in Holstein cattle caused by Naegleria fowleri.

PubMed

Daft, Barbara M; Visvesvara, Govinda S; Read, Deryck H; Kinde, Hailu; Uzal, Francisco A; Manzer, Michael D

2005-11-01

Primary amoebic meningoencephalitis is a fulminant infection of the human central nervous system caused by Naegleria fowleri, a free-living amoeba that thrives in artificially or naturally heated water. The infection usually is acquired while bathing or swimming in such waters. The portal of entry is the olfactory neuroepithelium. This report describes fatal meningoencephalitis caused by N. fowleri in Holstein cattle that consumed untreated surface water in an area of California where summer temperatures at times exceed 42 degrees C. In the summers of 1998 and 1999, severe multifocal necrosuppurative hemorrhagic meningoencephalitis was observed in brain samples from nine 10-20-month-old heifers with clinical histories of acute central nervous system disease. Olfactory lobes and cerebella were most severely affected. Lesions were also evident in periventricular and submeningeal neuropil as well as olfactory nerves. Naegleria fowleri was demonstrated by immunohistochemistry in brain and olfactory nerve lesions and was isolated from one brain. Even though cultures of drinking water did not yield N. fowleri, drinking water was the likely source of the amoeba. The disease in cattle closely resembles primary amoebic meningoencephalitis in humans. Naegleria meningoencephalitis should be included among differential diagnoses of central nervous system disease in cattle during the summer season in areas with high ambient temperatures.

The complex simplicity of the brittle star nervous system.

PubMed

Zueva, Olga; Khoury, Maleana; Heinzeller, Thomas; Mashanova, Daria; Mashanov, Vladimir

2018-01-01

Brittle stars (Ophiuroidea, Echinodermata) have been increasingly used in studies of animal behavior, locomotion, regeneration, physiology, and bioluminescence. The success of these studies directly depends on good working knowledge of the ophiuroid nervous system. Here, we describe the arm nervous system at different levels of organization, including the microanatomy of the radial nerve cord and peripheral nerves, ultrastructure of the neural tissue, and localization of different cell types using specific antibody markers. We standardize the nomenclature of nerves and ganglia, and provide an anatomically accurate digital 3D model of the arm nervous system as a reference for future studies. Our results helped identify several general features characteristic to the adult echinoderm nervous system, including the extensive anatomical interconnections between the ectoneural and hyponeural components, neuroepithelial organization of the central nervous system, and the supporting scaffold of the neuroepithelium formed by radial glial cells. In addition, we provide further support to the notion that the echinoderm radial glia is a complex and diverse cell population. We also tested the suitability of a range of specific cell-type markers for studies of the brittle star nervous system and established that the radial glial cells are reliably labeled with the ERG1 antibodies, whereas the best neuronal markers are acetylated tubulin, ELAV, and synaptotagmin B. The transcription factor Brn1/2/4 - a marker of neuronal progenitors - is expressed not only in neurons, but also in a subpopulation of radial glia. For the first time, we describe putative ophiuroid proprioceptors associated with the hyponeural part of the central nervous system. Together, our data help establish both the general principles of neural architecture common to the phylum Echinodermata and the specific ophiuroid features.

Gross anatomy and development of the peripheral nervous system.

PubMed

Catala, Martin; Kubis, Nathalie

2013-01-01

The nervous system is divided into the central nervous system (CNS) composed of the brain, the brainstem, the cerebellum, and the spinal cord and the peripheral nervous system (PNS) made up of the different nerves arising from the CNS. The PNS is divided into the cranial nerves III to XII supplying the head and the spinal nerves that supply the upper and lower limbs. The general anatomy of the PNS is organized according to the arrangement of the fibers along the rostro-caudal axis. The control of the development of the PNS has been unravelled during the last 30 years. Motor nerves arise from the ventral neural tube. This ventralization is induced by morphogenetic molecules such as sonic hedgehog. In contrast, the sensory elements of the PNS arise from a specific population of cells originating from the roof of the neural tube, namely the neural crest. These cells give rise to the neurons of the dorsal root ganglia, the autonomic ganglia and the paraganglia including the adrenergic neurons of the adrenals. Furthermore, the supportive glial Schwann cells of the PNS originate from the neural crest cells. Growth factors as well as myelinating proteins are involved in the development of the PNS. Copyright © 2013 Elsevier B.V. All rights reserved.

Aromatherapy and the central nerve system (CNS): therapeutic mechanism and its associated genes.

PubMed

Lv, Xiao Nan; Liu, Zhu Jun; Zhang, Huan Jing; Tzeng, Chi Meng

2013-07-01

Molecular medical research on aromatherapy has been steadily increasing for use as an adjuvant therapy in managing psychiatric disorders and to examine its therapeutic mechanisms. Most studies, as well as clinically applied experience, have indicated that various essential oils, such as lavender, lemon and bergamot can help to relieve stress, anxiety, depression and other mood disorders. Most notably, inhalation of essential oils can communicate signals to the olfactory system and stimulate the brain to exert neurotransmitters (e.g. serotonin and dopamine) thereby further regulating mood. However, little research has been done on the molecular mechanisms underlying these effects, thus their mechanism of action remains ambiguous. Several hypotheses have been proposed regarding the therapeutic mechanism of depression. These have mainly centered on possible deficiencies in monoamines, neurotrophins, the neuroendocrine system, c-AMP, cation channels as well as neuroimmune interactions and epigenetics, however the precise mechanism or mechanisms related to depression have yet to be elucidated. In the current study, the effectiveness of aromatherapy for alleviating psychiatric disorders was examined using data collected from previously published studies and our unpublished data. A possible signaling pathway from olfactory system to the central nerve system and the associated key molecular elements of aromatherapy are also proposed.

Whole-central nervous system functional imaging in larval Drosophila

PubMed Central

Lemon, William C.; Pulver, Stefan R.; Höckendorf, Burkhard; McDole, Katie; Branson, Kristin; Freeman, Jeremy; Keller, Philipp J.

2015-01-01

Understanding how the brain works in tight concert with the rest of the central nervous system (CNS) hinges upon knowledge of coordinated activity patterns across the whole CNS. We present a method for measuring activity in an entire, non-transparent CNS with high spatiotemporal resolution. We combine a light-sheet microscope capable of simultaneous multi-view imaging at volumetric speeds 25-fold faster than the state-of-the-art, a whole-CNS imaging assay for the isolated Drosophila larval CNS and a computational framework for analysing multi-view, whole-CNS calcium imaging data. We image both brain and ventral nerve cord, covering the entire CNS at 2 or 5 Hz with two- or one-photon excitation, respectively. By mapping network activity during fictive behaviours and quantitatively comparing high-resolution whole-CNS activity maps across individuals, we predict functional connections between CNS regions and reveal neurons in the brain that identify type and temporal state of motor programs executed in the ventral nerve cord. PMID:26263051

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.

Evaluating the evidence: is phrenic nerve stimulation a safe and effective tool for decreasing ventilator dependence in patients with high cervical spinal cord injuries and central hypoventilation?

PubMed

Sieg, Emily P; Payne, Russell A; Hazard, Sprague; Rizk, Elias

2016-06-01

Case reports, case series and case control studies have looked at the use of phrenic nerve stimulators in the setting of high spinal cord injuries and central hypoventilation syndromes dating back to the 1980s. We evaluated the evidence related to this topic by performing a systematic review of the published literature. Search terms "phrenic nerve stimulation," "phrenic nerve and spinal cord injury," and "phrenic nerve and central hypoventilation" were entered into standard search engines in a systematic fashion. Articles were reviewed by two study authors and graded independently for class of evidence according to published guidelines. The published evidence was reviewed, and the overall body of evidence was evaluated using the grading of recommendations, assesment, development and evaluations (GRADE) criteria Balshem et al. (J Clin Epidemiol 64:401-406, 2011). Our initial search yielded 420 articles. There were no class I, II, or III studies. There were 18 relevant class IV articles. There were no discrepancies among article ratings (i.e., kappa = 1). A meta-analysis could not be performed due to the low quality of the available evidence. The overall quality of the body of evidence was evaluated using GRADE criteria and fell within the "very poor" category. The quality of the published literature for phrenic nerve stimulation is poor. Our review of the literature suggests that phrenic nerve stimulation is a safe and effective option for decreasing ventilator dependence in high spinal cord injuries and central hypoventilation; however, we are left with critical questions that provide crucial directions for future studies.

Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen.

PubMed

Braak, H; Rüb, U; Gai, W P; Del Tredici, K

2003-05-01

The progressive, neurodegenerative process underlying idiopathic Parkinson's disease is associated with the formation of proteinaceous inclusion bodies that involve a few susceptible neuronal types of the human nervous system. In the lower brain stem, the process begins in the dorsal motor nucleus of the vagus nerve and advances from there essentially upwards through susceptible regions of the medulla oblongata, pontine tegmentum, midbrain, and basal forebrain until it reaches the cerebral cortex. With time, multiple components of the autonomic, limbic, and motor systems become severely impaired. All of the vulnerable subcortical grays and cortical areas are closely interconnected. Incidental cases of idiopathic Parkinson's disease may show involvement of both the enteric nervous system and the dorsal motor nucleus of the vagus nerve. This observation, combined with the working hypothesis that the stereotypic topographic expansion pattern of the lesions may resemble that of a falling row of dominos, prompts the question whether the disorder might originate outside of the central nervous system, caused by a yet unidentified pathogen that is capable of passing the mucosal barrier of the gastrointestinal tract and, via postganglionic enteric neurons, entering the central nervous system along unmyelinated praeganglionic fibers generated from the visceromotor projection cells of the vagus nerve. By way of retrograde axonal and transneuronal transport, such a causative pathogen could reach selectively vulnerable subcortical nuclei and, unimpeded, gain access to the cerebral cortex. The here hypothesized mechanism offers one possible explanation for the sequential and apparently uninterrupted manner in which vulnerable brain regions, subcortical grays and cortical areas become involved in idiopathic Parkinson's disease.

Penetration of blood-brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system.

PubMed

Zou, Dan; Wang, Wei; Lei, Daoxi; Yin, Ying; Ren, Peng; Chen, Jinju; Yin, Tieying; Wang, Bochu; Wang, Guixue; Wang, Yazhou

2017-01-01

For the treatment of glioma and other central nervous system diseases, one of the biggest challenges is that most therapeutic drugs cannot be delivered to the brain tumor tissue due to the blood-brain barrier (BBB). The goal of this study was to construct a nanodelivery vehicle system with capabilities to overcome the BBB for central nervous system administration. Doxorubicin as a model drug encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading efficiency and 97.05% encapsulation efficiency by orthogonal experimental design. The in vitro study demonstrated a slow and sustainable drug release in physiological conditions. In the cellular uptake studies, mixed micelles could effectively transport into both human umbilical vein endothelial cells and C6 cells. Furthermore, biodistribution imaging of mice showed that the DiR/GM1 mixed micelles were accumulated sustainably and distributed centrally in the brain. Experiments on zebrafish confirmed that drug-loaded GM1 micelles can overcome the BBB and enter the brain. Among all the treatment groups, the median survival time of C6-bearing rats after administering DOX/GM1 micelles was significantly prolonged. In conclusion, the ganglioside nanomicelles developed in this work can not only penetrate BBB effectively but also repair nerves and kill tumor cells at the same time.

Extraocular Muscles in Patients With Infantile Nystagmus

PubMed Central

Berg, Kathleen T.; Hunter, David G.; Bothun, Erick D.; Antunes-Foschini, Rosalia; McLoon, Linda K.

2013-01-01

Objective To test the hypothesis that the extraocular muscles (EOMs) of patients with infantile nystagmus have muscular and innervational adaptations that may have a role in the involuntary oscillations of the eyes. Methods Specimens of EOMs from 10 patients with infantile nystagmus and postmortem specimens from 10 control subjects were prepared for histologic examination. The following variables were quantified: mean myofiber cross-sectional area, myofiber central nucleation, myelinated nerve density, nerve fiber density, and neuromuscular junction density. Results In contrast to control EOMs, infantile nystagmus EOMs had significantly more centrally nucleated myofibers, consistent with cycles of degeneration and regeneration. The EOMs of patients with nystagmus also had a greater degree of heterogeneity in myofiber size than did those of controls, with no difference in mean myofiber cross-sectional area. Mean myelinated nerve density, nerve fiber density, and neuromuscular junction density were also significantly decreased in infantile nystagmus EOMs. Conclusions The EOMs of patients with infantile nystagmus displayed a distinct hypoinnervated phenotype. This represents the first quantification of changes in central nucleation and myofiber size heterogeneity, as well as decreased myelinated nerve, nerve fiber, and neuromuscular junction density. These results suggest that deficits in motor innervation are a potential basis for the primary loss of motor control. Clinical Relevance Improved understanding of the etiology of nystagmus may direct future diagnostic and treatment strategies. PMID:22411664

IN VITRO RESEARCH OF THE ALTERATION OF NEURONS IN VAGAL CORE IN MEDULLA OBLONGATA AT ASPHYXIC DEATHS

PubMed Central

Haliti, Naim; Islami, Hilmi; Elezi, Nevzat; Shabani, Ragip; Abdullahu, Bedri; Dragusha, Gani

2010-01-01

The aim of this study was to research the morphological changes of neurons in the vagus nerve nuclei in medulla oblongata in asphyxia related death cases. Morphological changes that were investigated were mainly in the dorsal motor respiratory center (DMRC), nucleus tractus solitarius (nTS) and nucleus ambigus (nA) in the medulla oblongata. In our research, the autopsy material from asphyxia related death cases was used from various etiologies: monoxide carbon (CO), liquid drowning, strangulation, electricity, clinical-pathological death, firing weapon, explosive weapon, sharp and blunt objects and death cases due to accident. The material selected for research was taken from medulla oblongata and lungs from all lobes. The material from the medulla oblongata and lungs was fixed in a 10% solution of buffered formalin. Special histochemical methods for central nervous system (CNS) were employed like: Cresyl echt violet, toluidin blue, Sevier-Munger modification and Grimelius. For stereometrical analysis of the quantitative density of the neurons the universal testing system Weibel M42 was used. The acquired results show that in sudden asphyxia related death cases, there are alterations in the nuclei of vagal nerve in form of: central chromatolysis, axonal retraction, axonal fragmentation, intranuclear vacuolization, cytoplasmic vacuolization, edema, condensation and dispersion of substance of Nissl, proliferation of oligodendrocytes, astrocytes and microglia. The altered population of vagus nerve neurons does not show an important statistica! significarne compared to the overall quantity of the neurons in the nuclei of the vagus nerve (p<0,05). PMID:20846134

A novel histochemical method of simultaneous detection by a single- or double-immunofluorescence and Bielschowsky's silver staining in teased rat sciatic nerves.

PubMed

Segura-Anaya, Edith; Flores-Miranda, Rommel; Martínez-Gómez, Alejandro; Dent, Myrna A R

2018-07-01

The Golgi silver method has been widely used in neuroscience for the study of normal and pathological morphology of neurons. The method has been steadily improved and Bielschowsky's silver staining method (BSSM) is widely used in various pathological conditions, like Alzheimer's disease. In this work, teased sciatic nerves were silver impregnated using BSSM. We also developed simultaneous staining by silver impregnation and single- or double-immunofluorescence of the same section in teased nerve preparations. We immunostained against non-myelinating Schwann cells and different myelinating Schwann cell domains. BSSM teased nerves show a strong staining of axons (black) and a gold-brown staining of myelinating and non-myelinating Schwann cells. We were also able to stain by immunofluorescence these BSSM teased nerves with specific molecular markers against non-myelinating Schwann cells, also against non-compact myelin such as the Schmidt-Lanterman incisures or paranodal regions and compact myelin, but not axons. In peripheral nerves, several silver impregnation methods have been used to stain nerves in paraffin sections, but not in teased nerves to enable the assessment of isolated nerve fibers. In conclusion, BSSM gives accurate information of nerve morphology and combining the procedure with immunofluorescence it would be very useful to study the molecular nerve domain organization of the nerve fibers, and to study the molecular pathology of axon degeneration, or myelin disorders, or of any peripheral neuropathy, also to study demyelination diseases in the central nervous system. Copyright © 2018. Published by Elsevier B.V.

Effects of pelvic, pudendal, or hypogastric nerve cuts on Fos induction in the rat brain following vaginocervical stimulation.

PubMed

Pfaus, James G; Manitt, Colleen; Coopersmith, Carol B

2006-12-30

In the female rat, genitosensory input is conveyed to the central nervous system predominantly through the pelvic, pudendal, and hypogastric nerves. The present study examined the relative contribution of those three nerves in the expression of Fos immunoreactivity within brain regions previously shown to be activated by vaginocervical stimulation (VCS). Bilateral transection of those nerves, or sham neurectomy, was conducted in separate groups of ovariectomized, sexually-experienced females. After recovery, females were primed with estrogen and progesterone and given either 50 manual VCSs with a lubricated glass rod over the course of 1 h. VCS increased the number of neurons expressing Fos immunoreactivity in the medial preoptic area, lateral septum, bed nucleus of the stria terminalis, ventromedial hypothalamus, and medial amygdala of sham neurectomized females. Transection of the pelvic nerve reduced Fos immunoreactivity in the medial preoptic area, bed nucleus of the stria terminalis, ventromedial hypothalamus, and medial amygdala, whereas transection of the pudendal nerve had no effect. In contrast, transection of the hypogastric nerve increased Fos immunoreactivity in the medial preoptic area and lateral septum, whereas transaction of the pelvic nerve increased Fos immunoreactivity in the lateral septum, following VCS. All females given VCS, except those with pelvic neurectomy, displayed a characteristic immobility during each application. These data confirm that the pelvic nerve is largely responsible for the neural and behavioral effects of VCS, and support a separate function for the hypogastric nerve.

A history of the optic nerve and its diseases.

PubMed

Reeves, C; Taylor, D

2004-11-01

We will trace the history of ideas about optic nerve anatomy and function in the Western world from the ancient Greeks to the early 20th century and show how these influenced causal theories of optic nerve diseases. Greek and Roman humoral physiology needed a hollow optic nerve, the obstruction of which prevented the flow of visual spirit to and from the brain and resulted in blindness. Medieval physicians understood that the presence of a fixed dilated pupil indicated optic nerve obstruction, preventing the passage of visual spirit, and that cataract surgery in such cases would not restore sight. During the Renaissance, the organ of vision was transferred from the lens to the optic nerve, which was generally believed to be on the axis of the eye. The acuity of central vision (at the optic disc) was explained by the concentration of visual spirit where the optic nerve met the retina. The growth of anatomy and influence of mechanical philosophy from the 17th century led to visual spirit being replaced with the concept of nerve force, which later became associated with electricity travelling along nerve fibres. This coincided with discourse about the nature of the nervous system and a shift in orientation from understanding illness holistically in terms of an individual's humoral imbalance to the concept of organ-based diseases. Both the microscope and the ophthalmoscope allowed visualisation of the optic nerve, but problems of interpretation persisted until conceptual transformations in medical science were made.

Ocular Nerve Growth Factor (NGF) and NGF Eye Drop Application as Paradigms to Investigate NGF Neuroprotective and Reparative Actions.

PubMed

Tirassa, Paola; Rosso, Pamela; Iannitelli, Angela

2018-01-01

The eye is a central nervous system structure that is uniquely accessible to local treatment. Through the ocular surface, it is possible to access the retina, optic nerve, and brain. Animal models of retina degeneration or optic nerve crush could thus serve as tools to investigate whether and how factors, which are anterogradely or retrogradely transported through the optic nerve, might contribute to activate neuroprotection and eventually regeneration. Among these factors, nerve growth factor (NGF) plays a crucial role during development of the visual system, as well as during the entire life span, and in pathological conditions. The ability of NGF to exert survival and trophic actions on the retina and brain cells when applied intraocularly and topically as eye drops is critically reviewed here, together with the effects of ocular neurotrophins on neuronal pathways influencing body rhythm, cognitions, and behavioral functions. The latest data from animal models and humans are presented, and the mechanism of action of ocularly administered NGF is discussed. NGF eye drops are proposed as an experimental strategy to investigate the role and cellular targets of neurotrophins in the mechanism(s) underlying neurodegeneration/regeneration and their involvement in the regulation of neurological and behavioral dysfunctions.

Calpains mediate axonal cytoskeleton disintegration during Wallerian degeneration

PubMed Central

Ma, Marek; Ferguson, Toby A.; Schoch, Kathleen M.; Li, Jian; Qian, Yaping; Shofer, Frances S.; Saatman, Kathryn E.; Neumar, Robert W.

2013-01-01

In both the central nervous system (CNS) and peripheral nervous system (PNS), transected axons undergo Wallerian degeneration. Even though Augustus Waller first described this process after transection of axons in 1850, the molecular mechanisms may be shared, at least in part, by many human diseases. Early pathology includes failure of synaptic transmission, target denervation, and granular disintegration of the axonal cytoskeleton (GDC). The Ca2+-dependent proteases calpains have been implicated in GDC but causality has not been established. To test the hypothesis that calpains play a causal role in axonal and synaptic degeneration in vivo, we studied transgenic mice that express human calpastatin (hCAST), the endogenous calpain inhibitor, in optic and sciatic nerve axons. Five days after optic nerve transection and 48 hours after sciatic nerve transection, robust neurofilament proteolysis observed in wild-type controls was reduced in hCAST transgenic mice. Protection of the axonal cytoskeleton in sciatic nerves of hCAST mice was nearly complete 48 hours post-transection. In addition, hCAST expression preserved the morphological integrity of neuromuscular junctions. However, compound muscle action potential amplitudes after nerve transection were similar in wild-type and hCAST mice. These results, in total, provide direct evidence that calpains are responsible for the morphological degeneration of the axon and synapse during Wallerian degeneration. PMID:23542511

Vocal cord collapse during phrenic nerve-paced respiration in congenital central hypoventilation syndrome.

PubMed

Domanski, Mark C; Preciado, Diego A

2012-01-01

Phrenic nerve pacing can be used to treat congenital central hypoventilation syndrome (CCHS). We report how the lack of normal vocal cord tone during phrenic paced respiration can result in passive vocal cord collapse and produce obstructive symptoms. We describe a case of passive vocal cord collapse during phrenic nerve paced respiration in a patient with CCHS. As far as we know, this is the first report of this etiology of airway obstruction. The patient, a 7-year-old with CCHS and normal waking vocal cord movement, continued to require nightly continuous positive airway pressure (CPAP) despite successful utilization of phrenic nerve pacers. On direct laryngoscopy, the patient's larynx was observed while the diaphragmatic pacers were sequentially engaged. No abnormal vocal cord stimulation was witnessed during engaging of either phrenic nerve stimulator. However, the lack of normal inspiratory vocal cord abduction during phrenic nerve-paced respiration resulted in vocal cord collapse and partial obstruction due to passive adduction of the vocal cords through the Bernoulli effect. Bilateral phrenic nerve stimulation resulted in more vocal cord collapse than unilateral stimulation. The lack of vocal cord abduction on inspiration presents a limit to phrenic nerve pacers.

Normative values for optical coherence tomography parameters in healthy children and interexaminer agreement for choroidal thickness measurements.

PubMed

Turan, Kadriye Erkan; Sekeroglu, Hande Taylan; Baytaroglu, Ata; Bezci, Figen; Karahan, Sevilay

2018-01-01

To (a) determine the normative values for optical coherence tomography (OCT) parameters such as central macular thickness, retinal nerve fiber layer thickness, and choroidal thickness in healthy children; (b) investigate the relationships of these parameters with axial length, central corneal thickness, refractive errors, and intraocular pressure; and (c) determine interexaminer agreement for choroidal thickness measurements. In this cross-sectional study, 120 healthy children aged 8-15 years underwent detailed ophthalmological examination and OCT measurements. Choroidal thickness was measured at three separate locations by two independent examiners. The mean global retinal nerve fiber layer thickness was 98.75 ± 9.45 μm (79.0-121.0). The mean central macular thickness was 232.29 ± 29.37 μm (190.0-376.0). The mean subfoveal choroidal thickness obtained by examiner 1 was 344.38 ± 68.83 μm and that obtained by examiner 2 was 344.04 ± 68.92 μm. Interexaminer agreement was between 99.6%-99.8% for choroidal thickness at three separate locations. Central macular thickness increased with axial length (r=0.245, p=0.007). Choroidal thickness increased with age (r=0.291, p=0.001) and decreased with axial length (r=-0.191, p=0.037). Global retinal nerve fiber layer thickness decreased with axial length (r=-0.247, p=0.007) and increased with central corneal thickness (r=0.208, p=0.022). Global retinal nerve fiber layer thickness positively correlated with choroidal thickness (r=0.354, p<0.001). Global retinal nerve fiber layer thickness (r=0.223, p=0.014) and choroidal thickness (r=0.272, p=0.003) increased with the spherical equivalent (D). Optical coherence tomography parameters showed a wide range of variability in children. Retinal nerve fiber layer thickness, central macular thickness, and choroidal thickness were found to be either inter-related or correlated with age, central corneal thickness, axial length, and refractive errors. Furthermore, manual measurements of choroidal thickness showed high interexaminer agreement. Because normative values for optical coherence tomography parameters differed in children, the measurements should be interpreted according to an age-appropriate database.

Efficacy and safety of nerve growth factor for the treatment of neurological diseases: a meta-analysis of 64 randomized controlled trials involving 6,297 patients

PubMed Central

Zhao, Meng; Li, Xiao-yan; Xu, Chun-ying; Zou, Li-ping

2015-01-01

OBJECTIVE: China is the only country where nerve growth factor is approved for large-scale use as a clinical medicine. More than 10 years ago, in 2003, nerve growth factor injection was listed as a national drug. The goal of this article is to evaluate comprehensively the efficacy and safety of nerve growth factor for the treatment of neurological diseases. DATA RETRIEVAL: A computer-based retrieval was performed from six databases, including the Cochrane Library, PubMed, EMBASE, Sino Med, CNKI, and the VIP database, searching from the clinical establishment of nerve growth factor for treatment until December 31, 2013. The key words for the searches were “nerve growth factor, randomized controlled trials” in Chinese and in English. DATA SELECTION: Inclusion criteria: any study published in English or Chinese referring to randomized controlled trials of nerve growth factor; patients with neurological diseases such as peripheral nerve injury, central nerve injury, cranial neuropathy, and nervous system infections; patients older than 7 years; similar research methods and outcomes assessing symptoms; and measurement of nerve conduction velocities. The meta-analysis was conducted using Review Manager 5.2.3 software. MAIN OUTCOME MEASURES: The total effective rate, the incidence of adverse effects, and the nerve conduction velocity were recorded for each study. RESULTS: Sixty-four studies involving 6,297 patients with neurological diseases were included. The total effective rate in the group treated with nerve growth factor was significantly higher than that in the control group (P < 0.0001, RR: 1.35, 95%CI: 1.30–1.40). The average nerve conduction velocity in the nerve growth factor group was significantly higher than that in the control group (P < 0.00001, MD: 4.59 m/s, 95%CI: 4.12–5.06). The incidence of pain or scleroma at the injection site in the nerve growth factor group was also higher than that in the control group (P < 0.00001, RR: 6.30, 95%CI: 3.53–11.27), but such adverse effects were mild. CONCLUSION: Nerve growth factor can significantly improve nerve function in patients with nervous system disease and is safe and effective. PMID:26109961

Pharmacological actions of Uncaria alkaloids, rhynchophylline and isorhynchophylline.

PubMed

Shi, Jing-Shan; Yu, Jun-Xian; Chen, Xiu-Ping; Xu, Rui-Xia

2003-02-01

The pharmacological actions of Uncaria alkaloids, rhynchophylline and isorhynchophylline extracted from Uncaria rhynchophylla Miq Jacks were reviewed. The alkaloids mainly act on cardiovascular system and central nervous system including the hypotension, brachycardia, antiarrhythmia, and protection of cerebral ischemia and sedation. The active mechanisms were related to blocking of calcium channel, opening of potassium channel, and regulating of nerve transmitters transport and metabolism, etc.

A novel PLP1 mutation associated with optic nerve enlargement in two siblings with Pelizaeus-Merzbacher disease: A new MRI finding.

PubMed

Pavlidou, Efterpi; Ramachandran, Vijaya; Govender, Veronica; Wilson, Clare; Das, Rini; Vlachou, Victoria; Pavlou, Evangelos; Saggar, Anand; Mankad, Kshitij; Kinali, Maria

2017-03-01

Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked disorder characterized by hypomyelination of the Central Nervous System due to mutations in the PLP1 gene. Certain mutations of the PLP1 gene correlate with specific clinical phenotypes and neuroimaging findings. We herein report a novel mutation of the PLP1 gene in two siblings with PMD associated with a rare and protean neuroimaging finding of optic nerve enlargement. To the best of our knowledge this is the first time that this novel mutation H133P of PLP1 gene is identified and clinically associated with optic nerve enlargement in PMD patients. Copyright © 2016 The Japanese Society of Child Neurology. All rights reserved.

Neurosciences and research on chemical weapons of mass destruction in Nazi Germany.

PubMed

Schmaltz, Florian

2006-09-01

As a side-product of industrial research, new chemical nerve agents (Tabun, Sarin, Soman) superior to those available to the Allied Forces were discovered in Nazi Germany. These agents were never used by Germany, even though they were produced at a large scale. This article explores the toxicological and physiological research into the mechanisms of action of these novel nerve agents, and the emergence of military research objectives in neurophysiological and neurotoxicological research. Recently declassified Allied military intelligence files document secret nerve agent research, leading to intensified research on anticholinesterase agents in the peripheral and the central nervous system. The article discusses the involvement of IG Farben scientists, educational, medical and military institutions, and of Nobel Prize laureate Richard Kuhn, director of the Kaiser Wilhelm Institute for Medical Research.

Transvenous stimulation of the phrenic nerve for the treatment of central sleep apnoea: 12 months' experience with the remedē® System.

PubMed

Jagielski, Dariusz; Ponikowski, Piotr; Augostini, Ralph; Kolodziej, Adam; Khayat, Rami; Abraham, William T

2016-11-01

Patients with central sleep apnoea (CSA) often have poor quality of life and are at increased risk of morbidity and mortality. This study sought to evaluate the 12-month clinical outcomes of patients with CSA treated with unilateral transvenous phrenic nerve stimulation in the prospective, multicentre, non-randomized remedē ® System pilot study. Forty-seven patients with CSA were treated with the remedē ® System (Respicardia Inc., Minnetonka, MN, USA) for a minimum of 3 months. Sleep-disordered breathing parameters were evaluated by polysomnography (PSG) at 3, 6, and 12-month follow-up. Sleep symptoms and quality of life were also evaluated. Forty-one patients completed all follow-up PSGs and were included in the analysis. At 12 months, there was sustained improvement compared with baseline in the apnoea-hypopnoea index (49.9 ± 15.1 vs. 27.5 ± 18.3 events/h, P < 0.001) and central apnoea index (28.2 ± 15.0 vs. 6.0 ± 9.2 events/h, P < 0.001). Sustained improvement in the oxygen desaturation index (46.1 ± 19.1 vs. 26.9 ± 18.0 events/h, P < 0.001), rapid eye movement sleep (11.4 ± 6.1% vs. 17.1 ± 8.0%, P < 0.001), and sleep efficiency (69.3 ± 16.9% vs. 75.6 ± 17.1%, P = 0.024) were also observed. There were also continued favourable effects on sleepiness and quality of life. Three deaths unrelated to remedē ® System therapy and five serious adverse events occurred over 12 months of follow-up. The present study demonstrates that in patients with CSA, unilateral transvenous phrenic nerve stimulation is associated with sustained improvement in key sleep parameters, sleep symptoms, and quality of life over 12 months of follow-up. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage.

PubMed

He, Yifan; Zhu, Jihong; Huang, Fang; Qin, Liu; Fan, Wenguo; He, Hongwen

2014-11-15

The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory behaviors and structural changes in related brain regions, in a mouse model of Alzheimer's disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learning and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltransferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic fibers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no significant differences in histology or behavior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present findings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer's disease, and indicate that tooth extraction should be avoided in these populations.

The gustatory system of lampreys.

PubMed

Barreiro-Iglesias, Antón; Anadón, Ramón; Rodicio, María Celina

2010-01-01

The present is a review of the gustatory system of lampreys, which are representative of the earliest vertebrates. They are the oldest extant vertebrates that possess taste buds. Because of the phylogenetic position of lampreys, the study of their gustatory system will provide important information to help understand the early evolution of this system in vertebrates. The taste buds of larval lampreys, which are papillae located on the first six pairs of gill arches facing the water current, respond to classical taste substances. They consist of two types of tall differentiated cells, serotonergic biciliated taste receptors ('light' cells) and microvillous sustentacular cells ('dark cells'). The taste buds also contain basal proliferative cells. Afferent gustatory fibers of the glossopharyngeal and vagal nerves innervate the taste buds of lampreys and contact the basal surface of the biciliated cells without entering the bud. Central processes of the glossopharyngeal and vagal cranial nerves terminate in a caudal rhombencephalic region that may correspond to the nucleus of the solitary tract of gnathostomes. To date, most studies in lampreys have focused on characterizing taste buds; future research should focus on the central processing of the gustatory information. Here we will review the current knowledge about the gustatory system of lampreys to provide a basis for establishing the direction of further studies of this chemosensory system. Copyright 2010 S. Karger AG, Basel.

Olfactory nerve--a novel invasion route of Neisseria meningitidis to reach the meninges.

PubMed

Sjölinder, Hong; Jonsson, Ann-Beth

2010-11-18

Neisseria meningitidis is a human-specific pathogen with capacity to cause septic shock and meningitis. It has been hypothesized that invasion of the central nervous system (CNS) is a complication of a bacteremic condition. In this study, we aimed to characterize the invasion route of N. meningitidis to the CNS. Using an intranasally challenged mouse disease model, we found that twenty percent of the mice developed lethal meningitis even though no bacteria could be detected in blood. Upon bacterial infection, epithelial lesions and redistribution of intracellular junction protein N-cadherin were observed at the nasal epithelial mucosa, especially at the olfactory epithelium, which is functionally and anatomically connected to the CNS. Bacteria were detected in the submucosa of the olfactory epithelium, along olfactory nerves in the cribriform plate, at the olfactory bulb and subsequently at the meninges and subarachnoid space. Furthermore, our data suggest that a threshold level of bacteremia is required for the development of meningococcal sepsis. Taken together, N. meningitidis is able to pass directly from nasopharynx to meninges through the olfactory nerve system. This study enhances our understanding how N. meningitidis invades the meninges. The nasal olfactory nerve system may be a novel target for disease prevention that can improve outcome and survival.

Deficiency in Monocarboxylate Transporter 1 (MCT1) in Mice Delays Regeneration of Peripheral Nerves following Sciatic Nerve Crush

PubMed Central

Morrison, Brett M.; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Rothstein, Jeffrey D.

2014-01-01

Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence and MCT1 tdTomato BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves in MCT1 heterozygous null mice are crushed and peripheral nerve regeneration quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly through failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush. PMID:25447940

Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush.

PubMed

Morrison, Brett M; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H; Lengacher, Sylvain; Magistretti, Pierre J; Pellerin, Luc; Rothstein, Jeffrey D

2015-01-01

Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence in wild-type mice and tdTomato fluorescence in MCT1 BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves of MCT1 heterozygous null mice are crushed and peripheral nerve regeneration was quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly due to failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush. Copyright © 2014 Elsevier Inc. All rights reserved.

Recovery of the sub-basal nerve plexus and superficial nerve terminals after corneal epithelial injury in mice.

PubMed

Downie, Laura E; Naranjo Golborne, Cecilia; Chen, Merry; Ho, Ngoc; Hoac, Cam; Liyanapathirana, Dasun; Luo, Carol; Wu, Ruo Bing; Chinnery, Holly R

2018-06-01

Our aim was to compare regeneration of the sub-basal nerve plexus (SBNP) and superficial nerve terminals (SNT) following corneal epithelial injury. We also sought to compare agreement when quantifying nerve parameters using different image analysis techniques. Anesthetized, female C57BL/6 mice received central 1-mm corneal epithelial abrasions. Four-weeks post-injury, eyes were enucleated and processed for PGP9.5 to visualize the corneal nerves using wholemount immunofluorescence staining and confocal microscopy. The percentage area of the SBNP and SNT were quantified using: ImageJ automated thresholds, ImageJ manual thresholds and manual tracings in NeuronJ. Nerve sum length was quantified using NeuronJ and Imaris. Agreement between methods was considered with Bland-Altman analyses. Four-weeks post-injury, the sum length of nerve fibers in the SBNP, but not the SNT, was reduced compared with naïve eyes. In the periphery, but not central cornea, of both naïve and injured eyes, nerve fiber lengths in the SBNP and SNT were strongly correlated. For quantifying SBNP nerve axon area, all image analysis methods were highly correlated. In the SNT, there was poor correlation between manual methods and auto-thresholding, with a trend towards underestimating nerve fiber area using auto-thresholding when higher proportions of nerve fibers were present. In conclusion, four weeks after superficial corneal injury, there is differential recovery of epithelial nerve axons; SBNP sum length is reduced, however the sum length of SNTs is similar to naïve eyes. Care should be taken when selecting image analysis methods to compare nerve parameters in different depths of the corneal epithelium due to differences in background autofluorescence. Copyright © 2018 Elsevier Ltd. All rights reserved.

NEUROSARCOIDOSIS MASQUERADING AS A CENTRAL NERVOUS SYSTEM TUMOR.

PubMed

Elia, Maxwell; Kombo, Ninani; Huang, John

2017-01-01

To report a case of neurosarcoidosis with an isolated brain lesion mimicking a low-grade glioma. A 38-year-old woman presented with 2 weeks of blurry vision in the left eye. Ophthalmic examination, visual field testing, fluorescein angiography, laboratory testing, and MRI of the brain were performed. Ophthalmic examination revealed left-sided optic nerve infiltration, and MRI of the brain demonstrated a solitary lesion in the brain. The visual symptoms and ophthalmic examination improved significantly with initiation of high-dose oral prednisone. Because the MRI appearance was concerning for malignancy, a brain biopsy was performed. Pathology demonstrated gliosis consistent with a low-grade central nervous system (CNS) glioma. One year later, after initial loss to ophthalmic follow-up, the right optic nerve became involved, and the patient was again treated successfully for presumed ocular sarcoidosis. At this time, serial neuroimaging demonstrated enlargement of the CNS lesion, prompting rebiopsy. Rebiopsy demonstrated a noncaseating granuloma, confirming the diagnosis of neurosarcoidosis. The patient was treated with 20 mg of methotrexate weekly and a prednisone taper with improvement in visual and neurologic symptoms. The authors present an unusual case of neurosarcoidosis masquerading as a CNS glioma. In cases of solitary CNS granulomas, radiographically differentiating neurosarcoidosis from a glioma can be challenging. In this case, serial ophthalmic examination identifying sequential involvement of both optic nerves helped to identify the underlying cause of the CNS disease as sarcoidosis.

Central projections and entries of capsaicin-sensitive muscle afferents.

PubMed

Della Torre, G; Lucchi, M L; Brunetti, O; Pettorossi, V E; Clavenzani, P; Bortolami, R

1996-03-25

The entry pathway and central distribution of A delta and C muscle afferents within the central nervous system (CNS) were investigated by combining electron microscopy and electrophysiological analysis after intramuscular injection of capsaicin. The drug was injected into the rat lateral gastrocnemius (LG) and extraocular (EO) muscles. The compound action potentials of LG nerve and the evoked field potentials recorded in semilunar ganglion showed an immediate and permanent reduction in A delta and C components. The morphological data revealed degenerating unmyelinated axons and terminals in the inner sublamina II and in the border of laminae I-II of the dorsal horn at L4-L5 and C1-C2 (subnucleus caudalis trigemini) spinal cord segments. Most degenerating terminals were the central bouton (C) of type I and II synaptic glomeruli. Furthermore, degenerating peripheral axonal endings (V2) presynaptic to normal C were found. Since V2 were previously found degenerated after cutting the oculomotor nerve (ON) or L4 ventral root, we conclude that some A delta and C afferents from LG and EO muscles entering the CNS by ON or ventral roots make axoaxonic synapses on other primary afferents to promote an afferent control of sensory input.

Genetic predisposition to peripheral nerve neoplasia: Diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes

PubMed Central

Rodriguez, Fausto J.; Stratakis, Constantine A.; Evans, D Gareth

2013-01-01

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately a third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney Complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia. PMID:22210082

Genetic predisposition to peripheral nerve neoplasia: diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes.

PubMed

Rodriguez, Fausto J; Stratakis, Constantine A; Evans, D Gareth

2012-03-01

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system, and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately one-third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET, respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia.

Establishment of neurovascular congruency in the mouse whisker system by an independent patterning mechanism.

PubMed

Oh, Won-Jong; Gu, Chenghua

2013-10-16

Nerves and vessels often run parallel to one another, a phenomenon that reflects their functional interdependency. Previous studies have suggested that neurovascular congruency in planar tissues such as skin is established through a "one-patterns-the-other" model, in which either the nervous system or the vascular system precedes developmentally and then instructs the other system to form using its established architecture as a template. Here, we find that, in tissues with complex three-dimensional structures such as the mouse whisker system, neurovascular congruency does not follow the previous model but rather is established via a mechanism in which nerves and vessels are patterned independently. Given the diversity of neurovascular structures in different tissues, guidance signals emanating from a central organizer in the specific target tissue may act as an important mechanism to establish neurovascular congruency patterns that facilitate unique target tissue function. Copyright © 2013 Elsevier Inc. All rights reserved.

Optic nerve head biomechanics in aging and disease.

PubMed

Downs, J Crawford

2015-04-01

This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression. Copyright © 2015 Elsevier Ltd. 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 has been done. In fish, vigorously growing neurites sprout from the cut axons and within a few days begin to re-enervate the brain. This review offers a new perspective on the role of glia, particularly astrocytes, as "gate-keepers;" i.e., as being permissive or inhibitory, by comparison between fish and mammals of glial function during ONR.

[Minamata disease: a neuropathological viewpoint].

PubMed

Eto, Komyo

2006-01-01

Minamata disease (methylmercury poisoning) was first officially discovered around Minamata Bay in the Kumamoto Prefecture on May 1st, 1956. This year, a commemoration marking fifty years since this discovery of Minamata disease will be held in Minamata City. Over the years, new facts have gradually surfaced, especially after 1995, with the resolution of the political problems surrounding Minamata disease. For example, it was recently reported that large amounts of methylmercury were generated by the chemical processes of the Chisso acetaldehyde plant and later dumped directly into Minamata Bay. This report revealed the August 1951 switch from using manganese dioxide to ferric sulfide as a reaction promoter to maintain the activity of the Hg catalyst. As a result of this switch, the amount of methylmercury generated in the process rapidly increased. Thus, the true cause of the acute onset of Minamata disease in patients with a high-dose contamination of methylmercury was made clear. The severe contamination by methylmercury continued until 1968, when the plant finally stopped discharging its waste water into Minamata Bay. In 1996, the National Institute for Minamata Disease started an experimental study of methylmercury poisoning using the common marmoset. Results from this study showed that the lesions characteristic of the central nervous system in cases of acute methylmercury poisoning were promoted by brain edema, while those of the peripheral nerves were caused by axonal degeneration. Peripheral nerves were regenerated in two animals after two and a half years. Lesions characteristic of Minamata disease are systematically found throughout the nervous system. These lesions are found in the calcarine areas of occipital lobes, the pre- and post-central lobes, and the temporal transverse gyri. Milder and more diffuse lesions are also found in the cerebrum, where secondary degeneration of the central parts of white matter and internal sagittal stratum are due to primary damage of neurons. Purkinje and granular cells decrease in number in the cerebellum depending on the dose of methylmercury and the duration of methylmercury exposure. In the spinal cord, there is no primary change, but secondary degeneration is found on pyramidal tracts due to damage of the motor neurons of the precentral cortices. Additionally, secondary degeneration of Goll's tract is seen due to the primary degeneration of sensory nerve fibers including ganglion cells, sciatic nerves, and sural nerves. The experiments on the methylmercury-treated common marmosets provided every feature of pathological change found in the nervous system in human autopsy cases, depending on the dose of methylmercury.

Cochleovestibular nerve development is integrated with migratory neural crest cells

PubMed Central

Sandell, Lisa L.; Butler Tjaden, Naomi E.; Barlow, Amanda J.; Trainor, Paul A.

2015-01-01

The cochleovestibular (CV) nerve, which connects the inner ear to the brain, is the nerve that enables the senses of hearing and balance. The aim of this study was to document the morphological development of the mouse CV nerve with respect to the two embryonic cells types that produce it, specifically, the otic vesicle-derived progenitors that give rise to neurons, and the neural crest cell (NCC) progenitors that give rise to glia. Otic tissues of mouse embryos carrying NCC lineage reporter transgenes were whole mount immunostained to identify neurons and NCC. Serial optical sections were collected by confocal microscopy and were compiled to render the three dimensional (3D) structure of the developing CV nerve. Spatial organization of the NCC and developing neurons suggest that neuronal and glial populations of the CV nerve develop in tandem from early stages of nerve formation. NCC form a sheath surrounding the CV ganglia and central axons. NCC are also closely associated with neurites projecting peripherally during formation of the vestibular and cochlear nerves. Physical ablation of NCC in chick embryos demonstrates that survival or regeneration of even a few individual NCC from ectopic positions in the hindbrain results in central projection of axons precisely following ectopic pathways made by regenerating NCC. PMID:24252775

Three-dimensional interactive and stereotactic atlas of head muscles and glands correlated with cranial nerves and surface and sectional neuroanatomy.

PubMed

Nowinski, Wieslaw L; Chua, Beng Choon; Johnson, Aleksandra; Qian, Guoyu; Poh, Lan Eng; Yi, Su Hnin Wut; Bivi, Aminah; Nowinska, Natalia G

2013-04-30

Three-dimensional (3D) relationships between head muscles and cranial nerves innervating them are complicated. Existing sources present these relationships in illustrations, radiologic scans, or autopsy photographs, which are limited for learning and use. Developed electronic atlases are limited in content, quality, functionality, and/or presentation. We create a truly 3D interactive, stereotactic and high quality atlas, which provides spatial relationships among head muscles, glands and cranial nerves, and correlates them to surface and sectional neuroanatomy. The head muscles and glands were created from a 3T scan by contouring them and generating 3D models. They were named and structured according to Terminologia anatomica. The muscles were divided into: extra-ocular, facial, masticatory and other muscles, and glands into mouth and other glands. The muscles, glands (and also head) were placed in a stereotactic coordinate system. This content was integrated with cranial nerves and neuroanatomy created earlier. To explore this complex content, a scalable user interface was designed with 12 modules including central nervous system (cerebrum, cerebellum, brainstem, spinal cord), cranial nerves, muscles, glands, arterial system, venous system, tracts, deep gray nuclei, ventricles, white matter, visual system, head. Anatomy exploration operations include compositing/decompositing, individual/group selection, 3D view-index mapping, 3D labeling, highlighting, distance measuring, 3D brain cutting, and axial/coronal/sagittal triplanar display. To our best knowledge, this is the first truly 3D, stereotactic, interactive, fairly complete atlas of head muscles, and the first attempt to create a 3D stereotactic atlas of glands. Its use ranges from education of students and patients to research to potential clinical applications. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Non-neuronal cardiac cholinergic system influences CNS via the vagus nerve to acquire a stress-refractory propensity.

PubMed

Oikawa, Shino; Kai, Yuko; Tsuda, Masayuki; Ohata, Hisayuki; Mano, Asuka; Mizoguchi, Naoko; Sugama, Shuei; Nemoto, Takahiro; Suzuki, Kenji; Kurabayashi, Atsushi; Muramoto, Kazuyo; Kaneda, Makoto; Kakinuma, Yoshihiko

2016-11-01

We previously developed cardiac ventricle-specific choline acetyltransferase (ChAT) gene-overexpressing transgenic mice (ChAT tgm), i.e. an in vivo model of the cardiac non-neuronal acetylcholine (NNA) system or non-neuronal cardiac cholinergic system (NNCCS). By using this murine model, we determined that this system was responsible for characteristics of resistance to ischaemia, or hypoxia, via the modulation of cellular energy metabolism and angiogenesis. In line with our previous study, neuronal ChAT-immunoreactivity in the ChAT tgm brains was not altered from that in the wild-type (WT) mice brains; in contrast, the ChAT tgm hearts were the organs with the highest expression of the ChAT transgene. ChAT tgm showed specific traits in a central nervous system (CNS) phenotype, including decreased response to restraint stress, less depressive-like and anxiety-like behaviours and anti-convulsive effects, all of which may benefit the heart. These phenotypes, induced by the activation of cardiac NNCCS, were dependent on the vagus nerve, because vagus nerve stimulation (VS) in WT mice also evoked phenotypes similar to those of ChAT tgm, which display higher vagus nerve discharge frequency; in contrast, lateral vagotomy attenuated these traits in ChAT tgm to levels observed in WT mice. Furthermore, ChAT tgm induced several biomarkers of VS responsible for anti-convulsive and anti-depressive-like effects. These results suggest that the augmentation of the NNCCS transduces an effective and beneficial signal to the afferent pathway, which mimics VS. Therefore, the present study supports our hypothesis that activation of the NNCCS modifies CNS to a more stress-resistant state through vagus nerve activity. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Leukemia inhibitory factor in the neuroimmune communication pathways in allergic asthma.

PubMed

Lin, Min-Juan; Lao, Xue-Jun; Liu, Sheng-Ming; Xu, Zhen-Hua; Zou, Wei-Feng

2014-03-20

In the pathogenesis of asthma, central sensitization is suggested to be an important neural mechanism, and neurotrophins and cytokines are likely to be the major mediators in the neuroimmune communication pathways of asthma. However, their impact on the central nervous system in allergic asthma remains unclear. We hypothesize that central neurogenic inflammation develops in the pathogenesis of allergic asthma, and nerve growth factor (NGF) and leukemia inhibitory factor (LIF) are important mediators in its development. An asthma model of rats was established by sensitization and challenged with ovalbumin (OVA). For further confirmation of the role of LIF in neurogenic inflammation, a subgroup was pretreated with intraperitoneally (i.p.) LIF antibody before OVA challenge. The levels of LIF and NGF were measured with reverse transcription and polymerase chain reaction (RT-PCR), in situ hybridization (ISH) and immunohistochemistry stain in lung tissue, airway-specific dorsal root ganglia (DRG, C7-T5) and brain stem of asthmatic rats, anti-LIF pretreated rats and controls. A significantly increased number of LIF- and NGF-immunoreactive cells were detected in lung tissue, DRG and the brain stem of asthmatic rats. In the asthma group a significantly increase level of mRNA encoding LIF and NGF in lung tissue was detected, but not in DRG and the brain stem. Pretreatment with LIF antibody decreased the level of LIF and NGF in all tissues. LIF is an important mediator in the crosstalk between nerve and immune systems. Our study demonstrate that the increased level of LIF and NGF in DRG and brain stem may be not based on result from de novo synthesis, but rather on result from retrograde nerve transport or passage across the blood-brain-barrier. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Afferent fibers and sensory ganglion cells within the oculomotor nerve in some mammals and man. II. Electrophysiological investigations.

PubMed

Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E

1978-01-01

The main aim of the present study was to localize with electrophysiological techniques the central projections and terminations of the aberrant trigeminal fibres contained in the oculomotor nerve of the lamb. After severing a trigeminal root, single-shock electrical stimulation of the trigeminal axons present in the central stump of the ipsilateral oculomotor nerve evoked field potentials in the area of, i) the subnucleus gelatinosus of the nucleus caudalis trigemini at the level of C1-C2; ii) the main sensory trigeminal nucleus; iii) the descending trigeminal nucleus and tract; iv) the adjacent reticular formation. Units whose discharge rate was influenced by such a stimulation were also found in the same territories. These regions actually exhibited degenerations after cutting an oculomotor nerve. We conclude, therefore, that the trigeminal fibres which leave the Vth nerve at the level of the cavernous sinus and enter the brain stem through the IIIrd nerve, end in the same structures which receive the terminations of the afferent fibres entering the brain stem through the sensory trigeminal root.

In-vivo spinal nerve sensing in MISS using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Chen, Hao; Xu, Weiliang; Broderick, Neil

2016-04-01

In modern Minimally Invasive Spine Surgery (MISS), lack of visualization and haptic feedback information are the main obstacles. The spinal cord is a part of the central nervous system (CNS). It is a continuation of the brain stem, carries motor and sensory messages between CNS and the rest of body, and mediates numerous spinal reflexes. Spinal cord and spinal nerves are of great importance but vulnerable, once injured it may result in severe consequences to patients, e.g. paralysis. Raman Spectroscopy has been proved to be an effective and powerful tool in biological and biomedical applications as it works in a rapid, non-invasive and label-free way. It can provide molecular vibrational features of tissue samples and reflect content and proportion of protein, nucleic acids lipids etc. Due to the distinct chemical compositions spinal nerves have, we proposed that spinal nerves can be identified from other types of tissues by using Raman spectroscopy. Ex vivo experiments were first done on samples taken from swine backbones. Comparative spectral data of swine spinal cord, spinal nerves and adjacent tissues (i.e. membrane layer of the spinal cord, muscle, bone and fatty tissue) are obtained by a Raman micro-spectroscopic system and the peak assignment is done. Then the average spectra of all categories of samples are averaged and normalized to the same scale to see the difference against each other. The results verified the feasibility of spinal cord and spinal nerves identification by using Raman spectroscopy. Besides, a fiber-optic Raman sensing system including a miniature Raman sensor for future study is also introduced. This Raman sensor can be embedded into surgical tools for MISS.

Ghrelin-mediated sympathoinhibition and suppression of inflammation in sepsis

PubMed Central

Cheyuo, Cletus; Jacob, Asha

2012-01-01

Sepsis, a systemic inflammatory response to infection, continues to carry a high mortality despite advances in critical care medicine. Elevated sympathetic nerve activity in sepsis has been shown to contribute to early hepatocellular dysfunction and subsequently multiple organ failure, resulting in a poor prognosis, especially in the elderly. Thus, suppression of sympathetic nerve activity represents a novel therapeutic option for sepsis. Ghrelin is a 28-amino acid peptide shown to inhibit sympathetic nerve activity and inflammation in animal models of tissue injury. Age-related ghrelin hyporesponsiveness has also been shown to exacerbate sepsis. However, the mechanistic relationship between ghrelin-mediated sympathoinhibition and suppression of inflammation remains poorly understood. This review assesses the therapeutic potential of ghrelin in sepsis in the context of the neuroanatomical and molecular basis of ghrelin-mediated suppression of inflammation through inhibition of central sympathetic outflow. PMID:22068604

BOTULISM. STUDIES ON THE MANNER IN WHICH THE TOXIN OF CLOSTRIDIUM BOTULINUM ACTS UPON THE BODY

PubMed Central

Dickson, Ernest C.; Shevky, Richard

1923-01-01

A survey of the results of these experiments shows, we believe conclusively, that in botulinus intoxication in cats, dogs, and rabbits there is a specific effect upon the portions of the autonomic nervous system which Gaskell (14) described as the bulbosacral and prosomatic outflows of connector fibers respectively, which results in a blocking of the nerve impulses of these nerves. The experimental as well as the clinical evidence indicates that there is no damage to the nerves of the thoracicolumbar outflow. The exact location of the damage has not been ascertained nor has the mechanism by which the nerve impulse is blocked been determined. The experiments show, however, that the lesions in these portions of the nervous system are not of central distribution but are peripheral, and that the block cannot be due to an organic break in the conduction apparatus but must be due to some derangement which is relatively unstable. If it were otherwise it would not be possible to induce a physiological response even by massive stimulation, nor could the response be subsequently repeated by stimuli which lie within the limits of normal intensity. The application of the results of these experiments to the clinical manifestations of botulism will be discussed in a later report after the effect of the toxin upon the skeletal motor nerves has been described. PMID:19868755

Clinical-Radiologic Correlation of Extraocular Eye Movement Disorders: Seeing beneath the Surface.

PubMed

Thatcher, Joshua; Chang, Yu-Ming; Chapman, Margaret N; Hovis, Keegan; Fujita, Akifumi; Sobel, Rachel; Sakai, Osamu

2016-01-01

Extraocular eye movement disorders are relatively common and may be a significant source of discomfort and morbidity for patients. The presence of restricted eye movement can be detected clinically with quick, easily performed, noninvasive maneuvers that assess medial, lateral, upward, and downward gaze. However, detecting the presence of ocular dysmotility may not be sufficient to pinpoint the exact cause of eye restriction. Imaging plays an important role in excluding, in some cases, and detecting, in others, a specific cause responsible for the clinical presentation. However, the radiologist should be aware that the imaging findings in many of these conditions when taken in isolation from the clinical history and symptoms are often nonspecific. Normal eye movements are directly controlled by the ocular motor cranial nerves (CN III, IV, and VI) in coordination with indirect input or sensory stimuli derived from other cranial nerves. Specific causes of ocular dysmotility can be localized to the cranial nerve nuclei in the brainstem, the cranial nerve pathways in the peripheral nervous system, and the extraocular muscles in the orbit, with disease at any of these sites manifesting clinically as an eye movement disorder. A thorough understanding of central nervous system anatomy, cranial nerve pathways, and orbital anatomy, as well as familiarity with patterns of eye movement restriction, are necessary for accurate detection of radiologic abnormalities that support a diagnostic source of the suspected extraocular movement disorder. © RSNA, 2016.

Auditory pathways: anatomy and physiology.

PubMed

Pickles, James O

2015-01-01

This chapter outlines the anatomy and physiology of the auditory pathways. After a brief analysis of the external, middle ears, and cochlea, the responses of auditory nerve fibers are described. The central nervous system is analyzed in more detail. A scheme is provided to help understand the complex and multiple auditory pathways running through the brainstem. The multiple pathways are based on the need to preserve accurate timing while extracting complex spectral patterns in the auditory input. The auditory nerve fibers branch to give two pathways, a ventral sound-localizing stream, and a dorsal mainly pattern recognition stream, which innervate the different divisions of the cochlear nucleus. The outputs of the two streams, with their two types of analysis, are progressively combined in the inferior colliculus and onwards, to produce the representation of what can be called the "auditory objects" in the external world. The progressive extraction of critical features in the auditory stimulus in the different levels of the central auditory system, from cochlear nucleus to auditory cortex, is described. In addition, the auditory centrifugal system, running from cortex in multiple stages to the organ of Corti of the cochlea, is described. © 2015 Elsevier B.V. All rights reserved.

Loudness of steady sounds - A new theory

NASA Technical Reports Server (NTRS)

Howes, W. L.

1979-01-01

A new mathematical theory for calculating the loudness of steady sounds from power summation and frequency interaction, based on psychoacoustic and physiological information, assuems that loudness is a subjective measure of the electrical energy transmitted along the auditory nerve to the central nervous system. The auditory system consists of the mechanical part modeled by a bandpass filter with a transfer function dependent on the sound pressure, and the electrical part where the signal is transformed into a half-wave reproduction represented by the electrical power in impulsive discharges transmitted along neurons comprising the auditory nerve. In the electrical part the neurons are distributed among artificial parallel channels with frequency bandwidths equal to 'critical bandwidths for loudness', within which loudness is constant for constant sound pressure. The total energy transmitted to the central nervous system is the sum of the energy transmitted in all channels, and the loudness is proportional to the square root of the total filtered sound energy distributed over all channels. The theory explains many psychoacoustic phenomena such as audible beats resulting from closely spaced tones, interaction of sound stimuli which affect the same neurons affecting loudness, and of individually subliminal sounds becoming audible if they lie within the same critical band.

An Investigation into the Effects of Peptide Neurotransmitters and Intracellular Second Messengers in Rat Central Neurons in Culture.

DTIC Science & Technology

1988-02-04

Purkinje neurons. 3. Neuromodulation of synaptic efficacy in an invertebrate preparation that may be a useful model system for the actions of histamine in...neurotransmitters, neuromodulators , affect brain function. Nerve cells are the functional units of the brain, and changes in neuronal activity are ultimately

Central nervous system complications of non-Hodgkin's lymphoma. The potential role for prophylactic therapy

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

Young, R.C.; Howser, D.M.; Anderson, T.

1979-03-01

In 38 patients with non-Hodgkin's lymphoma, involvement of the central nervous system (CNS) by malignant lymphoma developed during an eight year period. All patients had lymphomatous meningitis; clinical involvement of the spinal nerves or cranial nerves suggested the diagnosis. Spinal fluid was abnormal in 97% of the patients although a positive cytology could be documented in only 67% by lumbar puncture. The histology in 82% of the patients was diffuse. Involvement of the CNS in nodular lymphoma was uncommon (3%), and the histology in virtually all of these patients had converted to diffuse. At the time of diagnosis of CNSmore » disease, 95% of the patients had other evidence of advanced disease; 66% had bone marrow involvement. In only 18% of the patients did CNS disease develop while they werin clinical remission. Eighty-five percent of the patients treated with whole brain irradiation and intrathecal chemotherapy had a good clinical response. Knowledge of these risk factors permits definition of a group of patients who may benefit from CNS prophylaxis.« less

Distribution of serotonergic and dopaminergic nerve fibers in the salivary gland complex of the cockroach Periplaneta americana

PubMed Central

Baumann, Otto; Dames, Petra; Kühnel, Dana; Walz, Bernd

2002-01-01

Background The cockroach salivary gland consists of secretory acini with peripheral ion-transporting cells and central protein-producing cells, an extensive duct system, and a pair of reservoirs. Salivation is controled by serotonergic and dopaminergic innervation. Serotonin stimulates the secretion of a protein-rich saliva, dopamine causes the production of a saliva without proteins. These findings suggest a model in which serotonin acts on the central cells and possibly other cell types, and dopamine acts selectively on the ion-transporting cells. To examine this model, we have analyzed the spatial relationship of dopaminergic and serotonergic nerve fibers to the various cell types. Results The acinar tissue is entangled in a meshwork of serotonergic and dopaminergic varicose fibers. Dopaminergic fibers reside only at the surface of the acini next to the peripheral cells. Serotonergic fibers invade the acini and form a dense network between central cells. Salivary duct segments close to the acini are locally associated with dopaminergic and serotonergic fibers, whereas duct segments further downstream have only dopaminergic fibers on their surface and within the epithelium. In addition, the reservoirs have both a dopaminergic and a serotonergic innervation. Conclusion Our results suggest that dopamine is released on the acinar surface, close to peripheral cells, and along the entire duct system. Serotonin is probably released close to peripheral and central cells, and at initial segments of the duct system. Moreover, the presence of serotonergic and dopaminergic fiber terminals on the reservoir indicates that the functions of this structure are also regulated by dopamine and serotonin. PMID:12095424

Distribution of serotonergic and dopaminergic nerve fibers in the salivary gland complex of the cockroach Periplaneta americana.

PubMed

Baumann, Otto; Dames, Petra; Kühnel, Dana; Walz, Bernd

2002-06-24

The cockroach salivary gland consists of secretory acini with peripheral ion-transporting cells and central protein-producing cells, an extensive duct system, and a pair of reservoirs. Salivation is controlled by serotonergic and dopaminergic innervation. Serotonin stimulates the secretion of a protein-rich saliva, dopamine causes the production of a saliva without proteins. These findings suggest a model in which serotonin acts on the central cells and possibly other cell types, and dopamine acts selectively on the ion-transporting cells. To examine this model, we have analyzed the spatial relationship of dopaminergic and serotonergic nerve fibers to the various cell types. The acinar tissue is entangled in a meshwork of serotonergic and dopaminergic varicose fibers. Dopaminergic fibers reside only at the surface of the acini next to the peripheral cells. Serotonergic fibers invade the acini and form a dense network between central cells. Salivary duct segments close to the acini are locally associated with dopaminergic and serotonergic fibers, whereas duct segments further downstream have only dopaminergic fibers on their surface and within the epithelium. In addition, the reservoirs have both a dopaminergic and a serotonergic innervation. Our results suggest that dopamine is released on the acinar surface, close to peripheral cells, and along the entire duct system. Serotonin is probably released close to peripheral and central cells, and at initial segments of the duct system. Moreover, the presence of serotonergic and dopaminergic fiber terminals on the reservoir indicates that the functions of this structure are also regulated by dopamine and serotonin.

Central voice production and pathophysiology of spasmodic dysphonia.

PubMed

Mor, Niv; Simonyan, Kristina; Blitzer, Andrew

2018-01-01

Our ability to speak is complex, and the role of the central nervous system in controlling speech production is often overlooked in the field of otolaryngology. In this brief review, we present an integrated overview of speech production with a focus on the role of central nervous system. The role of central control of voice production is then further discussed in relation to the potential pathophysiology of spasmodic dysphonia (SD). Peer-review articles on central laryngeal control and SD were identified from PUBMED search. Selected articles were augmented with designated relevant publications. Publications that discussed central and peripheral nervous system control of voice production and the central pathophysiology of laryngeal dystonia were chosen. Our ability to speak is regulated by specialized complex mechanisms coordinated by high-level cortical signaling, brainstem reflexes, peripheral nerves, muscles, and mucosal actions. Recent studies suggest that SD results from a primary central disturbance associated with dysfunction at our highest levels of central voice control. The efficacy of botulinum toxin in treating SD may not be limited solely to its local effect on laryngeal muscles and also may modulate the disorder at the level of the central nervous system. Future therapeutic options that target the central nervous system may help modulate the underlying disorder in SD and allow clinicians to better understand the principal pathophysiology. NA.Laryngoscope, 128:177-183, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Cornea nerve fiber quantification and construction of phenotypes in patients with fibromyalgia

PubMed Central

Oudejans, Linda; He, Xuan; Niesters, Marieke; Dahan, Albert; Brines, Michael; van Velzen, Monique

2016-01-01

Cornea confocal microscopy (CCM) is a novel non-invasive method to detect small nerve fiber pathology. CCM generally correlates with outcomes of skin biopsies in patients with small fiber pathology. The aim of this study was to quantify the morphology of small nerve fibers of the cornea of patients with fibromyalgia in terms of density, length and branching and further phenotype these patients using standardized quantitative sensory testing (QST). Small fiber pathology was detected in the cornea of 51% of patients: nerve fiber length was significantly decreased in 44% of patients compared to age- and sex-matched reference values; nerve fiber density and branching were significantly decreased in 10% and 28% of patients. The combination of the CCM parameters and sensory tests for central sensitization, (cold pain threshold, mechanical pain threshold, mechanical pain sensitivity, allodynia and/or windup), yielded four phenotypes of fibromyalgia patients in a subgroup analysis: one group with normal cornea morphology without and with signs of central sensitization, and a group with abnormal cornea morphology parameters without and with signs of central sensitization. In conclusion, half of the tested fibromyalgia population demonstrates signs of small fiber pathology as measured by CCM. The four distinct phenotypes suggest possible differences in disease mechanisms and may require different treatment approaches. PMID:27006259

Drug Distribution into Peripheral Nerve.

PubMed

Liu, Houfu; Chen, Yan; Huang, Liang; Sun, Xueying; Fu, Tingting; Wu, Shengqian; Zhu, Xiaoyan; Zhen, Wei; Liu, Jihong; Lu, Gang; Cai, Wei; Yang, Ting; Zhang, Wandong; Yu, Xiaohong; Wan, Zehong; Wang, Jianfei; Summerfield, Scott G; Dong, Kelly; Terstappen, Georg C

2018-05-01

Little is known about the impact of the blood-nerve barrier (BNB) on drug distribution into peripheral nerves. In this study, we examined the peripheral nerve penetration in rats of 11 small-molecule drugs possessing diverse physicochemical and transport properties and ProTx-II, a tarantula venom peptide with molecular mass of 3826 Daltons. Each drug was administered as constant rate intravenous infusion for 6 hours (small molecules) or 24 hours (ProTx-II). Blood and tissues including brain, spinal cord, sciatic nerve, and dorsal root ganglion (DRG) were collected for drug concentration measurements. Unbound fractions of a set of compounds were determined by equilibrium dialysis method in rat blood, brains, spinal cords, sciatic nerves, and DRG. We also investigated the influence of N -[4-[2-(6,7-dimethoxy-3,4-dihydro-1 H -isoquinolin-2-yl)ethyl]phenyl]-5-methoxy-9-oxo-10 H -acridine-4-carboxamide (GF120918), a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) inhibitor, on the peripheral nerve and central nervous system (CNS) tissue penetration of imatinib. We found that: 1) the unbound fraction in brain tissue homogenate highly correlates with that in the spinal cord, sciatic nerve, and DRG for a set of compounds and thus provides a good surrogate for spinal cord and peripheral nerve tissues, 2) small-molecule drugs investigated can penetrate the DRG and sciatic nerve, 3) P-gp and BCRP have a limited impact on the distribution of small-molecule drugs into peripheral nerves, and 4) DRG is permeable to ProTx-II, but its distribution into sciatic nerve and CNS tissues is restricted. These results demonstrate that small-molecule drugs investigated can penetrate peripheral nerve tissues, and P-gp/BCRP may not be a limiting factor at the BNB. Biologics as large as ProTx-II can access the DRG but not sciatic nerve and CNS tissues. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Targeted Inactivation of a Developmentally Regulated Neural Plectin Isoform (Plectin 1c) in Mice Leads to Reduced Motor Nerve Conduction Velocity*

PubMed Central

Fuchs, Peter; Zörer, Michael; Reipert, Siegfried; Rezniczek, Günther A.; Propst, Friedrich; Walko, Gernot; Fischer, Irmgard; Bauer, Jan; Leschnik, Michael W.; Lüscher, Bernhard; Thalhammer, Johann G.; Lassmann, Hans; Wiche, Gerhard

2009-01-01

Cytolinker proteins stabilize cells mechanically, regulate cytoskeleton dynamics, and provide scaffolds for signaling molecules. For plectin, the prototype of these proteins, an unusual diversity of isoforms has been reported, which show distinct expression patterns, subcellular localizations, and functions. Plectin has been shown to have important functions in skin and muscle, but little is known about its role in neural cells. To address this issue, we generated two knock-out mouse lines, one which was selectively lacking plectin 1c (P1c), the major isoform expressed in neural cells, and another in which plectin was conditionally deleted in neuronal precursor cells. Using isoform-specific antibodies, we found P1c to be expressed late in development and to associate with postsynaptic dendrites of central nervous system neurons, motorneurons of spinal cord, sciatic nerve axons, and Schwann cells. Motor nerve conduction velocity was found significantly reduced in sciatic nerve from P1c-deficient as well as from conditional knock-out mice. This defect was traceable to an increased number of motor nerve fibers with small cross-sectional areas; the thicknesses of axons and of myelin sheaths were unaffected. This is the first report demonstrating an important role of plectin in a major nerve function. PMID:19625254

TRPV1, TRPA1, and TRPM8 channels in inflammation, energy redirection, and water retention: role in chronic inflammatory diseases with an evolutionary perspective.

PubMed

Straub, Rainer H

2014-09-01

Chronic inflammatory diseases are accompanied by a systemic response of the body, necessary to redirect energy-rich fuels to the activated immune system and to induce volume expansion. The systemic response is switched on by two major pathways: (a) circulating cytokines enter the brain, and (b) signals via sensory nerve fibers are transmitted to the brain. Concerning item b, sensory nerve terminals are equipped with a multitude of receptors that sense temperature, inflammation, osmolality, and pain. Thus, they can be important to inform the brain about peripheral inflammation. Central to these sensory modalities are transient receptor potential channels (TRP channels) on sensory nerve endings. For example, TRP vanilloid 1 (TRPV1) can be activated by heat, inflammatory factors (e.g., protons, bradykinin, anandamide), hyperosmolality, pungent irritants, and others. TRP channels are multimodal switches that transmit peripheral signals to the brain, thereby inducing a systemic response. It is demonstrated how and why these TRP channels (TRPV1, TRP ankyrin type 1 (TRPA1), and TRP melastatin type 8 (TRPM8)) are important to start up a systemic response of energy expenditure, energy allocation, and water retention and how this is linked to a continuously activated immune system in chronic inflammatory diseases.

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.

Integration of Synaptic Vesicle Cargo Retrieval with Endocytosis at Central Nerve Terminals

PubMed Central

Cousin, Michael A.

2017-01-01

Central nerve terminals contain a limited number of synaptic vesicles (SVs) which mediate the essential process of neurotransmitter release during their activity-dependent fusion. The rapid and accurate formation of new SVs with the appropriate cargo is essential to maintain neurotransmission in mammalian brain. Generating SVs containing the correct SV cargo with the appropriate stoichiometry is a significant challenge, especially when multiple modes of endocytosis exist in central nerve terminals, which occur at different locations within the nerve terminals. These endocytosis modes include ultrafast endocytosis, clathrin-mediated endocytosis (CME) and activity-dependent bulk endocytosis (ADBE) which are triggered by specific patterns of neuronal activity. This review article will assess the evidence for the role of classical adaptor protein complexes in SV retrieval, discuss the role of monomeric adaptors and how interactions between specific SV cargoes can facilitate retrieval. In addition it will consider the evidence for preassembled plasma membrane cargo complexes and their role in facilitating these endocytosis modes. Finally it will present a unifying model for cargo retrieval at the presynapse, which integrates endocytosis modes in time and space. PMID:28824381

The developing dorsal ganglion of the salp Thalia democratica, and the nature of the ancestral chordate brain

PubMed Central

C.Lacalli, T.

1998-01-01

The development of the dorsal ganglion of the salp, Thalia democratica, is described from electron microscope reconstructions up to the stage of central neuropile formation. The central nervous system (CNS) rudiment is initially tubular with an open central canal. Early developmental events include: (i) the formation of a thick dorsal mantle of neuroblasts from which paired dorsal paraxial neuropiles arise; (ii) the differentiation of clusters of primary motor neurons along the ventral margin of the mantle; and (iii) the development from the latter of a series of peripheral nerves. The dorsal paraxial neuropiles ultimately connect to the large central neuropile, which develops later. Direct contact between neuroblasts and muscle appears to be involved in the development of some anterior nerves. The caudal nerves responsible for innervating more distant targets in the posterior part of the body develop without such contacts, which suggests that a different patterning mechanism may be employed in this part of the neuromuscular system. The results are compared with patterns of brain organization in other chordates. Because the salp CNS is symmetrical and generally less reduced than that of ascidian larvae, it is more easily compared with the CNS of amphioxus and vertebrates. The dorsal paraxial centres in the salp resemble the dorsolateral tectal centres in amphioxus in both position and organization; the central neuropile in salps likewise resembles the translumenal system in amphioxus. The neurons themselves are similar in that many of their neurites appear to be derived from the apical surface instead of the basal surface of the cell. Such neurons, with extensively developed apical neurites, may represent a new cell type that evolved in the earliest chordates in conjunction with the formation of translumenal or intralumenal integrative centres. In comparing the salp ganglion with vertebrates, we suggest that the main core of the ganglion is most like the mes-metencephalic region of the vertebrate brain, i.e. the zone occupied by the midbrain, isthmus, and anterior hindbrain. Counterparts of more anterior regions (forebrain) and posterior ones (segmented hindbrain) appear to be absent in salps, but are found in other tunicates, suggesting that evolution has acted quite differently on the main subdivisions of the CNS in different types of tunicates.

Auricular Neuromodulation: The Emerging Concept beyond the Stimulation of Vagus and Trigeminal Nerves

PubMed Central

Mercante, Beniamina; Rangon, Claire-Marie

2018-01-01

Neuromodulation, thanks to intrinsic and extrinsic brain feedback loops, seems to be the best way to exploit brain plasticity for therapeutic purposes. In the past years, there has been tremendous advances in the field of non-pharmacological modulation of brain activity. This review of different neurostimulation techniques will focus on sites and mechanisms of both transcutaneous vagus and trigeminal nerve stimulation. These methods are scientifically validated non-invasive bottom-up brain modulation techniques, easily implemented from the outer ear. In the light of this, auricles could transpire to be the most affordable target for non-invasive manipulation of central nervous system functions. PMID:29361732

Diet-induced obesity and low testosterone increase neuroinflammation and impair neural function.

PubMed

Jayaraman, Anusha; Lent-Schochet, Daniella; Pike, Christian J

2014-09-16

Low testosterone and obesity are independent risk factors for dysfunction of the nervous system including neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we investigate the independent and cooperative interactions of testosterone and diet-induced obesity on metabolic, inflammatory, and neural health indices in the central and peripheral nervous systems. Male C57B6/J mice were maintained on normal or high-fat diet under varying testosterone conditions for a four-month treatment period, after which metabolic indices were measured and RNA isolated from cerebral cortex and sciatic nerve. Cortices were used to generate mixed glial cultures, upon which embryonic cerebrocortical neurons were co-cultured for assessment of neuron survival and neurite outgrowth. Peripheral nerve damage was determined using paw-withdrawal assay, myelin sheath protein expression levels, and Na+,K+-ATPase activity levels. Our results demonstrate that detrimental effects on both metabolic (blood glucose, insulin sensitivity) and proinflammatory (cytokine expression) responses caused by diet-induced obesity are exacerbated by testosterone depletion. Mixed glial cultures generated from obese mice retain elevated cytokine expression, although low testosterone effects do not persist ex vivo. Primary neurons co-cultured with glial cultures generated from high-fat fed animals exhibit reduced survival and poorer neurite outgrowth. In addition, low testosterone and diet-induced obesity combine to increase inflammation and evidence of nerve damage in the peripheral nervous system. Testosterone and diet-induced obesity independently and cooperatively regulate neuroinflammation in central and peripheral nervous systems, which may contribute to observed impairments in neural health. Together, our findings suggest that low testosterone and obesity are interactive regulators of neuroinflammation that, in combination with adipose-derived inflammatory pathways and other factors, increase the risk of downstream disorders including type 2 diabetes and Alzheimer's disease.

Systemic arterial baroreceptors in ducks and the consequences of their denervation on some cardiovascular responses to diving

PubMed Central

Jones, D. R.

1973-01-01

1. In the duck systemic arterial baroreceptors which cause bradycardia in response to induced hypertension are located in the walls of the ascending aorta, innervated by the depressor nerves. 2. The location of the baroreceptors was confirmed both histologically and by recording activity from the depressor nerve. Stimulation of the central cut end of a depressor nerve caused transient bradycardia and a fall in blood pressure which was maintained throughout the period of stimulation. 3. Cardiovascular adjustments to submergence of 2 min duration were monitored in intact, sham-operated and denervated ducks. The sham-operated and denervated ducks were used in the experiments some 20-50 days post-operation. The denervations were checked at post-mortem. 4. In the first series of experiments on young ducks mean arterial pressure during a 2 min dive fell by 30% in intact, 17·5% in sham-operated, and 48% in denervated ducks. In all ducks heart rate was reduced by 84-85%. 5. In a second series of experiments on older ducks sciatic artery blood flow was also recorded and mean arterial blood pressure fell by 9·2% in intact and by 53% in denervated animals, although there were no significant differences in heart rate during the 2 min dives. In normal animals sciatic vascular resistance increased after 2 min submergence by 7·86 ± 1·7 times, whereas in denervated ducks it increased by only 2·32 ± 0·5 times. 6. The role of systemic arterial baroreceptors in generation of the cardiovascular responses to submergence in ducks is discussed in terms of the input supplied by the baroreceptors to the central nervous system. ImagesPlate 1 PMID:4764429

Burkholderia pseudomallei Rapidly Infects the Brain Stem and Spinal Cord via the Trigeminal Nerve after Intranasal Inoculation

PubMed Central

St. John, James A.; Walkden, Heidi; Nazareth, Lynn; Beagley, Kenneth W.; Batzloff, Michael R.

2016-01-01

Infection with Burkholderia pseudomallei causes melioidosis, a disease with a high mortality rate (20% in Australia and 40% in Southeast Asia). Neurological melioidosis is particularly prevalent in northern Australian patients and involves brain stem infection, which can progress to the spinal cord; however, the route by which the bacteria invade the central nervous system (CNS) is unknown. We have previously demonstrated that B. pseudomallei can infect the olfactory and trigeminal nerves within the nasal cavity following intranasal inoculation. As the trigeminal nerve projects into the brain stem, we investigated whether the bacteria could continue along this nerve to penetrate the CNS. After intranasal inoculation of mice, B. pseudomallei caused low-level localized infection within the nasal cavity epithelium, prior to invasion of the trigeminal nerve in small numbers. B. pseudomallei rapidly invaded the trigeminal nerve and crossed the astrocytic barrier to enter the brain stem within 24 h and then rapidly progressed over 2,000 μm into the spinal cord. To rule out that the bacteria used a hematogenous route, we used a capsule-deficient mutant of B. pseudomallei that does not survive in the blood and found that it also entered the CNS via the trigeminal nerve. This suggests that the primary route of entry is via the nerves that innervate the nasal cavity. We found that actin-mediated motility could facilitate initial infection of the olfactory epithelium. Thus, we have demonstrated that B. pseudomallei can rapidly infect the brain and spinal cord via the trigeminal nerve branches that innervate the nasal cavity. PMID:27382023

An electrophysiological follow up of patients with n-hexane polyneuropathy.

PubMed Central

Chang, Y C

1991-01-01

Electroneurographic (ENeG) and evoked potential (EP) studies were regularly performed on 11 printing workers with n-hexane polyneuropathy after cessation of exposure. At the initial examination, the ENeG studies simulated a demyelinative process. Further slowing of nerve conduction velocity, or further decreasing of action potential amplitude, or both in the follow up ENeG study were found in about half the patients. The motor distal latency did not worsen. Nerve conduction returned to normal earlier in the sensory than in the motor nerves. After the patients had regained full motor capability, conduction velocities in motor nerves were still significantly slowed. These ENeG characteristics correlate with the pathological and pathophysiological changes in experimental hexa-carbon neuropathies. The initial findings from the EP studies indicated a conduction abnormality in the central nervous system (CNS). Delayed worsening occurred in the amplitude of visual EPs in three patients. On serial follow up, the interpeak latency and interpeak amplitude of visual EPs improved little. Residual abnormalities were also found in the interpeak latency of auditory EPs in the brainstem and in the absolute latency of scalp somatosensory EPs from the peroneal nerve. Astroglial proliferation in the CNS probably impedes recovery of the abnormalities in EP. PMID:1993154

Solitary Metastasis to the Facial/Vestibulocochlear Nerve Complex: Case Report and Review of the Literature.

PubMed

Ariai, M Shafie; Eggers, Scott D; Giannini, Caterina; Driscoll, Colin L W; Link, Michael J

2015-10-01

Distant metastasis of mucinous adenocarcinoma from the gastrointestinal tract, ovaries, pancreas, lungs, breast, or urogenital system is a well-described entity. Mucinous adenocarcinomas from different primary sites are histologically identical with gland cells producing a copious amount of mucin. This report describes a very rare solitary metastasis of a mucinous adenocarcinoma of unknown origin to the facial/vestibulocochlear nerve complex in the cerebellopontine angle. A 71-year-old woman presented with several month history of progressive neurological decline and a negative extensive workup performed elsewhere. She presented to our institution with complete left facial weakness, left-sided deafness, gait unsteadiness, headache and anorexia. A repeat magnetic resonance imaging scan of the head revealed a cystic, enhancing abnormality involving the left cerebellopontine angle and internal auditory canal. A left retrosigmoid craniotomy was performed and the lesion was completely resected. The final pathology was a mucinous adenocarcinoma of indeterminate origin. Postoperatively, the patient continued with her preoperative deficits and subsequently died of her systemic disease 6 weeks after discharge. The facial/vestibulocochlear nerve complex is an unusual location for metastatic disease in the central nervous system. Clinicians should consider metastatic tumor as the possible etiology of an unusual appearing mass in this location causing profound neurological deficits. The prognosis after metastatic mucinous adenocarcinoma to the cranial nerves in the cerebellopontine angle may be poor. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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.

Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents.

PubMed

Gui, Wen-Shan; Wei, Xiao; Mai, Chun-Lin; Murugan, Madhuvika; Wu, Long-Jun; Xin, Wen-Jun; Zhou, Li-Jun; Liu, Xian-Guo

2016-01-01

Chronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice. Mechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory deficits, depressive, and pain behaviors were substantially prevented by peri-sciatic administration of IL-1β neutralizing antibody in rats or deletion of IL-1 receptor type 1 in mice. Furthermore, the behavioral abnormalities induced by spared nerve injury were mimicked in naïve rats by repetitive intravenous injection of re combinant rat IL-1β (rrIL-1β) at a pathological concentration as determined from spared nerve injury rats. In addition, microglia were activated by both spared nerve injury and intravenous injection of rrIL-1β and the effect of spared nerve injury was substantially reversed by peri-sciatic administration of anti-IL-1β. Neuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression. © The Author(s) 2016.

Neural Connectivity and Immunocytochemical Studies of Anatomical Sites Related to Nauseogenic and Emetic Reflexes

NASA Technical Reports Server (NTRS)

Fox, Robert A. (Principal Investigator)

1992-01-01

The studies conducted in this research project examined several aspects of neuroanatomical structures and neurochemical processes related to motion sickness in animal models. A principle objective of these studies was to investigate neurochemical changes in the central nervous system that are related to motion sickness with the objective of defining neural mechanisms important to this malady. For purposes of exposition, the studies and research finding have been classified into five categories. These are: immunoreactivity in the brainstem, vasopressin effects, lesion studies of area postrema, role of the vagus nerve, and central nervous system structure related to adaptation to microgravity.

Neural development in the tardigrade Hypsibius dujardini based on anti-acetylated α-tubulin immunolabeling.

PubMed

Gross, Vladimir; Mayer, Georg

2015-01-01

The tardigrades (water bears) are a cosmopolitan group of microscopic ecdysozoans found in a variety of aquatic and temporarily wet environments. They are members of the Panarthropoda (Tardigrada + Onychophora + Arthropoda), although their exact position within this group remains contested. Studies of embryonic development in tardigrades have been scarce and have yielded contradictory data. Therefore, we investigated the development of the nervous system in embryos of the tardigrade Hypsibius dujardini using immunohistochemical techniques in conjunction with confocal laser scanning microscopy in an effort to gain insight into the evolution of the nervous system in panarthropods. An antiserum against acetylated α-tubulin was used to visualize the axonal processes and general neuroanatomy in whole-mount embryos of the eutardigrade H. dujardini. Our data reveal that the tardigrade nervous system develops in an anterior-to-posterior gradient, beginning with the neural structures of the head. The brain develops as a dorsal, bilaterally symmetric structure and contains a single developing central neuropil. The stomodeal nervous system develops separately and includes at least four separate, ring-like commissures. A circumbuccal nerve ring arises late in development and innervates the circumoral sensory field. The segmental trunk ganglia likewise arise from anterior to posterior and establish links with each other via individual pioneering axons. Each hemiganglion is associated with a number of peripheral nerves, including a pair of leg nerves and a branched, dorsolateral nerve. The revealed pattern of brain development supports a single-segmented brain in tardigrades and challenges previous assignments of homology between tardigrade brain lobes and arthropod brain segments. Likewise, the tardigrade circumbuccal nerve ring cannot be homologized with the arthropod 'circumoral' nerve ring, suggesting that this structure is unique to tardigrades. Finally, we propose that the segmental ganglia of tardigrades and arthropods are homologous and, based on these data, favor a hypothesis that supports tardigrades as the sister group of arthropods.

Biology of eating behavior in obesity.

PubMed

Schwartz, Gary J

2004-11-01

Understanding normal and dysfunctional energy regulation and body weight regulation requires neural evaluation of the signals involved in the control of food intake within a meal, as well as signals related to the availability of stored fuels. Work from our laboratory has focused on peripheral and central nervous system studies of behavior and physiology designed to improve our understanding of the role of gut-brain communication in the control of food intake and energy homeostasis. Gastrointestinal administration of nutrients reduces subsequent meal size, suggesting a potent role for peripheral nutrient sensing in the negative feedback control of ingestion. Vagal afferent nerves supply gastrointestinal sites stimulated during food intake, and these nerves are responsive to mechanical and nutrient chemical properties of ingested food. In addition, the presence of nutrients in these gastrointestinal sites stimulates the release of peptides that affect energy intake. These gut peptides also modulate the activity of peripheral gastrointestinal sensory nerves in ways that may contribute to their effects on food intake. In the central nervous system, adiposity hormones and their downstream mediators have been shown to work at both hindbrain and forebrain sites to affect food intake and metabolism. Importantly, recent data has shown that adiposity hormones acting in the brain increase the behavioral and neural potency of feeding inhibitory gastrointestinal stimuli. These data support the suggestion that insensitivity to adiposity hormones in obesity may be characterized by alterations in their ability to modulate the neural processing of food signals important in determining how much food is consumed during a meal.

Ischaemia-reperfusion injury in central retinal artery occlusion.

PubMed

Saxena, Sandeep; Mishra, Nibha; Meyer, Carsten H; Akduman, Levent

2013-10-21

A 53-year-old man presented with sudden painless diminution of vision in his right eye for 3 days. His fundus examination showed diffuse whitening of the retina with a cherry red spot at the fovea with cilioretinal artery sparing. On fluorescein angiography delayed arteriovenous transit was observed. Three-dimensional spectral domain optical coherence tomography was used to assess retinal nerve fibre layer thickness and average macular central subfield thickness on days 3, 7, 30 and 90. Marked retinal oedema due to ischaemia was observed on day 3 of occurrence of central retinal artery occlusion. On day 7, significant decrease in retinal nerve fibre thickness and macular thickness was noted suggestive of acute reperfusion injury. Retinal nerve fibre layer thickness and macular thickness returned to near normal on day 30 due to restoration of blood supply with wash out of stress mediators. Retinal atrophy was observed on day 90.

Ischaemia-reperfusion injury in central retinal artery occlusion

PubMed Central

Saxena, Sandeep; Mishra, Nibha; Meyer, Carsten H; Akduman, Levent

2013-01-01

A 53-year-old man presented with sudden painless diminution of vision in his right eye for 3 days. His fundus examination showed diffuse whitening of the retina with a cherry red spot at the fovea with cilioretinal artery sparing. On fluorescein angiography delayed arteriovenous transit was observed. Three-dimensional spectral domain optical coherence tomography was used to assess retinal nerve fibre layer thickness and average macular central subfield thickness on days 3, 7, 30 and 90. Marked retinal oedema due to ischaemia was observed on day 3 of occurrence of central retinal artery occlusion. On day 7, significant decrease in retinal nerve fibre thickness and macular thickness was noted suggestive of acute reperfusion injury. Retinal nerve fibre layer thickness and macular thickness returned to near normal on day 30 due to restoration of blood supply with wash out of stress mediators. Retinal atrophy was observed on day 90. PMID:24145508

Isolated monolateral neurosensory hearing loss as a rare sign of neuroborreliosis.

PubMed

Iero, I; Elia, M; Cosentino, F I I; Lanuzza, B; Spada, R S; Toscano, G; Tripodi, M; Belfiore, A; Ferri, R

2004-04-01

Lyme disease, or borreliosis, is a zoonosis transmitted by Borrelia burgdorferi which also involves the central nervous system (CNS), in 15% of affected individuals, with the occurrence of aseptic meningitis, fluctuating meningoencephalitis, or neuropathy of cranial and peripheral nerves. Encephalopathy with white matter lesions revealed by magnetic resonance imaging (MRI) scans in late, persistent stages of Lyme disease has been described. In this report, we describe a patient with few clinical manifestations involving exclusively the eighth cranial nerve, monolaterally and diffuse bilateral alterations of the white matter, particularly in the subcortical periventricular regions at cerebral MRI. This single patient study shows that the search for antibodies against Borrelia burgdoferi should always be performed when we face a leukoencephalopathy of unknown origin. An isolated lesion of the eighth cranial nerve can be the only neurologic sign in patients with leukoencephalopathy complicating Lyme disease.

Recording of electroneurograms from the nerves innervating the pancreas of a dog.

PubMed

Rozman, J; Zorko, B; Bunc, M

2001-12-15

Electroneurograms (ENGs) from the vagus, splanchnic and pancreatic nerves innervating the pancreas of a dog, were recorded with chronically implanted silicone multi-electrode circular cuffs in an intact pancreas and in a pancreas partly disabled with alloxan. The cuffs contained 33 platinum electrodes (0.6x1.5 mm) arranged in three parallel circular groups integrated into the inner surface of the cuff. Each circular group contained 11 electrodes at a distance of 0.5 mm apart, with 6 mm between the circular groups. The cuffs had an inner diameter of 2.5 mm and the length of 18 mm. In a 2-year study, the cuffs were implanted into two adult Beagle dogs (one female and one male). In the vagus nerve, the cuff was installed on the nerve at the neck, whilst in the splanchnic nerve, the cuff was installed on the nerve before the celiac ganglion, and in the pancreatic nerve, the cuff was installed on the nerve just before it enters the pancreas. In each of the three implanted cuffs, the electrodes of the central circular group were connected to each other and this signal provided one input to a multi-channel ENG amplifying system. The electrodes of each of the two outer spiral groups were connected to each other and then both these groups were short-circuited. This signal then provided another input to the multi-channel ENG amplifying system. The ENG amplifying system was designed to amplify the ENGs 100000 times and to pass frequencies of between 500 and 10 kHz. In our study, three recordings in each animal were conducted. Recordings in the intact pancreas were conducted 2 and 6 months after the implantation, while the recording in the partly disabled pancreas, was conducted 10 months after the implantation and 10 days after the disablement. Due to the fact that the results obtained in both animals were actually quite similar, we present the results of the recordings obtained in one animal. In both animals the cuffs were left implanted for more than 1 year and were used for pancreatic stimulation, although this is not in this paper. The results show that cuffs implanted chronically on the nerves innervating the pancreas of a dog could reliably record the ENGs. This information could be used effectively in further study of pancreatic innervation and its function. Moreover, the results suggest that cuffs could also be useful in recording the ENGs from other nerves of the autonomic nervous system that innervate various glands and internal organs.

Function of gonadotropin-releasing hormone in olfaction.

PubMed

Wirsig-Wiechmann, C R

2001-06-01

Gonadotropin-releasing hormone (GnRH) is present within neurons of the nervus terminalis, the zeroeth cranial nerve. In all vertebrate species, except in sharks where it is a separate nerve, the nervus terminalis consists of a chain of neurons embedded within olfactory or vomeronasal nerves in the nasal cavity. The function of the GnRH component of the nervus terminalis is thought to be neuromodulatory. Our research on GnRH effects on olfaction confirms this hypothesis. The processes of GnRH neural cell bodies located within chemosensory nerves project centrally into the ventral forebrain and peripherally into the lamina propria of the nasal chemosensory mucosa. GnRH receptors are expressed by chemosensory neurons as shown by RT-PCR/Southern blotting and GnRH agonist binding studies. Patch-clamp studies have shown that GnRH alters the responses of isolated chemosensory neurons to natural or electrophysiological stimulation through the modulation of voltage-gated and receptor-gated channels. Behavioral experiments demonstrate that interfering with the nasal GnRH system leads to deficits in mating behavior. These studies suggest that the function of the intranasal GnRH system is to modify olfactory information, perhaps at reproductively auspicious times. We speculate that the purpose of this altered olfactory sense is to make pheromones more detectable and salient.

Glucagon-like peptide-1 reduces pancreatic β-cell mass through hypothalamic neural pathways in high-fat diet-induced obese rats.

PubMed

Ando, Hisae; Gotoh, Koro; Fujiwara, Kansuke; Anai, Manabu; Chiba, Seiichi; Masaki, Takayuki; Kakuma, Tetsuya; Shibata, Hirotaka

2017-07-17

We examined whether glucagon-like peptide-1 (GLP-1) affects β-cell mass and proliferation through neural pathways, from hepatic afferent nerves to pancreatic efferent nerves via the central nervous system, in high-fat diet (HFD)-induced obese rats. The effects of chronic administration of GLP-1 (7-36) and liraglutide, a GLP-1 receptor agonist, on pancreatic morphological alterations, c-fos expression and brain-derived neurotrophic factor (BDNF) content in the hypothalamus, and glucose metabolism were investigated in HFD-induced obese rats that underwent hepatic afferent vagotomy (VgX) and/or pancreatic efferent sympathectomy (SpX). Chronic GLP-1 (7-36) administration to HFD-induced obese rats elevated c-fos expression and BDNF content in the hypothalamus, followed by a reduction in pancreatic β-cell hyperplasia and insulin content, thus resulting in improved glucose tolerance. These responses were abolished by VgX and SpX. Moreover, administration of liraglutide similarly activated the hypothalamic neural pathways, thus resulting in a more profound amelioration of glucose tolerance than native GLP-1 (7-36). These data suggest that GLP-1 normalizes the obesity-induced compensatory increase in β-cell mass and glucose intolerance through a neuronal relay system consisting of hepatic afferent nerves, the hypothalamus, and pancreatic efferent nerves.

Sympathetic nervous system and the kidney in hypertension.

PubMed

DiBona, Gerald F

2002-03-01

Long-term control of arterial pressure has been attributed to the kidney by virtue of its ability to couple the regulation of blood volume to the maintenance of sodium and water balance by the mechanisms of pressure natriuresis and diuresis. In the presence of a defect in renal excretory function, hypertension arises as the consequence of the need for an increase in arterial pressure to offset the abnormal pressure natriuresis and diuresis mechanisms, and to maintain sodium and water balance. There is growing evidence that an important cause of the defect in renal excretory function in hypertension is an increase in renal sympathetic nerve activity (RSNA). First, increased RSNA is found in animal models of hypertension and hypertensive humans. Second, renal denervation prevents or alleviates hypertension in virtually all animal models of hypertension. Finally, increased RSNA results in reduced renal excretory function by virtue of effects on the renal vasculature, the tubules, and the juxtaglomerular granular cells. The increase in RSNA is of central nervous system origin, with one of the stimuli being the action of angiotensin II, probably of central origin. By acting on brain stem nuclei that are important in the control of peripheral sympathetic vasomotor tone (e.g. rostral ventrolateral medulla), angiotensin II increases the basal level of RSNA and impairs its arterial baroreflex regulation. Therefore, the renal sympathetic nerves may serve as the link between central sympathetic nervous system regulatory sites and the kidney in contributing to the renal excretory defect in the development of hypertension.

The therapeutic potential of renin angiotensin aldosterone system (RAAS) in chronic pain: from preclinical studies to clinical trials.

PubMed

Bessaguet, Flavien; Magy, Laurent; Desmoulière, Alexis; Demiot, Claire

2016-01-01

The prevalence rate of chronic pain is 15% to 25% in adults while the therapeutic arsenal is still insufficient, especially in relieving neuropathic pain. Peripheral pain transmission is conducted by the small Aδ and C sensory nerve fibres. They express elements from the renin-angiotensin-aldosterone system (RAAS), a well-known blood pressure regulator. Recently, studies have demonstrated the role of angiotensin II, its derivatives and aldosterone in the modulation of pain perception, by interacting with receptors expressed by sensory nerve fibres or through the central nervous system. Here, we assess the effects of RAAS modulators in the conduction of pain with molecular, preclinical and clinical approaches, in normal or pathological conditions. Currently, some clinical studies have been carried out on the pain-relieving effect of RAAS modulators and suggest their potential in the management of chronic, inflammatory or neuropathic pain.

Patterns of innervation of neurones in the inferior mesenteric ganglion of the cat.

PubMed Central

Julé, Y; Krier, J; Szurszewski, J H

1983-01-01

The patterns of peripheral and central synaptic input to non-spontaneous, irregular discharging and regular discharging neurones in the inferior mesenteric ganglion of the cat were studied in vitro using intracellular recording techniques. All three types of neurones in rostral and caudal lobes received central synaptic input primarily from L3 and L4 spinal cord segments. Since irregular discharging neurones received synaptic input from intraganglionic regular discharging neurones, some of the central input to irregular discharging neurones may have been relayed through the regular discharging neurones. In the rostral lobes of the ganglion, more than 70% of the non-spontaneous and irregular discharging neurones tested received peripheral synaptic input from the lumbar colonic, intermesenteric and left and right hypogastric nerves. Most of the regular discharging neurones tested received synaptic input from the intermesenteric and lumbar colonic nerves; none of the regular discharging neurones received synaptic input from the hypogastric nerves. Some of the peripheral synaptic input from the lumbar colonic and intermesenteric nerves to irregular discharging neurones may have been relayed through the regular discharging neurones. Axons of non-spontaneous and irregular discharging neurones located in the rostral lobes travelled to the periphery exclusively in the lumbar colonic nerves. Antidromic responses were not observed in regular discharging neurones during stimulation of any of the major peripheral nerve trunks. This suggests these neurones were intraganglionic. In the caudal lobes, irregular discharging neurones received a similar pattern of peripheral synaptic input as did irregular discharging neurones located in the rostral lobes. The majority of irregular discharging neurones in the caudal lobes projected their axons to the periphery through the lumbar colonic nerves. Non-spontaneous neurones in the caudal lobes, in contrast to those located in the rostral lobes, received peripheral synaptic input primarily from the hypogastric nerves. Axons of the majority of non-spontaneous neurones located in the caudal lobes travelled to the periphery through hypogastric nerves. The results suggest that non-spontaneous neurones and irregular discharging neurones in the rostral lobes and the majority of irregular discharging neurones in the caudal lobes transact and integrate neural commands destined for abdominal viscera supplied by the lumbar colonic nerves. Non-spontaneous neurones in the caudal lobes transact and integrate neural commands destined for pelvic viscera supplied by the hypogastric nerves. PMID:6655582

Patterns of innervation of neurones in the inferior mesenteric ganglion of the cat.

PubMed

Julé, Y; Krier, J; Szurszewski, J H

1983-11-01

The patterns of peripheral and central synaptic input to non-spontaneous, irregular discharging and regular discharging neurones in the inferior mesenteric ganglion of the cat were studied in vitro using intracellular recording techniques. All three types of neurones in rostral and caudal lobes received central synaptic input primarily from L3 and L4 spinal cord segments. Since irregular discharging neurones received synaptic input from intraganglionic regular discharging neurones, some of the central input to irregular discharging neurones may have been relayed through the regular discharging neurones. In the rostral lobes of the ganglion, more than 70% of the non-spontaneous and irregular discharging neurones tested received peripheral synaptic input from the lumbar colonic, intermesenteric and left and right hypogastric nerves. Most of the regular discharging neurones tested received synaptic input from the intermesenteric and lumbar colonic nerves; none of the regular discharging neurones received synaptic input from the hypogastric nerves. Some of the peripheral synaptic input from the lumbar colonic and intermesenteric nerves to irregular discharging neurones may have been relayed through the regular discharging neurones. Axons of non-spontaneous and irregular discharging neurones located in the rostral lobes travelled to the periphery exclusively in the lumbar colonic nerves. Antidromic responses were not observed in regular discharging neurones during stimulation of any of the major peripheral nerve trunks. This suggests these neurones were intraganglionic. In the caudal lobes, irregular discharging neurones received a similar pattern of peripheral synaptic input as did irregular discharging neurones located in the rostral lobes. The majority of irregular discharging neurones in the caudal lobes projected their axons to the periphery through the lumbar colonic nerves. Non-spontaneous neurones in the caudal lobes, in contrast to those located in the rostral lobes, received peripheral synaptic input primarily from the hypogastric nerves. Axons of the majority of non-spontaneous neurones located in the caudal lobes travelled to the periphery through hypogastric nerves. The results suggest that non-spontaneous neurones and irregular discharging neurones in the rostral lobes and the majority of irregular discharging neurones in the caudal lobes transact and integrate neural commands destined for abdominal viscera supplied by the lumbar colonic nerves. Non-spontaneous neurones in the caudal lobes transact and integrate neural commands destined for pelvic viscera supplied by the hypogastric nerves.

Applications of optical coherence tomography in pediatric clinical neuroscience.

PubMed

Avery, Robert A; Rajjoub, Raneem D; Trimboli-Heidler, Carmelina; Waldman, Amy T

2015-04-01

For nearly two centuries, the ophthalmoscope has permitted examination of the retina and optic nerve-the only axons directly visualized by the physician. The retinal ganglion cells project their axons, which travel along the innermost retina to form the optic nerve, marking the beginning of the anterior visual pathway. Both the structure and function of the visual pathway are essential components of the neurologic examination as it can be involved in numerous acquired, congenital and genetic central nervous system conditions. The development of optical coherence tomography now permits the pediatric neuroscientist to visualize and quantify the optic nerve and retinal layers with unprecedented resolution. As optical coherence tomography becomes more accessible and integrated into research and clinical care, the pediatric neuroscientist may have the opportunity to utilize and/or interpret results from this device. This review describes the basic technical features of optical coherence tomography and highlights its potential clinical and research applications in pediatric clinical neuroscience including optic nerve swelling, optic neuritis, tumors of the visual pathway, vigabatrin toxicity, nystagmus, and neurodegenerative conditions. Georg Thieme Verlag KG Stuttgart · New York.

Nervous system development in lecithotrophic larval and juvenile stages of the annelid Capitella teleta.

PubMed

Meyer, Néva P; Carrillo-Baltodano, Allan; Moore, Richard E; Seaver, Elaine C

2015-01-01

Reconstructing the evolutionary history of nervous systems requires an understanding of their architecture and development across diverse taxa. The spiralians encompass diverse body plans and organ systems, and within the spiralians, annelids exhibit a variety of morphologies, life histories, feeding modes and associated nervous systems, making them an ideal group for studying evolution of nervous systems. We describe nervous system development in the annelid Capitella teleta (Blake JA, Grassle JP, Eckelbarger KJ. Capitella teleta, a new species designation for the opportunistic and experimental Capitella sp. I, with a review of the literature for confirmed records. Zoosymposia. 2009;2:25-53) using whole-mount in situ hybridization for a synaptotagmin 1 homolog, nuclear stains, and cross-reactive antibodies against acetylated α-tubulin, 5-HT and FMRFamide. Capitella teleta is member of the Sedentaria (Struck TH, Paul C, Hill N, Hartmann S, Hosel C, Kube M, et al. Phylogenomic analyses unravel annelid evolution. Nature. 2011;471:95-8) and has an indirectly-developing, lecithotrophic larva. The nervous system of C. teleta shares many features with other annelids, including a brain and a ladder-like ventral nerve cord with five connectives, reiterated commissures, and pairs of peripheral nerves. Development of the nervous system begins with the first neurons differentiating in the brain, and follows a temporal order from central to peripheral and from anterior to posterior. Similar to other annelids, neurons with serotonin-like-immunoreactivity (5HT-LIR) and FMRFamide-like-immunoreactivity (FMRF-LIR) are found throughout the brain and ventral nerve cord. A small number of larval-specific neurons and neurites are present, but are visible only after the central nervous system begins to form. These larval neurons are not visible after metamorphosis while the rest of the nervous system is largely unchanged in juveniles. Most of the nervous system that forms during larvogenesis in C. teleta persists into the juvenile stage. The first neurons differentiate in the brain, which contrasts with the early formation of peripheral, larval-specific neurons found in some spiralian taxa with planktotrophic larvae. Our study provides a clear indication that certain shared features among annelids - e.g., five connectives in the ventral nerve cord - are only visible during larval stages in particular species, emphasizing the need to include developmental data in ancestral character state reconstructions. The data provided in this paper will serve as an important comparative reference for understanding evolution of nervous systems, and as a framework for future molecular studies of development.

Multiple routes of invasion of wild-type Clade 1 highly pathogenic avian influenza H5N1 virus into the central nervous system (CNS) after intranasal exposure in ferrets.

PubMed

Yamada, Manabu; Bingham, John; Payne, Jean; Rookes, Jennifer; Lowther, Suzanne; Haining, Jessica; Robinson, Rachel; Johnson, Dayna; Middleton, Deborah

2012-10-01

Human infections with highly pathogenic avian influenza (HPAI) H5N1 have been associated with central nervous system involvement. The purpose of this study was to examine the route of invasion of wild-type HPAI H5N1 virus into the central nervous system (CNS) using a ferret model of infection. Sixteen ferrets were exposed by the intranasal route to 10(6) TCID(50) of A/Vietnam/1203/04, a Clade 1 strain originally isolated from a fatal human case. The ferrets were euthanased for histological and virological analysis at intervals after challenge at 1, 3, 5, 6 and 7 days post-inoculation (dpi). From 5 dpi encephalitis was seen in all examined ferrets. The detection of antigen in the olfactory epithelium, the olfactory bulb, and related nuclei, in that temporal sequence, supported the contention that this is a major infection route for this virus strain. The detection of antigen in the epithelial cells in the Eustachian tube on 1 dpi, followed by the cochlea and vestibulocochlear nerve on 5 dpi is consistent with a second anterograde route of invasion, namely the vestibulocochlear pathway. There was also antigen in the lining of the ventricles and central canal indicating spread via the cerebrospinal fluid. However, evidence for haematogenous dissemination in the form of antigen in the brain parenchyma surrounding blood vessels was not found. This study provides support to the contention that wild-type HPAI H5N1 virus strains may enter the CNS via cranial nerve pathways and that the ferret is an appropriate model to study preventive and therapeutic procedures involving neural infection with these viruses by this route.

Quantitative magnetic resonance (MR) neurography for evaluation of peripheral nerves and plexus injuries

PubMed Central

Barousse, Rafael; Socolovsky, Mariano; Luna, Antonio

2017-01-01

Traumatic conditions of peripheral nerves and plexus have been classically evaluated by morphological imaging techniques and electrophysiological tests. New magnetic resonance imaging (MRI) studies based on 3D fat-suppressed techniques are providing high accuracy for peripheral nerve injury evaluation from a qualitative point of view. However, these techniques do not provide quantitative information. Diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) are functional MRI techniques that are able to evaluate and quantify the movement of water molecules within different biological structures. These techniques have been successfully applied in other anatomical areas, especially in the assessment of central nervous system, and now are being imported, with promising results for peripheral nerve and plexus evaluation. DWI and DTI allow performing a qualitative and quantitative peripheral nerve analysis, providing valuable pathophysiological information about functional integrity of these structures. In the field of trauma and peripheral nerve or plexus injury, several derived parameters from DWI and DTI studies such as apparent diffusion coefficient (ADC) or fractional anisotropy (FA) among others, can be used as potential biomarkers of neural damage providing information about fiber organization, axonal flow or myelin integrity. A proper knowledge of physical basis of these techniques and their limitations is important for an optimal interpretation of the imaging findings and derived data. In this paper, a comprehensive review of the potential applications of DWI and DTI neurographic studies is performed with a focus on traumatic conditions, including main nerve entrapment syndromes in both peripheral nerves and brachial or lumbar plexus. PMID:28932698

Cloning and characteristics of fish glial fibrillary acidic protein: implications for optic nerve regeneration.

PubMed

Cohen, I; Shani, Y; Schwartz, M

1993-08-15

Mammalian central nervous system neurons do not regenerate after axonal injury, unlike their counterparts in fish and amphibians. After axonal injury, glial cells in mammals do not support regrowth of axons, while in fish they support the regeneration process. Controversy exists as to whether or not the intact fish optic nerve expresses glial fibrillary acidic protein, a well-known marker for mature astrocytes, and thus whether its astrocytes differ in this respect from those of the brain and spinal cord, as well as from optic nerve astrocytes of other species. In an attempt to resolve this question we cloned fish glial fibrillary acidic protein. Two different complementary DNA clones were isolated from a carp brain complementary DNA library, each encoding a different form of glial fibrillary acidic protein apparently originating from different genes. Monospecific polyclonal antibodies were raised against a peptide synthesized according to the predicted amino acid sequence, and used to identify and localize the fish glial fibrillary acidic protein. Two glial fibrillary acidic proteins (of 49 kDa and 51 kDa) were identified by the antibodies in all tested fish central nervous system tissues. The antibodies were then used to examine glial fibrillary acidic protein immunoreactivity in sections taken from uninjured and injured optic nerves of goldfish. Injury was followed by an elevation in glial fibrillary acidic protein immunoreactivity along the whole length of the nerve, except at the site of the injury, where--as in the case of vimentin--no immunoreactivity was detectable. However, in contrast to vimentin-positive glial cells, which repopulate the site of the injury soon after the optic nerve is injured, glial fibrillary acidic protein-positive glial cells remained outside the injury site for as long as 6 weeks after the injury. Despite the injury-induced changes in glial fibrillary acidic protein immunoreactivity, no change was observed in the level of transcript encoding glial fibrillary acidic protein after injury, while there was an increase in the amount of glial fibrillary acidic protein associated with the cytoskeleton and a reduction in the soluble form. These results suggest that the injury-induced changes in immunoreactivity on sections involve changes not in transcription or translation of glial fibrillary acidic protein, but in glial fibrillary acidic protein compartmentalization.

Modulation of experimental arthritis by vagal sensory and central brain stimulation.

PubMed

Bassi, Gabriel Shimizu; Dias, Daniel Penteado Martins; Franchin, Marcelo; Talbot, Jhimmy; Reis, Daniel Gustavo; Menezes, Gustavo Batista; Castania, Jaci Airton; Garcia-Cairasco, Norberto; Resstel, Leonardo Barbosa Moraes; Salgado, Helio Cesar; Cunha, Fernando Queiróz; Cunha, Thiago Mattar; Ulloa, Luis; Kanashiro, Alexandre

2017-08-01

Articular inflammation is a major clinical burden in multiple inflammatory diseases, especially in rheumatoid arthritis. Biological anti-rheumatic drug therapies are expensive and increase the risk of systemic immunosuppression, infections, and malignancies. Here, we report that vagus nerve stimulation controls arthritic joint inflammation by inducing local regulation of innate immune response. Most of the previous studies of neuromodulation focused on vagal regulation of inflammation via the efferent peripheral pathway toward the viscera. Here, we report that vagal stimulation modulates arthritic joint inflammation through a novel "afferent" pathway mediated by the locus coeruleus (LC) of the central nervous system. Afferent vagal stimulation activates two sympatho-excitatory brain areas: the paraventricular hypothalamic nucleus (PVN) and the LC. The integrity of the LC, but not that of the PVN, is critical for vagal control of arthritic joint inflammation. Afferent vagal stimulation suppresses articular inflammation in the ipsilateral, but not in the contralateral knee to the hemispheric LC lesion. Central stimulation is followed by subsequent activation of joint sympathetic nerve terminals inducing articular norepinephrine release. Selective adrenergic beta-blockers prevent the effects of articular norepinephrine and thereby abrogate vagal control of arthritic joint inflammation. These results reveals a novel neuro-immune brain map with afferent vagal signals controlling side-specific articular inflammation through specific inflammatory-processing brain centers and joint sympathetic innervations. Copyright © 2017 Elsevier Inc. All rights reserved.

The facial nerve: anatomy and associated disorders for oral health professionals.

PubMed

Takezawa, Kojiro; Townsend, Grant; Ghabriel, Mounir

2018-04-01

The facial nerve, the seventh cranial nerve, is of great clinical significance to oral health professionals. Most published literature either addresses the central connections of the nerve or its peripheral distribution but few integrate both of these components and also highlight the main disorders affecting the nerve that have clinical implications in dentistry. The aim of the current study is to provide a comprehensive description of the facial nerve. Multiple aspects of the facial nerve are discussed and integrated, including its neuroanatomy, functional anatomy, gross anatomy, clinical problems that may involve the nerve, and the use of detailed anatomical knowledge in the diagnosis of the site of facial nerve lesion in clinical neurology. Examples are provided of disorders that can affect the facial nerve during its intra-cranial, intra-temporal and extra-cranial pathways, and key aspects of clinical management are discussed. The current study is complemented by original detailed dissections and sketches that highlight key anatomical features and emphasise the extent and nature of anatomical variations displayed by the facial nerve.

Burkholderia pseudomallei Rapidly Infects the Brain Stem and Spinal Cord via the Trigeminal Nerve after Intranasal Inoculation.

PubMed

St John, James A; Walkden, Heidi; Nazareth, Lynn; Beagley, Kenneth W; Ulett, Glen C; Batzloff, Michael R; Beacham, Ifor R; Ekberg, Jenny A K

2016-09-01

Infection with Burkholderia pseudomallei causes melioidosis, a disease with a high mortality rate (20% in Australia and 40% in Southeast Asia). Neurological melioidosis is particularly prevalent in northern Australian patients and involves brain stem infection, which can progress to the spinal cord; however, the route by which the bacteria invade the central nervous system (CNS) is unknown. We have previously demonstrated that B. pseudomallei can infect the olfactory and trigeminal nerves within the nasal cavity following intranasal inoculation. As the trigeminal nerve projects into the brain stem, we investigated whether the bacteria could continue along this nerve to penetrate the CNS. After intranasal inoculation of mice, B. pseudomallei caused low-level localized infection within the nasal cavity epithelium, prior to invasion of the trigeminal nerve in small numbers. B. pseudomallei rapidly invaded the trigeminal nerve and crossed the astrocytic barrier to enter the brain stem within 24 h and then rapidly progressed over 2,000 μm into the spinal cord. To rule out that the bacteria used a hematogenous route, we used a capsule-deficient mutant of B. pseudomallei that does not survive in the blood and found that it also entered the CNS via the trigeminal nerve. This suggests that the primary route of entry is via the nerves that innervate the nasal cavity. We found that actin-mediated motility could facilitate initial infection of the olfactory epithelium. Thus, we have demonstrated that B. pseudomallei can rapidly infect the brain and spinal cord via the trigeminal nerve branches that innervate the nasal cavity. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Electrophysiological characterization of human rectal afferents

PubMed Central

Ng, Kheng-Seong; Brookes, Simon J.; Montes-Adrian, Noemi A.; Mahns, David A.

2016-01-01

It is presumed that extrinsic afferent nerves link the rectum to the central nervous system. However, the anatomical/functional existence of such nerves has never previously been demonstrated in humans. Therefore, we aimed to identify and make electrophysiological recordings in vitro from extrinsic afferents, comparing human rectum to colon. Sections of normal rectum and colon were procured from anterior resection and right hemicolectomy specimens, respectively. Sections were pinned and extrinsic nerves dissected. Extracellular visceral afferent nerve activity was recorded. Neuronal responses to chemical [capsaicin and “inflammatory soup” (IS)] and mechanical (Von Frey probing) stimuli were recorded and quantified as peak firing rate (range) in 1-s intervals. Twenty-eight separate nerve trunks from eight rectums were studied. Of these, spontaneous multiunit afferent activity was recorded in 24 nerves. Peak firing rates increased significantly following capsaicin [median 6 (range 3–25) spikes/s vs. 2 (1–4), P < 0.001] and IS [median 5 (range 2–18) spikes/s vs. 2 (1–4), P < 0.001]. Mechanosensitive “hot spots” were identified in 16 nerves [median threshold 2.0 g (range 1.4–6.0 g)]. In eight of these, the threshold decreased after IS [1.0 g (0.4–1.4 g)]. By comparison, spontaneous activity was recorded in only 3/30 nerves studied from 10 colons, and only one hot spot (threshold 60 g) was identified. This study confirms the anatomical/functional existence of extrinsic rectal afferent nerves and characterizes their chemo- and mechanosensitivity for the first time in humans. They have different electrophysiological properties to colonic afferents and warrant further investigation in disease states. PMID:27789454

A Cell Line Producing Recombinant Nerve Growth Factor Evokes Growth Responses in Intrinsic and Grafted Central Cholinergic Neurons

NASA Astrophysics Data System (ADS)

Ernfors, Patrik; Ebendal, Ted; Olson, Lars; Mouton, Peter; Stromberg, Ingrid; Persson, Hakan

1989-06-01

The rat β nerve growth factor (NGF) gene was inserted into a mammalian expression vector and cotransfected with a plasmid conferring resistance to neomycin into mouse 3T3 fibroblasts. From this transfection a stable cell line was selected that contains several hundred copies of the rat NGF gene and produces excess levels of recombinant NGF. Such genetically modified cells were implanted into the rat brain as a probe for in vivo effects of NGF on central nervous system neurons. In a model of the cortical cholinergic deficits in Alzheimer disease, we demonstrate a marked increase in the survival of, and fiber outgrowth from, grafts of fetal basal forebrain cholinergic neurons, as well as stimulation of fiber formation by intact adult intrinsic cholinergic circuits in the cerebral cortex. Adult cholinergic interneurons in intact striatum also sprout vigorously toward implanted fibroblasts. Our results suggest that this model has implications for future treatment of neurodegenerative diseases.

Simultaneous central retinal artery occlusion and optic nerve vasculitis in Crohn disease.

PubMed

Coussa, Razek Georges; Ali-Ridha, Andre; Vila, Natalia; Alshareef, Rayan; Chen, John

2017-04-01

To describe a case of Crohn disease presenting as occlusive vasculitis resulting in a central retinal artery occlusion (CRAO) in one eye and transient ischemic optic neuropathy in the fellow eye. An 18-year-old patient recently diagnosed with biopsy-proven Crohn disease presented with CRAO OD after a previous episode of transient visual loss OS. Extensive workup was negative for other autoimmune or infectious etiologies. The patient was started on intravenous methylprednisolone for 72 h followed by maintenance dose of azathioprine and oral prednisone. Signs of inflammation resolved gradually with some improvement of visual acuity despite developing optic atrophy. To our knowledge, this is the first case of unilateral CRAO and bilateral optic nerve occlusive vasculitis in Crohn disease, which should be considered as an etiology of retinal vascular occlusive disorders especially in young patients. It is important for ophthalmologists to be aware of the ophthalmic risks associated with Crohn disease as aggressive treatment with systemic steroids and immunosuppressive agents is often needed.

A reinterpretation of certain disorders affecting the eye muscles and their tissues

PubMed Central

Poonyathalang, Anuchit; Khanna, Sangeeta; Leigh, R John

2007-01-01

Recent discoveries about the orbital tissues prompt a re-evaluation of the way that clinicians think about disorders affecting the extraocular muscles, their nerves and motoneurons in the brainstem. The revolutionary discovery that the orbital layers of the extraocular muscles insert not onto the eyeball, but into fibromuscular pulleys that guide the orbital layers, provides explanations for the kinematic properties of eye rotations and clinical findings in some patients with strabismus. The demonstration that all extraocular fibers types, except pale global fibers, lack synaptic folding provides an explanation for why saccades may remain fast in patients with limited ocular mobility due to myasthenia gravis. More than one mechanism may account for the observation that patients with disorders affecting the eye muscles or their nerves can present with the appearance of central disorders of ocular motility, such as internuclear ophthalmoplegia. New approaches to analyzing saccades in patients with disjunctive eye movements provide the means to identify disorders affecting the peripheral or central components of the ocular motor system, or both. PMID:19668518

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 and aortic depressor nerve stimulation, respectively.

17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model

PubMed Central

Chen, Yan; Guo, Wenjie; Li, Wenjuan; Cheng, Meng; Hu, Ying; Xu, Wenming

2016-01-01

Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2) on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG) explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP) expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation. PMID:27872858

Development of affinity-based delivery of NGF from a chondroitin sulfate biomaterial.

PubMed

Butterfield, Karen Chao; Conovaloff, Aaron W; Panitch, Alyssa

2011-01-01

Chondroitin sulfate is a major component of the extracellular matrix in both the central and peripheral nervous systems. Chondroitin sulfate is upregulated at injury, thus methods to promote neurite extension through chondroitin sulfate-rich matrices and synthetic scaffolds are needed. We describe the use of both chondroitin sulfate and a novel chondroitin sulfate-binding peptide to control the release of nerve growth factor. Interestingly, the novel chondroitin sulfate-binding peptide enhances the controlled release properties of the chondroitin sulfate gels. While introduction of chondroitin sulfate into a scaffold inhibits primary cortical outgrowth, the combination of chondroitin sulfate, chondroitin sulfate-binding peptide and nerve growth factor promotes primary cortical neurite outgrowth in chondroitin sulfate gels.

Genetic control of Drosophila nerve cord development

NASA Technical Reports Server (NTRS)

Skeath, James B.; Thor, Stefan

2003-01-01

The Drosophila ventral nerve cord has been a central model system for studying the molecular genetic mechanisms that control CNS development. Studies show that the generation of neural diversity is a multistep process initiated by the patterning and segmentation of the neuroectoderm. These events act together with the process of lateral inhibition to generate precursor cells (neuroblasts) with specific identities, distinguished by the expression of unique combinations of regulatory genes. The expression of these genes in a given neuroblast restricts the fate of its progeny, by activating specific combinations of downstream genes. These genes in turn specify the identity of any given postmitotic cell, which is evident by its cellular morphology and choice of neurotransmitter.

Haemangioblastoma of a cervical sensory nerve root in Von Hippel-Lindau syndrome.

PubMed

McEvoy, A W; Benjamin, E; Powell, M P

2000-10-01

Spinal haemangioblastomas are rare, accounting for only about 7% of all central nervous system cases. The case of a 40-year-old woman with a haemangioblastoma arising solely from a cervical sensory nerve root is presented. At operation via a cervical laminectomy, it was possible to resect the tumour en masse with the sensory ramus, by extending the laminectomy through the exit foramen for C6. Haemangioblastomas are commonly intramedullary, and have only been reported in this location on one previous occasion. The patient has Von Hippel-Lindau syndrome and a history of multiple solid tumours. The possible role of the Von Hippel-Lindau tumour suppressor gene in the pathogenesis of these neoplasms is discussed.

Central projections of the nervus terminalis and the nervus praeopticus in the lungfish brain revealed by nitric oxide synthase.

PubMed

Schober, A; Meyer, D L; Von Bartheld, C S

1994-11-01

Lungfishes possess two cranial nerves that are associated with the olfactory system: the nervus terminalis enters the telencephalon with the olfactory nerve, and the nervus praeopticus enters the diencephalon at the level of the optic nerve. We investigated the central projections of the nervus terminalis and the nervus praeopticus in the Australian lungfish (Neoceratodus forsteri) and in the African lungfish (Protopterus dolloi) by NADPH-diaphorase histochemistry (nitric oxide synthase; NOS) and compared them with the projections of the nervus terminalis of the frog (Xenopus laevis). In Neoceratodus, NOS-positive fascicles of the nervus terminalis divide and project with a ventral component through the septum and with a dorsal component through the pallium; fibers of both trajectories extend caudally beyond the anterior commissure and join the lateral forebrain bundle. In the nervus praeopticus, about 300 fibers contain NOS; they innervate the preoptic nucleus and continue their course through the diencephalon; many fibers cross in the commissure of the posterior tuberculum. In Protopterus, ganglion cells of the nervus terminalis and of the nervus praeopticus contain NOS. NOS-positive fibers of the nervus terminalis project through the septal region but not through the pallium. Several major fascicles cross in the rostral part of the anterior commissure, where they are joined by a small number of NOS-containing fibers of the nervus praeopticus. Both nerves innervate the preoptic nucleus. The number and pathways of the fascicles of the nervus terminalis are not always symmetric between the two sides. The nervus terminalis fascicles remain in a ventral position, whereas the nervus praeopticus gives rise to the more dorsal fascicles. Many fibers of the two nerves extend throughout the diencephalon and cross in the commissure of the posterior tuberculum. These findings demonstrate many similarities but also significant differences between the contributions of the nervus terminalis and the nervus praeopticus to forebrain projections in the two lungfishes. They support the view that the nervus praeopticus is part of a nervus terminalis system comparable to that in frogs and other nonmammalian vertebrates.

[Bilateral optic neuropathy and non-Hodkin's lymphoma].

PubMed

El Kettani, A; Lamari, H; Lahbil, D; Rais, L; Zaghloul, K

2006-01-01

While ocular lesion is commonly known in lymphoma, optic neuropathy is very rare : 1,3% of lymphomas affecting the central nervous systems. Authors report the case of a 75 year old patient treated in the haematology department for 8 years, for a large cell B phenotype stage IV lymphoma for which he received 7 chemotherapy courses (CHOP protocol). After a 4 year remission period, he presented a relapse with a rapid progressive bilateral impairment of visual acuity observed for a week before his admission. The ophthalmologic exam revealed no light perception and no afferent reflex on the right eye. There was light perception and weak afferent reflex on the left eye. The anterior segment was normal on both eyes and fundus examination revealed a bilateral stage I papillar oedema. The general exam showed a right facial palsy and an impairment of general condition. The orbital CT scan revealed a significant thickening of both optic nerves caused by lymphomatous infiltration. A chemotherapy with highly dosed IV and intrathecal methotrexate was performed. the optic neuropathy is usually associated with a generalized lymphoma with central nervous system involvement, but sometimes can precede the systemic spread of the disease. Apart from infiltration, the optic nerve can be compressed by an intracranial or orbital tumor. The optic neuropathy can also be caused by lymphomatous leptomeningitis.

Cellular Localization of Aquaporin-1 in the Human and Mouse Trigeminal Systems

PubMed Central

Gu, Minxia; Marshall, Charles; Ding, Jiong; Hu, Gang; Xiao, Ming

2012-01-01

Previous studies reported that a subpopulation of mouse and rat trigeminal neurons express water channel aquaporin-1 (AQP1). In this study we make a comparative investigation of AQP1 localization in the human and mouse trigeminal systems. Immunohistochemistry and immunofluorescence results showed that AQP1 was localized to the cytoplasm and cell membrane of some medium and small-sized trigeminal neurons. Additionally, AQP1 was found in numerous peripheral trigeminal axons of humans and mice. In the central trigeminal root and brain stem, AQP1 was specifically expressed in astrocytes of humans, but was restricted to nerve fibers within the central trigeminal root and spinal trigeminal tract and nucleus in mice. Furthermore, AQP1 positive nerve fibers were present in the mucosal and submucosal layers of human and mouse oral tissues, but not in the muscular and subcutaneous layers. Fluorogold retrograde tracing demonstrated that AQP1 positive trigeminal neurons innervate the mucosa but not skin of cheek. These results reveal there are similarities and differences in the cellular localization of AQP1 between the human and mouse trigeminal systems. Selective expression of AQP1 in the trigeminal neurons innervating the oral mucosa indicates an involvement of AQP1 in oral sensory transduction. PMID:23029502

Phrenic nerve stimulation for the treatment of central sleep apnea.

PubMed

Abraham, William T; Jagielski, Dariusz; Oldenburg, Olaf; Augostini, Ralph; Krueger, Steven; Kolodziej, Adam; Gutleben, Klaus-Jürgen; Khayat, Rami; Merliss, Andrew; Harsch, Manya R; Holcomb, Richard G; Javaheri, Shahrokh; Ponikowski, Piotr

2015-05-01

The aim of this study was to evaluate chronic, transvenous, unilateral phrenic nerve stimulation to treat central sleep apnea (CSA) in a prospective, multicenter, nonrandomized study. CSA occurs predominantly in patients with heart failure and increases the risk for morbidity and mortality. Established therapies for CSA are lacking, and those available are limited by poor patient adherence. Fifty-seven patients with CSA underwent baseline polysomnography followed by transvenous phrenic nerve stimulation system implantation and follow-up. Feasibility was assessed by implantation success rate and therapy delivery. Safety was evaluated by monitoring of device- and procedure-related adverse events. Efficacy was evaluated by changes in the apnea-hypopnea index at 3 months. Quality of life at 6 months was evaluated using a sleepiness questionnaire, patient global assessment, and, in patients with heart failure at baseline, the Minnesota Living With Heart Failure Questionnaire. The study met its primary end point, demonstrating a 55% reduction in apnea-hypopnea index from baseline to 3 months (49.5 ± 14.6 episodes/h vs. 22.4 ± 13.6 episodes/h of sleep; p < 0.0001; 95% confidence interval for change: -32.3 to -21.9). Central apnea index, oxygenation, and arousals significantly improved. Favorable effects on quality of life and sleepiness were noted. In patients with heart failure, the Minnesota Living With Heart Failure Questionnaire score significantly improved. Device- or procedure-related serious adverse events occurred in 26% of patients through 6 months post therapy initiation, predominantly due to lead repositioning early in the study. Therapy was well tolerated. Efficacy was maintained at 6 months. Transvenous, unilateral phrenic nerve stimulation appears safe and effective for treating CSA. These findings should be confirmed in a prospective, randomized, controlled trial. (Chronic Evaluation of Respicardia Therapy; NCT01124370). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Lumbar Nerve Root Occupancy in the Foramen in Achondroplasia

PubMed Central

Modi, Hitesh N.; Song, Hae-Ryong; Yang, Jae Hyuk

2008-01-01

Lumbar stenosis is common in patients with achondroplasia because of narrowing of the neural canal. However, it is unclear what causes stenosis, narrowing of the central canal or foramina. We performed a morphometric analysis of the lumbar nerve roots and intervertebral foramen in 17 patients (170 nerve roots and foramina) with achondroplasia (eight symptomatic, nine asymptomatic) and compared the data with that from 20 (200 nerve roots and foramina) asymptomatic patients without achondroplasia presenting with low back pain without neurologic symptoms. The measurements were made on left and right parasagittal MRI scans of the lumbar spine. The foramen area and root area were reduced at all levels from L1 to L5 between the patients with achondroplasia (Groups I and II) and the nonachondroplasia group (Group III). The percentage of nerve root occupancy in the foramen between Group I and Group II as compared with the patients without achondroplasia was similar or lower. This implied the lumbar nerve root size in patients with achondroplasia was smaller than that of the normal population and thus there is no effective nerve root compression. Symptoms of lumbar stenosis in achondroplasia may be arising from the central canal secondary to degenerative disc disease rather than a true foraminal stenosis. Level of Evidence: Level I, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18259829

Key Role of CRF in the Skin Stress Response System

PubMed Central

Zmijewski, Michal A.; Zbytek, Blazej; Tobin, Desmond J.; Theoharides, Theoharis C.; Rivier, Jean

2013-01-01

The discovery of corticotropin-releasing factor (CRF) or CRH defining the upper regulatory arm of the hypothalamic-pituitary-adrenal (HPA) axis, along with the identification of the corresponding receptors (CRFRs 1 and 2), represents a milestone in our understanding of central mechanisms regulating body and local homeostasis. We focused on the CRF-led signaling systems in the skin and offer a model for regulation of peripheral homeostasis based on the interaction of CRF and the structurally related urocortins with corresponding receptors and the resulting direct or indirect phenotypic effects that include regulation of epidermal barrier function, skin immune, pigmentary, adnexal, and dermal functions necessary to maintain local and systemic homeostasis. The regulatory modes of action include the classical CRF-led cutaneous equivalent of the central HPA axis, the expression and function of CRF and related peptides, and the stimulation of pro-opiomelanocortin peptides or cytokines. The key regulatory role is assigned to the CRFR-1α receptor, with other isoforms having modulatory effects. CRF can be released from sensory nerves and immune cells in response to emotional and environmental stressors. The expression sequence of peptides includes urocortin/CRF→pro-opiomelanocortin→ACTH, MSH, and β-endorphin. Expression of these peptides and of CRFR-1α is environmentally regulated, and their dysfunction can lead to skin and systemic diseases. Environmentally stressed skin can activate both the central and local HPA axis through either sensory nerves or humoral factors to turn on homeostatic responses counteracting cutaneous and systemic environmental damage. CRF and CRFR-1 may constitute novel targets through the use of specific agonists or antagonists, especially for therapy of skin diseases that worsen with stress, such as atopic dermatitis and psoriasis. PMID:23939821

Innovations in prosthetic interfaces for the upper extremity.

PubMed

Kung, Theodore A; Bueno, Reuben A; Alkhalefah, Ghadah K; Langhals, Nicholas B; Urbanchek, Melanie G; Cederna, Paul S

2013-12-01

Advancements in modern robotic technology have led to the development of highly sophisticated upper extremity prosthetic limbs. High-fidelity volitional control of these devices is dependent on the critical interface between the patient and the mechanical prosthesis. Recent innovations in prosthetic interfaces have focused on several control strategies. Targeted muscle reinnervation is currently the most immediately applicable prosthetic control strategy and is particularly indicated in proximal upper extremity amputations. Investigation into various brain interfaces has allowed acquisition of neuroelectric signals directly or indirectly from the central nervous system for prosthetic control. Peripheral nerve interfaces permit signal transduction from both motor and sensory nerves with a higher degree of selectivity. This article reviews the current developments in each of these interface systems and discusses the potential of these approaches to facilitate motor control and sensory feedback in upper extremity neuroprosthetic devices.

Update on neuromyelitis optica: natural history and management

PubMed Central

Jindahra, Panitha; Plant, T

2012-01-01

Neuromyelitis optica or Devic disease is an inflammatory disorder of the central nervous system. It is caused by antibodies that attack aquaporin 4 water channels in the cell membrane of astrocytic foot processes at the blood brain barrier. It can involve the optic nerve, the spinal cord and beyond. Here we review its pathophysiology, clinical features, and therapy. PMID:28539779

Central nervous system borreliosis mimicking a pontine tumour.

PubMed

Latsch, Kirsten; Tappe, Dennis; Warmuth-Metz, Monika; Hebestreit, Helge

2006-11-01

In childhood, facial nerve palsy and headache are typical symptoms of second and third stage neuroborreliosis. While focal demyelination is occasionally observed on MRI scans, the appearance of a tumorous lesion is extremely rare. The case of a 10-year-old girl with neuroborreliosis mimicking a space-occupying lesion in the brainstem, without any previously recognized manifestations of borreliosis, is reported.

The oculomotor system of decapod cephalopods: eye muscles, eye muscle nerves, and the oculomotor neurons in the central nervous system.

PubMed

Budelmann, B U; Young, J Z

1993-04-29

Fourteen extraocular eye muscles are described in the decapods Loligo and Sepioteuthis, and thirteen in Sepia; they are supplied by four eye muscle nerves. The main action of most of the muscles is a linear movement of the eyeball, only three muscles produce strong rotations. The arrangement, innervation and action of the decapod eye muscles are compared with those of the seven eye muscles and seven eye muscle nerves in Octopus. The extra muscles in decapods are attached to the anterior and superior faces of the eyes. At least, the anterior muscles, and presumably also the superior muscles, are concerned with convergent eye movements for binocular vision during fixation and capture of prey by the tentacles. The remaining muscles are rather similar in the two cephalopod groups. In decapods, the anterior muscles include conjunctive muscles; these cross the midline and each presumably moves both eyes at the same time during fixation. In the squids Loligo and Sepioteuthis there is an additional superior conjunctive muscle of perhaps similar function. Some of the anterior muscles are associated with a narrow moveable plate, the trochlear cartilage; it is attached to the eyeball by trochlear membranes. Centripetal cobalt fillings showed that all four eye muscle nerves have fibres that originate from somata in the ipsilateral anterior lateral pedal lobe, which is the oculomotor centre. The somata of the individual nerves show different but overlapping distributions. Bundles of small presumably afferent fibres were seen in two of the four nerves. They do not enter the anterior lateral pedal lobe but run to the ventral magnocellular lobe; some afferent fibres enter the brachio-palliovisceral connective and run perhaps as far as the palliovisceral lobe.

Embryonic development of the innervation of the locust extensor tibiae muscle by identified neurons: formation and elimination of inappropriate axon branches.

PubMed

Myers, C M; Whitington, P M; Ball, E E

1990-01-01

Intracellular dye fills have been used to reveal the pattern of embryonic growth of each of the four neurons which innervate the extensor tibiae muscle (ETi) of the hind leg of the locust. The growth cone of the slow extensor tibiae motoneuron (SETi), the first of the four neurons to leave the central nervous system, pioneers nerve 3 (N3). The fast extensor motoneuron (FETi), the next neuron to grow out, follows earlier outgrowing motoneurons into the periphery in nerve 5 (N5) and then rejoins SETi in N3. As it transfers from N5 to N3, it is transiently dye-coupled to the Tr1 pioneer neuron which spans the gap between the two nerves. It then follows SETi onto the ETi muscle in the femur. The common inhibitory neuron and the dorsal unpaired median neuron (DUMETi) follow SETi and FETi in nerves 3B2 and 5B1, respectively. SETi's growth cone requires almost twice as long to reach ETi as those of the three later motoneurons, all of which follow preexisting neural pathways. At least three of the four developing motoneurons form one or more axon branches not found in the adult. These branches may occur (1) at segmental boundaries; (2) where the nerve, which the growth cone is following, itself branches or the growth cone encounters another nerve; or (3) when the axon continues to grow beyond its target muscle. These findings contrast with the apparent absence of inappropriate axon branches in another developing locust neuromuscular system and during the innervation of zebrafish myotomes, but resemble in some ways the transient production of inappropriate axonal branches reported for embryonic leech motoneurons.

Histone deacetylase expression patterns in developing murine optic nerve

PubMed Central

2014-01-01

Background Histone deacetylases (HDACs) play important roles in glial cell development and in disease states within multiple regions of the central nervous system. However, little is known about HDAC expression or function within the optic nerve. As a first step in understanding the role of HDACs in optic nerve, this study examines the spatio-temporal expression patterns of methylated histone 3 (K9), acetylated histone 3 (K18), and HDACs 1–6 and 8–11 in the developing murine optic nerve head. Results Using RT-qPCR, western blot and immunofluorescence, three stages were analyzed: embryonic day 16 (E16), when astrocyte precursors are found in the optic stalk, postnatal day 5 (P5), when immature astrocytes and oligodendrocytes are found throughout the optic nerve, and P30, when optic nerve astrocytes and oligodendrocytes are mature. Acetylated and methylated histone H3 immunoreactivity was co-localized in the nuclei of most SOX2 positive glia within the optic nerve head and adjacent optic nerve at all developmental stages. HDACs 1–11 were expressed in the optic nerve glial cells at all three stages of optic nerve development in the mouse, but showed temporal differences in overall levels and subcellular localization. HDACs 1 and 2 were predominantly nuclear throughout optic nerve development and glial cell maturation. HDACs 3, 5, 6, 8, and 11 were predominantly cytoplasmic, but showed nuclear localization in at least one stage of optic nerve development. HDACs 4, 9 and10 were predominantly cytoplasmic, with little to no nuclear expression at any time during the developmental stages examined. Conclusions Our results showing that HDACs 1, 2, 3, 5, 6, 8, and 11 were each localized to the nuclei of SOX2 positive glia at some stages of optic nerve development and maturation and extend previous reports of HDAC expression in the aging optic nerve. These HDACs are candidates for further research to understand how chromatin remodeling through acetylation, deacetylation and methylation contributes to glial development as well as their injury response. PMID:25011550

Generalized mechanical pain sensitivity over nerve tissues in patients with strictly unilateral migraine.

PubMed

Fernández-de-las-Peñas, César; Arendt-Nielsen, Lars; Cuadrado, María Luz; Pareja, Juan A

2009-06-01

No study has previously analyzed pressure pain sensitivity of nerve trunks in migraine. This study aimed to examine the differences in mechanical pain sensitivity over specific nerves between patients with unilateral migraine and healthy controls. Blinded investigators assessed pressure pain thresholds (PPT) over the supra-orbital nerves (V1) and peripheral nerve trunks of both upper extremities (median, radial, and ulnar nerves) in 20 patients with strictly unilateral migraine and 20 healthy matched controls. Pain intensity after palpation over both supra-orbital nerves was also assessed. A pressure algometer was used to quantify PPT, whereas a 10-point numerical pain rate scale was used to evaluate pain to palpation over the supra-orbital nerve. The analysis of covariance revealed that pain to palpation over the supra-orbital nerve was significantly higher (P<0.001) on the symptomatic side (mean: 3.4, SD: 1.5) as compared with the nonsymptomatic side (mean: 0.5, SD: 1.2) in patients with migraine and both the dominant (mean: 0.2, SD: 0.4) and nondominant (mean: 0.3, SD: 0.5) sides in healthy controls. PPT assessed over the supra-orbital nerve on the symptomatic side (mean: 1.05, SD: 0.2 kg/cm) was significantly lower (P<0.05) than PPT measurements on the nonsymptomatic side (mean: 1.35, SD: 0.3 kg/cm) and either the dominant (mean: 1.9, SD: 0.2 kg/cm) or nondominant (mean: 1.9, SD: 0.3 kg/cm) sides in controls (P<0.001). Finally, PPT assessed over the median, ulnar, and radial nerves were significantly lower in patients with migraine as compared with controls (P<0.001), without side-to-side differences (P>0.6). In patients with unilateral migraine, we found increased mechano-sensitivity of the supra-orbital nerve on the symptomatic side of the head. Outside the head, the same patients showed increased mechano-sensitivity of the main peripheral nerves of both upper limbs, without asymmetries. Such diffuse hypersensitivity of the peripheral nerves lends further evidence to the presence of a state of hyperexcitability of the central nervous system in patients with unilateral migraine.

Hyperventilation-induced nystagmus in a large series of vestibular patients.

PubMed

Califano, L; Melillo, M G; Vassallo, A; Mazzone, S

2011-02-01

The Hyperventilation Test is widely used in the "bed-side examination" of vestibular patients. It can either activate a latent nystagmus in central or peripheral vestibular diseases or it can interact with a spontaneous nystagmus, by reducing it or increasing it. Aims of this study were to determine the incidence, patterns and temporal characteristics of Hyperventilation-induced nystagmus in patients suffering from vestibular diseases, as well as its contribution to the differential diagnosis between vestibular neuritis and neuroma of the 8(th) cranial nerve, and its behaviour in some central vestibular diseases. The present study includes 1202 patients featuring, at vestibular examination, at least one sign of vestibular system disorders or patients diagnosed with a "Migraine-related vertigo" or "Chronic subjective dizziness". The overall incidence of Hyperventilation-induced nystagmus was 21.9%. It was detected more frequently in retrocochlear vestibular diseases rather than in end-organ vestibular diseases: 5.3% in Paroxysmal Positional Vertigo, 37.1% in Menière's disease, 37.6% in compensated vestibular neuritis, 77.2% in acute vestibular neuritis and 91.7% in neuroma of the 8(th) cranial nerve. In acute vestibular neuritis, three HVIN patterns were observed: Paretic pattern: temporary enhancement of the spontaneous nystagmus; Excitatory pattern: temporary inhibition of the spontaneous nystagmus; Strong excitatory pattern: temporary inversion of the spontaneous nystagmus. Excitatory patterns proved to be time-dependent in that they disappeared and were replaced by the paretic pattern over a period of maximum 18 days since the beginning of the disorder. In acoustic neuroma, Hyperventilation-induced nystagmus was frequently observed (91.7%), either in the form of an excitatory pattern (fast phases towards the affected site) or in the form of a paretic pattern (fast phases towards the healthy side). The direction of the nystagmus is only partially related to tumour size, whereas other mechanisms, such as demyelination or a break in nerve fibres, might have an important role in triggering the situation. Hyperventilation-induced nystagmus has frequently been detected in cases of demyelinating diseases and in cerebellar diseases: in multiple sclerosis, hyperventilation inhibits a central type of spontaneous nystagmus or evokes nystagmus in 75% of patients; in cerebellar diseases, hyperventilation evokes or enhances a central spontaneous nystagmus in 72.7% of patients. In conclusion the Hyperventilation Test can provide patterns of oculomotor responses that indicate a diagnostic investigation through cerebral magnetic resonance imaging enhanced by gadolinium, upon suspicion of neuroma of the 8(th) cranial nerve or of a central disease. In our opinion, however, Hyperventilation-induced nystagmus always needs to be viewed within the more general context of a complete examination of the vestibular and acoustic system.

PubMed Central

CALIFANO, L.; MELILLO, M.G.; VASSALLO, A.; MAZZONE, S.

2011-01-01

SUMMARY The Hyperventilation Test is widely used in the "bed-side examination" of vestibular patients. It can either activate a latent nystagmus in central or peripheral vestibular diseases or it can interact with a spontaneous nystagmus, by reducing it or increasing it. Aims of this study were to determine the incidence, patterns and temporal characteristics of Hyperventilation-induced nystagmus in patients suffering from vestibular diseases, as well as its contribution to the differential diagnosis between vestibular neuritis and neuroma of the 8th cranial nerve, and its behaviour in some central vestibular diseases. The present study includes 1202 patients featuring, at vestibular examination, at least one sign of vestibular system disorders or patients diagnosed with a "Migraine-related vertigo" or "Chronic subjective dizziness". The overall incidence of Hyperventilation-induced nystagmus was 21.9%. It was detected more frequently in retrocochlear vestibular diseases rather than in end-organ vestibular diseases: 5.3% in Paroxysmal Positional Vertigo, 37.1% in Menière's disease, 37.6% in compensated vestibular neuritis, 77.2% in acute vestibular neuritis and 91.7% in neuroma of the 8th cranial nerve. In acute vestibular neuritis, three HVIN patterns were observed: Paretic pattern: temporary enhancement of the spontaneous nystagmus; Excitatory pattern: temporary inhibition of the spontaneous nystagmus; Strong excitatory pattern: temporary inversion of the spontaneous nystagmus. Excitatory patterns proved to be time-dependent in that they disappeared and were replaced by the paretic pattern over a period of maximum 18 days since the beginning of the disorder. In acoustic neuroma, Hyperventilation-induced nystagmus was frequently observed (91.7%), either in the form of an excitatory pattern (fast phases towards the affected site) or in the form of a paretic pattern (fast phases towards the healthy side). The direction of the nystagmus is only partially related to tumour size, whereas other mechanisms, such as demyelination or a break in nerve fibres, might have an important role in triggering the situation. Hyperventilation-induced nystagmus has frequently been detected in cases of demyelinating diseases and in cerebellar diseases: in multiple sclerosis, hyperventilation inhibits a central type of spontaneous nystagmus or evokes nystagmus in 75% of patients; in cerebellar diseases, hyperventilation evokes or enhances a central spontaneous nystagmus in 72.7% of patients. In conclusion the Hyperventilation Test can provide patterns of oculomotor responses that indicate a diagnostic investigation through cerebral magnetic resonance imaging enhanced by gadolinium, upon suspicion of neuroma of the 8th cranial nerve or of a central disease. In our opinion, however, Hyperventilation-induced nystagmus always needs to be viewed within the more general context of a complete examination of the vestibular and acoustic system. PMID:21808459

Central amaurosis induced by an intraocular, posttraumatic fibrosarcoma in a cat.

PubMed

Barrett, P M; Merideth, R E; Alarcon, F L

1995-01-01

A 12-year-old, castrated male, domestic shorthair cat with a previous penetrating trauma to the left globe which progressed to a phthisical eye presented for acute blindness. Ophthalmic examination and electroretinography of the right eye were found to be normal. Following euthanasia, gross and microscopic examinations were completed. A left intraocular, posttraumatic fibrosarcoma with extension to the optic nerve and chiasm and induced right optic nerve fiber degeneration at the optic chiasm with necrosis leading to central amaurosis were diagnosed.

[NADPH-diaphorase activity in digestive system of gastropod molluscs Achatina fulica and Littorina littorea].

PubMed

Zaĭtseva, O V; Kuznetsova, T V; Markosova, T G

2009-01-01

Localization and peculiarities of NO-ergic elements were studied for he first time throughout the entire length of digestive tract of the marine gastropod mollusc Achatina fulica (Prosobranchia) and the terrestrial molusc Littorina littorea (Pulmonata) by using histochemical method of detection of NADPH-diaphorase (NADPHd). NO-ergic cells and fibers were revealed in all parts of the mollusc digestive tract beginning from pharynx. An intensive NADPHd activity was found in many intraepithelial cells of the open type and in their processes in intra- and subepithelial nerve plexuses, single subepithelial neurons, granular connective tissue cells, and numerous nerve fibers among muscle elements of he digestive tract wall as well as in nerves innervating the tract. NADPHd was also present in receptor cells of he oral area and in the central A. fulica ganglia participating in innervation of the digestive tract. The digestive tract NO-ergic system ofA. fulica has a more complex organization that that of L. littorea. In the A. fulica pharynx, stomach, and midgut, directly beneath epithelium, there is revealed a complex system of glomerular structures formed by thin NADPHd-positive nerve fibers coming from the side of epithelium. More superficially under the main groups of muscle elements, small agglomerations of NADPHd-positive neurons are seen, which could be considered as primitive, non-formed microganglia. Peculiarities of distribution and a possible functional role of NO-ergic elements in the digestive tract of molluscs are discussed as compared with other invertebrate and vertebrate animals.

Cancer around the brain

PubMed Central

Grisold, Wolfgang; Grisold, Anna

2014-01-01

Background Neuro-oncologists are familiar with primary brain tumors, intracerebral metastases meningeal carcinomatosis and extracerebral intracranial tumors as meningeoma. For these conditions, and also some other rare tumor entities several treatment options exist. Cancer can also involve structures around the brain as the dura, the base of the skull, the cavities of the skull and tissue around the bony skull, the skin, the tissue of the neck. and either compress, invade or spread in the central or peripheral nervous system. Methods A systematic literature research was conducted determining symptoms and signs, tumor sites of nerve invasion, tumor types, diagnostic techniques, mechanisms of nerve invasion, and important differential diagnosis. Additional cases from own experience were added for illustration. Results The mechanisms of tumor invasion of cranial nerves is heterogenous and not only involves several types of invasion, but also spread along the cranial nerves in antero- and retrograde fashion and even spread into different nerve territories via anastomosis. In addition the concept of angiosomas may have an influence on the spread of metastases. Conclusion In addition to the well described tumor spread in meningeal carcinomatosis and base of the skull metastases, dural spread, lesions of the bony skull, the cavities of the skull and skin of the face and tissue of the neck region need to be considered, and have an impact on therapeutic decisions. PMID:26034610

[Facial nerve injuries cause changes in central nervous system microglial cells].

PubMed

Cerón, Jeimmy; Troncoso, Julieta

2016-12-01

Our research group has described both morphological and electrophysiological changes in motor cortex pyramidal neurons associated with contralateral facial nerve injury in rats. However, little is known about those neural changes, which occur together with changes in surrounding glial cells. To characterize the effect of the unilateral facial nerve injury on microglial proliferation and activation in the primary motor cortex. We performed immunohistochemical experiments in order to detect microglial cells in brain tissue of rats with unilateral facial nerve lesion sacrificed at different times after the injury. We caused two types of lesions: reversible (by crushing, which allows functional recovery), and irreversible (by section, which produces permanent paralysis). We compared the brain tissues of control animals (without surgical intervention) and sham-operated animals with animals with lesions sacrificed at 1, 3, 7, 21 or 35 days after the injury. In primary motor cortex, the microglial cells of irreversibly injured animals showed proliferation and activation between three and seven days post-lesion. The proliferation of microglial cells in reversibly injured animals was significant only three days after the lesion. Facial nerve injury causes changes in microglial cells in the primary motor cortex. These modifications could be involved in the generation of morphological and electrophysiological changes previously described in the pyramidal neurons of primary motor cortex that command facial movements.

Enterocyte-afferent nerve interactions in dietary fat sensing.

PubMed

Mansouri, A; Langhans, W

2014-09-01

The central nervous system (CNS) constantly monitors nutrient availability in the body and, in particular, in the gastrointestinal (GI) tract to regulate nutrient and energy homeostasis. Extrinsic parasympathetic and sympathetic nerves are crucial for CNS nutrient sensing in the GI tract. These extrinsic afferent nerves detect the nature and amount of nutrients present in the GI tract and relay the information to the brain, which controls energy intake and expenditure accordingly. Dietary fat and fatty acids are sensed through various direct and indirect mechanisms. These sensing processes involve the binding of fatty acids to specific G protein-coupled receptors expressed either on the afferent nerve fibres or on the surface of enteroendocrine cells that release gut peptides, which themselves can modulate afferent nerve activity through their cognate receptors or have endocrine effects directly on the brain. Further dietary fat sensing mechanisms that are related to enterocyte fat handling and metabolism involve the release of several possible chemical mediators such as fatty acid ethanolamides or apolipoprotein A-IV. We here present evidence for yet another mechanism that may be based on ketone bodies resulting from enterocyte oxidation of dietary fat-derived fatty acids. The presently available evidence suggests that sympathetic rather than vagal afferents are involved, but further experiments are necessary to critically examine this concept. © 2014 John Wiley & Sons Ltd.

[Peripheral neuropathy in systemic lupus erythematosus with epineural vasculitis and antiphospholipid antibodies].

PubMed

Rafai, M A; Fadel, H; Boulaajaj, F Z; Gam, I; El Moutawakkil, B; Karkouri, M; Hakim, K; Slassi, I

2007-01-01

Neurological manifestations of systemic lupus erythematosus are frequent and polymorphic. Their frequency varies according to authors (24-75p.cent). Central nervous system complications predominate; peripheral features are rare, classically symmetrical polyneuropathy, multiple mononeuropathies or cranial nerve involvement. We report a case of a 48-year-old woman presenting a histologically documented sensitivo-motor polyneuropathy with severe motor involvement complicating lupus associated with antiphospholipides antibodies. Outcome was good after cyclophosphamid pulse. We discuss the frequency of peripheral involvement in systemic lupus erythematosus, pathogenic mechanisms, therapeutic possibilities and outcome of this complication.

Peripheral and central interactions between the renin-angiotensin system and the renal sympathetic nerves in control of renal function.

PubMed

DiBona, G F

2001-06-01

Increases in renal sympathetic nerve activity (RSNA) regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. As increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between RSNA and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, that is, the direct (via specific innervation) and indirect (via angiotensin II) contributions of increased RSNA to the regulation of renal function. The effects of increased RSNA on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with angiotensin-converting enzyme inhibitors or angiotensin II-type AT1 receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated following renal denervation. These interactions can also be extrarenal, that is, in the central nervous system, wherein RSNA and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, the permeable blood-brain barrier of which permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II type AT1 receptor antagonists, into the ventricular system or microinjected into the rostral ventrolateral medulla, are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (e.g., congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and RSNA are involved in influencing the neural control of renal function.

Prevention of experimental autoimmune encephalomyelitis by antibodies against α4βl integrin

NASA Astrophysics Data System (ADS)

Yednock, Ted A.; Cannon, Catherine; Fritz, Lawrence C.; Sanchez-Madrid, Francisco; Steinman, Lawrence; Karin, Nathan

1992-03-01

EXPERIMENTAL autoimmune encephalomyelitis (EAE) is an inflammatory condition of the central nervous system with similarities to multiple sclerosis1,2. In both diseases, circulating leukocytes penetrate the blood-brain barrier and damage myelin, resulting in impaired nerve conduction and paralysis3-5. We sought to identify the adhesion receptors that mediate the attachment of circulating leukocytes to inflamed brain endothelium in EAE, because this interaction is the first step in leukocyte entry into the central nervous system. Using an in vitro adhesion assay on tissue sections, we found that lymphocytes and monocytes bound selectively to inflamed EAE brain vessels. Binding was inhibited by antibodies against the integrin molecule α4βl, but not by antibodies against numerous other adhesion receptors. When tested in vivo, anti-α4 integrin effectively prevented the accumulation of leukocytes in the central nervous system and the development of EAE. Thus, therapies designed to interfere with α4βl integrin may be useful in treating inflammatory diseases of the central nervous system, such as multiple sclerosis.

Fatal Meningoencephalomyelitis due to the Tick-borne Encephalitis Virus: The First Detailed Neurological Observation in a Japanese Patient from the Central Part of Hokkaido Island.

PubMed

Tajima, Yasutaka; Yaguchi, Hiroaki; Mito, Yasunori

2018-01-01

To date, the only instance of tick-borne encephalitis (TBE) in Japan was reported from the southern part of Hokkaido Island in 1993; no other cases have been reported since then. We herein report the first case of TBE reported in the central part of Hokkaido Island, and describe the fatal clinical course of a patient who presented with meningoencephalomyelitis, which partly involved the nerve root. Magnetic resonance imaging (MRI) of the patient's cranium and spine revealed characteristic central nervous system involvement. Our case report is extremely relevant to efforts to protect public health and for precautions against TBE pandemics.

Olfactory ensheathing cells: nitric oxide production and innate immunity.

PubMed

Harris, Julie A; West, Adrian K; Chuah, Meng Inn

2009-12-01

Olfactory nerves extend from the nasal cavity to the central nervous system and provide therefore, a direct route for pathogenic infection of the brain. Since actual infection by this route remains relatively uncommon, powerful endogenous mechanisms for preventing microbial infection must exist, but these remain poorly understood. Our previous studies unexpectedly revealed that the unique glial cells that ensheath olfactory nerves, olfactory ensheathing cells (OECs), expressed components of the innate immune response. In this study, we show that OECs are able to detect and respond to bacterial challenge via the synthesis of nitric oxide. In vitro studies revealed that inducible nitric oxide synthase (iNOS) mRNA and protein were present in Escherichia coli- and Staphylococcus aureus-incubated OECs, but were barely detectable in untreated OECs. Neuronal NOS and endothelial NOS were not expressed by OECs pre- and post-bacterial incubation. Nuclear translocation of nuclear factor kappa B (NFkappaB), detectable in the majority of OECs 1 h following bacterial incubation, preceded iNOS induction which resulted in the production of nitric oxide. N(G)-methyl-L-arginine significantly attenuated nitric oxide (P < 0.001) and nitrite production (P < 0.001) by OECs. In rat olfactory mucosa which was compromised by irrigation with 0.17M zinc sulfate or 0.7% Triton X-100 to facilitate bacterial infiltration, OECs contributed to a robust synthesis of iNOS. These data strongly support the hypothesis that OECs are an essential component of the innate immune response against bacterial invasion of the central nervous system via olfactory nerves.

Glycogen function in adult central and peripheral nerves.

PubMed

Evans, Richard D; Brown, Angus M; Ransom, Bruce R

2013-08-01

We studied the roles of glycogen in axonal pathways of the central nervous system (CNS) and peripheral nervous system (PNS). By using electrophysiological recordings, in combination with biochemical glycogen assay, it was possible to determine whether glycogen was crucial to axon function under different conditions. Glycogen was present both in mouse optic nerve (MON) and in mouse sciatic nerve (MSN). Aglycemia caused loss of the compound action potential (CAP) in both pathways after a latency of 15 min (MON) and 120 min for myelinated axons (A fibers) in the MSN. With the exception of unmyelinated axons (C fibers) in the MSN, CAP decline began when usable glycogen was exhausted. Glycogen was located in astrocytes in the MON and in myelinating Schwann cells in the MSN; it was absent from the Schwann cells surrounding unmyelinated C fibers. In MON, astrocytic glycogen is metabolized to lactate and "shuttled" to axons to support metabolism. The ability of lactate to support A fiber conduction in the absence of glucose suggests a common pathway in both the CNS and the PNS. Lactate is released from MON and MSN in substantial quantities. That lactate levels fall in MSN in the presence of diaminobenzidine, which inhibits glycogen phosphorylase, strongly suggests that glycogen metabolism contributes to lactate release under resting conditions. Glycogen is a "backup" energy substrate in both the CNS and the PNS and, beyond sustaining excitability during glucose deprivation, has the capacity to subsidize the axonal energy demands during times of intense activity in the presence of glucose. Copyright © 2013 Wiley Periodicals, Inc.

Device-based approaches for renal nerve ablation for hypertension and beyond.

PubMed

Thorp, Alicia A; Schlaich, Markus P

2015-01-01

Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy of renal denervation over a sham procedure, prompting widespread re-evaluation of the therapy's efficacy. Disrupting renal afferent sympathetic signaling to the hypothalamus with renal denervation lowers central sympathetic tone, which has the potential to confer additional clinical benefits beyond blood pressure control. Specifically, there has been substantial interest in the use of renal denervation as either a primary or adjunct therapy in pathological conditions characterized by central sympathetic overactivity such as renal disease, heart failure and metabolic-associated disorders. Recent findings from pre-clinical and proof-of-concept studies appear promising with renal denervation shown to confer cardiovascular and metabolic benefits, largely independent of changes in blood pressure. This review explores the pathological rationale for targeting sympathetic renal nerves for blood pressure control. Latest developments in renal nerve ablation modalities designed to improve procedural success are discussed along with prospective findings on the efficacy of renal denervation to lower blood pressure in treatment-resistant hypertensive patients. Preliminary evidence in support of renal denervation as a possible therapeutic option in disease states characterized by central sympathetic overactivity is also presented.

Device-based approaches for renal nerve ablation for hypertension and beyond

PubMed Central

Thorp, Alicia A.; Schlaich, Markus P.

2015-01-01

Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy of renal denervation over a sham procedure, prompting widespread re-evaluation of the therapy's efficacy. Disrupting renal afferent sympathetic signaling to the hypothalamus with renal denervation lowers central sympathetic tone, which has the potential to confer additional clinical benefits beyond blood pressure control. Specifically, there has been substantial interest in the use of renal denervation as either a primary or adjunct therapy in pathological conditions characterized by central sympathetic overactivity such as renal disease, heart failure and metabolic-associated disorders. Recent findings from pre-clinical and proof-of-concept studies appear promising with renal denervation shown to confer cardiovascular and metabolic benefits, largely independent of changes in blood pressure. This review explores the pathological rationale for targeting sympathetic renal nerves for blood pressure control. Latest developments in renal nerve ablation modalities designed to improve procedural success are discussed along with prospective findings on the efficacy of renal denervation to lower blood pressure in treatment-resistant hypertensive patients. Preliminary evidence in support of renal denervation as a possible therapeutic option in disease states characterized by central sympathetic overactivity is also presented. PMID:26217232

A nationwide survey of combined central and peripheral demyelination in Japan.

PubMed

Ogata, Hidenori; Matsuse, Dai; Yamasaki, Ryo; Kawamura, Nobutoshi; Matsushita, Takuya; Yonekawa, Tomomi; Hirotani, Makoto; Murai, Hiroyuki; Kira, Jun-ichi

2016-01-01

To clarify the clinical features of combined central and peripheral demyelination (CCPD) via a nationwide survey. The following characteristics were used to define CCPD: T2 high-signal intensity lesions in the brain, optic nerves or spinal cord on MRI, or abnormalities on visual-evoked potentials; conduction delay, conduction block, temporal dispersion or F-wave abnormalities suggesting demyelinating neuropathy based on nerve conduction studies; exclusion of secondary demyelination. We conducted a nationwide survey in 2012, sending questionnaires to 1332 adult and paediatric neurology institutions in Japan. We collated 40 CCPD cases, including 29 women. Age at onset was 31.7±14.1 years (mean±SD). Sensory disturbance (94.9%), motor weakness (92.5%) and gait disturbance (79.5%) were common. Although cerebrospinal fluid protein levels were increased in 82.5%, oligoclonal IgG bands and elevated IgG indices were detected in 7.4% and 18.5% of cases, respectively. Fifteen of 21 patients (71.4%) had abnormal visual-evoked potentials. Antineurofascin 155 antibodies were positive in 5/11 (45.5%). Corticosteroids, intravenous immunoglobulins and plasmapheresis resulted in an 83.3%, 66.7% and 87.5% improvement, respectively, whereas interferon-β was effective in only 10% of cases. CCPD cases with simultaneous onset of central nervous system (CNS) and peripheral nervous system (PNS) involvement exhibited greater disability, but less recurrence and more frequent extensive cerebral and spinal cord MRI lesions compared to those with temporarily separated onset, whereas optic nerve involvement was more common in the latter. CCPD shows different characteristics from classical demyelinating diseases, and distinctive features exist between cases with simultaneous and temporarily separated onset of CNS and PNS involvement. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Bilateral tympanokeratomas (cholesteatomas) with bilateral otitis media, unilateral otitis interna and acoustic neuritis in a dog.

PubMed

Østevik, Liv; Rudlang, Kathrine; Holt Jahr, Tuva; Valheim, Mette; Njaa, Bradley Lyndon

2018-05-22

An aural cholesteatoma, more appropriately named tympanokeratoma, is an epidermoid cyst of the middle ear described in several species, including dogs, humans and Mongolian gerbils. The cyst lining consists of stratified, keratinizing squamous epithelium with central accumulation of a keratin debris. This case report describes vestibular ganglioneuritis and perineuritis in a dog with chronic otitis, bilateral tympanokeratomas and presumed extension of otic infection to the central nervous system. An 11-year-old intact male Dalmatian dog with chronic bilateral otitis externa and sudden development of symptoms of vestibular disease was examined. Due to the dog's old age the owner opted for euthanasia without any further examination or treatment and the dog was submitted for necropsy. Transection of the ears revealed grey soft material in the external ear canals and pearly white, dry material consistent with keratin in the tympanic bullae bilaterally. The brain and meninges were grossly unremarkable. Microscopical findings included bilateral otitis externa and media, unilateral otitis interna, ganglioneuritis and perineuritis of the spiral ganglion of the vestibulocochlear nerve and multifocal to coalescing, purulent meningitis. A keratinizing squamous epithelial layer continuous with the external acoustic meatus lined the middle ear compartments, consistent with bilateral tympanokeratomas. Focal bony erosion of the petrous portion of the temporal bone and squamous epithelium and Gram-positive bacterial cocci were evident in the left cochlea. The findings suggest that meningitis developed secondary to erosion of the temporal bone and ganglioneuritis and/or perineuritis of the vestibulocochlear nerve. Middle ear tympanokeratoma is an important and potentially life-threatening otic condition in the dog. Once a tympanokeratoma has developed expansion of the cyst can lead to erosion of bone and extension of otic infection to the inner ear, vestibulocochlear ganglion and nerve potentially leading to bacterial infection of the central nervous system.

Longitudinal analysis of hearing loss in a case of hemosiderosis of the central nervous system.

PubMed

Weekamp, H H; Huygen, P L M; Merx, J L; Kremer, H P H; Cremers, Cor W R J; Longridge, Neil S

2003-09-01

To describe cochleovestibular aspects of superficial hemosiderosis of the central nervous system. Superficial hemosiderosis of the central nervous system is a rare disease in which cochleovestibular impairment, cerebellar ataxia, and myelopathy are the most frequent signs. Chronic recurrent subarachnoidal hemorrhage with bleeding into the cerebrospinal fluid is the cause of deposition of hemosiderin in leptomeningeal and subpial tissue, cranial nerves, and spinal cord. Removing the cause of bleeding can prevent irreversible damage to these structures. Because this is the only effective treatment, an early diagnosis is crucial. Retrospective case review. Tertiary referral center. A 72-year-old woman with superficial hemosiderosis of the central nervous system that developed when she was age 39. Neurologic and imaging diagnostic examinations and longitudinal evaluation of cochleovestibular features were performed. Neurosurgery was not performed. Progressive bilateral sensorineural hearing loss and severe vestibular hyporeflexia developed within 15 years, which can be attributed to lesions in the cochleovestibular system. Additional pathology of the central nervous system developed later. The patient demonstrated cochlear and vestibular findings that are typical of this pathologic condition. It is the first documented case with extensive serial audiometry used to precisely outline the degree of hearing deterioration during the course of the disease.

Expanded Terminal Fields of Gustatory Nerves Accompany Embryonic BDNF Overexpression in Mouse Oral Epithelia

PubMed Central

Sun, Chengsan; Dayal, Arjun

2015-01-01

Brain-derived neurotrophic factor (BDNF) is expressed in gustatory epithelia and is required for gustatory neurons to locate and innervate their correct target during development. When BDNF is overexpressed throughout the lingual epithelium, beginning embryonically, chorda tympani fibers are misdirected and innervate inappropriate targets, leading to a loss of taste buds. The remaining taste buds are hyperinnervated, demonstrating a disruption of nerve/target matching in the tongue. We tested the hypothesis here that overexpression of BDNF peripherally leads to a disrupted terminal field organization of nerves that carry taste information to the brainstem. The chorda tympani, greater superficial petrosal, and glossopharyngeal nerves were labeled in adult wild-type (WT) mice and in adult mice in which BDNF was overexpressed (OE) to examine the volume and density of their central projections in the nucleus of the solitary tract. We found that the terminal fields of the chorda tympani and greater superficial petrosal nerves and overlapping fields that included these nerves in OE mice were at least 80% greater than the respective field volumes in WT mice. The shapes of terminal fields were similar between the two groups; however, the density and spread of labels were greater in OE mice. Unexpectedly, there were also group-related differences in chorda tympani nerve function, with OE mice showing a greater relative taste response to a concentration series of sucrose. Overall, our results show that disruption in peripheral innervation patterns of sensory neurons have significant effects on peripheral nerve function and central organization of their terminal fields. PMID:25568132

High frequency oscillations evoked by peripheral magnetic stimulation.

PubMed

Biller, S; Simon, L; Fiedler, P; Strohmeier, D; Haueisen, J

2011-01-01

The analysis of somatosensory evoked potentials (SEP) and / or fields (SEF) is a well-established and important tool for investigating the functioning of the peripheral and central human nervous system. A standard technique to evoke SEPs / SEFs is the stimulation of the median nerve by using a bipolar electrical stimulus. We aim at an alternative stimulation technique enabling stimulation of deep nerve structures while reducing patient stress and error susceptibility. In the current study, we apply a commercial transcranial magnetic stimulation system for peripheral magnetic stimulation of the median nerve. We compare the results of simultaneously recorded EEG signals to prove applicability of our technique to evoke SEPs including low frequency components (LFC) as well as high frequency oscillations (HFO). Therefore, we compare amplitude, latency and time-frequency characteristics of the SEP of 14 healthy volunteers after electric and magnetic stimulation. Both low frequency components and high frequency oscillations were detected. The HFOs were superimposed onto the primary cortical response N20. Statistical analysis revealed significantly lower amplitudes and increased latencies for LFC and HFO components after magnetic stimulation. The differences indicate the inability of magnetic stimulation to elicit supramaximal responses. A psycho-perceptual evaluation showed that magnetic stimulation was less unpleasant for 12 out of the 14 volunteers. In conclusion, we showed that LFC and HFO components related to median nerve stimulation can be evoked by peripheral magnetic stimulation.

Intraoperative observation of changes in cochlear nerve action potentials during exposure to electromagnetic fields generated by mobile phones.

PubMed

Colletti, Vittorio; Mandalà, Marco; Manganotti, Paolo; Ramat, Stefano; Sacchetto, Luca; Colletti, Liliana

2011-07-01

The rapid spread of devices generating electromagnetic fields (EMF) has raised concerns as to the possible effects of this technology on humans. The auditory system is the neural organ most frequently and directly exposed to electromagnetic activity owing to the daily use of mobile phones. In recent publications, a possible correlation between mobile phone usage and central nervous system tumours has been detected. Very recently a deterioration in otoacoustic emissions and in the auditory middle latency responses after intensive and long-term magnetic field exposure in humans has been demonstrated. To determine with objective observations if exposure to mobile phone EMF affects acoustically evoked cochlear nerve compound action potentials, seven patients suffering from Ménière's disease and undergoing retrosigmoid vestibular neurectomy were exposed to the effects of mobile phone placed over the craniotomy for 5 min. All patients showed a substantial decrease in amplitude and a significant increase in latency of cochlear nerve compound action potentials during the 5 min of exposure to EMF. These changes lasted for a period of around 5 min after exposure. The possibility that EMF can produce relatively long-lasting effects on cochlear nerve conduction is discussed and analysed in light of contrasting previous literature obtained under non-surgical conditions. Limitations of this novel approach, including the effects of the anaesthetics, craniotomy and surgical procedure, are presented in detail.

Clitoral Sexual Arousal: Neuronal Tracing Study From the Clitoris Through the Spinal Tracts

PubMed Central

Martin-Alguacil, Nieves; Schober, Justine M.; Sengelaub, Dale R.; Pfaff, Donald W.; Shelley, Deborah N.

2009-01-01

Purpose Although genital tactile stimulation is regarded as a precursor to sexual arousal and a recognized initiator of central nervous system arousal, specific afferent neural pathways transmit sensory stimuli of arousal, beginning at the epithelial level on the clitoris and following the course of arousal stimuli through the central nervous system. Limited knowledge exists of the pathway from the cutaneous receptors of nerves originating in the epithelial tissue of the clitoris and continuing to spinal cord afferents. Such information may contribute to an understanding of sexual arousal, particularly in female vertebrates. We further defined the neural pathways and mechanisms responsible for arousal originating in the epithelium of the clitoris as well as related neural pathways to the spinal cord in a murine model. Materials and Methods We performed a comprehensive review of the published relevant clinical and histological material from human and nonhuman vertebrate studies. In 29 adult female C57B1/6 mice the distribution of pelvic nerves and vessels was mapped. Gross dissection of 4 female mice was facilitated by resin injection of the vascular system in 2. Neuronal tracing was performed in 25 mice that received clitoral injection of wheat germ agglutinin-horseradish peroxidase into the clitoris and were sacrificed after 72 to 96 hours. The spinal cord and periclitoral tissue were removed and fixed. Immunohistochemistry was performed. Results Gross anatomy of the mouse clitoris showed that pudendal and hypogastric nerves have a major role in the innervation of the external genitalia. Neuronal tracing revealed that the greatest nerve density was noted in the L5/6 spinal cord. The distribution extended from S1 to L2 with no labeling seen in the L3 spinal cord. Wheat germ agglutinin-horseradish peroxidase labeling was seen caudal in levels S1 through L4 and rostral in L2. Conclusions Understanding the neuroanatomy of the clitoris using a murine model may provide a valuable tool for the study of sexual arousal disorders and the further understanding of sexual function related to neural pathologies and trauma. PMID:18707740

Interlimb Reflexes Induced by Electrical Stimulation of Cutaneous Nerves after Spinal Cord Injury

PubMed Central

Butler, Jane E.; Godfrey, Sharlene; Thomas, Christine K.

2016-01-01

Whether interlimb reflexes emerge only after a severe insult to the human spinal cord is controversial. Here the aim was to examine interlimb reflexes at rest in participants with chronic (>1 year) spinal cord injury (SCI, n = 17) and able-bodied control participants (n = 5). Cutaneous reflexes were evoked by delivering up to 30 trains of stimuli to either the superficial peroneal nerve on the dorsum of the foot or the radial nerve at the wrist (5 pulses, 300 Hz, approximately every 30 s). Participants were instructed to relax the test muscles prior to the delivery of the stimuli. Electromyographic activity was recorded bilaterally in proximal and distal arm and leg muscles. Superficial peroneal nerve stimulation evoked interlimb reflexes in ipsilateral and contralateral arm and contralateral leg muscles of SCI and control participants. Radial nerve stimulation evoked interlimb reflexes in the ipsilateral leg and contralateral arm muscles of control and SCI participants but only contralateral leg muscles of control participants. Interlimb reflexes evoked by superficial peroneal nerve stimulation were longer in latency and duration, and larger in magnitude in SCI participants. Interlimb reflex properties were similar for both SCI and control groups for radial nerve stimulation. Ascending interlimb reflexes tended to occur with a higher incidence in participants with SCI, while descending interlimb reflexes occurred with a higher incidence in able-bodied participants. However, the overall incidence of interlimb reflexes in SCI and neurologically intact participants was similar which suggests that the neural circuitry underlying these reflexes does not necessarily develop after central nervous system injury. PMID:27049521

Pressure wave injuries to the nervous system caused by high-energy missile extremity impact: Part II. Distant effects on the central nervous system--a light and electron microscopic study on pigs.

PubMed

Suneson, A; Hansson, H A; Seeman, T

1990-03-01

The aim of the present study was to investigate if distant effects could be detected within the central nervous system after impact of a high-energy missile in the left thigh of young pigs. Pressure transducers implanted in various parts of the body of the animal, including the brain, recorded a short-lasting burst of oscillating pressure waves with high frequencies and large amplitudes, traversing the body tissue with a velocity of about that of sound in water (1,460 m/s). The distance between the point of impact and the brain and cervical spinal cord is in the range of 0.5 m. Macroscopic examination revealed that there was no gross brain tissue disruption or visible blood-brain barrier dysfunction. Light microscopic examination demonstrated myelin invaginations in the largest axons and shrinkage of axoplasm. Electron microscopic examination revealed a reduction in the number of microtubules, especially in the larger axons in the brainstem. Disintegration of Nissl substance, i.e., chromatolysis, was noticed after 48 hr in many Purkinje nerve cells in the cerebellum, concomitantly with the appearance of an increased frequency of association between lamellar bodies and mitochondria. Changes could also be observed in the cervical spinal cord and, at reduced frequency and extent, in the optic nerve and in other parts of the brain. These effects were evident within a few minutes after the trauma and persisted even 48 hr after the extremity injury. It is concluded that distant effects, likely to be caused by the oscillating high-frequency pressure waves, appear in the central nervous system after a high-energy missile extremity impact.

Peripheral territory and neuropeptides of the trigeminal ganglion neurons centrally projecting through the oculomotor nerve demonstrated by fluorescent retrograde double-labeling combined with immunocytochemistry.

PubMed

Bortolami, R; Calzà, L; Lucchi, M L; Giardino, L; Callegari, E; Manni, E; Pettorossi, V E; Barazzoni, A M; Lalatta Costerbosa, G

1991-04-26

The peripheral territories of sheep trigeminal neurons which send their central process to the brainstem through the oculomotor nerve were investigated by the use of fluorescent tracers in double-labeling experiments. For this purpose Diamidino yellow (DY) injection into the oculomotor nerve was combined with Fast blue (FB) injection either into the extraocular muscles (EOMs), or the cornea, or the superior eyelid. Double-labeled DY + FB cells were found in the ophthalmic region of the trigeminal ganglion in addition to single-labeled DY or FB cells. The DY and DY + FB-labeled trigeminal cells were analysed immunocytochemically for their content of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, and cholecystokinin-8 (CCK-8)-like. All single-labeled DY cells showed SP-, CGRP- or CCK-8-like immunoreactivity. Double-labeled DY + FB neurons innervating the EOMs were immunoreactive for each of the three peptides, whereas double-labeled neurons supplying the cornea were only CGRP-like positive. The findings suggest that, in the sheep, trigeminal neurons which send their process centrally through the oculomotor nerve supply the EOMs, the cornea, and the superior eyelid and contain neuropeptides which are usually associated with pain sensation.

Holothurian Nervous System Diversity Revealed by Neuroanatomical Analysis

PubMed Central

Díaz-Balzac, Carlos A.; Lázaro-Peña, María I.; Vázquez-Figueroa, Lionel D.; Díaz-Balzac, Roberto J.; García-Arrarás, José E.

2016-01-01

The Echinodermata comprise an interesting branch in the phylogenetic tree of deuterostomes. Their radial symmetry which is reflected in their nervous system anatomy makes them a target of interest in the study of nervous system evolution. Until recently, the study of the echinoderm nervous system has been hindered by a shortage of neuronal markers. However, in recent years several markers of neuronal and fiber subpopulations have been described. These have been used to identify subpopulations of neurons and fibers, but an integrative study of the anatomical relationship of these subpopulations is wanting. We have now used eight commercial antibodies, together with three antibodies produced by our group to provide a comprehensive and integrated description and new details of the echinoderm neuroanatomy using the holothurian Holothuria glaberrima (Selenka, 1867) as our model system. Immunoreactivity of the markers used showed: (1) specific labeling patterns by markers in the radial nerve cords, which suggest the presence of specific nerve tracts in holothurians. (2) Nerves directly innervate most muscle fibers in the longitudinal muscles. (3) Similar to other deuterostomes (mainly vertebrates), their enteric nervous system is composed of a large and diverse repertoire of neurons and fiber phenotypes. Our results provide a first blueprint of the anatomical organization of cells and fibers that form the holothurian neural circuitry, and highlight the fact that the echinoderm nervous system shows unexpected diversity in cell and fiber types and their distribution in both central and peripheral nervous components. PMID:26987052

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.

High aspect ratio template and method for producing same for central and peripheral nerve repair

NASA Technical Reports Server (NTRS)

Sakamoto, Jeff S. (Inventor); Chan, Christina (Inventor); Tuszynski, Mark Henry (Inventor); Mehrotra, Sumit (Inventor); Gros, Thomas (Inventor)

2011-01-01

Millimeter to nano-scale structures manufactured using a multi-component polymer fiber matrix are disclosed. The use of dissimilar polymers allows the selective dissolution of the polymers at various stages of the manufacturing process. In one application, biocompatible matrixes may be formed with long pore length and small pore size. The manufacturing process begins with a first polymer fiber arranged in a matrix formed by a second polymer fiber. End caps may be attached to provide structural support and the polymer fiber matrix selectively dissolved away leaving only the long polymer fibers. These may be exposed to another product, such as a biocompatible gel to form a biocompatible matrix. The polymer fibers may then be selectively dissolved leaving only a biocompatible gel scaffold with the pores formed by the dissolved polymer fibers. The scaffolds may be used in, among other applications, the repair of central and peripheral nerves. Scaffolds for the repair of peripheral nerves may include a reservoir for the sustained release of nerve growth factor. The scaffolds may also include a multifunctional polyelectrolyte layer for the sustained release of nerve growth factor and enhance biocompatibility.

Structure and stability of internodal myelin in mouse models of hereditary neuropathy.

PubMed

Avila, Robin L; Inouye, Hideyo; Baek, Rena C; Yin, Xinghua; Trapp, Bruce D; Feltri, M Laura; Wrabetz, Lawrence; Kirschner, Daniel A

2005-11-01

Peripheral neuropathies often result in abnormalities in the structure of internodal myelin, including changes in period and membrane packing, as observed by electron microscopy (EM). Mutations in the gene that encodes the major adhesive structural protein of internodal myelin in the peripheral nervous system of humans and mice--P0 glycoprotein--correlate with these defects. The mechanisms by which P0 mutations interfere with myelin packing and stability are not well understood and cannot be provided by EM studies that give static and qualitative information on fixed material. To gain insights into the pathogenesis of mutant P0, we used x-ray diffraction, which can detect more subtle and dynamic changes in native myelin, to investigate myelin structure in sciatic nerves from murine models of hereditary neuropathies. We used mice with disruption of one or both copies of the P0 gene (models of Charcot-Marie-Tooth-like neuropathy [CMT1B] or Dejerine-Sottas-like neuropathy) and mice with a CMT1B resulting from a transgene encoding P0 with an amino terminal myc-tag. To directly test the structural role of P0, we also examined a mouse that expresses P0 instead of proteolipid protein in central nervous system myelin. To link our findings on unfixed nerves with EM results, we analyzed x-ray patterns from unembedded, aldehyde-fixed nerves and from plastic-embedded nerves. From the x-ray patterns recorded from whole nerves, we assessed the amount of myelin and its quality (i.e. relative thickness and regularity). Among sciatic nerves having different levels of P0, we found that unfixed nerves and, to a lesser extent, fixed but unembedded nerves gave diffraction patterns of sufficient quality to distinguish periods, sometimes differing by a few Angstroms. Certain packing abnormalities were preserved qualitatively by aldehyde fixation, and the relative amount and structural integrity of myelin among nerves could be distinguished. Measurements from the same nerve over time showed that the amount of P0 affected myelin's stability against swelling, thus directly supporting the hypothesis that packing defects underlie instability in "live" or intact myelin. Our findings demonstrate that diffraction can provide a quantitative basis for understanding, at a molecular level, the membrane packing defects that occur in internodal myelin in demyelinating peripheral neuropathies.

Talking back: Development of the olivocochlear efferent system.

PubMed

Frank, Michelle M; Goodrich, Lisa V

2018-06-26

Developing sensory systems must coordinate the growth of neural circuitry spanning from receptors in the peripheral nervous system (PNS) to multilayered networks within the central nervous system (CNS). This breadth presents particular challenges, as nascent processes must navigate across the CNS-PNS boundary and coalesce into a tightly intermingled wiring pattern, thereby enabling reliable integration from the PNS to the CNS and back. In the auditory system, feedforward spiral ganglion neurons (SGNs) from the periphery collect sound information via tonotopically organized connections in the cochlea and transmit this information to the brainstem for processing via the VIII cranial nerve. In turn, feedback olivocochlear neurons (OCNs) housed in the auditory brainstem send projections into the periphery, also through the VIII nerve. OCNs are motor neuron-like efferent cells that influence auditory processing within the cochlea and protect against noise damage in adult animals. These aligned feedforward and feedback systems develop in parallel, with SGN central axons reaching the developing auditory brainstem around the same time that the OCN axons extend out toward the developing inner ear. Recent findings have begun to unravel the genetic and molecular mechanisms that guide OCN development, from their origins in a generic pool of motor neuron precursors to their specialized roles as modulators of cochlear activity. One recurrent theme is the importance of efferent-afferent interactions, as afferent SGNs guide OCNs to their final locations within the sensory epithelium, and efferent OCNs shape the activity of the developing auditory system. This article is categorized under: Nervous System Development > Vertebrates: Regional Development. © 2018 Wiley Periodicals, Inc.

The origin and evolution of chordate nervous systems

PubMed Central

Holland, Linda Z.

2015-01-01

In the past 40 years, comparisons of developmental gene expression and mechanisms of development (evodevo) joined comparative morphology as tools for reconstructing long-extinct ancestral forms. Unfortunately, both approaches typically give congruent answers only with closely related organisms. Chordate nervous systems are good examples. Classical studies alone left open whether the vertebrate brain was a new structure or evolved from the anterior end of an ancestral nerve cord like that of modern amphioxus. Evodevo plus electron microscopy showed that the amphioxus brain has a diencephalic forebrain, small midbrain, hindbrain and spinal cord with parts of the genetic mechanisms for the midbrain/hindbrain boundary, zona limitans intrathalamica and neural crest. Evodevo also showed how extra genes resulting from whole-genome duplications in vertebrates facilitated evolution of new structures like neural crest. Understanding how the chordate central nervous system (CNS) evolved from that of the ancestral deuterostome has been truly challenging. The majority view is that this ancestor had a CNS with a brain that gave rise to the chordate CNS and, with loss of a discrete brain, to one of the two hemichordate nerve cords. The minority view is that this ancestor had no nerve cord; those in chordates and hemichordates evolved independently. New techniques such as phylostratigraphy may help resolve this conundrum. PMID:26554041

Functional Role of the Disulfide Isomerase ERp57 in Axonal Regeneration.

PubMed

Castillo, Valentina; Oñate, Maritza; Woehlbier, Ute; Rozas, Pablo; Andreu, Catherine; Medinas, Danilo; Valdés, Pamela; Osorio, Fabiola; Mercado, Gabriela; Vidal, René L; Kerr, Bredford; Court, Felipe A; Hetz, Claudio

2015-01-01

ERp57 (also known as grp58 and PDIA3) is a protein disulfide isomerase that catalyzes disulfide bonds formation of glycoproteins as part of the calnexin and calreticulin cycle. ERp57 is markedly upregulated in most common neurodegenerative diseases downstream of the endoplasmic reticulum (ER) stress response. Despite accumulating correlative evidence supporting a neuroprotective role of ERp57, the contribution of this foldase to the physiology of the nervous system remains unknown. Here we developed a transgenic mouse model that overexpresses ERp57 in the nervous system under the control of the prion promoter. We analyzed the susceptibility of ERp57 transgenic mice to undergo neurodegeneration. Unexpectedly, ERp57 overexpression did not affect dopaminergic neuron loss and striatal denervation after injection of a Parkinson's disease-inducing neurotoxin. In sharp contrast, ERp57 transgenic animals presented enhanced locomotor recovery after mechanical injury to the sciatic nerve. These protective effects were associated with enhanced myelin removal, macrophage infiltration and axonal regeneration. Our results suggest that ERp57 specifically contributes to peripheral nerve regeneration, whereas its activity is dispensable for the survival of a specific neuronal population of the central nervous system. These results demonstrate for the first time a functional role of a component of the ER proteostasis network in peripheral nerve regeneration.

Olfactory Nerve—A Novel Invasion Route of Neisseria meningitidis to Reach the Meninges

PubMed Central

Sjölinder, Hong; Jonsson, Ann-Beth

2010-01-01

Neisseria meningitidis is a human-specific pathogen with capacity to cause septic shock and meningitis. It has been hypothesized that invasion of the central nervous system (CNS) is a complication of a bacteremic condition. In this study, we aimed to characterize the invasion route of N. meningitidis to the CNS. Using an intranasally challenged mouse disease model, we found that twenty percent of the mice developed lethal meningitis even though no bacteria could be detected in blood. Upon bacterial infection, epithelial lesions and redistribution of intracellular junction protein N-cadherin were observed at the nasal epithelial mucosa, especially at the olfactory epithelium, which is functionally and anatomically connected to the CNS. Bacteria were detected in the submucosa of the olfactory epithelium, along olfactory nerves in the cribriform plate, at the olfactory bulb and subsequently at the meninges and subarachnoid space. Furthermore, our data suggest that a threshold level of bacteremia is required for the development of meningococcal sepsis. Taken together, N. meningitidis is able to pass directly from nasopharynx to meninges through the olfactory nerve system. This study enhances our understanding how N. meningitidis invades the meninges. The nasal olfactory nerve system may be a novel target for disease prevention that can improve outcome and survival. PMID:21124975

Renal sympathetic nerve, blood flow, and epithelial transport responses to thermal stress.

PubMed

Wilson, Thad E

2017-05-01

Thermal stress is a profound sympathetic stress in humans; kidney responses involve altered renal sympathetic nerve activity (RSNA), renal blood flow, and renal epithelial transport. During mild cold stress, RSNA spectral power but not total activity is altered, renal blood flow is maintained or decreased, and epithelial transport is altered consistent with a sympathetic stress coupled with central volume loaded state. Hypothermia decreases RSNA, renal blood flow, and epithelial transport. During mild heat stress, RSNA is increased, renal blood flow is decreased, and epithelial transport is increased consistent with a sympathetic stress coupled with a central volume unloaded state. Hyperthermia extends these directional changes, until heat illness results. Because kidney responses are very difficult to study in humans in vivo, this review describes and qualitatively evaluates an in vivo human skin model of sympathetically regulated epithelial tissue compared to that of the nephron. This model utilizes skin responses to thermal stress, involving 1) increased skin sympathetic nerve activity (SSNA), decreased skin blood flow, and suppressed eccrine epithelial transport during cold stress; and 2) increased SSNA, skin blood flow, and eccrine epithelial transport during heat stress. This model appears to mimic aspects of the renal responses. Investigations of skin responses, which parallel certain renal responses, may aid understanding of epithelial-sympathetic nervous system interactions during cold and heat stress. Copyright © 2016 Elsevier B.V. All rights reserved.

Cryotherapy in the management of trigeminal neuralgia: a review of the literature and report of three cases.

PubMed

Poon, C Y

2000-12-01

Trigeminal neuralgia is a unique neuropathic syndrome confined to the trigeminal system with no analog in the somatic dermatomes or the other cranial nerves. Medical treatment remains the first line of treatment with carbamezapine as the drug of choice. Surgery, central or peripheral is indicated when medical treatment fails or its side effects diminishes quality of life. No surgery offers a permanent cure. Recurrence rates are highest in the most peripheral techniques but these also have the lowest morbidity. Cryotherapy produces a reliable, prolonged and reversible nerve block with no aggravation of symptoms. It is a simple and repeatable procedure in patients who want to avoid major surgery or where it is contra-indicated.

The neurologic evaluation of patients with low-tension glaucoma.

PubMed

Corbett, J J; Phelps, C D; Eslinger, P; Montague, P R

1985-08-01

One hypothesized cause of low-tension glaucoma is chronic or intermittent ischemia of the optic nerve. Since the optic nerve and brain are both parts of the central nervous system and share a common blood supply, the authors wondered if patients with low-tension glaucoma might also have clinical or radiographic evidence of cerebral atrophy. In this study, 27 patients with low-tension glaucoma were examined using neurobehavioral testing, electroencephalography, computerized tomographic scan, neurological history, and physical examination. In only a small number of patients were these tests abnormal. However, 12 of the 27 patients gave a history of common or classic migraine. This unexpected finding raises the possibility that migraine-related ischemia might be the pathogenic mechanism in some cases of low-tension glaucoma.

Neuroprotection trek--the next generation: neuromodulation I. Techniques--deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation

NASA Technical Reports Server (NTRS)

Andrews, Russell J.

2003-01-01

Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.

Neuroprotection trek--the next generation: neuromodulation I. Techniques--deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation.

PubMed

Andrews, Russell J

2003-05-01

Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.

Current understanding of auditory neuropathy.

PubMed

Boo, Nem-Yun

2008-12-01

Auditory neuropathy is defined by the presence of normal evoked otoacoustic emissions (OAE) and absent or abnormal auditory brainstem responses (ABR). The sites of lesion could be at the cochlear inner hair cells, spiral ganglion cells of the cochlea, synapse between the inner hair cells and auditory nerve, or the auditory nerve itself. Genetic, infectious or neonatal/perinatal insults are the 3 most commonly identified underlying causes. Children usually present with delay in speech and language development while adult patients present with hearing loss and disproportionately poor speech discrimination for the degree of hearing loss. Although cochlear implant is the treatment of choice, current evidence show that it benefits only those patients with endocochlear lesions, but not those with cochlear nerve deficiency or central nervous system disorders. As auditory neuropathy is a disorder with potential long-term impact on a child's development, early hearing screen using both OAE and ABR should be carried out on all newborns and infants to allow early detection and intervention.

Triazines facilitate neurotransmitter release of synaptic terminals located in hearts of frog (Rana ridibunda) and honeybee (Apis mellifera) and in the ventral nerve cord of a beetle (Tenebrio molitor).

PubMed

Papaefthimiou, Chrisovalantis; Zafeiridou, Georgia; Topoglidi, Aglaia; Chaleplis, George; Zografou, Stella; Theophilidis, George

2003-07-01

Three triazine herbicides, atrazine, simazine and metribuzine, and some of their major metabolites (cyanuric acid and 6-azauracil) were investigated for their action on synaptic terminals using three different isolated tissue preparations from the atria of the frog, Rana ridibunda, the heart of the honeybee, Apis mellifera macedonica, and the ventral nerve cord of the beetle, Tenebrio molitor. The results indicate that triazines facilitate the release of neurotransmitters from nerve terminals, as already reported for the mammalian central nervous system. The no observed effect concentration, the maximum concentration of the herbicide diluted in the saline that has no effect on the physiological properties of the isolated tissue, was estimated for each individual preparation. According to their relative potency, the three triazines tested can be ranked as follows: atrazine (cyanuric acid), simazine>metribuzine (6-azauracil). The action of these compounds on the cholinergic (amphibians, insects), adrenergic (amphibian) and octopaminergic (insects) synaptic terminals is discussed.

[Peripheral nerves phenolisation in spasticity management - forgotten art or interesting perspective?

PubMed

Kiwerski, Jerzy; Turżańska, Karolina; Pluta, Ryszard; Drelich, Małgorzata; Zarębska, Aneta; Jabłoński, Mirosław

Spasticity is one of the most common obstacles in the process of rehabilitation after permanent central nervous system injury. Statistics show that the problem affects more than 12 billion people all over the world. Treatment of spasticity is necessary for proper rehabilitation, prevention of secondary disability, pain management and also strongly influences quality of life. Nowadays the most common formula used for the treatment of local spasticity is injection of botulinum toxin. Years ago and also nowadays physicians all over the world successfully used phenol as the chemodenervating factor. This technique today almost forgot in Poland but still used in other countries. Peripheral nerves phenolisation had been used in STOCER (Konstancin) since 1965. The procedure was performed once in 59 patients, twice in 13 patients and three times in 7 patients. Evaluation was based on clinical presentation completed with patient self evaluation form. Good - 36 cases (45%), moderate - 34 cases (43%), bad - 9 cases (12%). Peripheral nerve phenolisation seems to be an interesting alternative to botulinum toxin in the management of spasticity.

Cholesterol and myelin biogenesis.

PubMed

Saher, Gesine; Simons, Mikael

2010-01-01

Myelin consists of several layers of tightly compacted membranes wrapped around axons in the nervous system. The main function of myelin is to provide electrical insulation around the axon to ensure the rapid propagation of nerve conduction. As the myelinating glia terminally differentiates, they begin to produce myelin membranes on a remarkable scale. This membrane is unique in its composition being highly enriched in lipids, in particular galactosylceramide and cholesterol. In this review we will summarize the role of cholesterol in myelin biogenesis in the central and peripheral nervous system.

NEURONAL ACTION ON THE DEVELOPING BLOOD VESSEL PATTERN

PubMed Central

James, Jennifer M.; Mukouyama, Yoh-suke

2011-01-01

The nervous system relies on a highly specialized network of blood vessels for development and neuronal survival. Recent evidence suggests that both the central and peripheral nervous systems (CNS and PNS) employ multiple mechanisms to shape the vascular tree to meet its specific metabolic demands, such as promoting nerve-artery alignment in the PNS or the development the blood brain barrier in the CNS. In this article we discuss how the nervous system directly influences blood vessel patterning resulting in neuro-vascular congruence that is maintained throughout development and in the adult. PMID:21978864

Estimating a structural bottle neck for eye-brain transfer of visual information from 3D-volumes of the optic nerve head from a commercial OCT device

NASA Astrophysics Data System (ADS)

Malmberg, Filip; Sandberg-Melin, Camilla; Söderberg, Per G.

2016-03-01

The aim of this project was to investigate the possibility of using OCT optic nerve head 3D information captured with a Topcon OCT 2000 device for detection of the shortest distance between the inner limit of the retina and the central limit of the pigment epithelium around the circumference of the optic nerve head. The shortest distance between these boundaries reflects the nerve fiber layer thickness and measurement of this distance is interesting for follow-up of glaucoma.

The articulo-cardiac sympathetic reflex in spinalized, anesthetized rats.

PubMed

Nakayama, Tomohiro; Suzuki, Atsuko; Ito, Ryuzo

2006-04-01

Somatic afferent regulation of heart rate by noxious knee joint stimulation has been proven in anesthetized cats to be a reflex response whose reflex center is in the brain and whose efferent arc is a cardiac sympathetic nerve. In the present study we examined whether articular stimulation could influence heart rate by this efferent sympathetic pathway in spinalized rats. In central nervous system (CNS)-intact rats, noxious articular movement of either the knee or elbow joint resulted in an increase in cardiac sympathetic nerve activity and heart rate. However, although in acutely spinalized rats a noxious movement of the elbow joint resulted in a significant increase in cardiac sympathetic nerve activity and heart rate, a noxious movement of the knee joint had no such effect and resulted in only a marginal increase in heart rate. Because this marginal increase was abolished by adrenalectomy suggests that it was due to the release of adrenal catecholamines. In conclusion, the spinal cord appears to be capable of mediating, by way of cardiac sympathetic nerves, the propriospinally induced reflex increase in heart rate that follows noxious stimulation of the elbow joint, but not the knee joint.

Sympathetic neural control of the kidney in hypertension.

PubMed

DiBona, G F

1992-01-01

Efferent renal sympathetic nerve activity is elevated in human essential hypertension as well as in several forms of experimental hypertension in animals. In addition, bilateral complete renal denervation delays the development and/or attenuates the magnitude of the hypertension in several different forms of experimental hypertension in animals. Efferent renal sympathetic nerve activity is known to have dose-dependent effects on renal blood flow, the glomerular filtration rate, renal tubular sodium and water reabsorption, and the renin secretion rate, which are capable of contributing, singly or in combination, to the development, maintenance, and exacerbation of the hypertensive state. Of the many factors known to influence the central nervous system integrative regulation of efferent renal sympathetic nerve activity, two environmental factors, a high dietary sodium intake and environmental stress, are capable of significant interaction. This resultant increase in efferent renal sympathetic nerve activity and subsequent renal functional alterations can participate in the hypertensive process. This is especially evident in the presence of an underlying genetic predisposition to the development of hypertension. Thus, interactions between environmental and genetic influences can produce alterations in the sympathetic neural control of renal function that play an important role in hypertension.

ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density.

PubMed

Dahan, Albert; Dunne, Ann; Swartjes, Maarten; Proto, Paolo L; Heij, Lara; Vogels, Oscar; van Velzen, Monique; Sarton, Elise; Niesters, Marieke; Tannemaat, Martijn R; Cerami, Anthony; Brines, Michael

2013-11-08

Small nerve fiber loss and damage (SNFLD) is a frequent complication of sarcoidosis that is associated with autonomic dysfunction and sensory abnormalities, including pain syndromes that severely degrade the quality of life. SNFLD is hypothesized to arise from the effects of immune dysregulation, an essential feature of sarcoidosis, on the peripheral and central nervous systems. Current therapy of sarcoidosis-associated SNFLD consists primarily of immune suppression and symptomatic treatment; however, this treatment is typically unsatisfactory. ARA 290 is a small peptide engineered to activate the innate repair receptor that antagonizes inflammatory processes and stimulates tissue repair. Here we show in a blinded, placebo-controlled trial that 28 d of daily subcutaneous administration of ARA 290 in a group of patients with documented SNFLD significantly improves neuropathic symptoms. In addition to improved patient-reported symptom-based outcomes, ARA 290 administration was also associated with a significant increase in corneal small nerve fiber density, changes in cutaneous temperature sensitivity, and an increased exercise capacity as assessed by the 6-minute walk test. On the basis of these results and of prior studies, ARA 290 is a potential disease-modifying agent for treatment of sarcoidosis-associated SNFLD.

ARA 290 Improves Symptoms in Patients with Sarcoidosis-Associated Small Nerve Fiber Loss and Increases Corneal Nerve Fiber Density

PubMed Central

Dahan, Albert; Dunne, Ann; Swartjes, Maarten; Proto, Paolo L; Heij, Lara; Vogels, Oscar; van Velzen, Monique; Sarton, Elise; Niesters, Marieke; Tannemaat, Martijn R; Cerami, Anthony; Brines, Michael

2013-01-01

Small nerve fiber loss and damage (SNFLD) is a frequent complication of sarcoidosis that is associated with autonomic dysfunction and sensory abnormalities, including pain syndromes that severely degrade the quality of life. SNFLD is hypothesized to arise from the effects of immune dysregulation, an essential feature of sarcoidosis, on the peripheral and central nervous systems. Current therapy of sarcoidosis-associated SNFLD consists primarily of immune suppression and symptomatic treatment; however, this treatment is typically unsatisfactory. ARA 290 is a small peptide engineered to activate the innate repair receptor that antagonizes inflammatory processes and stimulates tissue repair. Here we show in a blinded, placebo-controlled trial that 28 d of daily subcutaneous administration of ARA 290 in a group of patients with documented SNFLD significantly improves neuropathic symptoms. In addition to improved patient-reported symptom-based outcomes, ARA 290 administration was also associated with a significant increase in corneal small nerve fiber density, changes in cutaneous temperature sensitivity, and an increased exercise capacity as assessed by the 6-minute walk test. On the basis of these results and of prior studies, ARA 290 is a potential disease-modifying agent for treatment of sarcoidosis-associated SNFLD. PMID:24136731

[The relationship between the sympathetic nerves and immunocytes in the spleen].

PubMed

Saito, H

1991-02-01

Ever since Galen, the ancient Greek physician, said "Melancholic women develop disease more than sanguine women," it has been said that the mental condition affects the physical condition. However, there is hardly any scientific verification. About half a century ago, Selye (1936) proposed a relationship between stress and immune function, and it is becoming increasingly clear that the nervous system and immune system interact with each other. Also researchers have strongly hoped to demonstrate the existence of specific pathways by which immunocytes can be directly regulated by the nervous elements instead of by the humoral influence of immunomodulators. In this study, the author showed by electron microscopic observation how the immunocytes in the guinea pig spleen are directly innervated. The sustentacular supporting element of the guinea pig spleen is the connective tissue system which includes the capsulo-trabecular, peri-vascular and reticular systems. The latter system is composed of the outer sheath of the reticular cell or its cellular processes which have abundant microfilaments and the inner minute connective tissue space in which lamina densa-like material, collagenous fibrils, elastic fibers and nervous elements are present. The sympathetic adrenergic nerves for the spleen enter the organ, and scatter around the arterial walls. All components of the connective tissue system are continuous with each other, and the nervous elements appearing in the reticular system are the elongated ones from other connective tissue systems, especially peri-vascular connective tissue. Thus, the adrenergic nerves are more abundant in the white pulp, into which the central artery penetrates, than in the red pulp which arterioles or capillaries pass through. The minute connective tissue space of the reticular system may be called the noradrenalin (NA) canal because catecholamine released from the naked adrenergic nerve terminals in this tissue diffuses and is stored in this enclosed space. The reticular system in the spleen divides the parenchyma into small non-endothelial vascular spaces owing to its meshwork, and free mobile immunocytes, such as T-cells, B-cells and macrophages, stagnate in these spaces. This stagnation of the mobile immunocytes and the presence of the adrenergic nerves in the NA canals provide the chance for the immunocytes and nerves to meet each other in the following fashion; the reticular cell sheaths show the exposed phenomena owing to the contraction of the microfilament-rich reticular cell processes, caused by noradrenalin in the NA canal, and the nervous elements in the NA canals can face the nonendothelial vascular spaces where mobile immunocytes pass freely.(ABSTRACT TRUNCATED AT 400 WORDS)

Determinants of peripapillary retinal nerve fiber layer thickness regarding ocular and systemic parameters - the MIPH Eye&Health Study.

PubMed

Schuster, Alexander Karl-Georg; Fischer, Joachim Ernst; Vossmerbaeumer, Christine; Vossmerbaeumer, Urs

2016-10-01

Optical coherence tomography (OCT) allows quantitative image analysis of retinal tissue in vivo. Peripapillary retinal nerve fiber layer (pRNFL) thickness is widely used for evaluation of retinal nerve fiber rarefaction in several optic neuropathies. This study evaluates associations of pRNFL thickness in healthy adult subjects in order to evaluate influencing factors. A cross-sectional study was performed in a working-age population. Only eyes without detectable ocular pathologies were included in the analysis. Among analyzed systemic cardiovascular parameters were age, gender, body-mass index, mean arterial blood pressure, HbA1c, high- and low-density-lipoproteins, and triglycerides. A comprehensive ophthalmological examination including refraction, tonometry, keratometry, and central corneal thickness measurmentwas performed. In addition, pRNFL thickness was imaged by spectral-domain OCT. Univariable and multivariable associations of pRNFL thickness in all four quadrants and on average with systemic and ocular parameters were calculated using a generalized estimating equation model. Three hundred and six subjects were included. pRNFL thickness measurements showed a significant association with spherical equivalent: pRNFL thickness decreased with increasing myopia in all quadrants (multivariable regression coefficients Beta: superior: 1.16, 95 % CI [0.62;1.71], p < 0.001; temporal: 0.87, [0.33;1.41], p = 0.001; inferior: 1.80, [1.18;2.42], p < 0.001; nasal: 2.60, [2.01;3.20], p < 0.001) and on average (1.51, [1.20;1.82], p < 0.001). A thicker central cornea thickness was related to lower pRNFL in the superior (-0.05, [-0.10; -0.01], p = 0.01), the inferior quadrant (-0.05, [-0.10;0.00], p = 0.03) and on average (-0.04, [-0.07; -0.01], p = 0.02). All other parameters were not  associated. Our findings highlight the importance of refraction when evaluating pRNFL thickness and its independence from other systemic parameters.

Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Activation of the Alpha-7 Nicotinic Acetylcholine Receptor

PubMed Central

Corsi-Zuelli, Fabiana Maria das Graças; Brognara, Fernanda; Quirino, Gustavo Fernando da Silva; Hiroki, Carlos Hiroji; Fais, Rafael Sobrano; Del-Ben, Cristina Marta; Ulloa, Luis; Salgado, Helio Cesar; Kanashiro, Alexandre; Loureiro, Camila Marcelino

2017-01-01

Schizophrenia is one of the most debilitating mental disorders and is aggravated by the lack of efficacious treatment. Although its etiology is unclear, epidemiological studies indicate that infection and inflammation during development induces behavioral, morphological, neurochemical, and cognitive impairments, increasing the risk of developing schizophrenia. The inflammatory hypothesis of schizophrenia is also supported by clinical studies demonstrating systemic inflammation and microglia activation in schizophrenic patients. Although elucidating the mechanism that induces this inflammatory profile remains a challenge, mounting evidence suggests that neuroimmune interactions may provide therapeutic advantages to control inflammation and hence schizophrenia. Recent studies have indicated that vagus nerve stimulation controls both peripheral and central inflammation via alpha-7 nicotinic acetylcholine receptor (α7nAChR). Other findings have indicated that vagal stimulation and α7nAChR-agonists can provide therapeutic advantages for neuropsychiatric disorders, such as depression and epilepsy. This review analyzes the latest results regarding: (I) the immune-to-brain pathogenesis of schizophrenia; (II) the regulation of inflammation by the autonomic nervous system in psychiatric disorders; and (III) the role of the vagus nerve and α7nAChR in schizophrenia. PMID:28620379

Peripheral facial weakness (Bell's palsy).

PubMed

Basić-Kes, Vanja; Dobrota, Vesna Dermanović; Cesarik, Marijan; Matovina, Lucija Zadro; Madzar, Zrinko; Zavoreo, Iris; Demarin, Vida

2013-06-01

Peripheral facial weakness is a facial nerve damage that results in muscle weakness on one side of the face. It may be idiopathic (Bell's palsy) or may have a detectable cause. Almost 80% of peripheral facial weakness cases are primary and the rest of them are secondary. The most frequent causes of secondary peripheral facial weakness are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immune disorders, drugs, degenerative diseases of the central nervous system, etc. The diagnosis relies upon the presence of typical signs and symptoms, blood chemistry tests, cerebrospinal fluid investigations, nerve conduction studies and neuroimaging methods (cerebral MRI, x-ray of the skull and mastoid). Treatment of secondary peripheral facial weakness is based on therapy for the underlying disorder, unlike the treatment of Bell's palsy that is controversial due to the lack of large, randomized, controlled, prospective studies. There are some indications that steroids or antiviral agents are beneficial but there are also studies that show no beneficial effect. Additional treatments include eye protection, physiotherapy, acupuncture, botulinum toxin, or surgery. Bell's palsy has a benign prognosis with complete recovery in about 80% of patients, 15% experience some mode of permanent nerve damage and severe consequences remain in 5% of patients.

Approaches to the treatment of Sjögren's syndrome.

PubMed

Fox, R I; Michelson, P

2000-12-01

Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by complaints of sicca symptoms (dry eye and mouth) and can be associated with other autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis, etc). As a result, SS can be difficult to diagnose. Currently, there are several criteria standards for SS, including the San Diego criteria and the European Study Group criteria. According to the San Diego criteria, the incidence of SS is about 0.5%, whereas for the European Study Group it ranges from 3% to 5%. This almost 10-fold difference in SS incidence has led to confusion for both the clinician and researcher. The tearing reflex involves a neural loop in which afferent nerve signals from the ocular surface are relayed centrally to the medulla. The input from the afferent nerves is then processed and sent back via efferent nerves stimulating blood vessels and secretory glands to provide and pump water for tears. Immune factors, such as cytokines, have a profound effect on the tearing mechanism by damaging secretory glands and releasing antibodies to influence the response of muscarinic M3 receptors. Thus, the interaction of neural and immune factors affects the secretory response of glands and contributes to the pathogenesis of SS sicca symptoms. The recent development of muscarinic agonists, such as pilocarpine and cevimeline, serves an important step in recognizing the interaction between the immune and neuroendocrine systems.

Median and ulnar neuropathies in university guitarists.

PubMed

Kennedy, Rachel H; Hutcherson, Kimberly J; Kain, Jennifer B; Phillips, Alicia L; Halle, John S; Greathouse, David G

2006-02-01

Descriptive study. To determine the presence of median and ulnar neuropathies in both upper extremities of university guitarists. Peripheral nerve entrapment syndromes of the upper extremities are well documented in musicians. Guitarists and plucked-string musicians are at risk for entrapment neuropathies in the upper extremities and are prone to mild neurologic deficits. Twenty-four volunteer male and female guitarists (age range, 18-26 years) were recruited from the Belmont University School of Music and the Vanderbilt University Blair School of Music. Individuals were excluded if they were pregnant or had a history of recent upper extremity or neck injury. Subjects completed a history form, were interviewed, and underwent a physical examination. Nerve conduction status of the median and ulnar nerves of both upper extremities was obtained by performing motor, sensory, and F-wave (central) nerve conduction studies. Descriptive statistics of the nerve conduction study variables were computed using Microsoft Excel. Six subjects had positive findings on provocative testing of the median and ulnar nerves. Otherwise, these guitarists had normal upper extremity neural and musculoskeletal function based on the history and physical examinations. When comparing the subjects' nerve conduction study values with a chart of normal nerve conduction studies values, 2 subjects had prolonged distal motor latencies (DMLs) of the left median nerve of 4.3 and 4.7 milliseconds (normal, < 4.2 milliseconds). Prolonged DMLs are compatible with median neuropathy at or distal to the wrist. Otherwise, all electrophysiological variables were within normal limits for motor, sensory, and F-wave (central) values. However, comparison studies of median and ulnar motor latencies in the same hand demonstrated prolonged differences of greater than 1.0 milliseconds that affected the median nerve in 2 additional subjects, and identified contralateral limb involvement in a subject with a prolonged distal latency. The other 20 subjects demonstrated normal comparison studies of the median and ulnar nerves in both upper extremities. In this descriptive study of a population of 24 university guitarists, 4 musicians (17%) were found to have electrophysiologic evidence of median neuropathy at or distal to the wrist or carpal tunnel syndrome. Ulnar nerve electrophysiological function was within normal limits for all subjects examined.

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.

More a finger than a nose: the trigeminal motor and sensory innervation of the Schnauzenorgan in the elephant-nose fish Gnathonemus petersii.

PubMed

Amey-Özel, Monique; von der Emde, Gerhard; Engelmann, Jacob; Grant, Kirsty

2015-04-01

The weakly electric fish Gnathonemus petersii uses its electric sense to actively probe the environment. Its highly mobile chin appendage, the Schnauzenorgan, is rich in electroreceptors. Physical measurements have demonstrated the importance of the position of the Schnauzenorgan in funneling the fish's self-generated electric field. The present study focuses on the trigeminal motor pathway that controls Schnauzenorgan movement and on its trigeminal sensory innervation and central representation. The nerves entering the Schnauzenorgan are very large and contain both motor and sensory trigeminal components as well as an electrosensory pathway. With the use of neurotracer techniques, labeled Schnauzenorgan motoneurons were found throughout the ventral main body of the trigeminal motor nucleus but not among the population of larger motoneurons in its rostrodorsal region. The Schnauzenorgan receives no motor or sensory innervation from the facial nerve. There are many anastomoses between the peripheral electrosensory and trigeminal nerves, but these senses remain separate in the sensory ganglia and in their first central relays. Schnauzenorgan trigeminal primary afferent projections extend throughout the descending trigeminal sensory nuclei, and a few fibers enter the facial lobe. Although no labeled neurons could be identified in the brain as the trigeminal mesencephalic root, some Schnauzenorgan trigeminal afferents terminated in the trigeminal motor nucleus, suggesting a monosynaptic, possibly proprioceptive, pathway. In this first step toward understanding multimodal central representation of the Schnauzenorgan, no direct interconnections were found between the trigeminal sensory and electromotor command system, or the electrosensory and trigeminal motor command. The pathways linking perception to action remain to be studied. © 2014 Wiley Periodicals, Inc.

Manipulation of norepinephrine metabolism with yohimbine in the treatment of autonomic failure

NASA Technical Reports Server (NTRS)

Biaggioni, I.; Robertson, R. M.; Robertson, D.

1994-01-01

It has been postulated that alpha 2-adrenergic receptors play a modulatory role in the regulation of blood pressure. Activation of alpha 2-receptors located in the central nervous system results in inhibition of sympathetic tone and decrease of blood pressure. This indeed may be the mechanism of action of central sympatholytic antihypertensives such as alpha-methyldopa. Presynaptic alpha 2-receptors also are found in adrenergic nerve terminals. These receptors act as a negative feedback mechanism by inhibiting the release of norepinephrine. The relevance of alpha 2-adrenergic receptors for blood pressure regulation can be explored with yohimbine, a selective antagonist of these receptors. Yohimbine increases blood pressure in resting normal volunteers. This effect is associated with an increase in both sympathetic nerve activity, reflecting an increase in central sympathetic outflow, and in norepinephrine spillover, reflecting potentiation of the release of norepinephrine from adrenergic nerve terminals. These actions, therefore, underscore the importance of alpha 2-adrenergic receptors for blood pressure regulation even under resting conditions. Patients with autonomic failure, even those with severe sympathetic deprivation, are hypersensitive to the pressor effects of yohimbine. This increased responsiveness can be explained by sensitization of adrenergic receptors, analogous to denervation supersensitivity, and by the lack of autonomic reflexes that would normally buffer any increase in blood pressure. Preliminary studies suggest that the effectiveness of yohimbine in autonomic failure can be enhanced with monoamine oxidase inhibitors. Used in combination, yohimbine increases norepinephrine release, whereas monoamine oxidase inhibitors inhibit its degradation. Therefore, yohimbine is not only a useful tool in the study of blood pressure regulation, but may offer a therapeutic option in autonomic dysfunction.

Polyethylene glycol restores axonal conduction after corpus callosum transection.

PubMed

Bamba, Ravinder; Riley, D Colton; Boyer, Richard B; Pollins, Alonda C; Shack, R Bruce; Thayer, Wesley P

2017-05-01

Polyethylene glycol (PEG) has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In this current experiment, coronal sectioning of the brains of Sprague-Dawley rats was performed after animal sacrifice. 3Brain high-resolution microelectrode arrays (MEA) were used to measure mean firing rate (MFR) and peak amplitude across the corpus callosum of the ex-vivo brain slices. The corpus callosum was subsequently transected and repeated measurements were performed. The cut ends of the corpus callosum were still apposite at this time. A PEG solution was applied to the injury site and repeated measurements were performed. MEA measurements showed that PEG was capable of restoring electrophysiology signaling after transection of central nerves. Before injury, the average MFRs at the ipsilateral, midline, and contralateral corpus callosum were 0.76, 0.66, and 0.65 spikes/second, respectively, and the average peak amplitudes were 69.79, 58.68, and 49.60 μV, respectively. After injury, the average MFRs were 0.71, 0.14, and 0.25 spikes/second, respectively and peak amplitudes were 52.11, 8.98, and 16.09 μV, respectively. After application of PEG, there were spikes in MFR and peak amplitude at the injury site and contralaterally. The average MFRs were 0.75, 0.55, and 0.47 spikes/second at the ipsilateral, midline, and contralateral corpus callosum, respectively and peak amplitudes were 59.44, 45.33, 40.02 μV, respectively. There were statistically differences in the average MFRs and peak amplitudes between the midline and non-midline corpus callosum groups ( P < 0.01, P < 0.05). These findings suggest that PEG restores axonal conduction between severed central nerves, potentially representing axonal fusion.

Polyethylene glycol restores axonal conduction after corpus callosum transection

PubMed Central

Bamba, Ravinder; Riley, D. Colton; Boyer, Richard B.; Pollins, Alonda C.; Shack, R. Bruce; Thayer, Wesley P.

2017-01-01

Polyethylene glycol (PEG) has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In this current experiment, coronal sectioning of the brains of Sprague-Dawley rats was performed after animal sacrifice. 3Brain high-resolution microelectrode arrays (MEA) were used to measure mean firing rate (MFR) and peak amplitude across the corpus callosum of the ex-vivo brain slices. The corpus callosum was subsequently transected and repeated measurements were performed. The cut ends of the corpus callosum were still apposite at this time. A PEG solution was applied to the injury site and repeated measurements were performed. MEA measurements showed that PEG was capable of restoring electrophysiology signaling after transection of central nerves. Before injury, the average MFRs at the ipsilateral, midline, and contralateral corpus callosum were 0.76, 0.66, and 0.65 spikes/second, respectively, and the average peak amplitudes were 69.79, 58.68, and 49.60 μV, respectively. After injury, the average MFRs were 0.71, 0.14, and 0.25 spikes/second, respectively and peak amplitudes were 52.11, 8.98, and 16.09 μV, respectively. After application of PEG, there were spikes in MFR and peak amplitude at the injury site and contralaterally. The average MFRs were 0.75, 0.55, and 0.47 spikes/second at the ipsilateral, midline, and contralateral corpus callosum, respectively and peak amplitudes were 59.44, 45.33, 40.02 μV, respectively. There were statistically differences in the average MFRs and peak amplitudes between the midline and non-midline corpus callosum groups (P < 0.01, P < 0.05). These findings suggest that PEG restores axonal conduction between severed central nerves, potentially representing axonal fusion. PMID:28616031

The Application of Nanomaterials in Stem Cell Therapy for Some Neurological Diseases.

PubMed

Zhang, Guilong; Khan, Ahsan Ali; Wu, Hao; Chen, Lukui; Gu, Yuchun; Gu, Ning

2018-02-08

Stem cell therapy provides great promising therapeutic benefits for various neurological disorders. Cell transplantation has emerged as cell replacement application for nerve damage. Recently, nanomaterials obtain wide development in various industrial and medical fields, and nanoparticles have been applied in the neurological field for tracking and treating nervous system diseases. Combining stem cells with nanotechnology has raised more and more attentions; and it has demonstrated that the combination has huge effects on clinical diagnosis and therapeutics in multiple central nervous system diseases, meanwhile, improves prognosis. The aim of this review was to give a brief overview of the application of nanomaterials in stem cell therapy for neurological diseases. Nanoparticles not only promote stem cell proliferation and differentiation in vitro or in vivo, but also play dominant roles on stem cell imaging and tracking. Furthermore, via delivering genes or drugs, nanoparticles can participate in stem cell therapeutic applications for various neurological diseases, such as ischemic stroke, spinal cord injury (SCI), multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD) and gliomas. However, nanoparticles have potential cytotoxic effects on nerve cells, which are related to their physicochemical properties. Nano-stem cell-based therapy as a promising strategy has the ability to affect neuronal repair and regeneration in the central nervous system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Sarin (GB, O-isopropyl methylphosphonofluoridate) neurotoxicity: critical review

PubMed Central

Abou-Donia, Mohamed B.; Siracuse, Briana; Gupta, Natasha; Sokol, Ashly Sobel

2017-01-01

Sarin (GB, O-isopropyl methylphosphonofluoridate) is a potent organophosphorus (OP) nerve agent that inhibits acetylcholinesterase (AChE) irreversibly. The subsequent build-up of acetylcholine (ACh) in the central nervous system (CNS) provokes seizures and, at sufficient doses, centrally-mediated respiratory arrest. Accumulation of ACh at peripheral autonomic synapses leads to peripheral signs of intoxication and overstimulation of the muscarinic and nicotinic receptors, which is described as “cholinergic crisis” (i.e. diarrhea, sweating, salivation, miosis, bronchoconstriction). Exposure to high doses of sarin can result in tremors, seizures, and hypothermia. More seriously, build-up of ACh at neuromuscular junctions also can cause paralysis and ultimately peripherally-mediated respiratory arrest which can lead to death via respiratory failure. In addition to its primary action on the cholinergic system, sarin possesses other indirect effects. These involve the activation of several neurotransmitters including gamma-amino-butyric acid (GABA) and the alteration of other signaling systems such as ion channels, cell adhesion molecules, and inflammatory regulators. Sarin exposure is associated with symptoms of organophosphate-induced delayed neurotoxicity (OPIDN) and organophosphate-induced chronic neurotoxicity (OPICN). Moreover, sarin has been involved in toxic and immunotoxic effects as well as organophosphate-induced endocrine disruption (OPIED). The standard treatment for sarin-like nerve agent exposure is post-exposure injection of atropine, a muscarinic receptor antagonist, accompanied by an oxime, an AChE reactivator, and diazepam. PMID:27705071

Boosting CNS axon regeneration by harnessing antagonistic effects of GSK3 activity.

PubMed

Leibinger, Marco; Andreadaki, Anastasia; Golla, Renate; Levin, Evgeny; Hilla, Alexander M; Diekmann, Heike; Fischer, Dietmar

2017-07-03

Implications of GSK3 activity for axon regeneration are often inconsistent, if not controversial. Sustained GSK3 activity in GSK3 S/A knock-in mice reportedly accelerates peripheral nerve regeneration via increased MAP1B phosphorylation and concomitantly reduces microtubule detyrosination. In contrast, the current study shows that lens injury-stimulated optic nerve regeneration was significantly compromised in these knock-in mice. Phosphorylation of MAP1B and CRMP2 was expectedly increased in retinal ganglion cell (RGC) axons upon enhanced GSK3 activity, but, surprisingly, no GSK3-mediated CRMP2 inhibition was detected in sciatic nerves, thus revealing a fundamental difference between central and peripheral axons. Conversely, genetic or shRNA-mediated conditional KO/knockdown of GSK3β reduced inhibitory phosphorylation of CRMP2 in RGCs and improved optic nerve regeneration. Accordingly, GSK3β KO-mediated neurite growth promotion and myelin disinhibition were abrogated by CRMP2 inhibition and largely mimicked in WT neurons upon expression of constitutively active CRMP2 (CRMP2 T/A ). These results underscore the prevalent requirement of active CRMP2 for optic nerve regeneration. Strikingly, expression of CRMP2 T/A in GSK3 S/A RGCs further boosted optic nerve regeneration, with axons reaching the optic chiasm within 3 wk. Thus, active GSK3 can also markedly promote axonal growth in central nerves if CRMP2 concurrently remains active. Similar to peripheral nerves, GSK3-mediated MAP1B phosphorylation/activation and the reduction of microtubule detyrosination contributed to this effect. Overall, these findings reconcile conflicting data on GSK3-mediated axon regeneration. In addition, the concept of complementary modulation of normally antagonistically targeted GSK3 substrates offers a therapeutically applicable approach to potentiate the regenerative outcome in the injured CNS.

Myokymia and neuromyotonia in veterinary medicine: a comparison with peripheral nerve hyperexcitability syndrome in humans.

PubMed

Vanhaesebrouck, An E; Bhatti, Sofie F M; Franklin, Robin J M; Van Ham, Luc

2013-08-01

Involuntary muscle hyperactivity can result from muscle or peripheral nerve hyperexcitability or central nervous system dysfunction. In humans, diseases causing hyperexcitability of peripheral nerves are grouped together under the term 'peripheral nerve hyperexcitability' (PNH). Hyperexcitability of the peripheral motor nerve can result into five different phenotypic main variants, i.e. fasciculations, myokymia, neuromyotonia, cramps and tetany, each with their own clinical and electromyographic characteristics. This review focuses on the most commonly described expressions of PNH in veterinary medicine, i.e. myokymia and neuromyotonia, in particular in young Jack Russell terriers. Data from 58 veterinary cases with generalized myokymia and neuromyotonia were analyzed, including unpublished treatment and follow-up data on eight Jack Russell terriers from a previous study and seven additional Jack Russell terriers. A dysfunction of the potassium channel or its associated proteins has been found in many human syndromes characterized by PNH, in particular in generalized myokymia and neuromyotonia, and is suspected to occur in veterinary medicine. Potential pathomechanisms of potassium channel dysfunction leading to signs of PNH are broad and include genetic mutations, antibody-mediated attack or ion channel maldistribution due to axonal degeneration or demyelination. A more accurate classification of the different PNH syndromes will facilitate a more rapid diagnosis and guide further research into natural occurring PNH in animals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Valproic Acid Promotes Survival of Facial Motor Neurons in Adult Rats After Facial Nerve Transection: a Pilot Study.

PubMed

Zhang, Lili; Fan, Zhaomin; Han, Yuechen; Xu, Lei; Liu, Wenwen; Bai, Xiaohui; Zhou, Meijuan; Li, Jianfeng; Wang, Haibo

2018-04-01

Valproic acid (VPA), a medication primarily used to treat epilepsy and bipolar disorder, has been applied to the repair of central and peripheral nervous system injury. The present study investigated the effect of VPA on functional recovery, survival of facial motor neurons (FMNs), and expression of proteins in rats after facial nerve trunk transection by functional measurement, Nissl staining, TUNEL, immunofluorescence, and Western blot. Following facial nerve injury, all rats in group VPA showed a better functional recovery, which was significant at the given time, compared with group NS. The Nissl staining results demonstrated that the number of FMNs survival in group VPA was higher than that in group normal saline (NS). TUNEL staining showed that axonal injury of facial nerve could lead to neuronal apoptosis of FMNs. But treatment of VPA significantly reduced cell apoptosis by decreasing the expression of Bax protein and increased neuronal survival by upregulating the level of brain-derived neurotrophic factor (BDNF) and growth associated protein-43 (GAP-43) expression in injured FMNs compared with group NS. Overall, our findings suggest that VPA may advance functional recovery, reduce lesion-induced apoptosis, and promote neuron survival after facial nerve transection in rats. This study provides an experimental evidence for better understanding the mechanism of injury and repair of peripheral facial paralysis.

Neurological disruption produced in hens by two organophosphate esters

PubMed Central

Baron, R. L.; Johnson, H.

1964-01-01

A histological and enzymatic examination was made of the neurological disruption produced in hens by two organophosphate esters. Intraperitoneal administration of DEF (tributyl phosphorotrithiolate) and Merphos (tributyl phosphorotrithioite) produced central and perpheral nervous system lesions accompanied by clinical signs of ataxia similar to those seen following administration of tri-o-cresyl phosphate. Histological examination (utilizing the Marchi stain) showed the occurence of spinal cord disruption before the onset of clinical ataxia. Oral administration of DEF and Merphos did not induce signs of peripheral weakness. However, severe lesions in the spinal cord and sciatic nerve were prominent. A discussion of the occurrence of central and peripheral nerve disruption either in the presence or absence of clinical ataxia is presented. Enzymatic examination of the effect of DEF on spinal cord and brain esterases at various intervals following administration showed a pattern of esterase inhibition similar to that found after tri-o-cresyl phosphate, dyflos and other organophosphates. Some prolonged inhibition is believed due to the extent of initial involvement rather than to selective prolonged inhibition. ImagesFig. 1Fig. 2 PMID:14228131

Minamata disease.

PubMed

Eto, K

2000-09-01

Minamata disease (methylmercury poisoning) was first discovered in 1956 around Minamata Bay, Kumamoto Prefecture, Japan. A second epidemic in Japan occurred in 1965 along the Agano River, Niigata Prefecture. This paper presents a brief review of Minamata disease with an emphasis on the cases found in Kumamoto Prefecture. At autopsy, the most conspicuous destructive lesion in the cerebrum was found in the anterior portions of the calcarine cortex. Less severe but similar lesions may be found in the post-central, pre-central and temporal transverse cortices. Secondary degeneration from primary lesions may be seen in cases with long survival. In the cerebellum, pathological changes occur deep in the hemisphere. The granule cell population was more affected, compared with Purkinje cells. Among peripheral nerves, sensory nerves were more affected than motor nerves. Our recent experimental studies that reveal knowledge of the pathogenesis of methylmercury poisoning will be discussed.

Immunolocalization of choline acetyltransferase of common type in the central brain mass of Octopus vulgaris

PubMed Central

Casini, A.; Vaccaro, R.; D'Este, L.; Sakaue, Y.; Bellier, J.P.; Kimura, H.; Renda, T.G.

2012-01-01

Acetylcholine, the first neurotransmitter to be identified in the vertebrate frog, is widely distributed among the animal kingdom. The presence of a large amount of acetylcholine in the nervous system of cephalopods is well known from several biochemical and physiological studies. However, little is known about the precise distribution of cholinergic structures due to a lack of a suitable histochemical technique for detecting acetylcholine. The most reliable method to visualize the cholinergic neurons is the immunohistochemical localization of the enzyme choline acetyltransferase, the synthetic enzyme of acetylcholine. Following our previous study on the distribution patterns of cholinergic neurons in the Octopus vulgaris visual system, using a novel antibody that recognizes choline acetyltransferase of the common type (cChAT), now we extend our investigation on the octopus central brain mass. When applied on sections of octopus central ganglia, immunoreactivity for cChAT was detected in cell bodies of all central brain mass lobes with the notable exception of the subfrontal and subvertical lobes. Positive varicosed nerves fibers where observed in the neuropil of all central brain mass lobes. PMID:23027350

Immunolocalization of choline acetyltransferase of common type in the central brain mass of Octopus vulgaris.

PubMed

Casini, A; Vaccaro, R; D'Este, L; Sakaue, Y; Bellier, J P; Kimura, H; Renda, T G

2012-07-19

Acetylcholine, the first neurotransmitter to be identified in the vertebrate frog, is widely distributed among the animal kingdom. The presence of a large amount of acetylcholine in the nervous system of cephalopods is well known from several biochemical and physiological studies. However, little is known about the precise distribution of cholinergic structures due to a lack of a suitable histochemical technique for detecting acetylcholine. The most reliable method to visualize the cholinergic neurons is the immunohistochemical localization of the enzyme choline acetyltransferase, the synthetic enzyme of acetylcholine. Following our previous study on the distribution patterns of cholinergic neurons in the Octopus vulgaris visual system, using a novel antibody that recognizes choline acetyltransferase of the common type (cChAT), now we extend our investigation on the octopus central brain mass. When applied on sections of octopus central ganglia, immunoreactivity for cChAT was detected in cell bodies of all central brain mass lobes with the notable exception of the subfrontal and subvertical lobes. Positive varicosed nerves fibers where observed in the neuropil of all central brain mass lobes.

Auditory Spatial Perception: Auditory Localization

DTIC Science & Technology

2012-05-01

cochlear nucleus, TB – trapezoid body, SOC – superior olivary complex, LL – lateral lemniscus, IC – inferior colliculus. Adapted from Aharonson and...Figure 5. Auditory pathways in the central nervous system. LE – left ear, RE – right ear, AN – auditory nerve, CN – cochlear nucleus, TB...fibers leaving the left and right inner ear connect directly to the synaptic inputs of the cochlear nucleus (CN) on the same (ipsilateral) side of

Fish oil protects the peripheral and central nervous systems against cisplatin-induced neurotoxicity.

PubMed

Kamisli, Suat; Ciftci, Osman; Cetin, Asli; Kaya, Kursat; Kamisli, Ozden; Celik, Hamit

2014-04-01

The protective effects of fish oil (FO) on cisplatin (CP)-induced central and peripheral neurotoxicity were investigated in rats. Rats (n = 28) were divided equally into four groups, the first group was kept as a control. In the second and third groups, CP and FO were given at doses of 7 mg/kg and 1 softgel/rat/day, respectively. In the fourth group, CP and FO were given together at the same doses. Although CP caused significant oxidative damage, via induction of lipid peroxidation and reduction in the antioxidant defense system potency, FO treatment largely reversed these effects. CP also resulted in histopathological damage, such as apoptosis, and electromyographical changes in the sciatic nerve. FO treatment partially prevented the histopathological and electromyographical effects of CP. CP has severe central and peripheral neurotoxic effects in rats and these effects were largely prevented by FO treatment. Thus, it appears that co-administration of FO with CP may be a useful approach to attenuate the negative effects of CP on the nervous system.

Role of chemoreception in cardiorespiratory acclimatization to, and deacclimatization from, hypoxia

PubMed Central

Powell, Frank L.; Bisgard, Gerald E.; Blain, Gregory M.; Poulin, Marc J.; Smith, Curtis A.

2013-01-01

During sojourn to high altitudes, progressive time-dependent increases occur in ventilation and in sympathetic nerve activity over several days, and these increases persist upon acute restoration of normoxia. We discuss evidence concerning potential mediators of these changes, including the following: 1) correction of alkalinity in cerebrospinal fluid; 2) increased sensitivity of carotid chemoreceptors; and 3) augmented translation of carotid chemoreceptor input (at the level of the central nervous system) into increased respiratory motor output via sensitization of hypoxic sensitive neurons in the central nervous system and/or an interdependence of central chemoreceptor responsiveness on peripheral chemoreceptor sensory input. The pros and cons of chemoreceptor sensitization and cardiorespiratory acclimatization to hypoxia and intermittent hypoxemia are also discussed in terms of their influences on arterial oxygenation, the work of breathing, sympathoexcitation, systemic blood pressure, and exercise performance. We propose that these adaptive processes may have negative implications for the cardiovascular health of patients with sleep apnea and perhaps even for athletes undergoing regimens of “sleep high-train low”! PMID:24371017

Role of chemoreception in cardiorespiratory acclimatization to, and deacclimatization from, hypoxia.

PubMed

Dempsey, Jerome A; Powell, Frank L; Bisgard, Gerald E; Blain, Gregory M; Poulin, Marc J; Smith, Curtis A

2014-04-01

During sojourn to high altitudes, progressive time-dependent increases occur in ventilation and in sympathetic nerve activity over several days, and these increases persist upon acute restoration of normoxia. We discuss evidence concerning potential mediators of these changes, including the following: 1) correction of alkalinity in cerebrospinal fluid; 2) increased sensitivity of carotid chemoreceptors; and 3) augmented translation of carotid chemoreceptor input (at the level of the central nervous system) into increased respiratory motor output via sensitization of hypoxic sensitive neurons in the central nervous system and/or an interdependence of central chemoreceptor responsiveness on peripheral chemoreceptor sensory input. The pros and cons of chemoreceptor sensitization and cardiorespiratory acclimatization to hypoxia and intermittent hypoxemia are also discussed in terms of their influences on arterial oxygenation, the work of breathing, sympathoexcitation, systemic blood pressure, and exercise performance. We propose that these adaptive processes may have negative implications for the cardiovascular health of patients with sleep apnea and perhaps even for athletes undergoing regimens of "sleep high-train low"!

A case of disseminated central nervous system sparganosis.

PubMed

Noiphithak, Raywat; Doungprasert, Gahn

2016-01-01

Sparganosis is a very rare parasitic infection in various organs caused by the larvae of tapeworms called spargana. The larva usually lodges in the central nervous system (CNS) and the orbit. However, lumbar spinal canal involvement, as noted in the present case, is extremely rare. We report a rare case of disseminated CNS sparganosis involving the brain and spinal canal and review the literature. A 54-year-old man presented with progressive low back pain and neurological deficit at the lumbosacral level for 2 months. Imaging indicated arachnoiditis and an abnormal lesion at the L4-5 vertebral level. The patient underwent laminectomy of the L4-5 with lesionectomy and lysis of adhesions between the nerve roots. Microscopic examination indicated sparganum infection. Further brain imaging revealed evidence of chronic inflammation in the left parieto-occipital area without evidence of live parasites. In addition, an ophthalmologist reported a nonactive lesion in the right conjunctiva. The patient recovered well after surgery, although he had residual back pain and bladder dysfunction probably due to severe adhesion of the lumbosacral nerve roots. CNS sparganosis can cause various neurological symptoms similar to those of other CNS infections. A preoperative enzyme-linked immunosorbent assay is helpful for diagnosis, especially in endemic areas. Surgical removal of the worm remains the treatment of choice.

EFFECT OF INTRAVITREAL RANIBIZUMAB ON GANGLION CELL COMPLEX AND PERIPAPILLARY RETINAL NERVE FIBER LAYER IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PubMed

Zucchiatti, Ilaria; Cicinelli, Maria V; Parodi, Maurizio Battaglia; Pierro, Luisa; Gagliardi, Marco; Accardo, Agostino; Bandello, Francesco

2017-07-01

To analyze the changes in ganglion cell complex and peripapillary retinal nerve fiber layer thickness, in central macular thickness and choroidal thickness on spectral domain optical coherence tomography in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab injections. All consecutive patients with untreated neovascular age-related macular degeneration received loading phase of three monthly intravitreal ranibizumab, followed by retreatments on a pro re nata protocol for 12 months. changes in ganglion cell complex and retinal nerve fiber layer at the end of follow-up. Secondary outcome: changes in best-corrected visual acuity, central macular thickness, and choroidal thickness at the end of follow-up. Choroidal thickness was measured at 500 μm, 1000 μm, and 1,500 μm intervals nasally, temporally, superiorly, and inferiorly to the fovea, respectively, on horizontal and vertical line scans centered on the fovea. Twenty-four eyes were included. Ganglion cell complex and peripapillary retinal nerve fiber layer thickness did not show statistically significant changes through 12 months (55.6 ± 18.5 and 81.9 ± 9.9 μm at baseline, 52.7 ± 19.3 and 84.6 ± 15.5 μm at month 12, P > 0.05). Central macular thickness showed progressive decrease from baseline to month 12, with maximum reduction at month 3 (P < 0.001). Statistically significant reduction in choroidal thickness was registered in the nasal 500, 1000, and 1,500 μm from the fovea, corresponding to the papillomacular region (from 169.6 ± 45.3 to 153.9 ± 46.9, P < 0.001). Intravitreal ranibizumab injections did not affect retinal nerve fiber layer and ganglion cell complex thickness in 1-year follow-up. Choroidal thickness in papillomacular area and central macular thickness was significantly reduced at the end of treatment. Further studies, with larger sample, longer follow-up, and greater number of injections, are warranted.

Diaphragm pacing after bilateral implantation of intradiaphragmatic phrenic stimulation electrodes through a transmediastinal endoscopic minimally invasive approach: pilot animal data.

PubMed

Assouad, Jalal; Masmoudi, Hicham; Gonzalez-Bermejo, Jesus; Morélot-Panzini, Capucine; Diop, Moustapha; Grunenwald, Dominique; Similowski, Thomas

2012-08-01

Phrenic nerve stimulation for diaphragm pacing allows patients with central respiratory paralysis to be weaned from mechanical ventilation. Two procedures are available, either intrathoracic (bilateral thoracotomy) or intradiaphragmatic (four ports laparoscopy). The present experimental work assesses the feasibility, safety and efficacy of a trans-mediastinal implantation of intradiaphragmatic phenic nerve stimulation electrodes using a flexible gastroscope through a cervical incision. We operated on nine ewes. After selective bronchial intubation, we dissected the latero-tracheal space and opened both mediastinal pleura. We then introduced a flexible gastroscope into the pleural cavities, in a sequential manner. The phrenic nerves were located and followed up to the diaphragm dome. Electrodes loaded within a long, pliable needle were introduced through the adjacent intercostal space and implanted in each hemidiaphragm, at a 'tendinous' location (as close as possible to the entry of the nerve in the central tendon), and at a more lateral 'muscular' location. Postoperatively, the animals were ventilated using bilateral phrenic nerve stimulation. After euthanasia, abdominal verification of the electrodes position was performed through a laparotomy. The mediastinal and pleural parts of the procedure were uneventful. The insertion of electrodes was associated with transdiaphragmatic puncture and small abdominal haematomas in the first two animals studied. After a slight modification of the insertion technique, this was not observed anymore. Phrenic nerve stimulation produced efficient ventilation, with tidal volumes significantly higher when delivered at the tendinous site than at the muscular site. The trans-mediastinal implantation of intradiaphragmatic phrenic nerve stimulation electrodes is feasible, appears reasonably safe, and allows efficient ventilation.

Permanent reorganization of Ia afferent synapses on motoneurons after peripheral nerve injuries

PubMed Central

Alvarez, Francisco J.; Bullinger, Katie L.; Titus, Haley E.; Nardelli, Paul; Cope, Timothy C.

2010-01-01

After peripheral nerve injuries to a motor nerve the axons of motoneurons and proprioceptors are disconnected from the periphery and monosynaptic connections from group I afferents and motoneurons become diminished in the spinal cord. Following successful reinnervation in the periphery, motor strength, proprioceptive sensory encoding, and Ia afferent synaptic transmission on motoneurons partially recover. Muscle stretch reflexes, however, never recover and motor behaviors remain uncoordinated. In this review, we summarize recent findings that suggest that lingering motor dysfunction might be in part related to decreased connectivity of Ia afferents centrally. First, sensory afferent synapses retract from lamina IX causing a permanent relocation of the inputs to more distal locations and significant disconnection from motoneurons. Second, peripheral reconnection between proprioceptive afferents and muscle spindles is imperfect. As a result, a proportion of sensory afferents that retain central connections with motoneurons might not reconnect appropriately in the periphery. A hypothetical model is proposed in which the combined effect of peripheral and central reconnection deficits might explain the failure of muscle stretch to initiate or modulate firing of many homonymous motoneurons. PMID:20536938

Activation of somatosensory afferents elicit changes in vaginal blood flow and the urethrogenital reflex via autonomic efferents.

PubMed

Cai, R S; Alexander, M Sipski; Marson, L

2008-09-01

We examined the effects of pudendal sensory nerve stimulation and urethral distention on vaginal blood flow and the urethrogenital reflex, and the relationship between somatic and autonomic pathways regulating sexual responses. Distention of the urethra and stimulation of the pudendal sensory nerve were used to evoke changes in vaginal blood flow (laser Doppler perfusion monitoring) and pudendal motor nerve activity in anesthetized, spinally transected female rats. Bilateral cuts of either the pelvic or hypogastric nerve or both autonomic nerves were made, and blood flow and pudendal nerve responses were reexamined. Stimulation of the pudendal sensory nerve or urethral distention elicited consistent increases in vaginal blood flow and rhythmic firing of the pudendal motor nerve. Bilateral cuts of the pelvic plus hypogastric nerves significantly reduced vaginal blood flow responses without altering pudendal motor nerve responses. Pelvic nerve cuts also significantly reduced vaginal blood flow responses. In contrast, hypogastric nerve cuts did not significantly change vaginal blood flow. Bilateral cuts of the pudendal sensory nerve blocked pudendal motor nerve responses but stimulation of the central end evoked vaginal blood flow and pudendal motor nerve responses. Stimulation of the sensory branch of the pudendal nerve elicits vasodilatation of the vagina. The likely mechanism is via activation of spinal pathways that in turn activate pelvic nerve efferents to produced changes in vaginal blood flow. Climatic-like responses (firing of the pudendal motor nerve) occur in response to stimulation of the pudendal sensory nerve and do not require intact pelvic or hypogastric nerves.

Adeno-Associated Viral-Mediated Catalase Expression Suppresses Optic Neuritis in Experimental Allergic Encephalomyelitis

NASA Astrophysics Data System (ADS)

Guy, John; Qi, Xiaoping; Hauswirth, William W.

1998-11-01

Suppression of oxidative injury by viral-mediated transfer of the human catalase gene was tested in the optic nerves of animals with experimental allergic encephalomyelitis (EAE). EAE is an inflammatory autoimmune disorder of primary central nervous system demyelination that has been frequently used as an animal model for the human disease multiple sclerosis (MS). The optic nerve is a frequent site of involvement common to both EAE and MS. Recombinant adeno-associated virus containing the human gene for catalase was injected over the right optic nerve heads of SJL/J mice that were simultaneously sensitized for EAE. After 1 month, cell-specific catalase activity, evaluated by quantitation of catalase immunogold, was increased approximately 2-fold each in endothelia, oligodendroglia, astrocytes, and axons of the optic nerve. Effects of catalase on the histologic lesions of EAE were measured by computerized analysis of the myelin sheath area (for demyelination), optic disc area (for optic nerve head swelling), extent of the cellular infiltrate, extravasated serum albumin labeled by immunogold (for blood-brain barrier disruption), and in vivo H2O2 reaction product. Relative to control, contralateral optic nerves injected with the recombinant virus without a therapeutic gene, catalase gene inoculation reduced demyelination by 38%, optic nerve head swelling by 29%, cellular infiltration by 34%, disruption of the blood-brain barrier by 64%, and in vivo levels of H2O2 by 61%. Because the efficacy of potential treatments for MS are usually initially tested in the EAE animal model, this study suggests that catalase gene delivery by using viral vectors may be a therapeutic strategy for suppression of MS.

An autopsy case of minamata disease (methylmercury poisoning)--pathological viewpoints of peripheral nerves.

PubMed

Eto, Komyo; Tokunaga, Hidehiro; Nagashima, Kazuo; Takeuchi, Tadao

2002-01-01

The outbreak of methylmercury poisoning in the geographic areas around Minamata Bay, Kumamoto, Japan in the 1950s has become known as Minamata disease. Based on earlier reports and extensive pathological studies on autopsied cases at the Kumamoto University School of Medicine, destructive lesions in the anterior portion of the calcarine cortex and depletion predominantly of granular cells in the cerebellar cortex came to be recognized as the hallmark and diagnostic yardstick of methylmercury poisoning in humans. As the number of autopsy cases of Minamata disease increased, it became apparent that the cerebral lesion was not restricted to the calcarine cortex but was relatively widespread. Less severe lesions, believed to be responsible for the motor symptoms of Minamata patients, were often found in the precentral, postcentral, and lateral temporal cortices. These patients also frequently presented with signs of sensory neuropathy affecting the distal extremities. Because of few sufficiently comprehensive studies, peripheral nerve degeneration has not been universally accepted as a cause of the sensory disturbances in Minamata patients. The present paper describes both biopsy and autopsy findings of the peripheral nerves in a male fisherman who died at the age of 64 years and showed the characteristic central nervous system lesions of Minamata disease at autopsy. A sural nerve biopsy with electron microscopy performed 1 month prior to his death showed endoneurial fibrosis and regenerated myelin sheaths. At autopsy the dorsal roots and sural nerve showed endoneurial fibrosis, loss of nerve fibers, and presence of Büngner's bands. The spinal cord showed Wallerian degeneration of the fasciculus gracilis (Goll's tract) with relative preservation of neurons in sensory ganglia. These findings support the contention that there is peripheral nerve degeneration in Minamata patients due to toxic injury from methylmercury.

Evolution of taste and solitary chemoreceptor cell systems.

PubMed

Finger, T E

1997-01-01

Vertebrates possess four distinct chemosensory systems distinguishable on the basis of structure, innervation and utilization: olfaction, taste, solitary chemoreceptor cells (SCC) and the common chemical sense (free nerve endings). Of these, taste and the SCC sense rely on secondary receptor cells situated in the epidermis and synapsing on sensory nerve fibers innervating them near their base. The SCC sense occurs in anamniote aquatic craniates, including hagfish, and may be used for feeding or predator avoidance. The sense of taste occurs only in vertebrates and is always utilized for feeding. The SCC system achieves a high degree of specialization in two teleosts: sea robins (Prionotus) and rocklings (Ciliata). In sea robins, SCCs are abundant on the three anterior fin rays of the pectoral fin which are free of fin webbing and are used in active exploration of the substrate. Behavioral and physiological studies show that this SCC system responds to feeding cues and drives feeding behavior. It is connected centrally like a somatosensory system. In contrast, the specialized SCC system of rocklings occurs on the anterior dorsal fin which actively samples the surrounding water. This system responds to mucus substances and may serve as a predator detector. The SCC system in rocklings is connected centrally like a gustatory system. Taste buds contain multiple receptor cell types, including a serotonergic Merkel-like cell. Taste receptor cells respond to nutritionally relevant substances. Due to similarities between SCCs and one type of taste receptor cell, the suggestion is made that taste buds may be compound sensory organs that include some cells related to SCCs and others related to cutaneous Merkel cells. The lack of taste buds in hagfish and their presence in all vertebrates may indicate that the phylogenetic development of taste buds coincided with the elaboration of head structures at the craniate-vertebrate transition.

Morphological evidence for local microcircuits in rat vestibular maculae

NASA Technical Reports Server (NTRS)

Ross, M. D.

1997-01-01

Previous studies suggested that intramacular, unmyelinated segments of vestibular afferent nerve fibers and their large afferent endings (calyces) on type I hair cells branch. Many of the branches (processes) contain vesicles and are presynaptic to type II hair cells, other processes, intramacular nerve fibers, and calyces. This study used serial section transmission electron microscopy and three-dimensional reconstruction methods to document the origins and distributions of presynaptic processes of afferents in the medial part of the adult rat utricular macula. The ultrastructural research focused on presynaptic processes whose origin and termination could be observed in a single micrograph. Results showed that calyces had 1) vesiculated, spine-like processes that invaginated type I cells and 2) other, elongate processes that ended on type II cells pre- as well as postsynaptically. Intramacular, unmyelinated segments of afferent nerve fibers gave origin to branches that were presynaptic to type II cells, calyces, calyceal processes, and other nerve fibers in the macula. Synapses with type II cells occurred opposite subsynaptic cisternae (C synapses); all other synapses were asymmetric. Vesicles were pleomorphic but were differentially distributed according to process origin. Small, clear-centered vesicles, approximately 40-60 nm in diameter, predominated in processes originating from afferent nerve fibers and basal parts of calyces. Larger vesicles approximately 70-120 nm in diameter having approximately 40-80 nm electron-opaque cores were dominant in processes originating from the necks of calyces. Results are interpreted to indicate the existence of a complex system of intrinsic feedforward (postsynaptic)-feedback (presynaptic) connections in a network of direct and local microcircuits. The morphological findings support the concept that maculae dynamically preprocess linear acceleratory information before its transmission to the central nervous system.

Study of Autophagy and Microangiopathy in Sural Nerves of Patients with Chronic Idiopathic Axonal Polyneuropathy

PubMed Central

Samuelsson, Kristin; Osman, Ayman A. M.; Angeria, Maria; Risling, Mårten; Mohseni, Simin; Press, Rayomand

2016-01-01

Twenty-five percent of polyneuropathies are idiopathic. Microangiopathy has been suggested to be a possible pathogenic cause of chronic idiopathic axonal polyneuropathy (CIAP). Dysfunction of the autophagy pathway has been implicated as a marker of neurodegeneration in the central nervous system, but the autophagy process is not explored in the peripheral nervous system. In the current study, we examined the presence of microangiopathy and autophagy-related structures in sural nerve biopsies of 10 patients with CIAP, 11 controls with inflammatory neuropathy and 10 controls without sensory polyneuropathy. We did not find any significant difference in endoneurial microangiopathic markers in patients with CIAP compared to normal controls, though we did find a correlation between basal lamina area thickness and age. Unexpectedly, we found a significantly larger basal lamina area thickness in patients with vasculitic neuropathy. Furthermore, we found a significantly higher density of endoneurial autophagy-related structures, particularly in patients with CIAP but also in patients with inflammatory neuropathy, compared to normal controls. It is unclear if the alteration in the autophagy pathway is a consequence or a cause of the neuropathy. Our results do not support the hypothesis that CIAP is primarily caused by a microangiopathic process in endoneurial blood vessels in peripheral nerves. The significantly higher density of autophagy structures in sural nerves obtained from patients with CIAP and inflammatory neuropathy vs. controls indicates the involvement of this pathway in neuropathy, particularly in CIAP, since the increase in density of autophagy-related structures was more pronounced in patients with CIAP than those with inflammatory neuropathy. To our knowledge this is the first report investigating signs of autophagy process in peripheral nerves in patients with CIAP and inflammatory neuropathy. PMID:27662650

Effect of Switching from Cilnidipine to Azelnidipine on Cardiac Sympathetic Nerve Function in Patients with Heart Failure Preserved Ejection Fraction.

PubMed

Kiuchi, Shunsuke; Hisatake, Shinji; Kabuki, Takayuki; Oka, Takashi; Dobashi, Shintaro; Fujii, Takahiro; Ikeda, Takanori

2018-01-27

Cardiac sympathetic nerve activity is known to play a key role in the development and progression of heart failure (HF). Azelnidipine, an L-type calcium channel blocker (CCB), inhibits the sympathetic nerve activity of the central system. In contrast, cilnidipine, an N-type CCB, inhibits the sympathetic nerve activity of the peripheral system. CCBs are recommended as class IIa in patients with HF preserved ejection fraction (HFpEF); however, there are no comparative data on the difference in effect of cilnidipine and azelnidipine in patients with HFpEF and hypertension. We investigated the difference in effect of azelnidipine compared with cilnidipine in patients with HFpEF. Twenty-four consecutive HF patients who received angiotensin II type1a receptor blocker and beta blocker from April 2013 to January 2015 were enrolled. Cilnidipine was switched to azelnidipine during the follow-up period. Blood pressures, heart rate, blood tests, echocardiography, and 123 I-metaiodobenzylguanidine (MIBG) cardiac-scintigraphy were measured before and after 6 months from azelnidipine administration. B-type natriuretic peptide tended to decrease after switching to azelnidipine; however, there were no significant differences between the pre-state and post-state (pre-state: 118.5 pg/mL and post-state: 78.4 pg/mL, P = 0.137). Other laboratory findings, including catecholamine, also did not change significantly. In echocardiography, there were no significant differences in systolic and diastolic functions at the pre-state and post-state. As for MIBG, there were no significant changes in heart/mediastinum ratio. However, washout rate was significantly reduced (pre-state: 42.9 and post-state: 39.6, P = 0.030). Azelnidipine improved the dysfunction of cardiac sympathetic nerve activity compared with cilnidipine in patients with HFpEF.

Unilateral or bilateral vagotomy induces ovulation in both ovaries of rats with polycystic ovarian syndrome.

PubMed

Linares, Rosa; Hernández, Denisse; Morán, Carolina; Chavira, Roberto; Cárdenas, Mario; Domínguez, Roberto; Morales-Ledesma, Leticia

2013-07-17

Injecting estradiol valerate (EV) to pre-pubertal or adult female rat results in effects similar to those observed in women with polycystic ovarian syndrome (PCOS). One of the mechanisms involved in PCOS development is the hyperactivity of the sympathetic nervous system. In EV-induced PCOS rats, the unilateral sectioning of the superior ovarian nerve (SON) restores ovulation of the innervated ovary. This suggests that, in addition to the sympathetic innervation, other neural mechanisms are involved in the development/maintenance of PCOS. The aims of present study were analyze if the vagus nerve is one of the neural pathways participating in PCOS development. Ten-day old rats were injected with EV dissolved in corn oil. At 24-days of age sham-surgery, unilateral, or bilateral sectioning of the vagus nerve (vagotomy) was performed on these rats. The animals were sacrificed at 90-92 days of age, when they presented vaginal estrous preceded by a pro-estrus smear. In EV-induced PCOS rats, unilateral or bilateral vagotomy restored ovulation in both ovaries. Follicle-stimulating hormone (FSH) levels in PCOS rats with unilateral or bilateral vagotomy were lower than in control rats. This result suggests that in EV-induced PCOS rats the vagus nerve is a neural pathway participating in maintaining PCOS. The vagus nerve innervates the ovaries directly and indirectly through its synapsis in the celiac-superior-mesenteric ganglion, where the somas of neurons originating in the SON are located. Then, it is possible that vagotomy effects in EV-induced PCOS rats may be explained as a lack of communication between the central nervous system and the ovaries.

Neuro-muscular transmission in blood vessels: phasic and tonic components. An in-vitro study of mesenteric arteries of the rat.

PubMed

Sjöblom-Widfeldt, N

1990-01-01

For many years noradrenaline was considered to be the exclusive transmitter released from sympathetic nerves. However, during recent years both ATP and NPY have been suggested to be co-transmitters to noradrenaline in these nerves. The present study aimed to investigate the functional relationship between these suggested transmitters during nerve stimulation with different frequencies and in different extracellular calcium concentrations. Also the importance of the pattern of nerve stimulation and the potentiation of the neurogenic response after a period of high-frequency nerve stimulation were investigated. Contractions caused by nerve stimulation and applied agonists were investigated in segments of small mesenteric arteries from rat. The biophysical, electrophysiological, and pharmacological properties of these vessels are well characterized in previous studies. The rapid contraction caused by a single nerve stimulus, the "single twitch", and the initial, phasic contraction caused by high-frequency nerve stimulation were only slightly affected by alpha-adrenoceptor blockade with prazosin, whereas the tonic response to high-frequency stimulation was markedly reduced. The phasic responses and those to low-frequency nerve stimulation thus appear to be due mainly to a non-adrenergic transmitter. After inhibiting the response to exogenous ATP by alpha beta-methylene ATP, the response to single impulses and to low-frequency nerve stimulation were markedly reduced, while those to high-frequency stimulation were unaffected. This suggests that ATP acts as a true transmitter in sympathetic nerves, being responsible mainly for rapid responses to low-frequency stimulation, and for the initial part of responses to high-frequency stimulation. When alpha beta-methylene ATP and prazosin were given in combination, no contraction was obtained during nerve stimulation at any frequency. However, if in this situation a contraction was induced by e.g. exogenous vasopressin, field stimulation caused a further, slow contraction. This additional response was undoubtedly neurogenic, but required high-frequency nerve stimulation. The response to nerve stimulation was found to be calcium-dependent, the calcium-dependency being more pronounced at low than at high stimulation frequencies. A continuous, high-frequency (8-16 Hz) nerve stimulation could greatly (5-15 fold) enhance the response to subsequent low-frequency nerve stimulation. This potentiation increased with the frequency of the conditioning stimulation and, within limits, with the number of impulses delivered. Also the extracellular calcium concentration during the conditioning stimulation determined the magnitude of the potentiation. This post-tetanic potentiation has many characteristics in common with the post-tetanic potentiation studied in the central and somatomotor nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)

Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat.

PubMed

Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

2007-04-01

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-kappaB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-kappaB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-kappaB super- repressor IkappaBalpha resulted in an inhibition of the NF-kappaB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IkappaBalpha overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-kappaB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-kappaB pathway in the development of neuropathic pain after peripheral nerve injury.

Neuro-immune lessons from an annelid: The medicinal leech.

PubMed

Tasiemski, Aurélie; Salzet, Michel

2017-01-01

An important question that remains unanswered is how the vertebrate neuroimmune system can be both friend and foe to the damaged nervous tissue. Some of the difficulty in obtaining responses in mammals probably lies in the conflation in the central nervous system (CNS), of the innate and adaptive immune responses, which makes the vertebrate neuroimmune response quite complex and difficult to dissect. An alternative strategy for understanding the relation between neural immunity and neural repair is to study an animal devoid of adaptive immunity and whose CNS is well described and regeneration competent. The medicinal leech offers such opportunity. If the nerve cord of this annelid is crushed or partially cut, axons grow across the lesion and conduction of signals through the damaged region is restored within a few days, even when the nerve cord is removed from the animal and maintained in culture. When the mammalian spinal cord is injured, regeneration of normal connections is more or less successful and implies multiple events that still remain difficult to resolve. Interestingly, the regenerative process of the leech lesioned nerve cord is even more successful under septic than under sterile conditions suggesting that a controlled initiation of an infectious response may be a critical event for the regeneration of normal CNS functions in the leech. Here are reviewed and discussed data explaining how the leech nerve cord sensu stricto (i.e. excluding microglia and infiltrated blood cells) recognizes and responds to microbes and mechanical damages. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preventive mechanisms of agmatine against ischemic acute kidney injury in rats.

PubMed

Sugiura, Takahiro; Kobuchi, Shuhei; Tsutsui, Hidenobu; Takaoka, Masanori; Fujii, Toshihide; Hayashi, Kentaro; Matsumura, Yasuo

2009-01-28

The excitation of renal sympathetic nervous system plays an important role in the development of ischemic acute kidney injury in rats. Recently, we found that agmatine, an adrenaline alpha(2)/imidazoline I(1)-receptor agonist, has preventive effects on ischemic acute kidney injury by suppressing the enhanced renal sympathetic nerve activity during renal ischemia and by decreasing the renal venous norepinephrine overflow after reperfusion. In the present study, we investigated preventive mechanisms of agmatine against ischemic acute kidney injury in rats. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after the contralateral nephrectomy. Pretreatment with efaroxan (30 mumol/kg, i.v.), an alpha(2)/I(1)-receptor antagonist, abolished the suppressive effects of agmatine on the enhanced renal sympathetic nerve activity during renal ischemia and on the elevated norepinephrine overflow after reperfusion, and eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal dysfunction and histological damage. On the other hand, pretreatment with yohimbine (6 mumol/kg, i.v.), an alpha(2)-receptor antagonist, eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal injury and norepinephrine overflow, without affecting the lowering effect of agmatine on renal sympathetic nerve activity. These results indicate that agmatine prevents the ischemic renal injury by sympathoinhibitory effect probably via I(1) receptors in central nervous system and by suppressing the norepinephrine overflow through alpha(2) or I(1) receptors on sympathetic nerve endings.

Microtubule-Targeting Agents Enter the Central Nervous System (CNS): Double-edged Swords for Treating CNS Injury and Disease.

PubMed

Hur, Eun-Mi; Lee, Byoung Dae

2014-12-01

Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs) are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS) are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

The Incidence of Intravascular Needle Entrance during Inferior Alveolar Nerve Block Injection.

PubMed

Taghavi Zenouz, Ali; Ebrahimi, Hooman; Mahdipour, Masoumeh; Pourshahidi, Sara; Amini, Parisa; Vatankhah, Mahdi

2008-01-01

Dentists administer thousands of local anesthetic injections every day. Injection to a highly vascular area such as pterygomandibular space during an inferior alveolar nerve block has a high risk of intravascular needle entrance. Accidental intravascular injection of local anesthetic agent with vasoconstrictor may result in cardiovascular and central nervous system toxicity, as well as tachycardia and hypertension. There are reports that indicate aspiration is not performed in every injection. The aim of the present study was to assess the incidence of intravascular needle entrance in inferior alveolar nerve block injections. Three experienced oral and maxillofacial surgeons performed 359 inferior alveolar nerve block injections using direct or indirect techniques, and reported the results of aspiration. Aspirable syringes and 27 gauge long needles were used, and the method of aspiration was similar in all cases. Data were analyzed using t-test. 15.3% of inferior alveolar nerve block injections were aspiration positive. Intravascular needle entrance was seen in 14.2% of cases using direct and 23.3% of cases using indirect block injection techniques. Of all injections, 15.8% were intravascular on the right side and 14.8% were intravascular on the left. There were no statistically significant differences between direct or indirect block injection techniques (P = 0.127) and between right and left injection sites (P = 0.778). According to our findings, the incidence of intravascular needle entrance during inferior alveolar nerve block injection was relatively high. It seems that technique and maneuver of injection have no considerable effect in incidence of intravascular needle entrance.

The Incidence of Intravascular Needle Entrance during Inferior Alveolar Nerve Block Injection

PubMed Central

Taghavi Zenouz, Ali; Ebrahimi, Hooman; Mahdipour, Masoumeh; Pourshahidi, Sara; Amini, Parisa; Vatankhah, Mahdi

2008-01-01

Background and aims Dentists administer thousands of local anesthetic injections every day. Injection to a highly vascular area such as pterygomandibular space during an inferior alveolar nerve block has a high risk of intravascular needle entrance. Accidental intravascular injection of local anesthetic agent with vasoconstrictor may result in cardiovascular and central nervous system toxicity, as well as tachycardia and hypertension. There are reports that indicate aspiration is not performed in every injection. The aim of the present study was to assess the incidence of intravascular needle entrance in inferior alveolar nerve block injections. Materials and methods Three experienced oral and maxillofacial surgeons performed 359 inferior alveolar nerve block injections using direct or indirect techniques, and reported the results of aspiration. Aspirable syringes and 27 gauge long needles were used, and the method of aspiration was similar in all cases. Data were analyzed using t-test. Results 15.3% of inferior alveolar nerve block injections were aspiration positive. Intravascular needle entrance was seen in 14.2% of cases using direct and 23.3% of cases using indirect block injection techniques. Of all injections, 15.8% were intravascular on the right side and 14.8% were intravascular on the left. There were no statistically significant differences between direct or indirect block injection techniques (P = 0.127) and between right and left injection sites (P = 0.778). Conclusion According to our findings, the incidence of intravascular needle entrance during inferior alveolar nerve block injection was relatively high. It seems that technique and maneuver of injection have no considerable effect in incidence of intravascular needle entrance. PMID:23285329

Nerve agent intoxication: Recent neuropathophysiological findings and subsequent impact on medical management prospects

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

Collombet, Jean-Marc, E-mail: jmcollombet@imassa.fr

This manuscript provides a survey of research findings catered to the development of effective countermeasures against nerve agent poisoning over the past decade. New neuropathophysiological distinctive features as regards organophosphate (OP) intoxication are presented. Such leading neuropathophysiological features include recent data on nerve agent-induced neuropathology, related peripheral or central nervous system inflammation and subsequent angiogenesis process. Hence, leading countermeasures against OP exposure are down-listed in terms of pre-treatment, protection or decontamination and emergency treatments. The final chapter focuses on the description of the self-repair attempt encountered in lesioned rodent brains, up to 3 months after soman poisoning. Indeed, an increasedmore » proliferation of neuronal progenitors was recently observed in injured brains of mice subjected to soman exposure. Subsequently, the latter experienced a neuronal regeneration in damaged brain regions such as the hippocampus and amygdala. The positive effect of a cytokine treatment on the neuronal regeneration and subsequent cognitive behavioral recovery are also discussed in this review. For the first time, brain cell therapy and neuronal regeneration are considered as a valuable contribution towards delayed treatment against OP intoxication. To date, efficient delayed treatment was lacking in the therapeutic resources administered to patients contaminated by nerve agents. - Highlights: > This review focuses on neuropathophysiology following nerve agent poisoning in mice. > Extensive data on long-term neuropathology and related inflammation are provided here. > Delayed self-repair attempts encountered in lesioned rodent brains are also described. > Cell therapy is considered as a valuable treatment against nerve agent intoxication.« less

Central Sensitization-Based Classification for Temporomandibular Disorders: A Pathogenetic Hypothesis

PubMed Central

Cattaneo, Ruggero; Marci, Maria Chiara; Pietropaoli, Davide; Ortu, Eleonora

2017-01-01

Dysregulation of Autonomic Nervous System (ANS) and central pain pathways in temporomandibular disorders (TMD) is a growing evidence. Authors include some forms of TMD among central sensitization syndromes (CSS), a group of pathologies characterized by central morphofunctional alterations. Central Sensitization Inventory (CSI) is useful for clinical diagnosis. Clinical examination and CSI cannot identify the central site(s) affected in these diseases. Ultralow frequency transcutaneous electrical nerve stimulation (ULFTENS) is extensively used in TMD and in dental clinical practice, because of its effects on descending pain modulation pathways. The Diagnostic Criteria for TMD (DC/TMD) are the most accurate tool for diagnosis and classification of TMD. However, it includes CSI to investigate central aspects of TMD. Preliminary data on sensory ULFTENS show it is a reliable tool for the study of central and autonomic pathways in TMD. An alternative classification based on the presence of Central Sensitization and on individual response to sensory ULFTENS is proposed. TMD may be classified into 4 groups: (a) TMD with Central Sensitization ULFTENS Responders; (b) TMD with Central Sensitization ULFTENS Nonresponders; (c) TMD without Central Sensitization ULFTENS Responders; (d) TMD without Central Sensitization ULFTENS Nonresponders. This pathogenic classification of TMD may help to differentiate therapy and aetiology. PMID:28932132

Regeneration of the eighth cranial nerve in the bullfrog, Rana catesbeiana.

PubMed

Newman, A; Honrubia, V

1992-01-01

The present study was done in order to document the ability of the eighth cranial nerve of the bullfrog (Rana catesbeiana) to regenerate, the anatomic characteristics of the regenerated fibers, and the specificity of projections from individual endorgan branches of the nerve. The eighth cranial nerve was sharply transected between the ganglion cells and the brain stem in 40 healthy bullfrogs and allowed to regenerate. Anatomic studies were performed in these animals a minimum of 3 months postoperatively. Horseradish peroxidase was used to label the whole vestibular nerve or its individual endorgan branches. Labeled regenerated fibers could be identified crossing the site of the nerve section and projecting centrally to the vestibular nuclei in a pattern similar to that of normal frogs. Labeling of individual branches showed that regenerated fibers innervated the same specific areas found in normal frogs. Unlike normal animals, both thick and thin fibers projected to the medial nucleus.

Screening for Electrophysiological Abnormalities in Chronic Hepatitis C Infection: Peripheral Neuropathy and Optic Neuropathy.

PubMed

Köşkderelioğlu, Aslı; Ortan, Pınar; Ari, Alpay; Gedizlioğlu, Muhteşem

2016-03-01

To investigate the existence of peripheral and optic neuropathies in asymptomatic individuals with hepatitis C infection. Thirty consecutive patients who were followed in a hepatitis C outpatient clinic were recruited for electrophysiological evaluation together with 30 age- and gender-compatible healthy controls. All patients had a detailed neurological examination. The information regarding the disease duration and management with interferons were collected. Nerve conduction studies and visual evoked potentials (VEP) were recorded in all subjects. The results of the patient and control groups were statistically compared. Of the patients with hepatitis C infection, 16 were females and 14 males. The mean age was 57.5 years, and the average disease duration was 6.43 years. The P100 latencies in the patient group were within normal limits, while the amplitudes were meaningfully small by comparison with the controls. There were some abnormalities in the nerve conduction studies of 15 patients. Sensorial neuropathy was detected in two patients, sensorimotor polyneuropathy in four, carpal tunnel syndrome in seven, and carpal tunnel syndrome and sensorimotor polyneuropathy as comorbid states in another two patients. The nerve conduction studies and VEP parameters were entirely normal in the control group. Hepatitis C-related neurological abnormalities may occur both in the central and peripheral nervous system. Mononeuritis multiplex, sensorial axonal neuropathy, and multiple mononeuropathies are some of the presentations of the peripheral nervous system involvement. The mode of infection is considered to be via vasculitic mechanisms. In addition, optic neuropathy is a known complication of interferon treatment. Autoantibodies, cytokines, chemokines, and cryoglobulins are accused to play roles in the pathogenesis. In this study, we investigated the involvement of the peripheral nervous system and optic nerves in a group of patients with hepatitis C. The results were in favor of peripheral nerve injury of various types and optic neuropathy of the axonal type.

Screening for Electrophysiological Abnormalities in Chronic Hepatitis C Infection: Peripheral Neuropathy and Optic Neuropathy

PubMed Central

KÖŞKDERELİOĞLU, Aslı; ORTAN, Pınar; ARI, Alpay; GEDİZLİOĞLU, Muhteşem

2016-01-01

Introduction To investigate the existence of peripheral and optic neuropathies in asymptomatic individuals with hepatitis C infection. Methods Thirty consecutive patients who were followed in a hepatitis C outpatient clinic were recruited for electrophysiological evaluation together with 30 age- and gender-compatible healthy controls. All patients had a detailed neurological examination. The information regarding the disease duration and management with interferons were collected. Nerve conduction studies and visual evoked potentials (VEP) were recorded in all subjects. The results of the patient and control groups were statistically compared. Results Of the patients with hepatitis C infection, 16 were females and 14 males. The mean age was 57.5 years, and the average disease duration was 6.43 years. The P100 latencies in the patient group were within normal limits, while the amplitudes were meaningfully small by comparison with the controls. There were some abnormalities in the nerve conduction studies of 15 patients. Sensorial neuropathy was detected in two patients, sensorimotor polyneuropathy in four, carpal tunnel syndrome in seven, and carpal tunnel syndrome and sensorimotor polyneuropathy as comorbid states in another two patients. The nerve conduction studies and VEP parameters were entirely normal in the control group. Conclusion Hepatitis C-related neurological abnormalities may occur both in the central and peripheral nervous system. Mononeuritis multiplex, sensorial axonal neuropathy, and multiple mononeuropathies are some of the presentations of the peripheral nervous system involvement. The mode of infection is considered to be via vasculitic mechanisms. In addition, optic neuropathy is a known complication of interferon treatment. Autoantibodies, cytokines, chemokines, and cryoglobulins are accused to play roles in the pathogenesis. In this study, we investigated the involvement of the peripheral nervous system and optic nerves in a group of patients with hepatitis C. The results were in favor of peripheral nerve injury of various types and optic neuropathy of the axonal type. PMID:28360761

Different effects of astrocytes and Schwann cells on regenerating retinal axons.

PubMed

Campbell, Gregor; Kitching, Juliet; Anderson, Patrick N; Lieberman, A Robert

2003-11-14

Following a crush injury of the optic nerve in adult rats, the axons of retinal ganglion cells, stimulated to regenerate by a lens injury and growing within the optic nerve, are associated predominantly with astrocytes: they remain of small diameter (0.1-0.5 microm) and unmyelinated for > or = 2 months after the operation. In contrast, when the optic nerve is cut and a segment of a peripheral nerve is grafted to the ocular stump of the optic nerve, the regenerating retinal axons are associated predominantly with Schwann cells: they are of larger diameter than in the previous experiment and include unmyelinated axons (0.2-2.5 microm) and myelinated axons (mean diameter 2.3 microm). Thus, the grafted peripheral nerve, and presumably its Schwann cells, stimulate enlargement of the regenerating retinal axons leading to partial myelination, whereas the injured optic nerve itself, and presumably its astrocytes, does not. The result points to a marked difference of peripheral (Schwann cells) and central (astrocytes) glia in their effect on regenerating retinal axons.

Permanent central synaptic disconnection of proprioceptors after nerve injury and regeneration. I. Loss of VGLUT1/IA synapses on motoneurons

PubMed Central

Titus-Mitchell, Haley E.; Bullinger, Katie L.; Kraszpulski, Michal; Nardelli, Paul; Cope, Timothy C.

2011-01-01

Motor and sensory proprioceptive axons reinnervate muscles after peripheral nerve transections followed by microsurgical reattachment; nevertheless, motor coordination remains abnormal and stretch reflexes absent. We analyzed the possibility that permanent losses of central IA afferent synapses, as a consequence of peripheral nerve injury, are responsible for this deficit. VGLUT1 was used as a marker of proprioceptive synapses on rat motoneurons. After nerve injuries synapses are stripped from motoneurons, but while other excitatory and inhibitory inputs eventually recover, VGLUT1 synapses are permanently lost on the cell body (75–95% synaptic losses) and on the proximal 100 μm of dendrite (50% loss). Lost VGLUT1 synapses did not recover, even many months after muscle reinnervation. Interestingly, VGLUT1 density in more distal dendrites did not change. To investigate whether losses are due to VGLUT1 downregulation in injured IA afferents or to complete synaptic disassembly and regression of IA ventral projections, we studied the central trajectories and synaptic varicosities of axon collaterals from control and regenerated afferents with IA-like responses to stretch that were intracellularly filled with neurobiotin. VGLUT1 was present in all synaptic varicosities, identified with the synaptic marker SV2, of control and regenerated afferents. However, regenerated afferents lacked axon collaterals and synapses in lamina IX. In conjunction with the companion electrophysiological study [Bullinger KL, Nardelli P, Pinter MJ, Alvarez FJ, Cope TC. J Neurophysiol (August 10, 2011). doi:10.1152/jn.01097.2010], we conclude that peripheral nerve injuries cause a permanent retraction of IA afferent synaptic varicosities from lamina IX and disconnection with motoneurons that is not recovered after peripheral regeneration and reinnervation of muscle by sensory and motor axons. PMID:21832035

Reversing hypomyelination in BACE1-null mice with Akt-DD overexpression.

PubMed

Hu, Xiangyou; Schlanger, Rita; He, Wanxia; Macklin, Wendy B; Yan, Riqiang

2013-05-01

β-Site amyloid precursor protein convertase enzyme 1 (BACE1), a type I transmembrane aspartyl protease required to cleave amyloid precursor protein for releasing a toxic amyloid peptide, also cleaves type I and type III neuregulin-1 (Nrg-1). BACE1 deficiency in mice causes hypomyelination during development and impairs remyelination if injured. In BACE1-null mice, the abolished cleavage of neuregulin-1 by BACE1 is speculated to cause reduced myelin sheath thickness in both the central nervous system and peripheral nervous system because reduced cleavage of Nrg-1 correlates with reduced Akt phosphorylation, a downstream signaling molecule of the Nrg-1/ErbB pathway. Here we tested specifically whether increasing Akt activity alone in oligodendrocytes would be sufficient to reverse the hypomyelination phenotype in BACE1-null mice. BACE1-null mice were bred with transgenic mice expressing constitutively active Akt (Akt-DD; mutations with D(308)T and D(473)S) in oligodendrocytes. Relative to littermate BACE1-null controls, BACE1(-/-)/Akt-DD mice exhibited enhanced expression of myelin basic protein and promoter of proteolipid protein. The elevated expression of myelin proteins correlated with a thicker myelin sheath in optic nerves; comparison of quantified g ratios with statistic significance was used to confirm this reversion. However, it appeared that myelin sheath thickness in the sciatic nerves was not increased in BACE1(-/-)/Akt-DD mice, as the g ratio was not significantly different from the control. Hence, increased Akt activity in BACE1-null myelinating cells only compensates for the loss of BACE1 activity in the central nervous system, which is consistent with the observation that overexpression of Akt-DD in Schwann cells did not induce hypermyelination. Our results suggest that signaling activity other than Akt may also contribute to proper myelination in peripheral nerves.

Centralization of the deuterostome nervous system predates chordates.

PubMed

Nomaksteinsky, Marc; Röttinger, Eric; Dufour, Héloïse D; Chettouh, Zoubida; Lowe, Chris J; Martindale, Mark Q; Brunet, Jean-François

2009-08-11

The origin of the chordate central nervous system (CNS) is unknown. One theory is that a CNS was present in the first bilaterian and that it gave rise to both the ventral cord of protostomes and the dorsal cord of deuterostomes. Another theory proposes that the chordate CNS arose by a dramatic process of dorsalization and internalization from a diffuse nerve net coextensive with the skin of the animal, such as enteropneust worms (Hemichordata, Ambulacraria) are supposed to have. We show here that juvenile and adult enteropneust worms in fact have a bona fide CNS, i.e., dense agglomerations of neurons associated with a neuropil, forming two cords, ventral and dorsal. The latter is internalized in the collar as a chordate-like neural tube. Contrary to previous assumptions, the greater part of the adult enteropneust skin is nonneural, although elements of the peripheral nervous system (PNS) are found there. We use molecular markers to show that several neuronal types are anatomically segregated in the CNS and PNS. These neuroanatomical features, whatever their homologies with the chordate CNS, imply that nervous system centralization predates the evolutionary separation of chordate and hemichordate lineages.

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.

Variability in cardiovascular control: the baroreflex reconsidered.

PubMed

Karemaker, John M; Wesseling, Karel H

2008-03-01

Although blood pressure control is often viewed as a paradigmatic example of a "homeostatic" biological control system, blood pressure levels can fluctuate considerably over shorter and longer time scales. In modern signal analysis, coherence between heart rate and blood pressure variability is used to estimate baroreflex gain. However, the shorter the measurement period, the more variability this gain factor reveals. We review evidence that this variability is not due to the technique used for the estimation, but may be an intrinsic property of the circulatory control mechanisms. The baroreflex is reviewed from its evolutionary origin, starting in fishes as a reflex mechanism to protect the gills from excessively high pressures by slowing the heart via the (parasympathetic) vagus nerve. Baroreflex inhibition of cardiovascular sympathetic nervous outflow is a later development; the maximally possible extent of sympathetic activity probably being set in the central nervous system by mechanisms other than blood pressure per se. In the sympathetic outflow tract not only baroreflex inhibition but also as yet unidentified, stochastic mechanisms decide to pass or not pass on the sympathetic activity to the periphery. In this short essay, the "noisiness" of the baroreflex as nervous control system is stressed. This property is observed in all elements of the reflex, even at the--supposedly--most basic relation between afferent receptor nerve input and efferent--vagus--nerve output signal.

Baroreflex Function in Rats after Simulated Microgravity

NASA Technical Reports Server (NTRS)

Hasser, Eileen M.

1997-01-01

Prolonged exposure of humans to decreased gravitational forces during spaceflight results in a number of adverse cardiovascular consequences, often referred to as cardiovascular deconditioning. Prominent among these negative cardiovascular effects are orthostatic intolerance and decreased exercise capacity. Rat hindlimb unweighting is an animal model which simulates weightlessness, and results in similar cardiovascular consequences. Cardiovascular reflexes, including arterial and cardiopulmonary baroreflexes, are required for normal adjustment to both orthostatic challenges and exercise. Therefore, the orthostatic intolerance and decreased exercise capacity associated with exposure to microgravity may be due to cardiovascular reflex dysfunction. The proposed studies will test the general hypothesis that hindlimb unweighting in rats results in impaired autonomic reflex control of the sympathetic nervous system. Specifically, we hypothesize that the ability to reflexly increase sympathetic nerve activity in response to decreases in arterial pressure or blood volume will be blunted due to hindlimb unweighting. There are 3 specific aims: (1) To evaluate arterial and cardiopulmonary baroreflex control of renal and lumbar sympathetic nerve activity in conscious rats subjected to 14 days of hindlimb unweighting; (2) To examine the interaction between arterial and cardiopulmonary baroreflex control of sympathetic nerve activity in conscious hindlimb unweighted rats; (3) to evaluate changes in afferent and/or central nervous system mechanisms in baroreflex regulation of the sympathetic nervous system. These experiments will provide information related to potential mechanisms for orthostatic and exercise intolerance due to microgravity.

Experimental Therapeutics Against the Toxic and Lethal Effects Resulting from Acute Exposure to Nerve Agents Without Carbamate Pretreatment in Guinea Pigs

DTIC Science & Technology

2010-09-01

or VX. Guinea pigs chronically instrumented for concurrent recordings of EEG, cardiorespiratory activities , diaphragm and skeletal muscle EMG were... activities , or any debilitating effects. The animals were asymptomatic within 30 min following therapy and survived the agent challenge 24 hr later. In...For a thorough efficacy evaluation, the animals were chronically instrumented to permit concurrent recordings of central nervous system activity

Comparison of stromal corneal nerves between normal and keratoconus patients using confocal microscopy.

PubMed

Ramírez Fernández, M; Hernández Quintela, E; Naranjo Tackman, R

2014-08-01

To evaluate the differences in stromal corneal nerves between normal patients and keratoconus patients. A total of 140 eyes of 70 normal patients (group A) and 122 eyes of 87 keratoconus patients (group B) were examined with the confocal microscope, with a central scan of the total corneal thickness being taken. The morphology and thickness of the corneal stromal nerves were evaluated by using the Navis v. 3.5.0. software. Nerve thickness was obtained from the mean between the widest and the narrowest portions of each stromal nerve. Corneal stromal nerves were observed as irregular linear hyper-reflective structures with wide and narrow portions in all cases. Mean corneal stromal nerves thickness in group A was 5.7±1.7 (range from 3.3 to 10.4 μ), mean corneal stromal nerves thickness in group B was 7.2±1.9 (range from 3.5 to 12.0 μ). There was a statistical significant difference (P<.05) in stromal corneal nerves thickness between group A and group B. Stromal corneal nerves morphology was similar in both groups, but stromal nerves were thicker in keratoconus patients. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

From fish to man: understanding endogenous remyelination in central nervous system demyelinating diseases.

PubMed

Dubois-Dalcq, Monique; Williams, Anna; Stadelmann, Christine; Stankoff, Bruno; Zalc, Bernard; Lubetzki, Catherine

2008-07-01

In the central nervous system (CNS) of man, evolutionary pressure has preserved some capability for remyelination while axonal regeneration is very limited. In contrast, two efficient programmes of regeneration exist in the adult fish CNS, neurite regrowth and remyelination. The rapidity of CNS remyelination is critical since it not only restores fast conduction of nerve impulses but also maintains axon integrity. If myelin repair fails, axons degenerate, leading to increased disability. In the human CNS demyelinating disease multiple sclerosis (MS), remyelination often takes place in the midst of inflammation. Here, we discuss recent studies that address the innate repair capabilities of the axon-glia unit from fish to man. We propose that expansion of this research field will help find ways to maintain or enhance spontaneous remyelination in man.

Passive immunization of fetal rats with antiserum to luteinizing hormone-releasing hormone (LHRH) or transection of the central roots of the nervus terminalis does not affect rat pups' preference for home nest.

PubMed

Schwanzel-Fukuda, M; Pfaff, D W

1987-01-01

Luteinizing hormone-releasing hormone (LHRH) is found immunocytochemically in cell bodies and fibers of the nervus terminalis, a cranial nerve which courses from the nasal septum through the cribriform plate of the ethmoid bone (medial to the olfactory and vomeronasal nerves) and enters the forebrain, caudal to the olfactory bulbs. Immunoreactive LHRH is first detected in the nervus terminalis of the fetal rat at 15 days of gestation, preceding its detection by immunocytochemistry in any other area of the brain, including the median eminence, and preceding detection of immunoreactive luteinizing hormone (LH) in the anterior pituitary. During development of the rat fetus, the nervus terminalis is the principal source of LHRH in the nervous system from days 15 through 19 of a 21 day gestation period. We tested the notion that the LHRH system of the nervus terminalis is important for olfactory performance by examining the effects of administration of antisera to LHRH during fetal development (versus saline controls), or medial olfactory peduncle transections, in the neonatal rat, which would sever the central projections of the nervus terminalis (versus lateral peduncle transection, complete transection of the olfactory peduncles and the central nervus terminalis or controls) on preferences of rat pups for home nest. The hypothesis that LHRH is important for this chemosensory response was not confirmed. Neither antisera to LHRH nor medical olfactory peduncle transection disrupted preference for home shavings. Only complete olfactory peduncle transection had a significant effect compared to unoperated and sham-operated controls.

Peripheral changes in endometriosis-associated pain

PubMed Central

Morotti, Matteo; Vincent, Katy; Brawn, Jennifer; Zondervan, Krina T.; Becker, Christian M.

2014-01-01

BACKGROUND Pain remains the cardinal symptom of endometriosis. However, to date, the underlying mechanisms are still only poorly understood. Increasing evidence points towards a close interaction between peripheral nerves, the peritoneal environment and the central nervous system in pain generation and processing. Recently, studies demonstrating nerve fibres and neurotrophic and angiogenic factors in endometriotic lesions and their vicinity have led to increased interest in peripheral changes in endometriosis-associated pain. This review focuses on the origin and function of these nerves and factors as well as possible peripheral mechanisms that may contribute to the generation and modulation of pain in women with endometriosis. METHODS We conducted a systematic search using several databases (PubMed, MEDLINE, EMBASE and CINAHL) of publications from January 1977 to October 2013 to evaluate the possible roles of the peripheral nervous system in endometriosis pathophysiology and how it can contribute to endometriosis-associated pain. RESULTS Endometriotic lesions and peritoneal fluid from women with endometriosis had pronounced neuroangiogenic properties with increased expression of new nerve fibres, a shift in the distribution of sensory and autonomic fibres in some locations, and up-regulation of several neurotrophins. In women suffering from deep infiltrating endometriosis and bowel endometriosis, in which the anatomical distribution of lesions is generally more closely related to pelvic pain symptoms, endometriotic lesions and surrounding tissues present higher nerve fibre densities compared to peritoneal lesions and endometriomas. More data are needed to fully confirm a direct correlation between fibre density in these locations and the amount of perceived pain. A better correlation between the presence of nerve fibres and pain symptoms seems to exist for eutopic endometrium. However, this appears not to be exclusive to endometriosis. No correlation between elevated neurotrophin levels and pain severity seems to exist, suggesting the involvement of other mediators in the modulation of pain. CONCLUSIONS The increased expression of neuotrophic factors and nerve fibres in endometriotic lesions, eutopic endometrium and the peritoneum imply a role of such peripheral changes in the pathogenesis of endometriosis-associated pain. However, a clear link between these findings and pain in patients with endometriosis has so far not been demonstrated. PMID:24859987

Acute painless monocular visual loss due to central retinal artery occlusion in a patient with Churg-Strauss vasculitis.

PubMed

Skrapari, Ioanna; Kagkelari, Eleftheria; Charitatos, Evangelos; Pantelidaki, Catherine; Gounaris, Theodoros; Sioula, Evagelia

2008-01-01

Ocular involvement in Churg-Strauss syndrome (CSS) is infrequent. We describe a case of a 50-year-old woman, with blood eosinophilia, involvement of the respiratory tract, skin, and peripheral nervous system, fulfilling the American College of Rheumatology criteria for CSS, who presented with left foot drop followed by left acute painless visual loss. Central retinal artery occlusion was diagnosed by fundoscopic findings (retinal whitening with a cherry-red spot). CSS was confirmed by sural nerve biopsy. Despite treatment with high-dose corticosteroids, cyclophosphamide, and anticoagulant therapy, visual acuity was not substantially improved. Acute blindness in CSS has been rarely described. Even more rarely, central retinal artery occlusion has been found to be the underlying cause of this infrequent clinical manifestation in CSS.

Sound damage and gentamicin treatment produce different patterns of damage to the efferent innervation of the chick cochlea.

PubMed

Ofsie, M S; Hennig, A K; Messana, E P; Cotanche, D A

1997-11-01

Both sound exposure and gentamicin treatment cause damage to sensory hair cells in the peripheral chick auditory organ, the basilar papilla. This induces a regeneration response which replaces hair cells and restores auditory function. Since functional recovery requires the re-establishment of connections between regenerated hair cells and the central nervous system, we have investigated the effects of sound damage and gentamicin treatment on the neuronal elements within the cochlea. Whole-mount preparations of basilar papillae were labeled with phalloidin to label the actin cytoskeleton and antibodies to neurofilaments, choline acetyltransferase, and synapsin to label neurons; and examined by confocal laser scanning microscopy. When chicks are treated with gentamicin or exposed to acoustic overstimulation, the transverse nerve fibers show no changes from normal cochleae assayed in parallel. Efferent nerve terminals, however, disappear from areas depleted of hair cells following acoustic trauma. In contrast, efferent nerve endings are still present in the areas of hair cell loss following gentamicin treatment, although their morphological appearance is greatly altered. These differences in the response of efferent nerve terminals to sound exposure versus gentamicin treatment may account, at least in part, for the discrepancies reported in the time of recovery of auditory function.

Effects of nicergoline on the cardiovascular system of dogs and rats.

PubMed

Huchet, A M; Mouillé, P; Chelly, J; Lucet, B; Doursout, M F; Lechat, P; Schmitt, H

1981-01-01

In pentobarbitalized closed-chest dogs, nicergoline (10--100 microgram/kg, i.v.) reduced blood pressure, heart rate, and splanchnic nerve activity. Intracisternal administration of nicergoline (3 microgram/kg) only reduced splanchnic nerve activity. In open-chest dogs, nicergoline reduced blood pressure, cardiac output, and total peripheral resistance but did not change heart rate. In pithed rats treated with a beta-adrenoceptor-blocking agent, nicergoline reduced the pressor responses to noradrenaline and adrenaline. Nicergoline slightly attenuated the pressor responses of dogs to noradrenaline and tyramine and, in addition, reversed the hypertension induced by adrenaline and dimethylphenylpiperazinium. Nicergoline (100 microgram/kg) increased the tachycardia induced in dogs by stimulation of the right cardiovascular nerve and prevented the inhibitory effect of clonidine on this response. However, nicergoline only partially antagonized the effect of clonidine once it was fully established. Nicergoline did not antagonize the hypotensive and bradycardic effects of clonidine when they were established. Nicergoline did not affect the vagally mediated bradycardia evoked by carotid nerve stimulation in beta-adrenoceptor-blocked dogs. The compound did not change blood pressure in Cl spinal cord transected dogs. In conclusion, nicergoline appears to decrease blood pressure by blocking alpha-adrenoceptors and, at least at some doses, by a central inhibition of the sympathetic tone. Nicergoline appears to be a preferential alpha 1-adrenoceptor-blocking agent.

Predictors of metastasis to lymph nodes posterior to the right recurrent laryngeal nerve in differentiated thyroid carcinoma: A prospective study.

PubMed

Liu, Ziwen; Sun, Mengqing; Xiao, Yiding; Yang, Jing; Zhang, Taiping; Zhao, Yupei

2017-07-01

To study the clinicopathological characteristics and the risk factors of lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) metastasis in differentiated thyroid carcinoma; and to identify the indication for LN-prRLN dissection. We treated 145 patients with differentiated thyroid carcinoma with appropriate surgical intervention. The specimens were examined by the pathologists. The right paratracheal lymph nodes were divided into two groups: anterior or posterior to right recurrent laryngeal nerve (VIa or VIp compartment, respectively). We recorded the clinical characteristics, histopathological features of the primary tumors, and lymph node metastasis of the patients. The results were statistically analyzed. There were 85 patients (58.6%) with central lymph node metastasis, of whom 61 (42.1%) had metastasis in VIa compartment; 16 patients (11.0%) had VIp subdistrict metastasis; and 25 patients had lateral lymph node metastasis. Multiplicity, larger tumor (≥1 cm), and coexistence of central lymph node metastasis, VIa compartment metastasis, and lateral lymph node metastasis were all significantly related with LN-prRLN metastasis, while sex, age, location of the tumor, and extrathyroid extension of the tumor showed no significant relation (p > 0.05). The incidence of LN-prRLN metastasis was lower than other central lymph nodes, as well as lymph nodes anterior to right recurrent laryngeal nerve. When there were multiple foci of tumors, or the tumor was larger than 1 cm, or central or lateral LN metastasis was indicated by preoperative ultrasound or confirmed by intraoperative frozen sections, it is strongly recommended that exploration and dissection of the LN-prRLN should only be performed by experienced surgeons. Copyright © 2016. Published by Elsevier Taiwan.

THICKNESS OF THE MACULA, RETINAL NERVE FIBER LAYER, AND GANGLION CELL-INNER PLEXIFORM LAYER IN THE AGE-RELATED MACULAR DEGENERATION: The Repeatability Study of Spectral Domain Optical Coherence Tomography.

PubMed

Shin, Il-Hwan; Lee, Woo-Hyuk; Lee, Jong-Joo; Jo, Young-Joon; Kim, Jung-Yeul

2018-02-01

To determine the repeatability of measuring the thickness of the central macula, retinal nerve fiber layer, and ganglion cell-inner plexiform layer (GC-IPL) using spectral domain optical coherence tomography (Cirrus HD-OCT) in eyes with age-related macular degeneration. One hundred and thirty-four eyes were included. The measurement repeatability was assessed by an experienced examiner who performed two consecutive measurements using a 512 × 128 macular cube scan and a 200 × 200 optic disk cube scan. To assess changes in macular morphology in patients with age-related macular degeneration, the patients were divided into the following three groups according to the central macular thickness (CMT): A group, CMT < 200 μm; B group, 200 μm ≤ CMT < 300 μm; and C group, CMT > 300 μm. Measurement repeatability was assessed using test-retest variability, a coefficient of variation, and an intraclass correlation coefficient. The mean measurement repeatability for the central macular, retinal nerve fiber layer, and GC-IPL thickness was high in the B group. The mean measurement repeatability for both the central macula and retinal nerve fiber layer thickness was high in the A and C groups, but was lower for the GC-IPL thickness. The measurement repeatability for GC-IPL thickness was high in the B group, but low in the A group and in the C group. The automated measurement repeatability for GC-IPL thickness was significantly lower in patients with age-related macular degeneration with out of normal CMT range. The effect of changes in macular morphology should be considered when analyzing GC-IPL thicknesses in a variety of ocular diseases.

[Regulation of acetylcholine synthesis in presynaptic endings of cholinergic neurons of the central nervous system].

PubMed

Tuchek, S; Dolezhal, V; Richny, Ia

1984-01-01

Data on the acetylcholine (ACh) synthesis in nerve cells with special attention to its control are summarized in the paper. At rest or during moderate synaptic activity, the concentration of ACh in the compartment of its synthesis probably corresponds to the equilibrium between the substrates and products in the reaction catalysed by choline acetyltransferase. The release of ACh is followed by a transfer of ACh from the compartment of its synthesis to the compartment of release, and, automatically, by the synthesis of new ACh until a new equilibrium is reached in the compartment of synthesis. In addition, synaptic activity and the release of ACh support the synthesis of new ACh in the following ways: choline carriers are disinhibited by lowering the concentration of ACh in the nerve endings, and the transport of choline from the extracellular fluid to the cell interior according to its electro-chemical gradient is thus facilitated; the concentration of choline in the extracellular fluid is increased in the vicinity of the nerve endings as a consequence of the hydrolysis of the released ACh; postactivation hyperpolarization of the nerve endings brings about an increase of the choline transport and concentration in the nerve endings; presumably, the stimulation of muscarinic receptors brings about a further increase in the choline concentration in the vicinity of the nerve endings by the phosphatidylcholine hydrolysis intensification in postsynaptic cells; the decrease in the concentration of acetyl-CoA (as a consequence of the resynthesis of ACh) increases the activity of pyruvate dehydrogenase and the production of acetyl-CoA; conceivably, the increase in the concentration of Ca2+ ions in the nerve endings assists direct passage of acetyl-CoA from the mitochondria to the cytosol of the nerve endings, where the synthesis of ACh occurs.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed

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

2015-09-04

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

Quantitative characterization of optic nerve atrophy in patients with multiple sclerosis

PubMed Central

Smith, Alex K; Lyttle, Bailey; Box, Bailey; Landman, Bennett A; Bagnato, Francesca; Pawate, Siddharama; Smith, Seth A

2017-01-01

Background Optic neuritis (ON) is one of the most common presentations of multiple sclerosis (MS). Magnetic resonance imaging (MRI) of the optic nerves is challenging because of retrobulbar motion, orbital fat and susceptibility artifacts from maxillary sinuses; therefore, axonal loss is investigated with the surrogate measure of a single heuristically defined point along the nerve as opposed to volumetric investigation. Objective The objective of this paper is to derive optic nerve volumetrics along the entire nerve length in patients with MS and healthy controls in vivo using high-resolution, clinically viable MRI. Methods An advanced, isotropic T2-weighted turbo spin echo MRI was applied to 29 MS patients with (14 patients ON+) or without (15 patients ON–) history of ON and 42 healthy volunteers. An automated tool was used to estimate and compare whole optic nerve and surrounding cerebrospinal fluid radii along the length of the nerve. Results and conclusion Only ON+ MS patients had a significantly reduced optic nerve radius compared to healthy controls in the central segment of the optic nerve. Using clinically available MRI methods, we show and quantify ON volume loss for the first time in MS patients. PMID:28932410

BMI, HOMA-IR, and Fasting Blood Glucose Are Significant Predictors of Peripheral Nerve Dysfunction in Adult Overweight and Obese Nondiabetic Nepalese Individuals: A Study from Central Nepal.

PubMed

Thapa, Lekhjung; Rana, P V S

2016-01-01

Objective. Nondiabetic obese individuals have subclinical involvement of peripheral nerves. We report the factors predicting peripheral nerve function in overweight and obese nondiabetic Nepalese individuals. Methodology. In this cross-sectional study, we included 50 adult overweight and obese nondiabetic volunteers without features of peripheral neuropathy and 50 healthy volunteers to determine the normative nerve conduction data. In cases of abnormal function, the study population was classified on the basis of the number of nerves involved, namely, "<2" or "≥2." Multivariable logistic regression analysis was carried out to predict outcomes. Results. Fasting blood glucose (FBG) was the significant predictor of motor nerve dysfunction (P = 0.039, 95% confidence interval (CI) = 1.003-1.127). Homeostatic model assessment of insulin resistance (HOMA-IR) was the significant predictor (P = 0.019, 96% CI = 1.420-49.322) of sensory nerve dysfunction. Body mass index (BMI) was the significant predictor (P = 0.034, 95% CI = 1.018-1.577) in case of ≥2 mixed nerves' involvement. Conclusion. FBG, HOMA-IR, and BMI were significant predictors of peripheral nerve dysfunction in overweight and obese Nepalese individuals.

Ultrastructural and cytochemical evidence for single impulse initiation zones in vestibular macular nerve fibers of rat

NASA Technical Reports Server (NTRS)

Ross, Muriel D.; Chee, Oliver; Black, Samuel; Cutler, Lynn

1991-01-01

Cupric ion-ferricyanide labeling methods and related ferrocyanide-stained tissues were used to locate the characterize, at the ultrastructural level, presumptive impulse initiation zones in the three types of vestibular macular nerve fibers. Large-diameter, M-type vestibular nerve fibers terminate in a calyx at the heminode, and labeling is coextensive with the base of the calyx. Intermediate, M/U-type nerve fibers have short, unmyelinated preterminal segments that sometimes bifurcate intamacularly, and small-diameter, U-type nerve fibers have long, unmyelinated preterminal axons and up to three branches. Preterminals of these nerve fibers display ultrastructural heterogeneity that is correlated with labeling patterns for sodium channels and/or associated polyanionic sites. They have a nodelike ultrastructure and label heavily from near the heminode to the base of the macula. Their intramacular branches, less organized ultrastructurally, label only slightly. Results indicate that vestibular nerve fibers have one impulse initiation zone, located near the heminode, that varies in length according to nerve fiber type. Structural heterogeneity may favor impulse conduction in the central direction, and length of the impulse initiation zone could influence nerve discharge patterns.

Reappraising entrapment neuropathies--mechanisms, diagnosis and management.

PubMed

Schmid, Annina B; Nee, Robert J; Coppieters, Michel W

2013-12-01

The diagnosis of entrapment neuropathies can be difficult because symptoms and signs often do not follow textbook descriptions and vary significantly between patients with the same diagnosis. Signs and symptoms which spread outside of the innervation territory of the affected nerve or nerve root are common. This Masterclass provides insight into relevant mechanisms that may account for this extraterritorial spread in patients with entrapment neuropathies, with an emphasis on neuroinflammation at the level of the dorsal root ganglia and spinal cord, as well as changes in subcortical and cortical regions. Furthermore, we describe how clinical tests and technical investigations may identify these mechanisms if interpreted in the context of gain or loss of function. The management of neuropathies also remains challenging. Common treatment strategies such as joint mobilisation, neurodynamic exercises, education, and medications are discussed in terms of their potential to influence certain mechanisms at the site of nerve injury or in the central nervous system. The mechanism-oriented approach for this Masterclass seems warranted given the limitations in the current evidence for the diagnosis and management of entrapment neuropathies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Nerve Growth Factor: Early Studies And Recent Clinical Trials.

PubMed

Rocco, Maria Luisa; Soligo, Marzia; Manni, Luigi; Aloe, Luigi

2018-04-11

Since its discovery, nerve growth factor (NGF) has long occupied a critical role in developmental and adult neurobiology for its many important regulatory functions on the survival, growth and differentiation of nerve cells in the peripheral and central nervous system. NGF is the first discovered member of a family of neurotrophic factors, collectively indicated as neurotrophins, (which include brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin 4/5). NGF was discovered for its action on the survival and differentiation of selected populations of peripheral neurons. Since then, an enormous number of basic and human studies were undertaken to explore the role of purified NGF to prevent the death of NGF-receptive cells. These studies revealed that NGF possesses important therapeutic properties, after topical administration, on human cutaneous pressure ulcer, corneal ulcers, glaucoma, retinal maculopathy, Retinitis Pigmentosa and in pediatric optic gliomas and brain traumas. The aim of this review is to present our previous, recent and ongoing clinical studies on the therapeutic properties of NGF. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Applications of Optical Coherence Tomography in Pediatric Clinical Neuroscience

PubMed Central

Avery, Robert A.; Rajjoub, Raneem D.; Trimboli-Heidler, Carmelina; Waldman, Amy T.

2015-01-01

For nearly two centuries, the ophthalmoscope has permitted examination of the retina and optic nerve—the only axons directly visualized by the physician. The retinal ganglion cells project their axons, which travel along the innermost retina to form the optic nerve, marking the beginning of the anterior visual pathway. Both the structure and function of the visual pathway are essential components of the neurologic examination as it can be involved in numerous acquired, congenital and genetic central nervous system conditions. The development of optical coherence tomography now permits the pediatric neuroscientist to visualize and quantify the optic nerve and retinal layers with unprecedented resolution. As optical coherence tomography becomes more accessible and integrated into research and clinical care, the pediatric neuroscientist may have the opportunity to utilize and/or interpret results from this device. This review describes the basic technical features of optical coherence tomography and highlights its potential clinical and research applications in pediatric clinical neuroscience including optic nerve swelling, optic neuritis, tumors of the visual pathway, vigabatrin toxicity, nystagmus, and neurodegenerative conditions. PMID:25803824

[Neurofibromatosis type 2 in childhood: a clinical characterization].

PubMed

Hinojosa-Mateo, C M; Reche-Sainz, J A; Hernandez-Nunez, A; Ramos-Lopez, M; Arpa-Fernandez, A; Natera-de Benito, D

2017-02-01

Neurofibromatosis type 2 (NF2) is a dominantly inherited neuroectodermal syndrome that predispose to the development of tumors of the central and peripheral nervous system. Additional features include eye and skin abnormalities. A 12-year old male with diagnosis of MF2 according to Baser et al and presentation in childhood was included. A comprehensive bibliographic review of evolution of the diagnostic criteria for NF2 in children was performed. The pattern of presentation of NF2 in childhood differs from adulthood in many aspects. Ophthalmologic and skin manifestations, and not an auditory dysfunction, are the most common initial symptoms in prepuberal-onset NF2. The most frequent symptoms and signs at presentation are posterior subcapsular cataract, skin manifestations as NF2 plaques and/or peripheral nerve tumors, and neurological dysfunction related to isolated or multiple cranial nerve deficits (other than nerve VIII), brainstem masses or spinal masses. As sensitivity of diagnostic criteria in children is low, those prepuberal patients with congenital or early-onset cataracts and typical skin manifestations of NF2 should be systematically assessed.

Optic Nerve Lymphoma. Report of Two Cases and Review of the Literature

PubMed Central

Kim, Jennifer L.; Mendoza, Pia; Rashid, Alia; Hayek, Brent; Grossniklaus, Hans E.

2014-01-01

Lymphoma may involve the optic nerve as isolated optic nerve lymphoma or in association with CNS or systemic lymphoma. We present two biopsy-proven non-Hodgkin lymphomas of the optic nerve and compare our findings with previously reported cases. We discuss the mechanism of metastasis, classification of optic nerve involvement, clinical features, radiologic findings, optic nerve biopsy indications and techniques, histologic features, and treatments. We propose a classification system of optic nerve lymphoma: isolated optic nerve involvement, optic nerve involvement with CNS disease, optic nerve involvement with systemic disease, and optic nerve involvement with primary intraocular lymphoma. Although it is an uncommon cause of infiltrative optic neuropathy, optic nerve metastasis should be considered in patients with a history of lymphoma. The recommended approach to a patient with presumed optic nerve lymphoma includes neuroimaging, and cerebrospinal fluid evaluation as part of the initial work-up, then judicious use of optic nerve biopsy, depending on the clinical situation. PMID:25595061

Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation.

PubMed

Napadow, Vitaly; Edwards, Robert R; Cahalan, Christine M; Mensing, George; Greenbaum, Seth; Valovska, Assia; Li, Ang; Kim, Jieun; Maeda, Yumi; Park, Kyungmo; Wasan, Ajay D

2012-06-01

Previous vagus nerve stimulation (VNS) studies have demonstrated antinociceptive effects, and recent noninvasive approaches, termed transcutaneous-vagus nerve stimulation (t-VNS), have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS. Counterbalanced, crossover study. Patients with chronic pelvic pain (CPP) due to endometriosis in a specialty pain clinic. INTERVENTIONS/OUTCOMES: We evaluated evoked pain analgesia for respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) compared with nonvagal auricular stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least 1 week apart. Outcome measures included deep-tissue pain intensity, temporal summation of pain, and anxiety ratings, which were assessed at baseline, during active stimulation, immediately following stimulation, and 15 minutes after stimulus cessation. RAVANS demonstrated a trend for reduced evoked pain intensity and temporal summation of mechanical pain, and significantly reduced anxiety in N = 15 CPP patients, compared with NVAS, with moderate to large effect sizes (η(2) > 0.2). Chronic pain disorders such as CPP are in great need of effective, nonpharmacological options for treatment. RAVANS produced promising antinociceptive effects for quantitative sensory testing (QST) outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain. Wiley Periodicals, Inc.

Effect of O-methyl-β-cyclodextrin-modified magnetic nanoparticles on the uptake and extracellular level of l-glutamate in brain nerve terminals.

PubMed

Horák, Daniel; Beneš, Milan; Procházková, Zuzana; Trchová, Miroslava; Borysov, Arsenii; Pastukhov, Artem; Paliienko, Konstantin; Borisova, Tatiana

2017-01-01

Changes in cholesterol concentration in the plasma membrane of presynaptic nerve terminals nonspecifically modulate glutamate transport and homeostasis in the central nervous system. Reduction of the cholesterol content in isolated rat brain nerve terminals (synaptosomes) using cholesterol-depleting agents decreases the glutamate uptake and increases the extracellular level of glutamate in nerve terminals. Extraction of cholesterol from the plasma membrane and its further removal from the synaptosomes by external magnetic field can be achieved by means of magnetic nanoparticles with immobilized cholesterol-depleting agent such as O-methyl-β-cyclodextrin (MCD). A simple approach is developed for preparation of maghemite (γ-Fe 2 O 3 ) nanoparticles containing chemically bonded MCD. The method is based on preparation of a silanization agent containing MCD. It is synthesized by the reaction of triethoxy(3-isocyanatopropyl)silane with MCD. Base-catalyzed silanization of superparamagnetic γ-Fe 2 O 3 provides a relatively stable colloid product containing 48μmol of MCDg -1 . MCD-modified γ-Fe 2 O 3 nanoparticles decrease the initial rate of the uptake and accumulation of l-[ 14 C]glutamate and increase the extracellular l-[ 14 C]glutamate level in the preparation of nerve terminals. The effect of MCD-immobilized nanoparticles is the same as that of MCD solution; moreover, magnetic manipulation of the nanoparticles enables removal of bonded cholesterol. Copyright © 2016 Elsevier B.V. All rights reserved.

The Effects of Different Factors on the Behavior of Neural Stem Cells

PubMed Central

Huang, Lixiang

2017-01-01

The repair of central nervous system (CNS) injury has been a worldwide problem in the biomedical field. How to reduce the damage to the CNS and promote the reconstruction of the damaged nervous system structure and function recovery has always been the concern of nerve tissue engineering. Multiple differentiation potentials of neural stem cell (NSC) determine the application value for the repair of the CNS injury. Thus, how to regulate the behavior of NSCs becomes the key to treating the CNS injury. So far, a large number of researchers have devoted themselves to searching for a better way to regulate the behavior of NSCs. This paper summarizes the effects of different factors on the behavior of NSCs in the past 10 years, especially on the proliferation and differentiation of NSCs. The final purpose of this review is to provide a more detailed theoretical basis for the clinical repair of the CNS injury by nerve tissue engineering. PMID:29358957

Review of literature of radial nerve injuries associated with humeral fractures-an integrated management strategy.

PubMed

Li, YuLin; Ning, GuangZhi; Wu, Qiang; Wu, QiuLi; Li, Yan; Feng, ShiQing

2013-01-01

Radial nerve palsy associated with fractures of the shaft of the humerus is the most common nerve lesion complicating fractures of long bones. However, the management of radial nerve injuries associated with humeral fractures is debatable. There was no consensus between observation and early exploration. The PubMed, Embase, Cochrane Central Register of Controlled Trials, Google Scholar, CINAHL, International Bibliography of the Social Sciences, and Social Sciences Citation Index were searched. Two authors independently searched for relevant studies in any language from 1966 to Jan 2013. Thirty studies with 2952 humeral fractures participants were identified. Thirteen studies favored conservative strategy. No significant difference between early exploration and no exploration groups (OR, 1.03, 95% CI 0.61, 1.72; I(2) = 0.0%, p = 0.918 n.s.). Three studies recommend early radial nerve exploration in patients with open fractures of humerus with radial nerve injury. Five studies proposed early exploration was performed in high-energy humeral shaft fractures with radial nerve injury. The conservative strategy was a good choice for patients with low-energy closed fractures of humerus with radial nerve injury. We recommend early radial nerve exploration (within the first 2 weeks) in patients with open fractures or high-energy closed fractures of humerus with radial nerve injury.

Effects of high-intensity interval training on optic nerve head and macular perfusion using optical coherence tomography angiography in healthy adults.

PubMed

Schmitz, Boris; Nelis, Pieter; Rolfes, Florian; Alnawaiseh, Maged; Klose, Andreas; Krüger, Michael; Eter, Nicole; Brand, Stefan-Martin; Alten, Florian

2018-07-01

High-intensity interval training (HIIT) has been identified to be efficient for increasing health-related fitness in general and in lifestyle-induced chronic diseases such as hypertension, obesity and metabolic syndrome. This study aimed to evaluate HIIT effects on optic nerve head (ONH) and macular perfusion in healthy adults using optical coherence tomography angiography (OCTA). Fifty-eight healthy participants (22.0 ± 2.02 years, 40 females (69.0%)) performed a 4-week HIIT with two exercise sessions/week: Group 1, 4 × 30 HIIT, running at maximal speed (all-out) for 4 × 30 s with 30 s active recovery, Group 2, 8 × 15 HIIT, running at maximal speed (all-out) for 8 × 15 s with 15 s active recovery. OCTA of the ONH and the macula was performed at baseline and follow-up to detect changes of the foveal avascular zone (FAZ). Flow density was evaluated in the superficial and deep plexus of the central macula, in the radial peripapillary capillary layer, the nerve head layer of the disc region and of the peripapillary region. The mean deep FAZ area and flow density of the superficial layer decreased by 14.00 ± 13.02% and 1.26 ± 3.20%, respectively, in response to overall HIIT (pre vs. post p <0.0001; p = 0.0041). The flow density of the nerve head layer in the peripapillary area showed an overall increase by 1.94 ± 2.39% (pre vs post p < 0.0001). All other parameters showed no difference. HIIT may be performed to induce changes in ophthalmic measures such as FAZ and nerve head perfusion. OCTA imaging of the central retina and the ONH could represent a sensitive tool for the early detection of systemic vascular changes. Copyright © 2018 Elsevier B.V. All rights reserved.

An interventional multispectral photoacoustic imaging platform for the guidance of minimally invasive procedures

NASA Astrophysics Data System (ADS)

Xia, Wenfeng; Nikitichev, Daniil I.; Mari, Jean Martial; West, Simeon J.; Ourselin, Sebastien; Beard, Paul C.; Desjardins, Adrien E.

2015-07-01

Precise and efficient guidance of medical devices is of paramount importance for many minimally invasive procedures. These procedures include fetal interventions, tumor biopsies and treatments, central venous catheterisations and peripheral nerve blocks. Ultrasound imaging is commonly used for guidance, but it often provides insufficient contrast with which to identify soft tissue structures such as vessels, tumors, and nerves. In this study, a hybrid interventional imaging system that combines ultrasound imaging and multispectral photoacoustic imaging for guiding minimally invasive procedures was developed and characterized. The system provides both structural information from ultrasound imaging and molecular information from multispectral photoacoustic imaging. It uses a commercial linear-array ultrasound imaging probe as the ultrasound receiver, with a multimode optical fiber embedded in a needle to deliver pulsed excitation light to tissue. Co-registration of ultrasound and photoacoustic images is achieved with the use of the same ultrasound receiver for both modalities. Using tissue ex vivo, the system successfully discriminated deep-located fat tissue from the surrounding muscle tissue. The measured photoacoustic spectrum of the fat tissue had good agreement with the lipid spectrum in literature.

Clinical implications of basic science discoveries: nociceptive neurons as targets to control immunity--potential relevance for transplantation.

PubMed

Larregina, A T; Divito, S J; Morelli, A E

2015-06-01

Increasing evidence indicates the existence of a complex cross-regulation between the most important biosensors of the human body: The immune and nervous systems. Cytokines control body temperature and trigger autoimmune disorders in the central nervous system, whereas neuropeptides released in peripheral tissues and lymphoid organs modulate inflammatory (innate) and adaptive immune responses. Surprisingly, the effects of nerve fibers and the antidromic release of its pro-inflammatory neuropeptides on the leukocytes of the immune system that mediate graft rejection are practically unknown. In the transplantation field, such area of research remains practically unexplored. A recent study by Riol-Blanco et al has revealed new details on how nociceptive nerves regulate the pro-inflammatory function of leukocytes in peripheral tissues. Although the mechanism(s) by which neuroinflammation affects the immune response against the allograft remains unknown, recent data suggest that this new area of research is worth exploring for potential development of novel complementary therapies for prevention/treatment of graft rejection. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Perineurial Glial Plasticity and the Role of TGF-β in the Development of the Blood-Nerve Barrier.

PubMed

Morris, Angela D; Lewis, Gwendolyn M; Kucenas, Sarah

2017-05-03

Precisely orchestrated interactions between spinal motor axons and their ensheathing glia are vital for forming and maintaining functional spinal motor nerves. Following perturbations to peripheral myelinating glial cells, centrally derived oligodendrocyte progenitor cells (OPCs) ectopically exit the spinal cord and myelinate peripheral nerves in myelin with CNS characteristics. However, whether remaining peripheral ensheathing glia, such as perineurial glia, properly encase the motor nerve despite this change in glial cell and myelin composition, remains unknown. Using zebrafish mutants in which OPCs migrate out of the spinal cord and myelinate peripheral motor axons, we assayed perineurial glial development, maturation, and response to injury. Surprisingly, in the presence of OPCs, perineurial glia exited the CNS normally. However, aspects of their development, response to injury, and function were altered compared with wildtype larvae. In an effort to better understand the plasticity of perineurial glia in response to myelin perturbations, we identified transforming growth factor-β1 as a partial mediator of perineurial glial development. Together, these results demonstrate the incredible plasticity of perineurial glia in the presence of myelin perturbations. SIGNIFICANCE STATEMENT Peripheral neuropathies can result from damage or dysregulation of the insulating myelin sheath surrounding spinal motor axons, causing pain, inefficient nerve conduction, and the ectopic migration of oligodendrocyte progenitor cells (OPCs), the resident myelinating glial cell of the CNS, into the periphery. How perineurial glia, the ensheathing cells that form the protective blood-nerve barrier, are impacted by this myelin composition change is unknown. Here, we report that certain aspects of perineurial glial development and injury responses are mostly unaffected in the presence of ectopic OPCs. However, perineurial glial function is disrupted along nerves containing centrally derived myelin, demonstrating that, although perineurial glial cells display plasticity despite myelin perturbations, the blood-nerve barrier is compromised in the presence of ectopic OPCs. Copyright © 2017 the authors 0270-6474/17/374790-18$15.00/0.

Corneal Confocal Microscopy Detects Corneal Nerve Damage in Patients Admitted With Acute Ischemic Stroke.

PubMed

Khan, Adnan; Akhtar, Naveed; Kamran, Saadat; Ponirakis, Georgios; Petropoulos, Ioannis N; Tunio, Nahel A; Dargham, Soha R; Imam, Yahia; Sartaj, Faheem; Parray, Aijaz; Bourke, Paula; Khan, Rabia; Santos, Mark; Joseph, Sujatha; Shuaib, Ashfaq; Malik, Rayaz A

2017-11-01

Corneal confocal microscopy can identify corneal nerve damage in patients with peripheral and central neurodegeneration. However, the use of corneal confocal microscopy in patients presenting with acute ischemic stroke is unknown. One hundred thirty patients (57 without diabetes mellitus [normal glucose tolerance], 32 with impaired glucose tolerance, and 41 with type 2 diabetes mellitus) admitted with acute ischemic stroke, and 28 age-matched healthy control participants underwent corneal confocal microscopy to quantify corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length. There was a significant reduction in corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length in stroke patients with normal glucose tolerance ( P <0.001, P <0.001, P <0.001), impaired glucose tolerance ( P =0.004, P <0.001, P =0.002), and type 2 diabetes mellitus ( P <0.001, P <0.001, P <0.001) compared with controls. HbA1c and triglycerides correlated with corneal nerve fiber density ( r =-0.187, P =0.03; r =-0.229 P =0.01), corneal nerve fiber length ( r =-0.228, P =0.009; r =-0.285; P =0.001), and corneal nerve branch density ( r =-0.187, P =0.033; r =-0.229, P =0.01). Multiple linear regression showed no independent associations between corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length and relevant risk factors for stroke. Corneal confocal microscopy is a rapid noninvasive ophthalmic imaging technique that identifies corneal nerve fiber loss in patients with acute ischemic stroke. © 2017 American Heart Association, Inc.

Neuroimmune interactions: potential target for mitigating or treating intestinal radiation injury.

PubMed

Wang, J; Hauer-Jensen, M

2007-09-01

Intestinal radiation injury is characterized by breakdown of the epithelial barrier and mucosal inflammation. In addition to replicative and apoptotic cell death, radiation also induces changes in cellular function, as well as alterations secondary to tissue injury. The recognition of these "non-cytocidal" radiation effects has enhanced the understanding of normal tissue radiation toxicity, thus allowing an integrated systems biology-based approach to modulating radiation responses and providing a mechanistic rationale for interventions to mitigate or treat radiation injuries. The enteric nervous system regulates intestinal motility, blood flow and enterocyte function. The enteric nervous system also plays a central role in maintaining the physiological state of the intestinal mucosa and in coordinating inflammatory and fibroproliferative processes. The afferent component of the enteric nervous system, in addition to relaying sensory information, also exerts important effector functions and contributes critically to preserving mucosal integrity. Interactions between afferent nerves, mast cells as well as other cells of the resident mucosal immune system serve to maintain mucosal homeostasis and to ensure an appropriate response to injury. Notably, enteric sensory neurons regulate the activation threshold of mast cells by secreting substance P, calcitonin gene-related peptide and other neuropeptides, whereas mast cells signal to enteric nerves by the release of histamine, nerve growth factor and other mediators. This article reviews how enteric neurons interact with mast cells and other immune cells to regulate the intestinal radiation response and how these interactions may be modified to mitigate intestinal radiation toxicity. These data are not only applicable to radiation therapy, but also to intestinal injury in a radiological terrorism scenario.

Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents.

PubMed

Albuquerque, Edson X; Pereira, Edna F R; Aracava, Yasco; Fawcett, William P; Oliveira, Maristela; Randall, William R; Hamilton, Tracey A; Kan, Robert K; Romano, James A; Adler, Michael

2006-08-29

The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer's disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning.

Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents

PubMed Central

Albuquerque, Edson X.; Pereira, Edna F. R.; Aracava, Yasco; Fawcett, William P.; Oliveira, Maristela; Randall, William R.; Hamilton, Tracey A.; Kan, Robert K.; Romano, James A.; Adler, Michael

2006-01-01

The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer’s disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning. PMID:16914529

Hemichordates and the origin of chordates

NASA Technical Reports Server (NTRS)

Gerhart, John; Lowe, Christopher; Kirschner, Marc

2005-01-01

Hemichordates, the phylum of bilateral animals most closely related to chordates, could reveal the evolutionary origins of chordate traits such as the nerve cord, notochord, gill slits and tail. The anteroposterior maps of gene expression domains for 38 genes of chordate neural patterning are highly similar for hemichordates and chordates, even though hemichordates have a diffuse nerve-net. About 40% of the domains are not present in protostome maps. We propose that this map, the gill slits and the tail date to the deuterostome ancestor. The map of dorsoventral expression domains, centered on a Bmp-Chordin axis, differs between the two groups; hemichordates resemble protostomes more than they do chordates. The dorsoventral axis might have undergone extensive modification in the chordate line, including centralization of the nervous system, segregation of epidermis, derivation of the notochord, and an inversion of organization.

Central localization of plasticity involved in appetitive conditioning in Lymnaea

PubMed Central

Straub, Volko A.; Styles, Benjamin J.; Ireland, Julie S.; O'Shea, Michael; Benjamin, Paul R.

2004-01-01

Learning to associate a conditioned (CS) and unconditioned stimulus (US) results in changes in the processing of CS information. Here, we address directly the question whether chemical appetitive conditioning of Lymnaea feeding behavior involves changes in the peripheral and/or central processing of the CS by using extracellular recording techniques to monitor neuronal activity at two stages of the sensory processing pathway. Our data show that appetitive conditioning does not affect significantly the overall CS response of afferent nerves connecting chemosensory structures in the lips and tentacles to the central nervous system (CNS). In contrast, neuronal output from the cerebral ganglia, which represent the first central processing stage for chemosensory information, is enhanced significantly in response to the CS after appetitive conditioning. This demonstrates that chemical appetitive conditioning in Lymnaea affects the central, but not the peripheral processing of chemosensory information. It also identifies the cerebral ganglia of Lymnaea as an important site for neuronal plasticity and forms the basis for detailed cellular studies of neuronal plasticity. PMID:15537733

Confocal Comparison of Corneal Reinnervation after Small Incision Lenticule Extraction (SMILE) and Femtosecond Laser In Situ Keratomileusis (FS-LASIK)

PubMed Central

Qin, Bing; Zhou, Zimei; Ni, Katherine; Le, Qihua; Xiang, Jun; Wei, Anji; Ma, Weiping; Zhou, Xingtao

2013-01-01

Purpose To evaluate corneal reinnervation, and the corresponding corneal sensitivity and keratocyte density after small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK). Methods In this prospective, non-randomized observational study, 18 patients (32 eyes) received SMILE surgery, and 22 patients (42 eyes) received FS-LASIK surgery to correct myopia. The corneal subbasal nerve density and microscopic morphological changes in corneal architecture were evaluated by confocal microscopy prior to surgery and at 1 week, 1 month, 3 months, and 6 months after surgery. A correlation analysis was performed between subbasal corneal nerve density and the corresponding keratocyte density and corneal sensitivity. Results The decrease in subbasal nerve density was less severe in SMILE-treated eyes than in FS-LASIK-treated eyes at 1 week (P = 0.0147), 1 month (P = 0.0243), and 3 months (P = 0.0498), but no difference was detected at the 6-month visit (P = 0.5277). The subbasal nerve density correlated positively with central corneal sensitivity in both groups (r = 0.416, P<0.0001, and r = 0.2567, P = 0.0038 for SMILE group and FS-LASIK group, respectively). The SMILE-treated eyes have a lower risk of developing peripheral empty space with epithelial cells filling in (P = 0.0005). Conclusions The decrease in subbasal nerve fiber density was less severe in the SMILE group than the FS-LASIK group in the first 3 months following the surgeries. The subbasal nerve density was correlated with central corneal sensitivity. PMID:24349069

Confocal comparison of corneal reinnervation after small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK).

PubMed

Li, Meiyan; Niu, Lingling; Qin, Bing; Zhou, Zimei; Ni, Katherine; Le, Qihua; Xiang, Jun; Wei, Anji; Ma, Weiping; Zhou, Xingtao

2013-01-01

To evaluate corneal reinnervation, and the corresponding corneal sensitivity and keratocyte density after small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK). In this prospective, non-randomized observational study, 18 patients (32 eyes) received SMILE surgery, and 22 patients (42 eyes) received FS-LASIK surgery to correct myopia. The corneal subbasal nerve density and microscopic morphological changes in corneal architecture were evaluated by confocal microscopy prior to surgery and at 1 week, 1 month, 3 months, and 6 months after surgery. A correlation analysis was performed between subbasal corneal nerve density and the corresponding keratocyte density and corneal sensitivity. The decrease in subbasal nerve density was less severe in SMILE-treated eyes than in FS-LASIK-treated eyes at 1 week (P = 0.0147), 1 month (P = 0.0243), and 3 months (P = 0.0498), but no difference was detected at the 6-month visit (P = 0.5277). The subbasal nerve density correlated positively with central corneal sensitivity in both groups (r = 0.416, P<0.0001, and r = 0.2567, P = 0.0038 for SMILE group and FS-LASIK group, respectively). The SMILE-treated eyes have a lower risk of developing peripheral empty space with epithelial cells filling in (P = 0.0005). The decrease in subbasal nerve fiber density was less severe in the SMILE group than the FS-LASIK group in the first 3 months following the surgeries. The subbasal nerve density was correlated with central corneal sensitivity.

Multiple sclerosis and optic nerve: an analysis of retinal nerve fiber layer thickness and color Doppler imaging parameters

PubMed Central

Akçam, H T; Capraz, I Y; Aktas, Z; Batur Caglayan, H Z; Ozhan Oktar, S; Hasanreisoglu, M; Irkec, C

2014-01-01

Purpose To compare both retinal nerve fiber layer thickness and orbital color Doppler ultrasonography parameters in patients with multiple sclerosis (MS) versus healthy controls. Methods This is an observational case–control study. Forty eyes from MS patients and twenty eyes from healthy volunteers were examined. Eyes were classified into three groups as group 1, eyes from MS patients with previous optic neuritis (n=20); group 2, eyes from MS patients without previous optic neuritis (n=20); and group 3, eyes from healthy controls (n=20). Following complete ophthalmologic examination and retinal nerve fiber layer thickness measurement for each group, blood flow velocities of posterior ciliary arteries, central retinal artery, ophthalmic artery, and superior ophthalmic vein were measured. Pourcelot index (resistive index), an indicator of peripheral vascular resistance, was also calculated. The statistical assessment was performed with the assistance of Pearson's Chi-square test, Mann–Whitney U-test, Kruskal–Wallis test, and Spearman's correlation test. Results The studied eyes exposed similar values in terms of intraocular pressure and central corneal thickness, implying no evidence in favor of glaucoma. All nerve fiber layer thickness values, except superior nasal quadrants, in group 1 were found to be significantly thinner than groups 2 and 3. Blood flow velocity and mean resistivity index parameters were similar in all the groups. Conclusions In MS patients, especially with previous optic neuritis, diminished retinal nerve fiber layer thickness was observed. Contrary to several studies in the current literature, no evidence supporting potential vascular origin of ocular involvement in MS was found. PMID:25081285

Comparative Kinetics and Distribution to Target Tissues of Organophosphates Using Physiologically - Based Pharmacokinetic Modeling

DTIC Science & Technology

2008-03-01

throughout history where nerve agents have been used on human populations, such as the subway bombing in Tokyo and Matsumoto, Japan. Data can be...kidney, fat, diaphragm, arterial blood, venous blood, bronchial passages, and the skin. The remaining tissues will be lumped together as either slowly...were then further developed as a weapon, whose primary effect is on the central nervous system. These agents are tabun, sarin, soman, and VX. They

Brain targeting of nerve growth factor using poly(butyl cyanoacrylate) nanoparticles.

PubMed

Kurakhmaeva, Kamila B; Djindjikhashvili, Irma A; Petrov, Valery E; Balabanyan, Vadim U; Voronina, Tatiana A; Trofimov, Sergey S; Kreuter, Jörg; Gelperina, Svetlana; Begley, David; Alyautdin, Renad N

2009-09-01

The nerve growth factor (NGF) is essential for the survival of both peripheral ganglion cells and central cholinergic neurons in the basal forebrain. The accelerated loss of central cholinergic neurons during Alzheimer's disease may be a determinant cause of dementia, and this observation may suggest a possible therapeutic benefit from treatment with NGF. In recent years, convincing data have been published involving neurotrophic factors for the modulation of dopaminergic transmission within the brain and concerning the ability of NGF to prevent the degeneration of dopaminergic neurons. In this connection, the administration of NGF may slow down the progression of Parkinson's disease. However, NGF, as well as other peptidic neurotrophic factors, does not significantly penetrate the blood-brain barrier (BBB) from the circulation. Therefore, any clinical usefulness of NGF as a potential CNS therapy will depend on the use of a suitable carrier system that enhances its transport through the BBB. The present study investigates brain delivery of NGF adsorbed on poly(butyl cyanoacrylate) (PBCA) nanoparticles coated with polysorbate 80 and the pharmacological efficacy of this delivery system in the model of acute scopolamine-induced amnesia in rats as well as in the model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonian syndrome. As shown by the passive avoidance reflex (PAR) test, the intravenous administration of the nanoparticle-bound NGF successfully reversed scopolamine-induced amnesia and improved recognition and memory. This formulation also demonstrated a significant reduction of the basic symptoms of Parkinsonism (oligokinesia, rigidity, tremor). In addition, the efficient transport of NGF across the BBB was confirmed by direct measurement of NGF concentrations in the murine brain. These results demonstrate that the PBCA nanoparticles coated with polysorbate 80 are an effective carrier system for the transport of NGF to the central nervous system across the BBB following intravenous injection. This approach may improve the NGF-based therapy of age-related neurodegenerative diseases.

Object localization through the lateral line system of fish: theory and experiment.

PubMed

Goulet, Julie; Engelmann, Jacob; Chagnaud, Boris P; Franosch, Jan-Moritz P; Suttner, Maria D; van Hemmen, J Leo

2008-01-01

Fish acquire information about their aquatic environment by means of their mechanosensory lateral-line system. This system consists of superficial and canal neuromasts that sense perturbations in the water surrounding them. Based on a hydrodynamic model presented here, we propose a mechanism through which fish can localize the source of these perturbations. In doing so we include the curvature of the fish body, a realistic lateral line canal inter-pore distance for the lateral-line canals, and the surface boundary layer. Using our model to explore receptor behavior based on experimental data of responses to dipole stimuli we suggest that superficial and canal neuromasts employ the same mechanism, hence provide the same type of input to the central nervous system. The analytical predictions agree well with spiking responses recorded experimentally from primary lateral-line nerve fibers. From this, and taking into account the central organization of the lateral-line system, we present a simple biophysical model for determining the distance to a source.

Rewiring the gustatory system: specificity between nerve and taste bud field is critical for normal salt discrimination.

PubMed

Spector, Alan C; Blonde, Ginger; Garcea, Mircea; Jiang, Enshe

2010-01-15

Forty years have passed since it was demonstrated that a cross-regenerated gustatory nerve in the rat tongue adopts the stimulus-response properties of the taste receptor field it cross-reinnervates. Nevertheless, the functional consequences of channeling peripheral taste signals through inappropriate central circuits remain relatively unexplored. Here we tested whether histologically confirmed cross-regeneration of the chorda tympani nerve (CT) into the posterior tongue in the absence of the glossopharyngeal nerve (GL) (CT-PostTongue) or cross-regeneration of the GL into the anterior tongue in the absence of the CT (GL-AntTongue) would maintain presurgically trained performance in an operant NaCl vs. KCl taste discrimination task in rats. Before surgery all groups were averaging over 90% accuracy. Oral amiloride treatment dropped performance to virtually chance levels. During the first week after surgery, sham-operated rats, GL-transected rats, and rats with regenerated CTs displayed highly competent discrimination performance. In contrast, CT-transected rats were severely impaired (59% accuracy). Both the CT-PostTongue and the GL-AntTongue groups were impaired to a similar degree as CT-transected rats. These initially impaired groups improved their performance over the weeks of postsurgical testing, suggesting that the rats were capable of relearning the task with discriminable signals in the remaining taste nerves. This relearned performance was dependent on input from amiloride-sensitive receptors likely in the palate. Overall, these results suggest that normal competence in a salt discrimination task is dependent on the taste receptor field origin of the input as well as the specific nerve transmitting the signals to its associated circuits in the brain. Copyright 2009 Elsevier B.V. All rights reserved.

Lentiviral-mediated Targeted NF-κB Blockade in Dorsal Spinal Cord Glia Attenuates Sciatic Nerve Injury-induced Neuropathic Pain in the Rat.

PubMed

Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

2007-04-01

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor κB (NF-κB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-κB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-κB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-κB super- repressor IκBα resulted in an inhibition of the NF-κB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IκBα overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-κB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-κB pathway in the development of neuropathic pain after peripheral nerve injury. Copyright © 2007 The American Society of Gene Therapy. Published by Elsevier Inc. All rights reserved.

Consecutive assessment of FA and ADC values of normal lumbar nerve roots from the junction of the dura mater.

PubMed

Miyagi, Ryo; Sakai, Toshinori; Yamabe, Eiko; Yoshioka, Hiroshi

2015-06-27

Diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) are widely used in the evaluation of the central nervous system and recently have been reported as a potential tool for diagnosis of the peripheral nerve or the lumbar nerve entrapment. The purpose of this study was to evaluate consecutive changes in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of normal lumbar nerve roots from the junction of the dura mater. The lumbar spinal nerves were examined in 6 male healthy volunteers (mean age, 35 years) with no experiences of sciatica, with a 3.0-T MR unit using a five-element phased-array surface coil. DTI was performed with the following imaging parameters: 11084.6/73.7 ms for TR/TE; b-value, 800 s/mm2; MPG, 33 directions; slice thickness, 1.5 mm; and total scan time, 7 min 35 s. ADC and FA values at all consecutive points along the L4, L5 and S1 nerves were quantified on every 1.5 mm slice from the junction of the dura mater using short fiber tracking. ADC values of all L4, 5, and S1 nerve roots decreased linearly up to 15 mm from the dura junction and was constant distally afterward. ADC values in the proximal portion demonstrated S1 > L5 > L4 (p < 0.05). On the other hand, FA values increased linearly up to 15 mm from the dura junction, and was constant distally afterward. FA values in the proximal portion showed L4 > L5 > S1 (p < 0.05). Our study demonstrated that ADC and FA values of each L4, 5, and S1 at the proximal portion from the junction of the dura matter changed linearly. It would be useful to know the normal profile of DTI values by location of each nerve root so that we can detect subtle abnormalities in each nerve root.

Laryngeal and tracheal afferent nerve stimulation evokes swallowing in anaesthetized guinea pigs

PubMed Central

Tsujimura, Takanori; Udemgba, Chioma; Inoue, Makoto; Canning, Brendan J

2013-01-01

We describe swallowing reflexes evoked by laryngeal and tracheal vagal afferent nerve stimulation in anaesthetized guinea pigs. The swallowing reflexes evoked by laryngeal citric acid challenges were abolished by recurrent laryngeal nerve (RLN) transection and mimicked by electrical stimulation of the central cut ends of an RLN. By contrast, the number of swallows evoked by upper airway/pharyngeal distensions was not significantly reduced by RLN transection but they were virtually abolished by superior laryngeal nerve transection. Laryngeal citric acid-evoked swallowing was mimicked by laryngeal capsaicin challenges, implicating transient receptor potential vanilloid 1 (TRPV1)-expressing laryngeal afferent nerves arising from the jugular ganglia. The swallowing evoked by citric acid and capsaicin and evoked by electrical stimulation of either the tracheal or the laryngeal mucosa occurred at stimulation intensities that were typically subthreshold for evoking cough in these animals. Swallowing evoked by airway afferent nerve stimulation also desensitized at a much slower rate than cough. We speculate that swallowing is an essential component of airway protection from aspiration associated with laryngeal and tracheal afferent nerve activation. PMID:23858010

Vitamin B-12 status and neurologic function in older people: a cross-sectional analysis of baseline trial data from the Older People and Enhanced Neurological Function (OPEN) study.

PubMed

Miles, Lisa M; Allen, Elizabeth; Mills, Kerry; Clarke, Robert; Uauy, Ricardo; Dangour, Alan D

2016-09-01

Aging is associated with a progressive decline in vitamin B-12 status. Overt vitamin B-12 deficiency causes neurologic disturbances in peripheral and central motor and sensory systems, but the public health impact for neurologic disease of moderately low vitamin B-12 status in older people is unclear. Evidence from observational studies is limited by heterogeneity in the definition of vitamin B-12 status and imprecise measures of nerve function. We aimed to determine whether vitamin B-12 status is associated with electrophysiologic indexes of peripheral or central neurologic function in asymptomatic older people with moderately low vitamin B-12 status. We used a cross-sectional analysis of baseline data from the Older People and Enhanced Neurological Function study conducted in Southeast England. This trial investigated the effectiveness of vitamin B-12 supplementation on electrophysiologic indexes of neurologic function in asymptomatic older people (mean age: 80 y) with moderately low vitamin B-12 status (serum vitamin B-12 concentrations ≥107 and <210 pmol/L without anemia, n = 201). Vitamin B-12 status was assessed with the use of total vitamin B-12, holotranscobalamin, and a composite indicator of vitamin B-12 status (cB-12). Electrophysiologic measures of sensory and motor components of peripheral and central nerve function were assessed in all participants by a single observer. In multivariate models, there was no evidence of an association of vitamin B-12, holotranscobalamin, or cB-12 with any nerve conduction outcome. There was also no evidence of an association of vitamin B-12 status with clinical markers of neurologic function. This secondary analysis of high-quality trial data did not show any association of any measure of vitamin B-12 status with either peripheral or central neurologic function or any clinical markers of neurologic function in older people with moderately low vitamin B-12 status. The results of this study are unlikely to be generalizable to a less healthy older population with more severe vitamin B-12 deficiency. This trial was registered at www.controlled-trials.com as ISRCTN54195799. © 2016 American Society for Nutrition.

The logistics of myelin biogenesis in the central nervous system.

PubMed

Snaidero, Nicolas; Simons, Mikael

2017-07-01

Rapid nerve conduction depends on myelin, but not all axons in the central nervous system (CNS) are myelinated to the same extent. Here, we review our current understanding of the biology of myelin biogenesis in the CNS. We focus on how the different steps of myelination are interconnected and how distinct patterns of myelin are generated. Possibly, a "basal" mode of myelination is laying the groundwork in areas devoted to basic homeostasis early in development, whereas a "targeted" mode generates myelin in regions controlling more complex tasks throughout adulthood. Such mechanisms may explain why myelination progresses in some areas according to a typical chronological and topographic sequence, while in other regions it is regulated by environmental stimuli contributing to interindividual variability of myelin structure. GLIA 2017;65:1021-1031. © 2017 Wiley Periodicals, Inc.

Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury*

PubMed Central

van Niekerk, Erna A.; Tuszynski, Mark H.; Lu, Paul; Dulin, Jennifer N.

2016-01-01

Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system. PMID:26695766

The spiral ganglion: connecting the peripheral and central auditory systems

PubMed Central

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

2011-01-01

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

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.

An augmented CO2 chemoreflex and overactive orexin system are linked with hypertension in young and adult spontaneously hypertensive rats.

PubMed

Li, Aihua; Roy, Sarah H; Nattie, Eugene E

2016-09-01

Activation of central chemoreceptors by CO2 increases sympathetic nerve activity (SNA), arterial blood pressure (ABP) and breathing. These effects are exaggerated in spontaneously hypertensive rats (SHRs), resulting in an augmented CO2 chemoreflex that affects both breathing and ABP. The augmented CO2 chemoreflex and the high ABP are measureable in young SHRs (postnatal day 30-58) and become greater in adult SHRs. Blockade of orexin receptors can normalize the augmented CO2 chemoreflex and the high ABP in young SHRs and normalize the augmented CO2 chemoreflex and significantly lower the high ABP in adult SHRs. In the hypothalamus, SHRs have more orexin neurons, and a greater proportion of them increase their activity with CO2 . The orexin system is overactive in SHRs and contributes to the augmented CO2 chemoreflex and hypertension. Modulation of the orexin system may be beneficial in the treatment of neurogenic hypertension. Activation of central chemoreceptors by CO2 increases arterial blood pressure (ABP), sympathetic nerve activity and breathing. In spontaneously hypertensive rats (SHRs), high ABP is associated with enhanced sympathetic nerve activity and peripheral chemoreflexes. We hypothesized that an augmented CO2 chemoreflex and overactive orexin system are linked with high ABP in both young (postnatal day 30-58) and adult SHRs (4-6 months). Our main findings are as follows. (i) An augmented CO2 chemoreflex and higher ABP in SHRs are measureable at a young age and increase in adulthood. In wakefulness, the ventilatory response to normoxic hypercapnia is higher in young SHRs (mean ± SEM: 179 ± 11% increase) than in age-matched normotensive Wistar-Kyoto rats (114 ± 9% increase), but lower than in adult SHRs (226 ± 10% increase; P < 0.05). The resting ABP is higher in young SHRs (122 ± 5 mmHg) than in age-matched Wistar-Kyoto rats (99 ± 5 mmHg), but lower than in adult SHRs (152 ± 4 mmHg; P < 0.05). (ii) Spontaneously hypertensive rats have more orexin neurons and more CO2 -activated orexin neurons in the hypothalamus. (iii) Antagonism of orexin receptors with a dual orexin receptor antagonist, almorexant, normalizes the augmented CO2 chemoreflex in young and adult SHRs and the high ABP in young SHRs and significantly lowers ABP in adult SHRs. (iv) Attenuation of peripheral chemoreflexes by hyperoxia does not abolish the augmented CO2 chemoreflex (breathing and ABP) in SHRs, which indicates an important role for the central chemoreflex. We suggest that an overactive orexin system may play an important role in the augmented central CO2 chemoreflex and in the development of hypertension in SHRs. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

[Roles of biologically active peptide in regulation of feeding behavior and energy homeostasis].

PubMed

Sakurai, Takeshi

2003-09-01

The mechanisms for regulating food intake involve a complicated interplay between peripheral systems (including gastrointestinal peptide secretion, leptin, and vagal afferent nerve responses) and central nervous system (CNS) neuropeptides and/or monoamines. Many hypothalamic neuropeptides are involved in the regulation of energy homeostasis and feeding behavior, including melanocortins, Agouti-related peptide, neuropeptide-Y, cocaine, and amphetamine-regulated transcript, orexin, and melanine concentrating hormone (MCH) as well as monamines (serotonin, dopamine, norepinephrine). Many of these systems are regulated by peripheral metabolic cues including plasma leptin levels. This review summarizes roles of neuropeptides in the regulatory mechanism of feeding and energy homeostasis.

Estimating 3D topographic map of optic nerve head from a single fundus image

NASA Astrophysics Data System (ADS)

Wang, Peipei; Sun, Jiuai

2018-04-01

Optic nerve head also called optic disc is the distal portion of optic nerve locating and clinically visible on the retinal surface. It is a 3 dimensional elliptical shaped structure with a central depression called the optic cup. This shape of the ONH and the size of the depression can be varied due to different retinopathy or angiopathy, therefore the estimation of topography of optic nerve head is significant for assisting diagnosis of those retinal related complications. This work describes a computer vision based method, i.e. shape from shading (SFS) to recover and visualize 3D topographic map of optic nerve head from a normal fundus image. The work is expected helpful for assessing those complications associated the deformation of optic nerve head such as glaucoma and diabetes. The illumination is modelled as uniform over the area around optic nerve head and its direction estimated from the available image. The Tsai discrete method has been employed to recover the 3D topographic map of the optic nerve head. The initial experimental result demonstrates our approach works on most of fundus images and provides a cheap, but good alternation for rendering and visualizing the topographic information of the optic nerve head for potential clinical use.

N,N-diethyldithiocarbamate promotes oxidative stress prior to myelin structural changes and increases myelin copper content

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

Viquez, Olga M.; Lai, Barry; Ahn, Jae Hee

2009-08-15

Dithiocarbamates are a commercially important class of compounds that can produce peripheral neuropathy in humans and experimental animals. Previous studies have supported a requirement for copper accumulation and enhanced lipid peroxidation in dithiocarbamate-mediated myelinopathy. The study presented here extends previous investigations in two areas. Firstly, although total copper levels have been shown to increase within the nerve it has not been determined whether copper is increased within the myelin compartment, the primary site of lesion development. Therefore, the distribution of copper in sciatic nerve was characterized using synchrotron X-ray fluorescence microscopy to determine whether the neurotoxic dithiocarbamate, N,N-diethyldithiocarbamate, increases coppermore » levels in myelin. Secondly, because lipid peroxidation is an ongoing process in normal nerve and the levels of lipid peroxidation products produced by dithiocarbamate exposure demonstrated an unusual cumulative dose response in previous studies the biological impact of dithiocarbamate-mediated lipid peroxidation was evaluated. Experiments were performed to determine whether dithiocarbamate-mediated lipid peroxidation products elicit an antioxidant response through measuring the protein expression levels of three enzymes, superoxide dismutase 1, heme oxygenase 1, and glutathione transferase {alpha}, that are linked to the antioxidant response element promoter. To establish the potential of oxidative injury to contribute to myelin injury the temporal relationship of the antioxidant response to myelin injury was determined. Myelin structure in peripheral nerve was assessed using multi-exponential transverse relaxation measurements (MET{sub 2}) as a function of exposure duration, and the temporal relationship of protein expression changes relative to the onset of changes in myelin integrity were determined. Initial assessments were also performed to explore the potential contribution of dithiocarbamate-mediated inhibition of proteasome function and inhibition of cuproenzyme activity to neurotoxicity, and also to assess the potential of dithiocarbamates to promote oxidative stress and injury within the central nervous system. These evaluations were performed using an established model for dithiocarbamate-mediated demyelination in the rat utilizing sciatic nerve, spinal cord and brain samples obtained from rats exposed to N,N-diethyldithiocarbamate (DEDC) by intra-abdominal pumps for periods of 2, 4, and 8 weeks and from non exposed controls. The data supported the ability of DEDC to increase copper within myelin and to enhance oxidative stress prior to structural changes detectable by MET{sub 2}. Evidence was also obtained that the excess copper produced by DEDC in the central nervous system is redox active and promotes oxidative injury.« less

Calcium Signaling in Mitral Cell Dendrites of Olfactory Bulbs of Neonatal Rats and Mice during Olfactory Nerve Stimulation and Beta-Adrenoceptor Activation

ERIC Educational Resources Information Center

Yuan, Qi; Mutoh, Hiroki; Debarbieux, Franck; Knopfel, Thomas

2004-01-01

Synapses formed by the olfactory nerve (ON) provide the source of excitatory synaptic input onto mitral cells (MC) in the olfactory bulb. These synapses, which relay odor-specific inputs, are confined to the distally tufted single primary dendrites of MCs, the first stage of central olfactory processing. Beta-adrenergic modulation of electrical…

Diagnosis and management of Lyme neuroborreliosis.

PubMed

Halperin, John J

2018-01-01

The nervous system is involved in 10-15% of patients infected with B. burgdorferi, B. afzelii and B. garinii. This review will address widespread misconceptions about the clinical phenomenology, diagnostic approach and response to treatment of neuroborreliosis. Areas covered: Improvements in diagnostic testing have allowed better definition of the clinical spectrum of neuroborreliosis, with lymphocytic meningitis and uni- or multifocal inflammation of peripheral/cranial nerves predominating. Despite widespread concern that post-treatment cognitive/behavioral symptoms might be attributable to persisting infection or aberrant inflammation within the central nervous system a large body of evidence indicates this is extremely improbable. Importantly, recent studies show most neuroborreliosis can be treated with fairly brief courses of oral antibiotics. All high-level evidence confirms that prolonged courses of antibiotics carry harm with no commensurate benefit. Expert commentary: Lyme disease in the US, and corresponding disorders in Europe, are well defined neuro-infectious diseases that are highly responsive to antibiotic therapy. Although the nervous system is slow to recover after insults (e.g. persistent facial weakness after appropriately treated facial nerve palsy) there is no evidence that prolonged post-treatment neurocognitive symptoms are related to nervous system infection - either as a triggering event or as a cause of ongoing symptoms.

Tetracycline-regulated expression of OLIG2 gene in human dental pulp stem cells lead to mouse sciatic nerve regeneration upon transplantation.

PubMed

Askari, N; Yaghoobi, M M; Shamsara, M; Esmaeili-Mahani, S

2015-10-01

Numerous studies have indicated dental pulp stem cells (DPSCs) potency to differentiate into several types of cell lineages. Oligodendrocyte lineage transcription factor 2 (OLIG2) plays an important role in the oligodendrogenic pathway. In this study, a tetracycline (Tet)-inducible system expressing OLIG2 gene was transfected into human DPSCs to direct their differentiation toward oligodendrocyte progenitor cells (OPCs). Following induction, the expression of stage-specific markers was studied by Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR), immunocytochemistry and western blotting. In the following, the cells were transplanted into the mouse model of local sciatic demyelination damage by lysolecithin. Recovery of lysolecithin-induced lesions in sciatic nerve was studied by treadmill exercise, von Frey filament test and hind paw withdrawal in response to a thermal stimulus. Improvement of behavioral symptoms was efficiently observed from the second week to the sixth week post-transplantation. Our findings showed that exogenous expression of the OLIG2 gene by a Tet-regulated system could be used as an efficient way to induce the differentiation of DPSCs into functional oligodendrocytes. Meanwhile, the DPSC-derived OPCs have relevant therapeutic potential in the animal model of sciatic nerve injury and therefore might represent a valuable tool for stem cell-based therapy in inflammatory and degenerative diseases of the peripheral and central nervous systems (CNSs). Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Brucellosis and polyneuroradiculomyeloencephalitis. A case report.

PubMed

Riestra-Castañeda, R; González-Garrido, A; González-Cornejo, S

1996-01-01

Reports on simultaneous central and peripheral nervous system involvement in a patient with brucellosis are very rare. We report of one young female patient with a long history of consumption of non-pasteurized dairy products in which clinical and laboratory findings confirmed the existence of an active brucellosis with nervous system impairment. Cerebrospinal fluid (CSF) analyses were negative. Electrophysiology and positive findings on sural nerve biopsy complemented the diagnosis of polyneuroradiculomyeloencephalitis. Treatment with a combination of doxycycline and rifampin for 2 months was successfully applied. No relapse or sequelae occurred in the patient after 12 months of follow up.

The Blocking Flap for Ulnar Nerve Instability After In Situ Release: Technique and a Grading System of Ulnar Nerve Instability to Guide Treatment.

PubMed

Tang, Peter

2017-12-01

In situ ulnar nerve release has been gaining popularity as a simple, effective, and low-morbidity procedure for the treatment of cubital tunnel syndrome. One concern with the technique is how to manage the unstable ulnar nerve after release. It is unclear how much nerve subluxation will lead to problems and surprisingly there is no grading system to assess ulnar nerve instability. I propose such a grading system, as well as a new technique to stabilize the unstable ulnar nerve. The blocking flap technique consists of raising a rectangular flap off the flexor/pronator fascia and attaching it to the posterior subcutaneous flap so that it blocks the nerve from subluxation/dislocation.

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 Wistar-Kyoto rats.

Local delivery of glial cell line-derived neurotrophic factor improves facial nerve regeneration after late repair.

PubMed

Barras, Florian M; Kuntzer, Thierry; Zurn, Anne D; Pasche, Philippe

2009-05-01

Facial nerve regeneration is limited in some clinical situations: in long grafts, by aged patients, and when the delay between nerve lesion and repair is prolonged. This deficient regeneration is due to the limited number of regenerating nerve fibers, their immaturity and the unresponsiveness of Schwann cells after a long period of denervation. This study proposes to apply glial cell line-derived neurotrophic factor (GDNF) on facial nerve grafts via nerve guidance channels to improve the regeneration. Two situations were evaluated: immediate and delayed grafts (repair 7 months after the lesion). Each group contained three subgroups: a) graft without channel, b) graft with a channel without neurotrophic factor; and c) graft with a GDNF-releasing channel. A functional analysis was performed with clinical observation of facial nerve function, and nerve conduction study at 6 weeks. Histological analysis was performed with the count of number of myelinated fibers within the graft, and distally to the graft. Central evaluation was assessed with Fluoro-Ruby retrograde labeling and Nissl staining. This study showed that GDNF allowed an increase in the number and the maturation of nerve fibers, as well as the number of retrogradely labeled neurons in delayed anastomoses. On the contrary, after immediate repair, the regenerated nerves in the presence of GDNF showed inferior results compared to the other groups. GDNF is a potent neurotrophic factor to improve facial nerve regeneration in grafts performed several months after the nerve lesion. However, GDNF should not be used for immediate repair, as it possibly inhibits the nerve regeneration.

R1 autonomic nervous system in acute kidney injury.

PubMed

Hering, Dagmara; Winklewski, Pawel J

2017-02-01

Acute kidney injury (AKI) is a rapid loss of kidney function resulting in accumulation of end metabolic products and associated abnormalities in fluid, electrolyte and acid-base homeostasis. The pathophysiology of AKI is complex and multifactorial involving numerous vascular, tubular and inflammatory pathways. Neurohumoral activation with heightened activity of the sympathetic nervous system and renin-angiotensin-aldosterone system play a critical role in this scenario. Inflammation and/or local renal ischaemia are underlying mechanisms triggering renal tissue hypoxia and resultant renal microcirculation dysfunction; a common feature of AKI occurring in numerous clinical conditions leading to a high morbidity and mortality rate. The contribution of renal nerves to the pathogenesis of AKI has been extensively demonstrated in a series of experimental models over the past decades. While this has led to better knowledge of the pathogenesis of human AKI, therapeutic approaches to improve patient outcomes are scarce. Restoration of autonomic regulatory function with vagal nerve stimulation resulting in anti-inflammatory effects and modulation of centrally-mediated mechanisms could be of clinical relevance. Evidence from experimental studies suggests that a therapeutic splenic ultrasound approach may prevent AKI via activation of the cholinergic anti-inflammatory pathway. This review briefly summarizes renal nerve anatomy, basic insights into neural control of renal function in the physiological state and the involvement of the autonomic nervous system in the pathophysiology of AKI chiefly due to sepsis, cardiopulmonary bypass and ischaemia/reperfusion experimental model. Finally, potentially preventive experimental pre-clinical approaches for the treatment of AKI aimed at sympathetic inhibition and/or parasympathetic stimulation are presented. © 2016 John Wiley & Sons Australia, Ltd.

In vivo morphology of the limbal palisades of vogt correlates with progressive stem cell deficiency in aniridia-related keratopathy.

PubMed

Lagali, Neil; Edén, Ulla; Utheim, Tor Paaske; Chen, Xiangjun; Riise, Ruth; Dellby, Anette; Fagerholm, Per

2013-08-07

To investigate morphologic alterations in the limbal palisades of Vogt in a progressive form of limbal stem cell deficiency. Twenty Norwegian subjects (40 eyes) with congenital aniridia and 9 healthy family members (18 eyes) without aniridia were examined. Clinical grade of aniridia-related keratopathy (ARK) was assessed by slit-lamp biomicroscopy, and tear production and quality, corneal thickness, and sensitivity were additionally measured. The superior and inferior limbal palisades of Vogt and central cornea were examined by laser scanning in vivo confocal microscopy (IVCM). In an aniridia patient with grade 0 ARK, a transparent cornea and normal limbal palisade morphology were found. In grade 1 ARK, 5 of 12 eyes had degraded palisade structures. In the remaining grade 1 eyes and in all 20 eyes with stage 2, 3, and 4 ARK, palisade structures were absent by IVCM. Increasing ARK grade significantly correlated with reduced visual acuity and corneal sensitivity, increased corneal thickness, degree of degradation of superior and inferior palisade structures, reduced peripheral nerves, increased inflammatory cell invasion, and reduced density of basal epithelial cells and central subbasal nerves. Moreover, limbal basal epithelial cell density and central corneal subbasal nerve density were both significantly reduced in aniridia compared to healthy corneas (P = 0.002 and 0.003, respectively). Progression of limbal stem cell deficiency in aniridia correlates with degradation of palisade structures, gradual transformation of epithelial phenotype, onset of inflammation, and a corneal nerve deficit. IVCM can be useful in monitoring early- to late-stage degenerative changes in stem cell-deficient patients.

Operating unit time use is associated with anaesthesia type in below-knee surgery in adults.

PubMed

Lohela, T J; Chase, R P; Hiekkanen, T A; Kontinen, V K; Hynynen, M J

2017-03-01

Peripheral nerve blocks could reduce the operating unit and theatre time spent on high-risk patients who are particularly vulnerable to complications of general anaesthesia or have medications that prevent application of central neuraxial blocks. Medical record data of 617 and 254 elderly adults undergoing below-knee surgery in Jorvi and Meilahti hospitals (Helsinki University Hospital) between January 2010 and December 2012 were used to investigate the influence of anaesthetic technique on operating theatre times and on operating unit times using flexible parametric survival models. We report operating theatre and unit exit ratios (i.e. hazard ratios but using ratios of exit rates) for different types of anaesthesia. Adjusted analyses: In Jorvi Hospital, anaesthesia type was associated with large initial differentials in operating theatre times. The theatre exit ratios remained lower for general anaesthesia and central neuraxial blocks compared to peripheral nerve blocks until 30 min. In Meilahti Hospital, anaesthesia type did not influence theatre time, but was the best predictor of operating unit times. Compared to peripheral nerve blocks, the exit ratio remained lower for general anaesthesia until five operating unit hours in both hospitals and for central neuraxial blocks until 1 h in Meilahti Hospital and until 3 h in Jorvi Hospital. Holding area was used more in Jorvi Hospital compared to Meilahti Hospital. Peripheral nerve block anaesthesia reduces time spent in the operating unit and can reduce time spent in the operating theatre if induced in holding area outside of theatre. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Downregulation of ClC-3 in dorsal root ganglia neurons contributes to mechanical hypersensitivity following peripheral nerve injury.

PubMed

Pang, Rui-Ping; Xie, Man-Xiu; Yang, Jie; Shen, Kai-Feng; Chen, Xi; Su, Ying-Xue; Yang, Chao; Tao, Jing; Liang, Si-Jia; Zhou, Jia-Guo; Zhu, He-Quan; Wei, Xu-Hong; Li, Yong-Yong; Qin, Zhi-Hai; Liu, Xian-Guo

2016-11-01

ClC-3 chloride channel/antiporter has been demonstrated to play an important role in synaptic transmission in central nervous system. However, its expression and function in sensory neurons is poorly understood. In present work, we found that ClC-3 is expressed at high levels in dorsal root ganglia (DRG). Co-immunofluorescent data showed that ClC-3 is mainly distributed in A- and C-type nociceptive neurons. ClC-3 expression in DRG is decreased in the spared nerve injury (SNI) model of neuropathic pain. Knockdown of local ClC-3 in DRG neurons with siRNA increased mechanical sensitivity in naïve rats, while overexpression of ClC-3 reversed the hypersensitivity to mechanical stimuli after peripheral nerve injury. In addition, genetic deletion of ClC-3 enhances mouse mechanical sensitivity but did not affect thermal and cold threshold. Restoration of ClC-3 expression in ClC-3 deficient mice reversed the mechanical sensitivity. Mechanistically, loss of ClC-3 enhanced mechanical sensitivity through increasing the excitability of DRG neurons. These data indicate that ClC-3 is an endogenous inhibitor of neuropathic pain development. Downregulation of ClC-3 by peripheral nerve injury is critical for mechanical hypersensitivity. Our findings suggest that ClC-3 is a novel therapeutic target for treating neuropathic pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Epigenetic modification of DRG neuronal gene expression subsequent to nerve injury: etiological contribution to complex regional pain syndromes (Part I).

PubMed

Wang, Fuzhou; Stefano, George B; Kream, Richard M

2014-06-25

DRG is of importance in relaying painful stimulation to the higher pain centers and therefore could be a crucial target for early intervention aimed at suppressing primary afferent stimulation. Complex regional pain syndrome (CRPS) is a common pain condition with an unknown etiology. Recently added new information enriches our understanding of CRPS pathophysiology. Researches on genetics, biogenic amines, neurotransmitters, and mechanisms of pain modulation, central sensitization, and autonomic functions in CRPS revealed various abnormalities indicating that multiple factors and mechanisms are involved in the pathogenesis of CRPS. Epigenetics refers to mitotically and meiotically heritable changes in gene expression that do not affect the DNA sequence. As epigenetic modifications potentially play an important role in inflammatory cytokine metabolism, neurotransmitter responsiveness, and analgesic sensitivity, they are likely key factors in the development of chronic pain. In this dyad review series, we systematically examine the nerve injury-related changes in the neurological system and their contribution to CRPS. In this part, we first reviewed and summarized the role of neural sensitization in DRG neurons in performing function in the context of pain processing. Particular emphasis is placed on the cellular and molecular changes after nerve injury as well as different models of inflammatory and neuropathic pain. These were considered as the potential molecular bases that underlie nerve injury-associated pathogenesis of CRPS.

Neurologic disorders of mineral metabolism and parathyroid disease.

PubMed

Agrawal, Lily; Habib, Zeina; Emanuele, Nicholas V

2014-01-01

Disorders of mineral metabolism may cause neurologic manifestations of the central and peripheral nervous systems. This is because plasma calcium stabilizes excitable membranes in the nerve and muscle tissue, magnesium is predominantly intracellular and is required for activation of many intracellular enzymes, and extracellular magnesium affects synaptic transmission. This chapter reviews abnormalities in electrolytes and minerals which can be associated with several neuromuscular symptoms including neuromuscular irritability, mental status changes, cardiac and smooth muscle changes, etc. © 2014 Elsevier B.V. All rights reserved.

Development of a microinstillation model of inhalation exposure to assess lung injury following exposure to toxic chemicals and nerve agents in Guinea pigs.

PubMed

Nambiar, Madhusoodana P; Wright, Benjamin S; Rezk, Peter E; Smith, Kelvin B; Gordon, Richard K; Moran, Theodore S; Richards, Shannon M; Sciuto, Alfred M

2006-01-01

Respiratory disturbances due to chemical warfare nerve agents (CWNAs) are the starting point of mass casualty and the primary cause of death by these weapons of terror and mass destruction. However, very few studies have been implemented to assess respiratory toxicity and exacerbation induced by CWNAs, especially methylphosphonothioic acid S-(2-(bis(1-methylethyl)amino)ethyl)O-ethyl ester (VX). In this study, we developed a microinstillation technique of inhalation exposure to assess lung injury following exposure to CWNAs and toxic chemicals. Guinea pigs were gently intubated by placing a microcatheter into the trachea 1.5 to 2.0 cm centrally above the bifurcation. This location is crucial to deliver aerosolized agents uniformly to the lung's lobes. The placement of the tube is calculated by measuring the distance from the upper front teeth to the tracheal bifurcation, which is typically 8.5 cm for guinea pigs of equivalent size and a weight range of 250 g to 300 g. The catheter is capable of withstanding 100 psi pressure; the terminus has five peripheral holes to pump air that aerosolizes the nerve agent that is delivered in the central hole. The microcatheter is regulated by a central control system to deliver the aerosolized agent in a volume lower than the tidal volume of the guinea pigs. The average particle size of the nerve agent delivered was 1.48 +/- 0.07 micrometer. The microinstillation technology has been validated by exposing the animals to Coomassie brilliant blue, which showed a uniform distribution of the dye in different lung lobes. In addition, the concentration of the dye in the lungs correlated with the dose/time of exposure. Furthermore, histopathological analysis confirmed the absence of barotraumas following micoinstillation. This novel technique delivers the agent safely, requires less amount of agent, avoids exposure to skin, pelt, and eye, and circumvents the concern of deposition of the particles in the nasal and palette due to the switching of breathing from nasal to oronasal in whole-body dynamic chamber or nose only exposure. Currently, we are using this inhalation exposure technique to investigate lung injuries and respiratory disturbances following direct exposure to VX.

[RESEARCH PROGRESS OF PERIPHERAL NERVE SURGERY ASSISTED BY Da Vinci ROBOTIC SYSTEM].

PubMed

Shen, Jie; Song, Diyu; Wang, Xiaoyu; Wang, Changjiang; Zhang, Shuming

2016-02-01

To summarize the research progress of peripheral nerve surgery assisted by Da Vinci robotic system. The recent domestic and international articles about peripheral nerve surgery assisted by Da Vinci robotic system were reviewed and summarized. Compared with conventional microsurgery, peripheral nerve surgery assisted by Da Vinci robotic system has distinctive advantages, such as elimination of physiological tremors and three-dimensional high-resolution vision. It is possible to perform robot assisted limb nerve surgery using either the traditional brachial plexus approach or the mini-invasive approach. The development of Da Vinci robotic system has revealed new perspectives in peripheral nerve surgery. But it has still been at the initial stage, more basic and clinical researches are still needed.

Pulsed radiofrequency of the composite nerve supply to the knee joint as a new technique for relieving osteoarthritic pain: a preliminary report.

PubMed

Vas, Lakshmi; Pai, Renuka; Khandagale, Nishigandha; Pattnaik, Manorama

2014-01-01

We report a new technique for pulsed radiofrequency (PRF) of the entire nerve supply of the knee as an option in treating osteoarthritis (OA) of knee. We targeted both sensory and motor nerves supplying all the structures around the knee: joint, muscles, and skin to address the entire nociception and stiffness leading to peripheral and central sensitization in osteoarthritis. Ten patients with pain, stiffness, and loss of function in both knees were treated with ultrasonography (USG) guided PRF of saphenous, tibial, and common peroneal nerves along with subsartorial, peripatellar, and popliteal plexuses. USG guided PRF of the femoral nerve was also done to address the innervation of the quadriceps muscle. Assessment of pain (Numerical Rating Scale [NRS], pain DETECT, knee function [Western Ontario and McMaster Universities Osteoarthritis Index- WOMAC]) were documented pre and post PRF at 3 and 6 months. Knee radiographs (Kellgren-Lawrence [K-L] grading) were done before PRF and one week later. All the patients showed a sustained improvement of NRS, pain DETECT, and WOMAC at 3 and 6 months. The significant improvement of patellar position and tibio-femoral joint space was concordant with the patient's reporting of improvement in stiffness and pain. The sustained pain relief and muscle relaxation enabled the patients to optimize physiotherapy thereby improving endurance training to include the daily activities of life. We conclude that OA knee pain is a product of neuromyopathy and that PRF of the sensory and motor nerves appeared to be a safe, effective, and minimally invasive technique. The reduction of pain and stiffness improved the knee function and probably reduced the peripheral and central sensitization.

A case with central and peripheral hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome) plus cataract.

PubMed

Sato, Ikuko; Onuma, Akira; Goto, Nobue; Sakai, Fumiaki; Fujiwara, Ikuma; Uematsu, Mitsugu; Osaka, Hitoshi; Okahashi, Satomi; Nonaka, Ikuya; Tanaka, Soichiro; Haginoya, Kazuhiro

2011-01-15

Hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome) is a rare disease, characterized by both central and peripheral hypomyelination. We describe a 21-year-old male with mildly progressive ataxia, mental retardation, pituitary hypogonadotropic hypogonadism, delayed dentition, and cataract. Brain magnetic resonance imaging showed hypomyelinated white matter, cerebellar atrophy, and a thin corpus callosum. The literature suggests that abnormal findings upon sural nerve biopsy may indicate peripheral hypomyelination, even in the absence of clinically and physiologically evident peripheral neuropathy. A sural nerve biopsy of this patient was normal, and this finding is further discussed. Taken together with previous reports, this case suggests that 4H syndrome can be regarded as a spectrum disorder, the cardinal signs of which may be central hypomyelination, ataxia, hypogonadotropic hypogonadism, and hypodontia. Copyright © 2010 Elsevier B.V. All rights reserved.

Oral Microbiome Link to Neurodegeneration in Glaucoma

PubMed Central

Astafurov, Konstantin; Elhawy, Eman; Ren, Lizhen; Dong, Cecilia Q.; Igboin, Christina; Hyman, Leslie; Griffen, Ann; Mittag, Thomas; Danias, John

2014-01-01

Background Glaucoma is a progressive optic nerve degenerative disease that often leads to blindness. Local inflammatory responses are implicated in the pathology of glaucoma. Although inflammatory episodes outside the CNS, such as those due to acute systemic infections, have been linked to central neurodegeneration, they do not appear to be relevant to glaucoma. Based on clinical observations, we hypothesized that chronic subclinical peripheral inflammation contributes to neurodegeneration in glaucoma. Methods Mouthwash specimens from patients with glaucoma and control subjects were analyzed for the amount of bacteria. To determine a possible pathogenic mechanism, low-dose subcutaneous lipopolysaccharide (LPS) was administered in two separate animal models of glaucoma. Glaucomatous neurodegeneration was assessed in the retina and optic nerve two months later. Changes in gene expression of toll-like receptor 4 (TLR4) signaling pathway and complement as well as changes in microglial numbers and morphology were analyzed in the retina and optic nerve. The effect of pharmacologic blockade of TLR4 with naloxone was determined. Findings Patients with glaucoma had higher bacterial oral counts compared to control subjects (p<0.017). Low-dose LPS administration in glaucoma animal models resulted in enhancement of axonal degeneration and neuronal loss. Microglial activation in the optic nerve and retina as well as upregulation of TLR4 signaling and complement system were observed. Pharmacologic blockade of TLR4 partially ameliorated the enhanced damage. Conclusions The above findings suggest that the oral microbiome contributes to glaucoma pathophysiology. A plausible mechanism by which increased bacterial loads can lead to neurodegeneration is provided by experiments in animal models of the disease and involves activation of microglia in the retina and optic nerve, mediated through TLR4 signaling and complement upregulation. The finding that commensal bacteria may play a role in the development and/or progression of glaucomatous pathology may also be relevant to other chronic neurodegenerative disorders. PMID:25180891

The sympathetic nervous system in polycystic ovary syndrome: a novel therapeutic target?

PubMed

Lansdown, Andrew; Rees, D Aled

2012-12-01

Polycystic ovary syndrome (PCOS) is a common endocrine condition associated with long-term health risks, including type 2 diabetes and vascular dysfunction in addition to reproductive sequelae. Many of the common features of PCOS, such as central obesity, hyperinsulinaemia and obstructive sleep apnoea (OSA), are associated with chronic sympathetic overactivity, suggesting that sympathoexcitation may be involved in the pathogenesis of this condition. Rodent models of polycystic ovaries have shown that ovarian sympathetic outflow may be increased, accompanied by elevated intra-ovarian synthesis of nerve growth factor (NGF) which may be involved in initiation of ovarian pathology. Patients with PCOS have evidence of increased muscle sympathetic nerve activity (MSNA), altered heart rate variability and attenuated heart rate recovery postexercise, compared with age- and BMI-matched controls, suggesting a generalized increase in sympathetic nerve activity. Active weight loss can reduce MSNA and whole body noradrenaline spillover, whereas low-frequency electroacupuncture decreased MSNA in overweight women with PCOS. Treatment of OSA with continuous positive airways pressure may reduce plasma noradrenaline levels and diastolic blood pressure and improve cardiac sympathovagal balance. Renal sympathetic denervation also reduced MSNA, noradrenaline spillover and blood pressure in two PCOS subjects with hypertension, accompanied by improved insulin sensitivity. The sympathetic nervous system may thus offer a new therapeutic target in PCOS but larger and longer-term studies are needed before these treatments can be considered in clinical practice. © 2012 Blackwell Publishing Ltd.

[Pathomechanism of Autoantibody Production in the Nervous System Diseases].

PubMed

Shimizu, Fumitaka; Kanda, Takashi

2018-04-01

Antibodies to different brain and peripheral nerve proteins have recently been found to be associated with several different autoimmune diseases. They can bind to either neuronal or non-neuronal antigens and may have a pathogenic role by themselves or in synergy with other inflammatory mediators after penetrating the blood-brain barrier or the blood-nerve barrier. In this review, we will describe the association with the impairment of immune tolerance, innate immunity, and autoantibody production of myasthenia gravis (MG), systemic lupus erythematosus (SLE), and Guillain-Barré syndrome (GBS). Impairment of central tolerance, which is characterized by the repertoire selection of immature T-lymphocytes in the thymus, is seen in patients with MG who are positive for anti-Ach R antibodies. Impairment of peripheral tolerance due to activation of autoreactive T-cells and suppression of regulatory T-cells is seen in SLE. In addition, molecular mimicry between the lipooligosaccharides of Campylobacter jejuni and gangliosides of the peripheral nerves results in the production of anti-gangliosides antibodies in GBS. Next, we will describe the antibody-mediated pathology in neuromyelitis optica and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. The binding of anti-aquaporin-4 antibodies or anti-NMDAR antibodies to their respective targets initiates target internalization and complement- or antibody-dependent cellular cytotoxicity of the target cells. Further understanding of antibody-mediated pathology may suggest novel therapeutic strategies.

Fluorescent sensors for the detection of chemical warfare agents.

PubMed

Burnworth, Mark; Rowan, Stuart J; Weder, Christoph

2007-01-01

Along with biological and nuclear threats, chemical warfare agents are some of the most feared weapons of mass destruction. Compared to nuclear weapons they are relatively easy to access and deploy, which makes them in some aspects a greater threat to national and global security. A particularly hazardous class of chemical warfare agents are the nerve agents. Their rapid and severe effects on human health originate in their ability to block the function of acetylcholinesterase, an enzyme that is vital to the central nervous system. This article outlines recent activities regarding the development of molecular sensors that can visualize the presence of nerve agents (and related pesticides) through changes of their fluorescence properties. Three different sensing principles are discussed: enzyme-based sensors, chemically reactive sensors, and supramolecular sensors. Typical examples are presented for each class and different fluorescent sensors for the detection of chemical warfare agents are summarized and compared.

Nutrients and neurodevelopment: lipids.

PubMed

González, Horacio F; Visentin, Silvana

2016-10-01

Nutrients, lipids in particular, make up the central nervous system structure and play major functional roles: they stimulate development, migration, and nerve cell differentiation. They are part of gray matter, white matter, nerve nuclei, and synaptogenesis. Breast milk contains lipids which are crucial for infant brain development. The lipid profile of breast milk was used as a guideline for the development of breast milk substitutes. However, to date, no substitute has matched it. Complementary feeding should include docosahexaenoic acid, arachidonic acid, other polyunsaturated fatty acids, saturated fatty acids, and complex lipids found in milk fat. The lipid composition of breast milk depends on maternal intake and nutritional status during pregnancy and breast-feeding. It has a great impact on development. Our goal is to review scientific literature regarding the role of lipids on infant brain development and the importance of breast milk lipid composition, maternal diet, and complementary feeding. Sociedad Argentina de Pediatría.

Neurotrophin signaling and visceral hypersensitivity.

PubMed

Qiao, Li-Ya

2014-06-01

Neurotrophin family are traditionally recognized for their nerve growth promoting function and are recently identified as crucial factors in regulating neuronal activity in the central and peripheral nervous systems. The family members including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) are reported to have distinct roles in the development and maintenance of sensory phenotypes in normal states and in the modulation of sensory activity in disease. This paper highlights receptor tyrosine kinase (Trk) -mediated signal transduction by which neurotrophins regulate neuronal activity in the visceral sensory reflex pathways with emphasis on the distinct roles of NGF and BDNF signaling in physiologic and pathophysiological processes. Viscero-visceral cross-organ sensitization exists widely in human diseases. The role of neurotrophins in mediating neural cross talk and interaction in primary afferent neurons in the dorsal root ganglia (DRG) and neurotrophin signal transduction in the context of cross-organ sensitization are also discussed.

A Rare Presentation of Cranial Polyneuropathy Without Rash Caused by Varicella Zoster Virus

PubMed Central

Tecellioglu, Mehmet; Kamisli, Suat; Erbay, Mehmet Fatih; Kamisli, Ozden; Ozcan, Cemal

2017-01-01

Introduction: Varicella Zoster Virus (VZV) is associated with many disorders of the central and peripheral nervous systems including neuralgia, meningitis, meningoencephalitis, cerebellitis, vasculopathy, myelopathy, Ramsay-Hunt syndrome, and polyneuritis cranialis. Cranial nerves V, VI, VII, VIII, IX, X, XI, and/or XII may be affected. The neurological disorders caused by VZV usually present with rash, but may rarely present without rash. Case report: We herein present a case of polyneuritis cranialis without rash caused by VZV affecting cranial nerves VII, VIII, IX, and X. After excluding other causes of the condition, we diagnosed VZV infection based on VZV DNA in the CSF and an elevated anti-VZV IgG level in serum. The patient responded well to antiviral therapy. Conclusion: VZV infection should be kept in mind during the differential diagnosis of polyneuritis cranialis; it is important to note that VZV re-activation may occur without rash. PMID:28974853

[Sacral nerve stimulation in the treatment of the lower urinary tract function disorders].

PubMed

Miotła, Paweł; Kulik-Rechberger, Beata; Skorupski, Paweł; Rechberger, Tomasz

2011-11-01

Functional disorders of the female lower urinary tract like urge incontinence, idiopathic urinary retention and symptoms of urgency-frequency occasionally do not respond properly to classical behavioral and pharmacological therapy Therefore, additional alternative therapies are needed to alleviate these bothersome symptoms. Sacral neuromodulation (SNS) utilize mild electrical pulses which activate or suppress neural reflexes responsible for voiding by stimulating the sacral nerves that innervate the bladder, external urethral sphincter and pelvic floor muscles. The exact mechanism of SNS action is not yet fully understood but it is assumed that it influences the neuroaxis at different levels of the central nervous system and restores the balance between inhibitory and activatory control over the voiding reflex. There is numerous evidence on the success of SNS not only in the treatment of refractory urge incontinence in adult and children but also in idiopathic urinary retention and symptoms of urgency-frequency

Inhibition of the sympathetic nervous system by a series of heterocyclic congeners of dopamine.

PubMed

Sharabi, F M; Long, J P; Cannon, J G; Hatheway, G J

1976-12-01

A series of heterocyclic congeners of dopamine (GJH-series) with different positions of phenolic oxygens and with the possibility of cis and trans isomerism at the 4a-10b ring juncture was evaluated in vitro and in vivo for dopaminergic activity. Two compounds, GJH-166 and GJH-171, were found to suppress the positive chronotropic response induced by stimulation of the right cardioaccelerator nerves. These effects were antagonized by haloperidol. GJH-166, in doses as low as 9.5 x 10(-4) mugmol/kg reduced the resting heart rate in cats anesthetized with alpha-chloralose. GJH-166 and GJH-171 antagonized pressor responses induced by bilateral carotid occlusion and stimulation of the central stump of the sciatic nerve. The results outlined in this manuscript support the hypothesis that the extended conformation of the dihydroxyhenylethylamine moiety of dopamine with a trans isomeric form is favorable for dopaminergic agonist activity.

Gap Junction-Mediated Signaling from Motor Neurons Regulates Motor Generation in the Central Circuits of Larval Drosophila.

PubMed

Matsunaga, Teruyuki; Kohsaka, Hiroshi; Nose, Akinao

2017-02-22

In this study, we used the peristaltic crawling of Drosophila larvae as a model to study how motor patterns are regulated by central circuits. We built an experimental system that allows simultaneous application of optogenetics and calcium imaging to the isolated ventral nerve cord (VNC). We then investigated the effects of manipulating local activity of motor neurons (MNs) on fictive locomotion observed as waves of MN activity propagating along neuromeres. Optical inhibition of MNs with halorhodopsin3 in a middle segment (A4, A5, or A6), but not other segments, dramatically decreased the frequency of the motor waves. Conversely, local activation of MNs with channelrhodopsin2 in a posterior segment (A6 or A7) increased the frequency of the motor waves. Since peripheral nerves mediating sensory feedback were severed in the VNC preparation, these results indicate that MNs send signals to the central circuits to regulate motor pattern generation. Our results also indicate segmental specificity in the roles of MNs in motor control. The effects of the local MN activity manipulation were lost in shaking-B 2 ( shakB 2 ) or ogre 2 , gap-junction mutations in Drosophila , or upon acute application of the gap junction blocker carbenoxolone, implicating electrical synapses in the signaling from MNs. Cell-type-specific RNAi suggested shakB and ogre function in MNs and interneurons, respectively, during the signaling. Our results not only reveal an unexpected role for MNs in motor pattern regulation, but also introduce a powerful experimental system that enables examination of the input-output relationship among the component neurons in this system. SIGNIFICANCE STATEMENT Motor neurons are generally considered passive players in motor pattern generation, simply relaying information from upstream interneuronal circuits to the target muscles. This study shows instead that MNs play active roles in the control of motor generation by conveying information via gap junctions to the central pattern-generating circuits in larval Drosophila , providing novel insights into motor circuit control. The experimental system introduced in this study also presents a new approach for studying intersegmentally coordinated locomotion. Unlike traditional electrophysiology methods, this system enables the simultaneous recording and manipulation of populations of neurons that are genetically specified and span multiple segments. Copyright © 2017 the authors 0270-6474/17/372045-16$15.00/0.

Clinical neurophysiology and quantitative sensory testing in the investigation of orofacial pain and sensory function.

PubMed

Jääskeläinen, Satu K

2004-01-01

Chronic orofacial pain represents a diagnostic and treatment challenge for the clinician. Some conditions, such as atypical facial pain, still lack proper diagnostic criteria, and their etiology is not known. The recent development of neurophysiological methods and quantitative sensory testing for the examination of the trigeminal somatosensory system offers several tools for diagnostic and etiological investigation of orofacial pain. This review presents some of these techniques and the results of their application in studies on orofacial pain and sensory dysfunction. Clinical neurophysiological investigation has greater diagnostic accuracy and sensitivity than clinical examination in the detection of the neurogenic abnormalities of either peripheral or central origin that may underlie symptoms of orofacial pain and sensory dysfunction. Neurophysiological testing may also reveal trigeminal pathology when magnetic resonance imaging has failed to detect it, so these methods should be considered complementary to each other in the investigation of orofacial pain patients. The blink reflex, corneal reflex, jaw jerk, sensory neurography of the inferior alveolar nerve, and the recording of trigeminal somatosensory-evoked potentials with near-nerve stimulation have all proved to be sensitive and reliable in the detection of dysfunction of the myelinated sensory fibers of the trigeminal nerve or its central connections within the brainstem. With appropriately small thermodes, thermal quantitative sensory testing is useful for the detection of trigeminal small-fiber dysfunction (Adelta and C). In neuropathic conditions, it is most sensitive to lesions causing axonal injury. By combining different techniques for investigation of the trigeminal system, an accurate topographical diagnosis and profile of sensory fiber pathology can be determined. Neurophysiological and quantitative sensory tests have already highlighted some similarities among various orofacial pain conditions and have shown heterogeneity within clinical diagnostic categories. With the aid of neurophysiological recordings and quantitative sensory testing, it is possible to approach a mechanism-based classification of orofacial pain.

Correlation between central corneal thickness and visual field defects, cup to disc ratio and retinal nerve fiber layer thickness in primary open angle glaucoma patients.

PubMed

Sarfraz, Muhammad Haroon; Mehboob, Mohammad Asim; Haq, Rana Intisar Ul

2017-01-01

To evaluate the correlation between Central Corneal Thickness (CCT) and Visual Field (VF) defect parameters like Mean Deviation (MD) and Pattern Standard Deviation (PSD), Cup-to-Disc Ratio (CDR) and Retinal Nerve Fibre Layer Thickness (RNFL-T) in Primary Open-Angle Glaucoma (POAG) patients. This cross sectional study was conducted at Armed Forces Institute of Ophthalmology (AFIO), Rawalpindi from September 2015 to September 2016. Sixty eyes of 30 patients with diagnosed POAG were analysed. Correlation of CCT with other variables was studied. Mean age of study population was 43.13±7.54 years. Out of 30 patients, 19 (63.33%) were males and 11 (36.67%) were females. Mean CCT, MD, PSD, CDR and RNFL-T of study population was 528.57±25.47µm, -9.11±3.07, 6.93±2.73, 0.63±0.13 and 77.79±10.44µm respectively. There was significant correlation of CCT with MD, PSD and CDR (r=-0.52, p<0.001; r=-0.59, p<0.001;r=-0.41, p=0.001 respectively). The correlation of CCT with RNFL-T was not statistically significant (r=-0.14, p=0.284). Central corneal thickness had significant correlation with visual field parameters like mean deviation and pattern standard deviation, as well as with cup-to-disc ratio. However, central corneal thickness had no significant relationship with retinal nerve fibre layer thickness.

Developmental and Regional Patterns of GAP-43 Immunoreactivity in a Metamorphosing Brain

PubMed Central

Simmons, Andrea Megela; Tanyu, Leslie H.; Horowitz, Seth S.; Chapman, Judith A.; Brown, Rebecca A.

2012-01-01

Growth-associated protein-43 is typically expressed at high levels in the nervous system during development. In adult animals, its expression is lower, but still observable in brain areas showing structural or functional plasticity. We examined patterns of GAP-43 immunoreactivity in the brain of the bullfrog, an animal whose nervous system undergoes considerable reorganization across metamorphic development and retains a strong capacity for plasticity in adulthood. Immunolabeling was mostly diffuse in hatchling tadpoles, but became progressively more discrete as larval development proceeded. In many brain areas, intensity of immunolabel peaked at metamorphic climax, the time of final transition from aquatic to semi-terrestrial life. Changes in intensity of GAP-43 expression in the medial vestibular nucleus, superior olivary nucleus, and torus semicircularis appeared correlated with stage-dependent functional changes in processing auditory stimuli. Immunolabeling in the Purkinje cell layer of the cerebellum and in the cerebellar nucleus was detectable at most developmental time points. Heavy immunolabel was present from early larval stages through the end of climax in the thalamus (ventromedial, anterior, posterior, central nuclei). Immunolabel in the tadpole telencephalon was observed around the lateral ventricles, and in the medial septum and ventral striatum. In postmetamorphic animals, immunoreactivity was confined mainly to the ventricular zones and immediately adjacent cell layers. GAP-43 expression was present in olfactory, auditory and optic cranial nerves throughout larval and postmetamorphic life. The continued expression of GAP-43 in brain nuclei and in cranial nerves throughout development and into adulthood reflects the high regenerative potential of the bullfrog’s central nervous system. PMID:18431052

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 activity were attenuated during active cycling. These results suggest that central command primarily regulates the strength, not the occurrence, of a muscle sympathetic burst during low-intensity dynamic leg exercise.

Retinal nerve fiber layer thickness and neuropsychiatric manifestations in systemic lupus erythematosus.

PubMed

Shulman, S; Shorer, R; Wollman, J; Dotan, G; Paran, D

2017-11-01

Background Cognitive impairment is frequent in systemic lupus erythematosus. Atrophy of the corpus callosum and hippocampus have been reported in patients with systemic lupus erythematosus, and diffusion tensor imaging studies have shown impaired white matter integrity, suggesting that white matter damage in systemic lupus erythematosus may underlie the cognitive impairment as well as other neuropsychiatric systemic lupus erythematosus manifestations. Retinal nerve fiber layer thickness, as assessed by optical coherence tomography, has been suggested as a biomarker for white matter damage in neurologic disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. Retinal nerve fiber layer thinning may occur early, even in patients with mild clinical symptoms. Aim The objective of this study was to assess the association of retinal nerve fiber layer thickness, as a biomarker of white matter damage in systemic lupus erythematosus patients, with neuropsychiatric systemic lupus erythematosus manifestations, including cognitive impairment. Methods Twenty-one consecutive patients with systemic lupus erythematosus underwent neuropsychological testing using a validated computerized battery of tests as well as the Rey-Auditory verbal learning test. All 21 patients, as well as 11 healthy, age matched controls, underwent optical coherence tomography testing to assess retinal nerve fiber layer thickness. Correlations between retinal nerve fiber layer thickness and results in eight cognitive domains assessed by the computerized battery of tests as well as the Rey-Auditory verbal learning test were assessed in patients with systemic lupus erythematosus, with and without neuropsychiatric systemic lupus erythematosus, and compared to retinal nerve fiber layer thickness in healthy controls. Results No statistically significant correlation was found between retinal nerve fiber layer thickness in patients with systemic lupus erythematosus as compared to healthy controls. When evaluating by subgroups, no correlation was found between patients with or without neuropsychiatric systemic lupus erythematosus or cognitive impairment and retinal nerve fiber layer thickness. Conclusion Retinal nerve fiber layer thickness of systemic lupus erythematosus patients was not found to be statistically different compared to controls. Within systemic lupus erythematosus patients there was no correlation between retinal nerve fiber layer thickness and cognitive impairment or other neuropsychiatric systemic lupus erythematosus manifestations.

Micromachined devices for interfacing neurons

NASA Astrophysics Data System (ADS)

Stieglitz, Thomas; Beutel, Hansjoerg; Blau, Cornelia; Meyer, Joerg-Uwe

1998-07-01

Micromachining technologies were established to fabricate microelectrode arrays and devices for interfacing parts of the central or peripheral nervous system. The devices were part of a neural prosthesis that allows simultaneous multichannel recording and multisite stimulation of neurons. Overcoming the brittle mechanics of silicon devices and challenging housing demands close to the nerve we established a process technology to fabricate light-weighted and highly flexible polyimide based devices. Platinum and iridium thin-film electrodes were embedded in the polyimide. With reactive ion etching we got the possibility to simply integrate interconnections and to form nearly arbitrary outer shapes of the devices. We designed multichannel devices with up to 24 electrodes in the shape of plates, hooks and cuffs for different applications. In vitro tests exhibited stable electrode properties and no cytotoxicity of the materials and the devices. Sieve electrodes were chronically implanted in rats to interface the regenerating sciatic nerve. After six months, recordings and stimulation of the nerve via electrodes on the micro-device proved functional reinnervation of the limb. Concentric circular structures were designed for a retina implant for the blind. In preliminary studies in rabbits, evoked potentials in the visual cortex corresponded to stimulation sites of the implant.

Enhancement of muscle contraction in the stomach of the crab Cancer borealis: a possible hormonal role for GABA.

PubMed

Suljak, Steven W; Rose, Christopher M; Sabatier, Christelle; Le, Thuc; Trieu, Quoc; Verley, Derek R; Lewis, Alexandra M; Birmingham, John T

2010-06-01

Gamma-aminobutyric acid (GABA) is best known as an inhibitory neurotransmitter in the mammalian central nervous system. Here we show, however, that GABA has an excitatory effect on nerve-evoked contractions and on excitatory junctional potentials (EJPs) of the gastric mill 4 (gm4) muscle from the stomach of the crab Cancer borealis. The threshold concentration for these effects was between 1 and 10 micromol l(-1). Using immunohistochemical techniques, we found that GABA is colocalized with the vesicle-associated protein synapsin in nearby nerves and hence is presumably released there. However, since these nerves do not innervate the muscle directly, we conclude that these release sites are not the likely source of the GABA responsible for muscle modulation. We also extracted hemolymph from the crab pericardial cavity, which contains the pericardial organs, a major neurosecretory structure. Through reversed-phase liquid chromatography-mass spectrometry analysis we determined the concentration of GABA in the hemolymph to be 3.3 +/- 0.7 micromol l(-1), high enough to modulate the muscle. These findings suggest that the gm4 muscle could be modulated by GABA produced by and released from a distant neurohemal organ.

[Clinicopathological study of non-Langerhans cell histiocytosis in central nervous system].

PubMed

Zhang, Tingting; Fu, Yongjuan; Lu, Dehong; Li, Cunjiang; Piao, Yueshan

2015-09-01

To explore the clinicopathological features and imaging characteristics of non-Langerhans cell histiocytosis in central nerve system, thus to facilitate the diagnosis and differential diagnosis. A total of ten cases were enrolled in the study, with seven cases of Rosai-Dorfman disease (RDD) and three cases of xanthoma disseminatum (XD). Data on the clinicopathological features, imaging, immunophenotype and prognosis were collected and analyzed. Seven patients with RDD, 5 males and 2 females with the mean age of 46.7 years old, all presented as dural-based or intraparenchymal hypo- to isointense lesions on T1 and T2 with post-contrast enhancement. The polymorphous admixture of histiocytes, lymphocytes and plasma cells was observed in a fibrous stroma, with emperipolesis of some histiocytes. The immunohistostaining of CD11c, CD68, MAC387 and S-100 was positive in the histiocytes, while the staining of CD1α was negative. Five patients recovered after the operation, while one patient died of the disease. All the 3 XD patients were female, with the median age of 20.7 years old. All XD patients presented as multiple intraparenchymal hypointense lesions on T1 and hyperintense lesions on T2 with post-contrast enhancement. The infiltration of foam-like histiocytes, a few Touton giant cells, lymphocytes and eosnophils was observed in all XD patients. The immunohistostaining of CD68 and CD11c was positive in the histiocytes and that of MAC387 partly positive, while the staining of S-100 and CD1α was negative. One XD patient survived well, while another one died of the disease. The diagnosis of RDD and XD should be based on their typical morphology and immunophenotype and should be differentiated from Langerhans cell histiocytosis and other non-Langerhans cell histiocytosis. Non-Langerhans cell histiocytosis in central nerve system often presents untypical clinical presentation and imaging features, thus the communication and cooperation between clinician and pathologist is needed.

Influence of eye size and beam entry angle on dose to non-targeted tissues of the eye during stereotactic x-ray radiosurgery of AMD

NASA Astrophysics Data System (ADS)

Cantley, Justin L.; Hanlon, Justin; Chell, Erik; Lee, Choonsik; Smith, W. Clay; Bolch, Wesley E.

2013-10-01

Age-related macular degeneration is a leading cause of vision loss for the elderly population of industrialized nations. The IRay® Radiotherapy System, developed by Oraya® Therapeutics, Inc., is a stereotactic low-voltage irradiation system designed to treat the wet form of the disease. The IRay System uses three robotically positioned 100 kVp collimated photon beams to deliver an absorbed dose of up to 24 Gy to the macula. The present study uses the Monte Carlo radiation transport code MCNPX to assess absorbed dose to six non-targeted tissues within the eye—total lens, radiosensitive tissues of the lens, optic nerve, distal tip of the central retinal artery, non-targeted portion of the retina, and the ciliary body--all as a function of eye size and beam entry angle. The ocular axial length was ranged from 20 to 28 mm in 2 mm increments, with the polar entry angle of the delivery system varied from 18° to 34° in 2° increments. The resulting data showed insignificant variations in dose for all eye sizes. Slight variations in the dose to the optic nerve and the distal tip of the central retinal artery were noted as the polar beam angle changed. An increase in non-targeted retinal dose was noted as the entry angle increased, while the dose to the lens, sensitive volume of the lens, and ciliary body decreased as the treatment polar angle increased. Polar angles of 26° or greater resulted in no portion of the sensitive volume of the lens receiving an absorbed dose of 0.5 Gy or greater. All doses to non-targeted structures reported in this study were less than accepted thresholds for post-procedure complications.

Changes in the frequency of swallowing during electrical stimulation of superior laryngeal nerve in rats.

PubMed

Tsuji, Kojun; Tsujimura, Takanori; Magara, Jin; Sakai, Shogo; Nakamura, Yuki; Inoue, Makoto

2015-02-01

The aim of the present study was to investigate the adaptation of the swallowing reflex in terms of reduced swallowing reflex initiation following continuous superior laryngeal nerve stimulation. Forty-four male Sprague Dawley rats were anesthetized with urethane. To identify swallowing, electromyographic activity of the left mylohyoid and thyrohyoid muscles was recorded. To evoke the swallowing response, the superior laryngeal nerve (SLN), recurrent laryngeal nerve, or cortical swallowing area was electrically stimulated. Repetitive swallowing evoked by continuous SLN stimulation was gradually reduced, and this reduction was dependent on the resting time duration between stimulations. Prior SLN stimulation also suppressed subsequent swallowing initiation. The reduction in evoked swallows induced by recurrent laryngeal nerve or cortical swallowing area stimulation was less than that following superior laryngeal nerve stimulation. Decerebration had no effect on the reduction in evoked swallows. Prior subthreshold stimulation reduced subsequent initiation of swallowing, suggesting that there was no relationship between swallowing movement evoked by prior stimulation and the subsequent reduction in swallowing initiation. Overall, these data suggest that reduced sensory afferent nerve firing and/or trans-synaptic responses, as well as part of the brainstem central pattern generator, are involved in adaptation of the swallowing reflex following continuous stimulation of swallow-inducing peripheral nerves and cortical areas. Copyright © 2014 Elsevier Inc. All rights reserved.

Taste preference changes throughout different life stages in male rats

PubMed Central

Yamamoto, Takashi; Ueda, Katsura; Nakatsuka, Michiko; Kumabe, Shunji; Inui, Tadashi; Iwai, Yasutomo

2017-01-01

Taste preference, a key component of food choice, changes with aging. However, it remains unclear how this occurs. To determine differences in taste preference between rats in different life stages, we examined the consumption of taste solutions and water using a two-bottle test. Male Sprague-Dawley rats of different ages were used: juvenile (3–6 weeks), young adult (8–11 weeks), adult (17–20 weeks), middle-aged (34–37 weeks), and old-aged (69–72 weeks). The intakes of the high and low concentration solutions presented simultaneously were measured. We observed that the old-aged group had lower preference ratios for 0.3 M sucrose and 0.1 M MSG in comparison with other groups. The preference ratio for 0.03 mM QHCl was higher in the middle-aged group than in the three younger groups and higher in the old-aged group than the juvenile group. The taste preferences for HCl and NaCl did not significantly differ among the age groups. The old-aged group tended to prefer high concentrations of sucrose, QHCl, NaCl, and MSG to low concentrations, indicating age-related decline in taste sensitivity. We also aimed to investigate differences between life stages in the electrophysiological responses of the chorda tympani nerve, one of the peripheral gustatory nerves, to taste stimuli. The electrophysiological recordings showed that aging did not alter the function of the chorda tympani nerve. This study showed that aging induced alterations in taste preference. It is likely that these alterations are a result of functional changes in other peripheral taste nerves, the gastrointestinal system, or the central nervous system. PMID:28742813

Compartmentalized beta subunit distribution determines characteristics and ethanol sensitivity of somatic, dendritic, and terminal large-conductance calcium-activated potassium channels in the rat central nervous system.

PubMed

Wynne, P M; Puig, S I; Martin, G E; Treistman, S N

2009-06-01

Neurons are highly differentiated and polarized cells, whose various functions depend upon the compartmentalization of ion channels. The rat hypothalamic-neurohypophysial system (HNS), in which cell bodies and dendrites reside in the hypothalamus, physically separated from their nerve terminals in the neurohypophysis, provides a particularly powerful preparation in which to study the distribution and regional properties of ion channel proteins. Using electrophysiological and immunohistochemical techniques, we characterized the large-conductance calcium-activated potassium (BK) channel in each of the three primary compartments (soma, dendrite, and terminal) of HNS neurons. We found that dendritic BK channels, in common with somatic channels but in contrast to nerve terminal channels, are insensitive to iberiotoxin. Furthermore, analysis of dendritic BK channel gating kinetics indicates that they, like somatic channels, have fast activation kinetics, in contrast to the slow gating of terminal channels. Dendritic and somatic channels are also more sensitive to calcium and have a greater conductance than terminal channels. Finally, although terminal BK channels are highly potentiated by ethanol, somatic and dendritic channels are insensitive to the drug. The biophysical and pharmacological properties of somatic and dendritic versus nerve terminal channels are consistent with the characteristics of exogenously expressed alphabeta1 versus alphabeta4 channels, respectively. Therefore, one possible explanation for our findings is a selective distribution of auxiliary beta1 subunits to the somatic and dendritic compartments and beta4 to the terminal compartment. This hypothesis is supported immunohistochemically by the appearance of distinct punctate beta1 or beta4 channel clusters in the membrane of somatic and dendritic or nerve terminal compartments, respectively.

Interactive effects of mechano- and chemo-receptor inputs on cardiorespiratory outputs in the toad.

PubMed

Wang, T; Taylor, E W; Reid, S G; Milsom, W K

2004-04-20

Arterial blood pressure (P(b)), pulmocutaneous blood flow (Q(pc)), heart rate (f(H)), and fictive ventilation (motor activity in the Vth cranial nerve, V(int)), were recorded from decerebrated, paralysed toads receiving unidirectional ventilation with experimental gas mixtures over a range of lung inflation. At the onset of spontaneous bouts of fictive ventilation, (Q(pc)) and P(b) increased immediately, often with changes in heart rate, implying central cardiorespiratory interactions. Inflation of the lungs with different gas mixtures revealed that the effect of hypercarbia on V(int) was reduced by lung inflation and that feedback from pulmonary stretch receptors may summate with central feedforward control of f(H) and (Q(pc)) in an interactive fashion. The results of bolus injections of cyanide into the carotid or the pulmonary circulations suggest there are oxygen sensitive receptors in both circuits that affect the cardiovascular system directly and respiratory activity by complex central interactions with inputs from central chemoreceptors and pulmonary stretch receptors.

Pathophysiology of Small-Fiber Sensory System in Parkinson's Disease

PubMed Central

Lin, Chin-Hsien; Chao, Chi-Chao; Wu, Shao-Wei; Hsieh, Paul-Chen; Feng, Fang-Ping; Lin, Yea-Huey; Chen, Ya-Mei; Wu, Ruey-Meei; Hsieh, Sung-Tsang

2016-01-01

Abstract Sensory symptoms are frequent nonmotor complaints in patients with Parkinson's disease (PD). However, few investigations integrally explored the physiology and pathology of the thermonociceptive pathway in PD. We aim to investigate the involvement of the thermonociceptive pathway in PD. Twenty-eight PD patients (16 men, with a mean age and standard deviation of 65.6 ± 10.7 years) free of neuropathic symptoms and systemic disorders were recruited for the study and compared to 23 age- and gender-matched control subjects (12 men, with a mean age and standard deviation of 65.1 ± 9.9 years). We performed skin biopsy, contact heat-evoked potential (CHEP), and quantitative sensory tests (QST) to study the involvement of the thermonociceptive pathway in PD. The duration of PD was 7.1 ± 3.2 (range 2–17 years) years and the UPDRS part III score was 25.6 ± 9.7 (range 10–48) during the off period. Compared to control subjects, PD patients had reduced intra-epidermal nerve fiber (IENF) density (2.48 ± 1.65 vs 6.36 ± 3.19 fibers/mm, P < 0.001) and CHEP amplitude (18.02 ± 10.23 vs 33.28 ± 10.48 μV, P < 0.001). Twenty-three patients (82.1%) had abnormal IENF densities and 18 (64.3%) had abnormal CHEP. Nine patients (32.1%) had abnormal thermal thresholds in the feet. In total 27 patients (96.4%) had at least 1 abnormality in IENF, CHEP, or thermal thresholds of the foot, indicating dysfunctions in the small-fiber nerve system. In control subjects, CHEP amplitude linearly correlated with IENF density (P < 0.001). In contrast, this relationship disappeared in PD (P = 0.312) and CHEP amplitude was negatively correlated with motor severity of PD independent of age, gender, and anti-PD medication dose (P = 0.036), suggesting the influences of central components on thermonociceptive systems in addition to peripheral small-fiber nerves in PD. The present study suggested impairment of small-fiber sensory system at both peripheral and central levels is an intrinsic feature of PD, and skin biopsy, CHEP, and QST provided an integral approach for assessing such dysfunctions. PMID:26962835

75 FR 4623 - Qualification of Drivers; Exemption Applications; Vision

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-28

... reasons, including amblyopia, optic nerve hyperplasia, retinopathy of prematurity, macular hole, central serous retinopathy, prosthesis, macular degeneration, cataract, extropia, diabetic retinopathy, aphakia...

Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury.

PubMed

van Niekerk, Erna A; Tuszynski, Mark H; Lu, Paul; Dulin, Jennifer N

2016-02-01

Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Concise Review: Dental Pulp Stem Cells: A Novel Cell Therapy for Retinal and Central Nervous System Repair.

PubMed

Mead, Ben; Logan, Ann; Berry, Martin; Leadbeater, Wendy; Scheven, Ben A

2017-01-01

Dental pulp stem cells (DPSC) are neural crest-derived ecto-mesenchymal stem cells that can relatively easily and non-invasively be isolated from the dental pulp of extracted postnatal and adult teeth. Accumulating evidence suggests that DPSC have great promise as a cellular therapy for central nervous system (CNS) and retinal injury and disease. The mode of action by which DPSC confer therapeutic benefit may comprise multiple pathways, in particular, paracrine-mediated processes which involve a wide array of secreted trophic factors and is increasingly regarded as the principal predominant mechanism. In this concise review, we present the current evidence for the use of DPSC to repair CNS damage, including recent findings on retinal ganglion cell neuroprotection and regeneration in optic nerve injury and glaucoma. Stem Cells 2017;35:61-67. © 2016 AlphaMed Press.

TNFa/TNFR2 signaling is required for glial ensheathment at the dorsal root entry zone

PubMed Central

Smith, Cody J.; Bagnat, Michel; Deppmann, Christopher D.

2017-01-01

Somatosensory information from the periphery is routed to the spinal cord through centrally-projecting sensory axons that cross into the central nervous system (CNS) via the dorsal root entry zone (DREZ). The glial cells that ensheath these axons ensure rapid propagation of this information. Despite the importance of this glial-axon arrangement, how this afferent nerve is assembled during development is unknown. Using in vivo, time-lapse imaging we show that as centrally-projecting pioneer axons from dorsal root ganglia (DRG) enter the spinal cord, they initiate expression of the cytokine TNFalpha. This induction coincides with ensheathment of these axons by associated glia via a TNF receptor 2 (TNFR2)-mediated process. This work identifies a signaling cascade that mediates peripheral glial-axon interactions and it functions to ensure that DRG afferent projections are ensheathed after pioneer axons complete their navigation, which promotes efficient somatosensory neural function. PMID:28379965

Effect of intercostal nerve block combined with general anesthesia on the stress response in patients undergoing minimally invasive mitral valve surgery.

PubMed

Zhan, Yanping; Chen, Guo; Huang, Jian; Hou, Benchao; Liu, Weicheng; Chen, Shibiao

2017-10-01

The aim of the present study was to investigate the effect of intercostal nerve block combined with general anesthesia on the stress response and postoperative recovery in patients undergoing minimally invasive mitral valve surgery (MIMVS). A total of 30 patients scheduled for MIMVS were randomly divided into two groups (n=15 each): Group A, which received intercostal nerve block combined with general anesthesia and group B, which received general anesthesia alone. Intercostal nerve block in group A was performed with 0.5% ropivacaine from T3 to T7 prior to anesthesia induction. In each group, general anesthesia was induced using midazolam, sufentanil, propofol and vecuronium. Central venous blood samples were collected to determine the concentrations of cortisol, glucose, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) at the following time points: During central venous catheterization (T 1 ), 5 min prior to cardiopulmonary bypass (T 2 ), perioperative (T 3 ) and 24 h following surgery (T 4 ). Clinical data, including parameters of opioid (sufentanil) consumption, time of mechanical ventilation, duration of intensive care unit (ICU) stay, visual analog scale scores and any complications arising from intercostal nerve block, were recorded. Levels of cortisol, glucose, IL-6 and TNF-α in group A were significantly lower than those in group B at T 2 (all P<0.001; cortisol, P<0.05), T 3 (all P<0.001) and T 4 (all P<0.001; glucose, P<0.05), suggesting that intercostal nerve block combined with general anesthesia may inhibit the stress response to MIMVS. Additionally, intercostal nerve block combined with general anesthesia may significantly reduce sufentanil consumption (P<0.001), promote early tracheal extubation (P<0.001), shorten the duration of ICU stay (P<0.01) and attenuate postoperative pain (P<0.001), compared with general anesthesia alone. Thus, these results suggest that intercostal nerve block combined with general anesthesia conforms to the concept of rapid rehabilitation surgery and may be suitable for clinical practice.

The sympathetic hazards of airborne ultrasound on ultrasound sensitive mice.

PubMed

Ohmori, M; Ogawa, K

1982-01-01

A commercially available ultrasonic equipment (55-50 kHz/sec, 425 W) operated at a distance of 4 m air space caused death in some mice. The physical energy propagated was quite small, being calculated at less than 0.21 W/cm2. Among many strains of mice, the RIII strain was especially sensitive to ultrasound, and the peak of sensitivity was at 3 to 4 weeks of age at which the mortality rate was 95/149 (64%). No death occurred when mice were pretreated by (a) removing all body hair, (b) by administration of morphine hydrochloridum with a tail reaction, and (c) administration of a sympathetic blocking agent. From these results it is assumed that the ultrasound energy absorbed by the body fur reaches the hypothalamus through the sensory nerves of the hair roots. After the hypothalamus where central sympathetic nerve functions are localized, the stimulus passes down the descending tract of the sympathetic nerve, reaching the cardiac nerves via the autonomic nerve ganglion. Thus, death could occur by shock of the sympathetic nerve reflex.

On the nature of the afferent fibers of oculomotor nerve.

PubMed

Manni, E; Draicchio, F; Pettorossi, V E; Carobi, C; Grassi, S; Bortolami, R; Lucchi, M L

1989-03-01

The oculogyric nerves contain afferent fibers originating from the ophthalmic territory, the somata of which are located in the ipsilateral semilunar ganglion. These primary sensory neurons project to the Subnucleus Gelatinosus of the Nucleus Caudalis Trigemini, where they make presynaptic contact with the central endings of the primary trigeminal afferents running in the fifth cranial nerve. After complete section of the trigeminal root, the antidromic volleys elicited in the trunk of the third cranial nerve by stimulating SG of NCT consisted of two waves belonging to the A delta and C groups. The area of both components of the antidromic volleys decreased both after bradykinin and hystamine injection into the corresponding cutaneous region and after thermic stimulation of the ipsilateral trigeminal ophthalmic territory. The reduction of such potentials can be explained in terms of collision between the antidromic volleys and those elicited orthodromically by chemical and thermic stimulation. Also, capsaicin applied on the nerve induced an immediate increase, followed by a long lasting decrease, of orthodromic evoked response area. These findings bring further support to the nociceptive nature of the afferent fibers running into the oculomotor nerve.

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.

Comprehensive Craniospinal Radiation for Controlling Central Nervous System Leukemia

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

Walker, Gary V.; Shihadeh, Ferial; Kantarjian, Hagop

Purpose: To determine the benefit of radiation therapy (RT) in resolution of neurologic symptoms and deficits and whether the type of RT fields influences central nervous system (CNS) control in adults with CNS leukemia. Methods and Materials: A total of 163 adults from 1996 to 2012 were retrospectively analyzed. Potential associations between use of radiation and outcome were investigated by univariate and multivariate analysis. Results: The median survival time was 3.8 months after RT. Common presenting symptoms were headache in 79 patients (49%), cranial nerve VII deficit in 46 (28%), and cranial nerve II deficit in 44 (27%). RT was deliveredmore » to the base of skull in 48 patients (29%), to the whole brain (WB) in 67 (41%), and to the craniospinal axis (CS) in 48 (29%). Among 149 patients with a total of 233 deficits, resolution was observed in 34 deficits (15%), improvement in 126 deficits (54%), stability in 34 deficits (15%), and progression in 39 deficits (17%). The 12-month CNS progression-free survival was 77% among those receiving CS/WB and 51% among those receiving base of skull RT (P=.02). On multivariate analysis, patients who did not undergo stem cell transplantation after RT and base of skull RT were associated with worse CNS progression-free survival. Conclusions: Improvement or resolution of symptoms occurred in two thirds of deficits after RT. Comprehensive radiation to the WB or CS seems to offer a better outcome, especially in isolated CNS involvement.« less

Antinociceptive effect of cyclic phosphatidic acid and its derivative on animal models of acute and chronic pain.

PubMed

Kakiuchi, Yasutaka; Nagai, Jun; Gotoh, Mari; Hotta, Harumi; Murofushi, Hiromu; Ogawa, Tomoyo; Ueda, Hiroshi; Murakami-Murofushi, Kimiko

2011-05-14

Cyclic phosphatidic acid (cPA) is a structural analog of lysophosphatidic acid (LPA), but possesses different biological functions, such as the inhibition of autotaxin (ATX), an LPA-synthesizing enzyme. As LPA is a signaling molecule involved in nociception in the peripheral and central systems, cPA is expected to possess analgesic activity. We characterized the effects of cPA and 2-carba-cPA (2ccPA), a chemically stable cPA analog, on acute and chronic pain. (1) The systemic injection of 2ccPA significantly inhibited somato-cardiac and somato-somatic C-reflexes but not the corresponding A-reflexes in anesthetized rats. (2) 2ccPA reduced sensitivity measured as the paw withdrawal response to electrical stimulation applied to the hind paws of mice through the C-fiber, but not Aδ or Aβ. (3) In mice, pretreatment with 2ccPA dose-dependently inhibited the second phase of formalin-induced licking and biting responses. (4) In mice, pretreatment and repeated post-treatments with 2ccPA significantly attenuated thermal hyperalgesia and mechanical allodynia following partial ligation of the sciatic nerve. (5) In rats, repeated post-treatments with 2ccPA also significantly attenuated thermal hyperalgesia and mechanical allodynia following chronic sciatic nerve constriction. Our results suggest that cPA and its stable analog 2ccPA inhibit chronic and acute inflammation-induced C-fiber stimulation, and that the central effects of 2ccPA following repeated treatments attenuate neuropathic pain.

Tissue-Engineered Nanofibrous Nerve Grafts for Enhancing the Rate of Nerve Regeneration

DTIC Science & Technology

2015-10-01

structured nanofibrous biodegradable nerve graft system that present ECM protein, neurotrophic factor, and pre-seeded with bone marrow stromal cells in...nanofibrous biodegradable nerve graft system that present extracellular matrix (ECM) protein, nerve growth factor, and pre-seeded with bone marrow stromal...proposed novel structured nanofibrous biodegradable grafts will provide the micro environment, bioactivity, transport features and mechanics ideal for

Guillain-Barre syndrome

MedlinePlus

... the body's defense (immune) system mistakenly attacks part of the nervous system. This leads to nerve inflammation that causes muscle ... Nerve supply to the pelvis Brain and nervous system References Katirji B. Disorders of peripheral nerves. In: Daroff RB, Jankovic J, Mazziotta ...

Degenerative changes and cell death in long-living homo- and heterotopic transplants from embryonic germ layers of rat neocortex.

PubMed

Petrova, E S; Otellin, V A

2003-09-01

Morphological study of allotransplants of rat embryonic neocortex 14-18 months after transplantation into the neocortex, lateral cerebral ventricle, and sciatic nerve of adult animals revealed death of nerve and glial cells in the delayed postoperation period independently on the site of transplantation. After heterotopic transplantation the count of degenerated neurons was 2 times higher that after homotopic transplantation. In heterotopic transplants a considerable number of grafted neurons underwent reversible and irreversible degenerative changes accompanied by their premature aging. Neuronal death is probably determined by insufficiency of trophic influence from afferent structures and target tissues. We hypothesized that antiapoptotic preparations can be used for prevention of transplanted cell death. It was also found that degeneration of neurons was associated with impaired vascularization of transplants and pronounced immune reaction of the recipient in late posttransplantation period. Transplantation of embryonic brain structures can serve as a model system in studies concerning involutive and pathological processes in the central nervous system and in the search for factors improving survival of neurons.

Transfer characteristics of the hair cell's afferent synapse

NASA Astrophysics Data System (ADS)

Keen, Erica C.; Hudspeth, A. J.

2006-04-01

The sense of hearing depends on fast, finely graded neurotransmission at the ribbon synapses connecting hair cells to afferent nerve fibers. The processing that occurs at this first chemical synapse in the auditory pathway determines the quality and extent of the information conveyed to the central nervous system. Knowledge of the synapse's input-output function is therefore essential for understanding how auditory stimuli are encoded. To investigate the transfer function at the hair cell's synapse, we developed a preparation of the bullfrog's amphibian papilla. In the portion of this receptor organ representing stimuli of 400-800 Hz, each afferent nerve fiber forms several synaptic terminals onto one to three hair cells. By performing simultaneous voltage-clamp recordings from presynaptic hair cells and postsynaptic afferent fibers, we established that the rate of evoked vesicle release, as determined from the average postsynaptic current, depends linearly on the amplitude of the presynaptic Ca2+ current. This result implies that, for receptor potentials in the physiological range, the hair cell's synapse transmits information with high fidelity. auditory system | exocytosis | glutamate | ribbon synapse | synaptic vesicle

Sympathetic nervous system influences on the kidney. Role in hypertension.

PubMed

DiBona, G F

1989-03-01

Efferent renal sympathetic nerve activity (ERSNA) is elevated in human essential hypertension as well as several forms of experimental hypertension in animals. In addition, bilateral complete renal denervation delays the development and/or attenuates the magnitude of the hypertension in several different forms of experimental hypertension in animals. Efferent renal sympathetic nerve activity is known to have dose-dependent effects on renal blood flow and glomerular filtration rate, renal tubular sodium and water reabsorption, and renin secretion rate that are capable of contributing, singly or in combination, to the development, maintenance, and exacerbation of the hypertensive state. Of the many factors known to influence the central nervous system integrative regulation of ERSNA, two environmental factors, dietary sodium intake and environmental stress, are capable of significant interaction. This resultant increase in ERSNA and subsequent renal functional alterations can participate in the hypertensive process. This is especially evident in the presence of an underlying genetic predisposition to the development of hypertension. Thus, interactions between environmental and genetic influences can produce alterations in the sympathetic neural control of renal function that play an important role in hypertension.

The Central Nervous Connections Involved in the Vomiting Reflex

NASA Technical Reports Server (NTRS)

Brizzee, K. R.; Mehler, W. R.

1986-01-01

The vomiting reflex may be elicited by a number of different types or classes of stimuli involving many varieties of receptor structures and considerable diversity in afferent pathways and central connections. Central relay or mediating structures thus may vary widely according to the type of initial emetic stimulus. The emetic circuits which have been most completely delineated to date are probably those in which the Chemoreceptor Trigger Zone (CTZ) in the Area Postrema (AP) functions as a key mediating structure. Even in this system, however, there are large gaps in our knowledge of the nerve tracts and central nervous connections involved. Knowledge of most other emetic circuits subserving the emetic reflex resulting from many diverse types of stimuli such, for example, as emotional stress (e.g. psychogenic vomiting, Wruble et al. 1982), pain (e.g. testicular trauma), and chemical or mechanical irritation of the gastrointestinal tract or urinary tract is quite incomplete at this time, thus precluding any very adequate description of their central connections at present. One physiological system, however, which has received considerable attention recently in relation to the vomiting reflex elicited by motion stimuli is the vestibular system. Due to the paucity of data on central nervous connections of several or the non-vestibular types of emetic stimuli cited above, we will devote most of our attention in this brief review to the central connections of the vestibular system which seem likely to be involved in the vomiting response to motion stimuli. However, the latter part of the review will be concerned with the concept of the reticular vomiting centre in relation to the ParviCellular Reticular Formation (PCRF), and will thus probably pertain to all of the many classes of emetic stimuli since it will address the question of the final common emetic pathway.

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.

Cerebrovascular Manifestations of Neurosarcoidosis: An Underrecognized Aspect of the Imaging Spectrum.

PubMed

Bathla, G; Watal, P; Gupta, S; Nagpal, P; Mohan, S; Moritani, T

2017-12-28

Involvement of the central nervous system by sarcoidosis, also referred to as neurosarcoidosis, is seen clinically in about 5% of patients with systemic disease. CNS involvement most frequently affects the leptomeninges and cranial nerves, though the ventricular system, brain parenchyma, and pachymeninges may also be involved. Even though the involvement of the intracranial vascular structures is well-known on postmortem studies, there is scant literature on imaging manifestations secondary to the vessel wall involvement, being confined mostly to isolated case reports and small series. The authors present a review of various cerebrovascular manifestations of neurosarcoidosis, along with a brief synopsis of the existing literature. © 2018 by American Journal of Neuroradiology.

Effects of long-term non-traumatic noise exposure on the adult central auditory system. Hearing problems without hearing loss.

PubMed

Eggermont, Jos J

2017-09-01

It is known that hearing loss induces plastic changes in the brain, causing loudness recruitment and hyperacusis, increased spontaneous firing rates and neural synchrony, reorganizations of the cortical tonotopic maps, and tinnitus. Much less in known about the central effects of exposure to sounds that cause a temporary hearing loss, affect the ribbon synapses in the inner hair cells, and cause a loss of high-threshold auditory nerve fibers. In contrast there is a wealth of information about central effects of long-duration sound exposures at levels ≤80 dB SPL that do not even cause a temporary hearing loss. The central effects for these moderate level exposures described in this review include changes in central gain, increased spontaneous firing rates and neural synchrony, and reorganization of the cortical tonotopic map. A putative mechanism is outlined, and the effect of the acoustic environment during the recovery process is illustrated. Parallels are drawn with hearing problems in humans with long-duration exposures to occupational noise but with clinical normal hearing. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of losartan on differential reflex control of sympathetic nerve activity in chronic kidney disease.

PubMed

Yao, Yimin; Hildreth, Cara M; Farnham, Melissa M; Saha, Manash; Sun, Qi-Jian; Pilowsky, Paul M; Phillips, Jacqueline K

2015-06-01

The effect of angiotensin II type I receptor (AT1R) inhibition on the pattern of reflex sympathetic nerve activity (SNA) to multiple target organs in the Lewis polycystic kidney (LPK) rat model of chronic kidney disease was determined. Mean arterial pressure (MAP), splanchnic SNA (sSNA), renal SNA (rSNA) and lumbar SNA (lSNA) were recorded in urethane-anaesthetized LPK and Lewis controls (total n = 39). Baroreflex, peripheral and central chemoreflex, and somatosensory reflex control of SNA (evoked by phenylephrine/sodium nitroprusside infusion, 10% O2 in N2 or 100% N2 ventilation, 5% CO2 ventilation and sciatic nerve stimulation, respectively) were determined before and after administration of losartan (AT1R antagonist 3 mg/kg, intravenous). Baseline MAP was higher in LPK rats and baroreflex control of sSNA and rSNA, but not lSNA, was reduced. Losartan reduced MAP in both strains and selectively improved baroreflex gain for sSNA (-1.2 ± 0.1 vs. -0.7 ± 0.07 %/mmHg; P < 0.05) in LPK. The peripheral and central chemoreflex increased MAP and all SNA in Lewis controls, but reduced or had no effect on these parameters, respectively, in LPK. The SNA response to somatosensory stimulation was biphasic, with latency to second peak less in LPK. Losartan ameliorated the depressor and sympathoinhibitory responses to peripheral chemoreflex stimulation in the LPK, but did not alter the central chemoreflex or somatosympathetic responses. Inhibition of the AT1R selectively improved baroreflex control of sSNA and peripheral chemoreflex control of all three sympathetic nerve outflows in the LPK rat, suggesting these anomalies in reflex function are driven in part by angiotensin II.

The central projections of the laryngeal nerves in the rat

PubMed Central

Pascual-Font, Arán; Hernández-Morato, Ignacio; McHanwell, Stephen; Vázquez, Teresa; Maranillo, Eva; Sañudo, Jose; Valderrama-Canales, Francisco J

2011-01-01

The larynx serves respiratory, protective, and phonatory functions. The motor and sensory innervation to the larynx controlling these functions is provided by the superior laryngeal nerve (SLN) and the recurrent laryngeal nerve (RLN). Classical studies state that the SLN innervates the cricothyroid muscle and provides sensory innervation to the supraglottic cavity, whereas the RLN supplies motor innervation to the remaining intrinsic laryngeal muscles and sensory innervation to the infraglottic cavity, but recent data suggest a more complex anatomical and functional organisation. The current neuroanatomical tracing study was undertaken to provide a comprehensive description of the central brainstem connections of the axons within the SLN and the RLN, including those neurons that innervate the larynx. The study has been carried out in 41 adult male Sprague–Dawley rats. The central projections of the laryngeal nerves were labelled following application of biotinylated dextran amines onto the SLN, the RLN or both. The most remarkable result of the study is that in the rat the RLN does not contain any afferent axons from the larynx, in contrast to the pattern observed in many other species including man. The RLN supplied only special visceromotor innervation to the intrinsic muscles of the larynx from motoneurons in the nucleus ambiguus (Amb). All the afferent axons innervating the larynx are contained within the SLN, and reach the nucleus of the solitary tract. The SLN also contained secretomotor efferents originating from motoneurons in the dorsal motor nucleus of the vagus, and special visceral efferent fibres from the Amb. In conclusion, the present study shows that in the rat the innervation of the larynx differs in significant ways from that described in other species. PMID:21599662

Synergistic interactions between airway afferent nerve subtypes regulating the cough reflex in guinea-pigs

PubMed Central

Mazzone, Stuart B; Mori, Nanako; Canning, Brendan J

2005-01-01

Cough initiated from the trachea and larynx in anaesthetized guinea-pigs is mediated by capsaicin-insensitive, mechanically sensitive vagal afferent neurones. Tachykinin-containing, capsaicin-sensitive C-fibres also innervate the airways and have been implicated in the cough reflex. Capsaicin-sensitive nerves act centrally and synergistically to modify reflex bronchospasm initiated by airway mechanoreceptor stimulation. The hypothesis that polymodal mechanoreceptors and capsaicin-sensitive afferent nerves similarly interact centrally to regulate coughing was addressed in this study. Cough was evoked from the tracheal mucosa either electrically (16 Hz, 10 s trains, 1–10 V) or by citric acid (0.001–2 m). Neither capsaicin nor bradykinin evoked a cough when applied to the trachea of anaesthetized guinea-pigs, but they substantially reduced the electrical threshold for initiating the cough reflex. The TRPV1 receptor antagonist capsazepine prevented the increased cough sensitivity induced by capsaicin. These effects of topically applied capsaicin and bradykinin were not due to interactions between afferent nerve subtypes within the tracheal wall or a direct effect on the cough receptors, as they were mimicked by nebulizing 1 mg ml−1 bradykinin into the lower airways and by microinjecting 0.5 nmol capsaicin into nucleus of the solitary tract (nTS). Citric acid-induced coughing was also potentiated by inhalation of bradykinin. The effects of tracheal capsaicin challenge on cough were mimicked by microinjecting substance P (0.5–5 nmol) into the nTS and prevented by intracerebroventricular administration (20 nmol h−1) of the neurokinin receptor antagonists CP99994 or SB223412. Tracheal application of these antagonists was without effect. C-fibre activation may thus sensitize the cough reflex via central mechanisms. PMID:16051625

Serum biochemical markers of central nerve system damage in children with acute elemental mercury intoxicatıon.

PubMed

Yılmaz, F M; Yılmaz, H; Tutkun, E; Uysal, S; Carman, K B; Dılber, C; Ercan, M

2014-01-01

Acute mercury intoxication among children can occur through unintentional exposure, and neurotoxicity is one of the main findings in acute exposures. In this study, we aimed to study the central nerve system markers, namely neuron-specific enolase (NSE), S100B, and glutamate receptor (GRIA 1) levels and discuss the mechanisms of central nerve system damage and whether these parameters could be used as markers of acute elemental mercury intoxication neurotoxicity. This is a case-control study which includes 169 children with acute elemental mercury intoxication, who were exposed to mercury in the school laboratory from a broken jar, and 45 sex- and age-matched controls without mercury exposure. Patient group were divided into three subgroups according to the neurological examination performed during the admission. Neuropathy Group included the children with neurological symptoms including peripheral neuropathy and decreased muscle strength (n = 39) (with or without dilated pupils). Dilated Pupil Group included the children who had mid-dilated/dilated pupils (n = 52). Asymptomatic Exposure Group included the children who did not have any neurological symptoms (n = 78). Serum NSE, S100B, GRIA 1, blood, and urine mercury levels were determined. NSE, S100B, GRIA 1, and blood mercury levels were significantly higher in exposed group than the nonexposed subjects (Median values NSE 22.4 ng/mL, 17.2 ng/mL; S100B 0.09 ng/mL, 0.08 ng/mL; GRIA 1 70.6 pg/mL, 54.1 pg/mL, and blood mercury 15.2 μg/L, 0.23 μg/L for exposed and nonexposed groups, respectively). GRIA 1 levels found to differ between exposed and nonexposed groups and it has also been found to be increased in the subgroups with positive neurological findings compared to that in neurological finding negative groups. S100B levels were found to be increased in exposed and having neurological symptom groups. There was not a significant difference between exposed-not having neurological symptom patients and control group. NSE levels were found to be higher in all subgroups when compared to those in controls, however there was not a significant difference between the subgroups. Serum NSE, GRIA 1, and S100B were increased with mercury exposure. GRIA 1 and S100B levels were observed to have the power to discriminate neurological symptom positive and negative groups. The increase in S100B levels are thought to be protecting the neurons and preventing further NSE elevations.

Expression of inducible heat shock proteins Hsp27 and Hsp70 in the visual pathway of rats subjected to various models of retinal ganglion cell injury.

PubMed

Chidlow, Glyn; Wood, John P M; Casson, Robert J

2014-01-01

Inducible heat shock proteins (Hsps) are upregulated in the central nervous system in response to a wide variety of injuries. Surprisingly, however, no coherent picture has emerged regarding the magnitude, duration and cellular distribution of inducible Hsps in the visual system following injury to retinal ganglion cells (RGCs). The current study sought, therefore, to achieve the following two objectives. The first aim of this study was to systematically characterise the patterns of Hsp27 and -70 expression in the retina and optic nerve in four discrete models of retinal ganglion cell (RGC) degeneration: axonal injury (ON crush), somato-dendritic injury (NMDA-induced excitotoxicity), chronic hypoperfusion (bilateral occlusion of the carotid arteris) and experimental glaucoma. The second aim was to document Hsp27 and -70 expression in the optic tract, the subcortical retinorecipient areas of the brain, and the visual cortex during Wallerian degeneration of RGC axons. Hsp27 was robustly upregulated in the retina in each injury paradigm, with the chronic models, 2VO and experimental glaucoma, displaying a more persistent Hsp27 transcriptional response than the acute models. Hsp27 expression was always associated with astrocytes and with a subset of RGCs in each of the models excluding NMDA. Hsp27 was present within astrocytes of the optic nerve/optic tract in control rats. During Wallerian degeneration, Hsp27 was upregulated in the optic nerve/optic tract and expressed de novo by astrocytes in the lateral geniculate nucleus and the stratum opticum of the superior colliculus. Conversely, the results of our study indicate Hsp70 was minimally induced in any of the models of injury, either in the retina, or in the optic nerve/optic tract, or in the subcortical, retinorecipient areas of the brain. The findings of the present study augment our understanding of the involvement of Hsp27 and Hsp70 in the response of the visual system to RGC degeneration.

Peripheral choline acetyltransferase in rat skin demonstrated by immunohistochemistry.

PubMed

Hanada, Keiji; Kishimoto, Saburo; Bellier, Jean-Pierre; Kimura, Hiroshi

2013-03-01

Conventional choline acetyltransferase immunohistochemistry has been used widely for visualizing central cholinergic neurons and fibers but not often for labeling peripheral structures, probably because of their poor staining. The recent identification of the peripheral type of choline acetyltransferase (pChAT) has enabled the clear immunohistochemical detection of many known peripheral cholinergic elements. Here, we report the presence of pChAT-immunoreactive nerve fibers in rat skin. Intensely stained nerve fibers were distributed in association with eccrine sweat glands, blood vessels, hair follicles and portions just beneath the epidermis. These results suggest that pChAT-positive nerves participate in the sympathetic cholinergic innervation of eccrine sweat glands. Moreover, pChAT also appears to play a role in cutaneous sensory nerve endings. These findings are supported by the presence of many pChAT-positive neuronal cells in the sympathetic ganglion and dorsal root ganglion. Thus, pChAT immunohistochemistry should provide a novel and unique tool for studying cholinergic nerves in the skin.

DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons

PubMed Central

Zhao, Jian-Yuan; Liang, Lingli; Gu, Xiyao; Li, Zhisong; Wu, Shaogen; Sun, Linlin; Atianjoh, Fidelis E.; Feng, Jian; Mo, Kai; Jia, Shushan; Lutz, Brianna Marie; Bekker, Alex; Nestler, Eric J.; Tao, Yuan-Xiang

2017-01-01

Nerve injury induces changes in gene transcription in dorsal root ganglion (DRG) neurons, which may contribute to nerve injury-induced neuropathic pain. DNA methylation represses gene expression. Here, we report that peripheral nerve injury increases expression of the DNA methyltransferase DNMT3a in the injured DRG neurons via the activation of the transcription factor octamer transcription factor 1. Blocking this increase prevents nerve injury-induced methylation of the voltage-dependent potassium (Kv) channel subunit Kcna2 promoter region and rescues Kcna2 expression in the injured DRG and attenuates neuropathic pain. Conversely, in the absence of nerve injury, mimicking this increase reduces the Kcna2 promoter activity, diminishes Kcna2 expression, decreases Kv current, increases excitability in DRG neurons and leads to spinal cord central sensitization and neuropathic pain symptoms. These findings suggest that DNMT3a may contribute to neuropathic pain by repressing Kcna2 expression in the DRG. PMID:28270689

Effects of capsaicin in the motor nerve.

PubMed

Pettorossi, V E; Bortolami, R; Della Torre, G; Brunetti, O

1994-08-01

The injection of capsaicin into the lateral gastrocnemius (LG) muscle of the rat induced an immediate and sustained reduction in the A delta and C components of the compound action potential (CAP) of the LG motor nerve. Conversely, the drug did not immediately affect the CAP wave belonging to fast-conducting fibers or the motor responses to LG nerve stimulation. It seems that capsaicin only affects the group III and IV afferents of LG nerve. However, a week after the injection the capsaicin also altered the motor responses, as shown by the threshold enhancement and amplitude reduction of the muscle twitch and by the decrease of the A alpha-beta CAP components. This late motor impairment was attributed to a central depression following a reduction of capsaicin-sensitive neuron input into the CNS. However, this motor effect was transient since the LG nerve regained the preinjection excitability level in a week and the muscle twitch amplitude reached the control value in a month.

Inflammatory Papillitis in Uveitis: Response to Treatment and Use of Optic Nerve Optical Coherence Tomography for Monitoring.

PubMed

Cho, Heeyoon; Pillai, Parvathy; Nicholson, Laura; Sobrin, Lucia

2016-01-01

To describe the clinical course of uveitis-associated inflammatory papillitis and evaluate the utility and reproducibility of optic nerve spectral domain optical coherence tomography (SD-OCT). Data on 22 eyes of 14 patients with uveitis-related papillitis and optic nerve imaging were reviewed. SD-OCT measure reproducibility was determined and parameters were compared in active vs. inactive uveitis. Papillitis resolution lagged behind uveitis resolution in three patients. For SD-OCT measures, the intraclass correlation coefficients were 99.1-100% and 86.9-100% for intraobserver and interobserver reproducibility, respectively. All SD-OCT optic nerve measures except inferior and nasal peripapillary retinal thicknesses were significantly higher in active vs. inactive uveitis after correction for multiple hypotheses testing. Mean optic nerve central thickness decreased from 545.1 to 362.9 µm (p = 0.01). Resolution of inflammatory papillitis can lag behind resolution of uveitis. SD-OCT assessment of papillitis is reproducible and correlates with presence vs. resolution of uveitis.

AN ELECTRON MICROSCOPE STUDY OF NERVES INFECTED WITH HUMAN POLIOMYELITIS VIRUS

PubMed Central

De Robertis, E.; Schmitt, F. O

1949-01-01

Sciatic nerves of rhesus monkeys infected with CAM and Wis. '45 strains of human poliomyelitis virus were fixed in formalin, sectioned, fragmented, and examined in the electron microscope. Most of the neurotubules of nerves infected with the CAM strain have normal appearance but a very small number show the presence of dense particles irregularly aligned within the edges of the neurotubules. The diameters of the particles range between 160 and 500 Å, the mean being 330 Å. The particles were found in regions along the nerve which varied with the time after infection, indicating a central movement of the morphological alteration of the order of 2 mm. per hour. Relatively abundant dense particulate material was found in nerves infected with Wis. '45 strain virus and the particles were chiefly attached to the edges of the neurotubules and in the adjacent areas of the field. The dense particles appear to be associated with the virus infection but no further characterization is possible at this time. PMID:18140661

[Segmental schwannomatosis in upper-extremity: 5 cases report and literature review].

PubMed

Wang, Zhi-Xin; Chen, Shan-Lin; Yi, Chuan-Jun; Li, Chun; Rong, Yan-Bo; Tian, Guang-Lei

2013-10-18

Multiple schwannomas localized in a single body part not crossing the midline constitute a rare variant of neurofibromatosis, segmental schwannomatosis. We report our experience with 5 cases of segmental schwannomatosis of the upper extremity and review the related literature to improve our skills in diagnosis and differentiation. Five patients with segmental schwannomatosis received surgical treatment in our department from 2003 to 2012, of whom 4 were female and the other one male. The mean age was 38 years, ranging from 29 to 48 years. In retrospect, we discussed the clinical appearance, histologic characteristics, genetic data and surgical management. A total of 351 patients with schwannomas were treated in the recent decade. There were 326 patients with solitary schwannoma, accounting for 92.88%, 25 with neurofibromatosis type 2 (NF-2), occupying 7.12% and 5 with segmental schwannomatosis representing 1.42% of the total. Schwannomas are limited in one upper extremity and randomly located at ulnar nerve, median nerve and radial nerve and their branches, with no obvious predisposition. Their family history was negative for cutaneous tumors or central nervous system disease. Neurological examinations did not reveal symptoms related to vestibular nerves or optic nerves, which excluded NF-2 preliminarily. The prior symptom of three cases was pain which could be irradiated to the nerve distribution area. No pain but slight numbness was found in two cases. MRI disclosed multiple masses along the course of the nerves. They were isointense to muscle on T1-weighed images and hyperintense to subcutaneous fat on T2-weighed images. All schwannomas were resected and histological sections exhibited a characteristic feature of schwannoma. Follow-up work of 4.5 years was done to 4 cases and no recurrence or impairment of nerves was found. Segmental schwannomatosis is characterized by multiple schwannomas localized in one limb (upper extremity in our cases) without vestibular nerve tumors, most frequently seen in females at the age of 30-60 years. Segmental schwannomatosis is rarely seen in the previous literature. We found around 20 cases in English articles and no cases in domestic articles. In consideration of the clinical appearances of these 5 cases and the genetic research in the related literature, we recommend that segmental schwannomatosis is a distinct form of neurofibromatosis which needs to be more studied. We should also pay more attention to differentiating this disease from other forms of neurofibromatosis.

Long-Term Experience with First-Generation Implantable Neurostimulation Device in Central Sleep Apnea Treatment.

PubMed

Fox, Henrik; Bitter, Thomas; Horstkotte, Dieter; Oldenburg, Olaf; Gutleben, Klaus-Jürgen

2017-05-01

Sleep-disordered breathing (SDB) and Cheyne-Stokes respiration (CSR) are associated with shorter survival in patients with heart failure. A novel treatment method for this patient group is unilateral phrenic nerve stimulation by the remedē® system (Respicardia Inc., Minnetonka, MN, USA), a transvenously implantable neurostimulation device, which has recently been studied in a large randomized, controlled trial. Previous literature has shown efficacy and safety of the treatment with this first-generation device, but hardly any data are available on long-term clinical parameters, the remedē® device's battery lifetime, device exchangeability, lead position stability, surgical accessibility, and manageability. We performed remedē® device replacements in consecutive patients for battery depletion, and documented clinical parameters, longevity, operation procedure, complications, and difficulties. All patients were on neurostimulation treatment by phrenic nerve neurostimulation when device replacement became necessary. Apnea-hypopnea index (from 45 ± 4/h to 9 ± 4/h), oxygen-desaturation index (from 35 ± 7/h to 7 ± 6/h), and time spent with oxygen saturation of <90% (T < 90% from 5 ± 7% to 0 ± 0%) were improved and improvements remained constant throughout the 4-year follow-up. Mean battery life was 4.2 ± 0.2 years and mean replacement procedure time was 25 ± 5.1 minutes. Apart from conventional X-ray documentation of stable lead positions in a long-term setting, no radiation or contrast dye usage was needed and no major complications occurred. In addition, clinical exercise capacity and sleepiness symptoms improved. Novel remedē® device shows sustained therapy efficacy and safety in terms of stable lead positions over 4 years. Long-term phrenic nerve neurostimulation therapy for central SDB/CSR appears feasible in a clinical routine setting. © 2017 Wiley Periodicals, Inc.

Population pharmacokinetics of bupivacaine in combined lumbar and sciatic nerve block

PubMed Central

Eljebari, Hanene; Jebabli, Nadia; Salouage, Issam; Gaies, Emna; Lakhal, Mohamed; Boussofara, Mehdi; Klouz, Anis

2014-01-01

Objectives: The primary aim of this study was to establish the population pharmacokinetic (PPK) model of bupivacaine after combined lumbar plexus and sciatic nerve blocks and secondary aim is to assess the effect of patient's characteristics including age, body weight and sex on pharmacokinetic parameters. Materials and Methods: A total of 31 patients scheduled for elective lower extremity surgery with combined lumbar and sciatic nerve block using plain bupivacaine 0.5% were included. The total bupivacaine plasma concentrations were measured before injection and after two blocks placement and at selected time points. Monitoring of bupivacaine was made by high performance liquid chromatography (HPLC) with ultraviolet detection. Non-linear mixed effects modeling was used to analyze the PPK of bupivacaine. Results: One compartment model with first order absorption, two input compartments and a central elimination was selected. The Shapiro-Wilks test of normality for normalized prediction distribution errors for this model (P = 0.156) showed this as a valid model. The selected model predicts a population clearance of 930 ml/min (residual standard error [RSE] = 15.48%, IC 95% = 930 ± 282.24) with inter individual variability of 75.29%. The central volume of distribution was 134 l (RSE = 12.76%, IC = 134 ± 33.51 L) with inter individual variability of 63.40%. The absorption of bupivacaine in two sites Ka1 and Ka2 were 0.00462/min for the lumbar site and 0.292/min for the sciatic site. Age, body weight and sex have no effect on the bupivacaine pharmacokinetics in this studied population. Conclusion: The developed model helps us to assess the systemic absorption of bupivacaine at two injections sites. PMID:24741194

Cranial nerves in the Australian lungfish, Neoceratodus forsteri, and in fossil relatives (Osteichthyes: Dipnoi).

PubMed

Kemp, A

2017-02-01

Three systems, two sensory and one protective, are present in the skin of the living Australian lungfish, Neoceratodus forsteri, and in fossil lungfish, and the arrangement and innervation of the sense organs is peculiar to lungfish. Peripheral branches of nerves that innervate the sense organs are slender and unprotected, and form before any skeletal structures appear. When the olfactory capsule develops, it traps some of the anterior branches of cranial nerve V, which emerged from the chondrocranium from the lateral sphenotic foramen. Cranial nerve I innervates the olfactory organ enclosed within the olfactory capsule and cranial nerve II innervates the eye. Cranial nerve V innervates the sense organs of the snout and upper lip, and, in conjunction with nerve IX and X, the sense organs of the posterior and lateral head. Cranial nerve VII is primarily a motor nerve, and a single branch innervates sense organs in the mandible. There are no connections between nerves V and VII, although both emerge from the brain close to each other. The third associated system consists of lymphatic vessels covered by an extracellular matrix of collagen, mineralised as tubules in fossils. Innervation of the sensory organs is separate from the lymphatic system and from the tubule system of fossil lungfish. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recurrent laryngeal nerve landmarks during thyroidectomy.

PubMed

Ngo Nyeki, A-R; Njock, L-R; Miloundja, J; Evehe Vokwely, J-E; Bengono, G

2015-11-01

This study was designed to describe the various anatomical relations of the recurrent laryngeal nerve (RLN) during thyroid surgery in a Central African population. A prospective study was conducted between January 2012 and December 2012 in 5 otorhinolaryngology and head and neck surgery departments in Cameroon and Gabon. All patients undergoing total or subtotal thyroidectomy or loboisthmectomy with recurrent laryngeal nerve dissection, with no history of previous thyroid surgery, RLN dissection or tumour infiltration of the RLN, were included. Fifty-six patients were included, corresponding to 36 loboisthmectomies and 20 total or subtotal thyroidectomies. A total of 62 recurrent laryngeal nerves were identified: 32 on the right and 30 on the left. The course of the recurrent laryngeal nerve in relation to branches of the inferior thyroid artery (ITA) was retrovascular in 53.1% of cases on the right and 76.6% of cases on the left; transvascular in 15.6% of cases on the right and 13.4% of cases on the left. The course of the recurrent laryngeal nerve was modified by thyroid disease in 12.9% of cases. Six cases (9.7%) of extralaryngeal division of the recurrent laryngeal nerve were observed. No case of non-recurrent nerve was observed in this series. The anatomical relations of the recurrent laryngeal nerve with the inferior thyroid artery were very inconstant in this series and were predominantly retrovascular or transvascular in relation to the branches of the artery. The presence of extralaryngeal branches and modification of the course of the nerve by thyroid disease also introduced additional difficulties during recurrent laryngeal nerve dissection. The anatomical relations of the right recurrent laryngeal nerve in this African population differ from the classically described prevascular course. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Quantitative and qualitative morphology of rabbit retinal glia. A light microscopical study on cells both in situ and isolated by papaine.

PubMed

Reichenbach, A

1987-01-01

Rabbit retinal glia was studied by light microscopy of both stained sections of frozen retinae and enzymatically isolated cells. In the vast majority of this tissue, except for a small region around the optic nerve head, the glia consists solely of radial glia, i.e. Müller cells whose morphology was found to depend markedly on their topographic localization within the retina. Müller cells in the periphery are short and have thick vitreal processes bearing a single large endfoot. Central Müller cells are long and slender; through the thickening nerve fibre layer they send vitreal processes which are subdivided into several fine branches ending with multiple small endfeet. Müller cells in the retinal centre are far more closely packed than those in the periphery; everywhere, however, a constant ratio of Müller cells: neurons of about 1:15 was found, except for the juxta-optic nerve head region where this ratio is slightly reduced. Where the central retina reaches a thickness requiring Müller cell lengths of more than 130 micron, additional non-radial glial cells occur within the nerve fibre layer. The majority of these cells seem to be astrocytes. Their number per retinal area increases with the thickening of both the whole retina and the nerve fibre layer. The occurrence of these non-radial glial cells leads to an enhancement of the glia:neuron index in the retinal centre. Possible mechanisms of physiological control of gliogenesis are discussed.

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.

Development of the terminal nerve system in the shark Scyliorhinus canicula.

PubMed

Quintana-Urzainqui, Idoia; Anadón, Ramón; Candal, Eva; Rodríguez-Moldes, Isabel

2014-01-01

The nervus terminalis (or terminal nerve) system was discovered in an elasmobranch species more than a century ago. Over the past century, it has also been recognized in other vertebrate groups, from agnathans to mammals. However, its origin, functions or relationship with the olfactory system are still under debate. Despite the abundant literature about the nervus terminalis system in adult elasmobranchs, its development has been overlooked. Studies in other vertebrates have reported newly differentiated neurons of the terminal nerve system migrating from the olfactory epithelium to the telencephalon as part of a 'migratory mass' of cells associated with the olfactory nerve. Whether the same occurs in developing elasmobranchs (adults showing anatomically separated nervus terminalis and olfactory systems) has not yet been determined. In this work we characterized for the first time the development of the terminal nerve and ganglia in an elasmobranch, the lesser spotted dogfish (Scyliorhinus canicula), by means of tract-tracing techniques combined with immunohistochemical markers for the terminal nerve (such as FMRF-amide peptide), for the developing components of the olfactory system (Gα0 protein, GFAP, Pax6), and markers for early postmitotic neurons (HuC/D) and migrating immature neurons (DCX). We discriminated between embryonic olfactory and terminal nerve systems and determined that both components may share a common origin in the migratory mass. We also localized the exact point where they split off near the olfactory nerve-olfactory bulb junction. The study of the development of the terminal nerve system in a basal gnathostome contributes to the knowledge of the ancestral features of this system in vertebrates, shedding light on its evolution and highlighting the importance of elasmobranchs for developmental and evolutionary studies. © 2014 S. Karger AG, Basel.

Subarachnoid and Intracerebral Hemorrhage in Patients with Churg-Strauss Syndrome: Two Case Reports

PubMed Central

Go, Myeong Hoon; Park, Jeong Un; Kang, Jae Gyu

2012-01-01

Churg-Strauss syndrome (CSS) is a systemic necrotizing vasculitis of the small and medium vessels, associated with extravascular eosinophilic granulomas, peripheral eosinophilia, and asthma. The exact etiology of CSS is unknown. This syndrome commonly affects the lungs, peripheral nerves, skin, heart, and gastrointestinal tract, but rarely the central nervous system. Subarachnoid and intracerebral hemorrhage in CSS patients is extremely rare; however, clinicians should consider that CSS may be a cause of intracranial hemorrhage and its high rate of mortality and morbidity. The authors report on two cases of subarachnoid and intracerebral hemorrhage with CSS and discuss a brief review of CSS. PMID:23210058

Roles for the sympathetic nervous system, renal nerves, and CNS melanocortin-4 receptor in the elevated blood pressure in hyperandrogenemic female rats.

PubMed

Maranon, Rodrigo; Lima, Roberta; Spradley, Frank T; do Carmo, Jussara M; Zhang, Howei; Smith, Andrew D; Bui, Elizabeth; Thomas, R Lucas; Moulana, Mohadetheh; Hall, John E; Granger, Joey P; Reckelhoff, Jane F

2015-04-15

Women with polycystic ovary syndrome (PCOS) have hyperandrogenemia and increased prevalence of risk factors for cardiovascular disease, including elevated blood pressure. We recently characterized a hyperandrogenemic female rat (HAF) model of PCOS [chronic dihydrotestosterone (DHT) beginning at 4 wk of age] that exhibits similar characteristics as women with PCOS. In the present studies we tested the hypotheses that the elevated blood pressure in HAF rats is mediated in part by sympathetic activation, renal nerves, and melanocortin-4 receptor (MC4R) activation. Adrenergic blockade with terazosin and propranolol or renal denervation reduced mean arterial pressure (MAP by telemetry) in HAF rats but not controls. Hypothalamic MC4R expression was higher in HAF rats than controls, and central nervous system MC4R antagonism with SHU-9119 (1 nmol/h icv) reduced MAP in HAF rats. Taking a genetic approach, MC4R null and wild-type (WT) female rats were treated with DHT or placebo from 5 to 16 wk of age. MC4R null rats were obese and had higher MAP than WT control rats, and while DHT increased MAP in WT controls, DHT failed to further increase MAP in MC4R null rats. These data suggest that increases in MAP with chronic hyperandrogenemia in female rats are due, in part, to activation of the sympathetic nervous system, renal nerves, and MC4R and may provide novel insights into the mechanisms responsible for hypertension in women with hyperandrogenemia such as PCOS. Copyright © 2015 the American Physiological Society.

[Anti-VGKC antibody-associated limbic encephalitis/Morvan syndrome].

PubMed

Misawa, Tamako; Mizusawa, Hidehiro

2010-04-01

Anti-voltage-gated potassium channel antibodies (anti-VGKC-Ab) cause hyperexcitability of the peripheral nerve and central nervous system. Peripheral nerve hyperexcitability is the chief manifestation of Issacs syndrome and cramp-fasciculation syndrome. Morvan syndrome is characterized by neuromyotonia with autonomic and CNS involvement. Manifestations involving the CNS without peripheral involvement are characteristic of limbic encephalitis and epilepsy. The clinical features of anti-VGKC-Ab-associated limbic encephalitis are subacute onset of episodic memory impairment, disorientation and agitation. Hyponatremia is also noted in most patients. Cortico-steroid therapy, plasma exchange and intravenous immunoglobulin are effective in treating to not only the clinical symptoms but also hyponatremia. Unlike other anti-VGKC-Ab-associated neurological disorders, paraneoplastic cases are rare. Thus, anti-VGKC-Ab-associated limbic encephalopathy is considered to be an autoimmune, non-paraneoplastic, potentially treatable encephalitis. Morvan syndrome is characterized by widespread neurological symptoms involving the peripheral nervous system (neuromyotonia), autonomic system (hyperhidrosis, severe constipation, urinary incontinence, and cardiac arrhythmia) and the CNS (severe insomnia, hallucinations, impairment of short-term memory and epilepsy). Many patients have an underlying tumor, for example thymoma, lung cancer, testicular cancer and lymphoma; this indicates the paraneoplastic nature of the disease. Needle electro-myography reveals myokimic discharge. In nerve conduction study, stimulus-induced repetitive descharges are frequently demonstrated in involved muscles. Plasma exchange is an effective treatment approach, and tumor resection also improves symptoms. Both VGKC-Ab-associated limbic encephalitis and Morvan syndrome can be successfully treated. Therefore, when these diseases are suspected, it's important to measure the anti-VGKC-Ab level.

Disrupting vagal feedback affects birdsong motor control.

PubMed

Méndez, Jorge M; Dall'asén, Analía G; Goller, Franz

2010-12-15

Coordination of different motor systems for sound production involves the use of feedback mechanisms. Song production in oscines is a well-established animal model for studying learned vocal behavior. Whereas the online use of auditory feedback has been studied in the songbird model, very little is known about the role of other feedback mechanisms. Auditory feedback is required for the maintenance of stereotyped adult song. In addition, the use of somatosensory feedback to maintain pressure during song has been demonstrated with experimentally induced fluctuations in air sac pressure. Feedback information mediating this response is thought to be routed to the central nervous system via afferent fibers of the vagus nerve. Here, we tested the effects of unilateral vagotomy on the peripheral motor patterns of song production and the acoustic features. Unilateral vagotomy caused a variety of disruptions and alterations to the respiratory pattern of song, some of which affected the acoustic structure of vocalizations. These changes were most pronounced a few days after nerve resection and varied between individuals. In the most extreme cases, the motor gestures of respiration were so severely disrupted that individual song syllables or the song motif were atypically terminated. Acoustic changes also suggest altered use of the two sound generators and upper vocal tract filtering, indicating that the disruption of vagal feedback caused changes to the motor program of all motor systems involved in song production and modification. This evidence for the use of vagal feedback by the song system with disruption of song during the first days after nerve cut provides a contrast to the longer-term effects of auditory feedback disruption. It suggests a significant role for somatosensory feedback that differs from that of auditory feedback.

Disrupting vagal feedback affects birdsong motor control

PubMed Central

Méndez, Jorge M.; Dall'Asén, Analía G.; Goller, Franz

2010-01-01

Coordination of different motor systems for sound production involves the use of feedback mechanisms. Song production in oscines is a well-established animal model for studying learned vocal behavior. Whereas the online use of auditory feedback has been studied in the songbird model, very little is known about the role of other feedback mechanisms. Auditory feedback is required for the maintenance of stereotyped adult song. In addition, the use of somatosensory feedback to maintain pressure during song has been demonstrated with experimentally induced fluctuations in air sac pressure. Feedback information mediating this response is thought to be routed to the central nervous system via afferent fibers of the vagus nerve. Here, we tested the effects of unilateral vagotomy on the peripheral motor patterns of song production and the acoustic features. Unilateral vagotomy caused a variety of disruptions and alterations to the respiratory pattern of song, some of which affected the acoustic structure of vocalizations. These changes were most pronounced a few days after nerve resection and varied between individuals. In the most extreme cases, the motor gestures of respiration were so severely disrupted that individual song syllables or the song motif were atypically terminated. Acoustic changes also suggest altered use of the two sound generators and upper vocal tract filtering, indicating that the disruption of vagal feedback caused changes to the motor program of all motor systems involved in song production and modification. This evidence for the use of vagal feedback by the song system with disruption of song during the first days after nerve cut provides a contrast to the longer-term effects of auditory feedback disruption. It suggests a significant role for somatosensory feedback that differs from that of auditory feedback. PMID:21113000