Individual Nerve Research Articles

SNARE proteins as molecular masters of interneuronal communication

In the beginning of the 20th century the groundbreaking work of Ramon y Cajal firmly established the doctrine, according to which neurons are the basic structural and functional units of the nervous system. Von Weldeyer coined the term neuron in 1891, but the huge leap forward in neuroscience was due to Cajal's meticulous microscopic observations of brain sections stained with an improved version of Golgi's la reazione nera (black reaction). The latter improvement of Golgi's technique made it possible to visualize the arborizations of single neurons that were colored brownish black even to their finest branchlets, standing out with unsurpassable clarity upon a transparent yellow background. All was sharp as a sketch with Chinese ink. The high quality of both the visualization of individual nerve cells and the work performed on studying the anatomy of the central nervous system lead Ramon y Cajal to the conclusion that axons output the nervous impulses to the dendrites or the soma of other target neurons. The name dendrite was coined by His in 1889 and axon by von Kolliker in 1896, but it was Ramon y Cajal who developed and provided extensive anatomical evidence for the idea that neurons are dynamically polarized and within each the transmission of information is from the dendrites towards the axon. Biomedical Reviews 2010; 21: 17-23.

Visualising vagal afferent neurons and their terminals whilst silencing TRPV1

Visualising vagal afferent neurons and their terminals whilst silencing TRPV1

Focal Peripheral Neuropathies (4th ed)

This is a review of a new edition of JD Stewart's <em>Focal Peripheral Neuropathies</em>

Infraclavicular Brachial Plexus Block for Regional Anaesthesia of the Lower Arm

Several approaches exist to produce local anaesthetic blockade of the brachial plexus. It is not clear which is the technique of choice for providing surgical anaesthesia of the lower arm although infraclavicular blockade (ICB) has several purported advantages. We therefore performed a systematic review of ICB compared to the other brachial plexus blocks (BPBs). To evaluate the efficacy and safety of ICB compared to other BPBs in providing regional anaesthesia of the lower arm. We searched CENTRAL (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to September 22nd 2008) and EMBASE (1980 to September 22nd 2008). We also searched conference proceedings (from 2004 to 2008) and the www.clinicaltrials.gov registry. No language restriction was applied. We included any randomized controlled trials (RCTs) that compared ICB with other BPBs as the sole anaesthetic techniques for surgery on the lower arm. The primary outcome was adequate surgical anaesthesia within 30 minutes of block completion. Secondary outcomes included sensory block of individual nerves, tourniquet pain, onset time of sensory blockade, block performance time, block-associated pain and complications related to the block. We identified 15 studies with 1020 participants, of whom 510 received ICB and 510 received other BPBs. The control group intervention was the axillary block in 10 studies, mid-humeral block in two studies, supraclavicular block in two studies and parascalene block in one study. Three studies employed ultrasound-guided ICB. The risk of failed surgical anaesthesia and of complications were low and similar for ICB and all other BPBs. Tourniquet pain was less likely with ICB (risk ratio (RR) 0.47, 95% CI 0.24 to 0.92, P = 0.03). When compared to a single-injection axillary block, ICB was better at providing complete sensory block of the musculocutaneous nerve (RR for failure 0.46, 95% CI 0.27 to 0.60, P < 0.0001) and the axillary nerve (RR of failure 0.37, 95% CI 0.24 to 0.58, P < 0.0001). ICB was faster to perform than multiple-injection axillary (mean difference (MD) -2.7 min, 95% CI -4.2 to -1.1, P = 0.0006) or midhumeral blocks (MD -4.8 min, 95% CI -6.0 to -3.6, P < 0.00001) but this was offset by a longer sensory block onset time (MD 3.9 min, 95% CI 3.2 to 4.5, P < 0.00001). ICB is a safe and simple technique for providing surgical anaesthesia of the lower arm, with an efficacy comparable to other BPBs. The advantages of ICB include a lower likelihood of tourniquet pain during surgery, and more reliable blockade of the musculocutaneous and axillary nerves when compared to a single-injection axillary block. The efficacy of ICB is likely to be improved if adequate time is allowed for block onset (at least 30 minutes) and if a volume of at least 40 ml is injected. Since publication of many of the trials included in this review, it has become clear that a distal posterior cord motor response is the appropriate endpoint for electrostimulation-guided ICB; we recommend it be used in all future comparative studies. There is also a need for additional RCTs comparing ultrasound-guided ICB with other BPBs.

Harmful Effect of Land-Based Endurance Exercise in Rats with Diabetic Nerve

Repetitive limb movements made during aerobic exercises, such as walking and jogging that are frequently prescribed for diabetes control, can induce nerve strain, which has been reported to induce nerve ischemia. Nerves in a diabetic background are more vulnerable to ischemia. We investigated the effects of repetitive treadmill and swimming exercises on nerves in diabetic rats. Rats with diabetic neuropathy were randomly allocated to one of three groups, namely, control (n = 7), treadmill (n = 8), and swimming (n = 8) groups. After 12 wk of exercise, sural and sciatic nerves were harvested and analyzed by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Western blotting. In sural nerves, percentages of TUNEL-positive cells and BAX/GAPDH level were higher in the treadmill than that in the swimming group. In sciatic nerves, there was no significant difference among three groups. : Endurance exercises increase Schwann cell apoptosis in distal peripheral nerves. Greater loadings during exercise were found to increase Schwann cell apoptosis. Land-based endurance exercises may have a harmful effect on peripheral nerves in certain individuals with diabetes.

Atrial Tachyarrhythmias and Repolarization Changes Induced by Discrete Activation of Dorsal Mediastinal Cardiac Nerves in Canines

Chronotropic "vagal responses" elicited by high-frequency stimulation have been used to identify atrial targets for ablative treatment of atrial tachyarrhythmias (AT), whereas an anatomic approach consisting of extensive ablation of the ganglionated plexus areas has been proposed as an alternative. Therefore, there is a need for precise delineation of juxtacardiac nerves involved in AT initiation and clarification of their regional influences throughout the atria in relation to AT sites of origin, beyond chronotropic effects related to sinus node modulation. Unipolar electrograms were recorded from 191 biatrial epicardial sites in 13 anesthetized canines, with concomitant left atrial endocardial recording from 63 sites in 5 of 13 animals. When electric stimuli were delivered to dorsal mediastinal nerves during the atrial refractory period, atrial premature depolarizations initiating AT were elicited in all animals, most frequently without prior sinus cycle length modification. Among 63 episodes, the sites of origin of early AT beats were localized to (1) the posterolateral left atrial wall in the pulmonary vein region (33%), (2) superior left atrial loci along the Bachmann bundle (55%), and (3) the region of Bachmann bundle insertion into the superior right atrial wall (11%). Moreover, the AT sites of origin were spatially concordant with regional waveform changes during the repolarization phase of unipolar recordings. AT induction and repolarization changes were abolished after atropine administration. Activation of individual dorsal mediastinal nerves induces AT arising from distinct sites of origin which are spatially concordant with regional atrial repolarization changes.

Multiple phases of excitation and inhibition in central respiratory drive potentials of thoracic motoneurones in the rat

Intracellular recordings were made from motoneurones with axons in the intercostal nerves of T9 or T10 in adult rats, with neuromuscular blockade and artificial ventilation, under hypercapnia and under either anaesthesia or decerebration. In nearly all motoneurones, central respiratory drive potentials (CRDPs) were seen, which included an excitatory wave in inspiration, in expiration, or in both of these. This was the case both for motoneurones with axons in the internal intercostal nerve (n = 81) and for those with axons in the external intercostal nerve (n = 5). In the decerebrates, motoneurones with purely inspiratory CRDPs were rare (1/44), but those excited in both phases (showing biphasic CRDPs) were common (22/44). For about one-third of biphasic CRDPs (11/30), the inspiratory depolarization was seen to reverse to a hyperpolarization when the motoneurone was depolarized, which was interpreted as indicating concurrent inhibition and excitation during this phase. A few motoneurones were seen where depolarization revealed signs of inhibition in both phases. The results confirm the novel observations of biphasic excitation in individual intercostal nerve branches, EMG sites and motor units reported in a companion paper. They also provide new insights into the functional roles of inhibition in motoneurones physiologically activated in natural rhythmic behaviours.

Cuban Epidemic Optic Neuropathy and its Relationship to Toxic and Hereditary Optic Neuropathy

The similarities and differences between toxic/nutritional and hereditary optic neuropathy and the pathophysiologic mechanisms that they have in common are described. This is based on data from the epidemic suffered in Cuba in 1992, which affected the optic nerves of many individuals and the experience of the authors in dealing with various toxic optic neuropathies, as well as Leber’s hereditary optic neuropathy.

Traumatic Superior Orbital Fissure Syndrome: Assessment of Cranial Nerve Recovery in 33 Cases

Superior orbital fissure syndrome is a rare complication that occurs in association with craniofacial trauma. The characteristics of superior orbital fissure syndrome are attributable to a constellation of cranial nerve III, IV, and VI palsies. This is the largest series describing traumatic superior orbital fissure syndrome that assesses the recovery of individual cranial nerve function after treatment. In a review from 1988 to 2002, 33 patients with superior orbital fissure syndrome were identified from 11,284 patients (0.3 percent) with skull and facial fractures. Severity of cranial nerve injury and functional recovery were evaluated by extraocular muscle movement. Patients were evaluated on average 6 days after initial injury, and average follow-up was 11.8 months. There were 23 male patients. The average age was 31 years. The major mechanism of injury was motorcycle accident (67 percent). Twenty-two received conservative treatment, five were treated with steroids, and six patients underwent surgical decompression of the superior orbital fissure. After initial injury, cranial nerve VI suffered the most damage, whereas cranial nerve IV sustained the least. In the first 3 months, recovery was greatest in cranial nerve VI. At 9 months, function was lowest in cranial nerve VI and highest in cranial nerve IV. Eight patients (24 percent) had complete recovery of all cranial nerves. Functional recovery of all cranial nerves reached a plateau at 6 months after trauma. Cranial nerve IV suffered the least injury, whereas cranial nerve VI experienced the most neurologic deficits. Cranial nerve palsies improved to their final recovery endpoints by 6 months. Surgical decompression is considered when there is evidence of bony compression of the superior orbital fissure.

Modulation of the Frequency Response of Shaker Potassium Channels by the Quiver Peptide Suggesting a Novel Extracellular Interaction Mechanism

:Recent studies have indicated that the Shaker potassium channel regulates sleep in Drosophila. The Drosophila quiver (qvr) gene encodes a novel potassium channel subunit that modulates the Shaker potassium channel. The Qvr peptide contains a signal sequence for extracellular localization and may regulate a unique feature of the Shaker IA current that confers special neuronal excitability patterns. Thus, studies of the Shaker channel properties in the qvr mutant background should provide an opportunity to uncover a new form of physiologic modulation of potassium channels. We have begun to investigate the impact of qvr protein on the Shaker channel properties and its implications in synaptic function in vivo. We studied synaptic transmission at the larval neuromuscular junction and characterized the transient potassium current IA in larval muscles. We identified two different functional states of IA in qvr larval muscles, as reflected by two distinct components, IAF and IAS, differing in their kinetics of recovery from inactivation and sensitivity to a K+ channel blocker. Correspondingly, qvr mutant larvae exhibit multiple synaptic discharges following individual nerve stimuli during repetitive activity.

In Vivo Visualization of Cranial Nerve Pathways in Humans Using Diffusion-Based Tractography

Diffusion-based tractography has emerged as a powerful technique for 3-dimensional tract reconstruction and imaging of white matter fibers; however, tractography of the cranial nerves has not been well studied. In particular, the feasibility of tractography of the individual cranial nerves has not been previously assessed. 3-Tesla magnetic resonance imaging scans, including anatomic magnetic resonance images and diffusion tensor images, were used for this study. Tractography of the cranial nerves was performed using 3D Slicer software. The reconstructed 3-dimensional tracts were overlaid onto anatomic images for determination of location and course of intracranial fibers. Detailed tractography of the cranial nerves was obtained, although not all cranial nerves were imaged with similar anatomic fidelity. Some tracts were imaged in great detail (cranial nerves II, III, and V). Tractography of the optic apparatus allowed tracing from the optic nerve to the occipital lobe, including Meyer's loop. Trigeminal tractography allowed visualization of the gasserian ganglion as well as postganglionic fibers. Tractography of cranial nerve III shows the course of the fibers through the midbrain. Lower cranial nerves (cranial nerves IX, XI, and XII) could not be imaged well. Tractography of the cranial nerves is feasible, although technical improvements are necessary to improve the tract reconstruction of the lower cranial nerves. Detailed assessment of anatomy and the ability of overlaying the tracts onto anatomic magnetic resonance imaging scans is essential, particularly in the posterior fossa, to ensure that the tracts have been reconstructed with anatomic fidelity.

The Ocular Pathology of Terson's Syndrome

To improve understanding of vision loss and clinical findings, we studied gross and microscopic pathology of retinas and optic nerves of individuals with Terson's syndrome. Retrospective case series with clinicopathologic correlation. We included 109 deceased individuals with Terson's syndrome. Histologic sections and gross photographs from 109 cases of Terson's Syndrome, accessed from 1955 to 1992 at the Wm R. Green Laboratory of Ocular Pathology, were studied and photographed; a representative case is described in detail. Abnormalities in retina and optic nerve. Hemorrhages occur in vitreous, subhyaloid, sub-internal limiting membrane (ILM), intraretinal, and subretinal spaces, in association with macular holes, retinal detachments, and optic neuropathy. Subhyaloid hemorrhages have diffuse morphology, whereas sub-ILM are well-demarcated. Continuous and noncontinuous blood occurs along optic nerves, within nerve sheaths, and in the subdural and subarachnoid spaces. Blood occurring in various layers and locations of the retina, particularly the macula, causes various complications that influence clinical management and visual outcome. Morphology differentiates subhyaloid from sub-ILM hemorrhage. Patterns of hemorrhages of optic nerve contribute to understanding mechanisms of Terson's syndrome. The authors have no proprietary or commercial interest in any of the materials discussed in this article.

P- and R-type Ca 2+ channels regulating spinal glycinergic nerve terminals

The contributions of P- and R-type Ca 2+ channels on glycinergic nerve endings (boutons) projecting to the rat spinal sacral commissural nucleus (SDCN) neurons are not understood. Thus, we investigated the functional role of P- and R-type Ca 2+ channels by measuring the inhibitory postsynaptic currents (eIPSCs) evoked from individual nerve endings (boutons) by focal electrical stimulation. The current amplitude and failure rate (Rf) of glycinergic eIPSCs varied directly with changes in [Ca 2+] o. Low concentration of ω-Aga IVA (P-type selective antagonist) suppressed eIPSCs as much as high concentration (both P- and Q-type selective) indicating little contribution of Q-type Ca 2+ channels. Antagonism of R-type Ca 2+ channels with SNX-482 and Ni 2+ greatly decreased the current amplitude and increased failure rate (Rf) of glycinergic eIPSCs. Overall, our results suggest that the dominant control of glycine release depends on Ca 2+ entry through P- and R-type Ca 2+ channels that ubiquitously populate spinal glycine release sites.

Ultrasonographic guided axillary plexus blocks with low volumes of local anaesthetics: a crossover volunteer study

Our study group recently evaluated an ED(95) local anaesthetic volume of 0.11 ml.mm(-2) cross-sectional nerve area for the ulnar nerve. This prospective, randomised, double-blind crossover study investigated whether this volume is sufficient for brachial plexus blocks at the axillary level. Ten volunteers received an ultrasonographic guided axillary brachial plexus block either with 0.11 ('low' volume) or 0.4 ('high' volume) ml.mm(-2) cross-sectional nerve area with mepivacaine 1%. The mean (SD) volume was in the low volume group 4.0 (1.0) and 14.8 (3.8) ml in the high volume group. The success rate for the individual nerve blocks was 27 out of 30 in the low volume group (90%) and 30 out of 30 in the high volume group (100%), resulting in 8 out of 10 (80%) vs 10 out of 10 (100%) complete blocks in the low vs the high volume groups, respectively (NS). The mean (SD) sensory onset time was 25.0 (14.8) min in the low volume group and 15.8 (6.8) min in the high volume group (p < 0.01). The mean (SD) duration of sensory block was 125 (38) min in the low volume group and 152 (70) min in the high volume group (NS). This study confirms our previous published ED(95) volume for mepivacaine 1% to block peripheral nerves. The volume of local anaesthetic has some influence on the sensory onset time.

Novel use of X-ray micro computed tomography to image rat sciatic nerve and integration into scaffold

This paper describes how specimens of nervous tissue can be prepared for successful imaging in X-ray Micro Computed Tomography (μCT), and how this method can be used to study the integration of nervous tissue into a polymeric scaffold. The sample preparation involves staining the biological tissue with osmium tetroxide to increase its X-ray attenuation, and a technique for maintaining the specimen in a moist environment during the experiment to prevent drying and shrinkage. Using this method it was possible to observe individual nerve fascicles and their relationship to the 3-D tissue structure. A scaffold supporting a regenerated sciatic nerve was similarly stained to distinguish the nervous tissue from the scaffold, and to observe how the nerve grew through a 2.5mm long, 100μm×100μm cross-section channel polyimide array. Furthermore, blood vessels could be identified in these images, and it was possible to monitor how a large proximal blood vessel split through the channel scaffold and proceeded down individual channels. This paper explains how μCT is a useful tool both for studying the location and extent of growth into a polymeric scaffold, and for determining whether the regenerated tissue has blood supply.

Predicting Auditory Nerve Survival Using the Compound Action Potential

Advances in cochlear hair-cell regeneration, neural regeneration, and genetic therapy encourage continued development of diagnostic tests that can accurately specify the appropriate target within the cochlea and auditory nerve for delivery of therapeutic agents. In this study, we test the hypothesis that the morphology of the acoustically evoked compound action potential (CAP) may reflect the condition of the auditory nerve in individuals with sensorineural hearing loss. CAPs to tone burst stimuli at octave frequencies from 1 to 16 kHz were recorded at low- to high-stimulus levels from sedated Mongolian gerbils with partial lesions of the auditory nerve (n = 10). Distortion-product otoacoustic emissions were measured to ensure preservation of normal outer hair-cell function. CAPs were analyzed with conventional measures of N1 latency and amplitude and by fitting the CAPs with a mathematical model that includes a parameter (N) representing the number of nerve fibers contributing to the CAP and a parameter (f) representing the oscillation frequency of the CAP waveform. Nerve fiber density and percent normal nerve area were estimated from cross-sections of the auditory nerve bundle. Despite substantial lesions in the auditory nerve, CAP thresholds remained within normal or were only moderately elevated and were not correlated with histological measures of nerve fiber density and normal nerve area. At high-stimulus levels, the model parameter N was strongly correlated with nerve fiber density for three of the five test frequencies and with normal nerve area for all five test frequencies. Correlations between N1 amplitude measures at high-stimulus levels and our histological measures were also significant for the majority of test frequencies, but they were generally weaker than the correlations for the model parameter N. The model parameter f, at low- and high-stimulus levels, was also positively correlated with measures of normal nerve area. Consistent with previous findings, physiological measures of threshold were not correlated with partial lesions of the auditory nerve. The model parameter N at high-stimulus levels was strongly correlated with normal nerve area suggesting, that it is a good predictor of auditory nerve survival. The model parameter N also seemed to be a better predictor of the condition of the auditory nerve than the conventional measure of N1 amplitude. Because the model parameter f was correlated with normal nerve area at low- and high-stimulus levels, it may provide information on the functional status of the auditory nerve.

Regeneration of the visual system in gastropods (Mollusca)

Abstract. The topic of tissue and organ regeneration has been of interest to life scientists ever since the phenomenon was noticed. The reason for this is obvious: if one can learn what drives and controls regeneration, i.e., how lost or damaged structures can be replaced, one not only has a better chance to understand an animal's embryogenesis and evolutionary relationship with other taxa, but one would also be in a better position to treat organ loss or tissue damage in humans. In this context, the possible restitution of individual sensory neurons or nerve projections has been of special interest to us. We identified central visual projections in several gastropod species and found that: (1) projections are very extensive across the brain and (2) they have connections with other systems and organs (including, most likely, non‐ocular skin photoreceptors) that may be involved in the integration of signals from different sensors. Investigations of afferent and efferent visual elements at a morphological level should help reveal the neuronal basis of a gastropod's behavioral reactions.

“What is it that you do again?”: thinking about criminal responsibility

I study the intersection between contemporary neuroscience and the theory of criminal responsibility. Hanging around disciplinary intersections like this can be fun: people don’t always look where they are going and if you wait long enough you might witness a crash or two. Casting aside the metaphor, my job begins by identifying the problems and tensions that emerge from the different ways in which we view the world. What might those problems be in the case of neuroscience and criminal responsibility? Well, we can divide it into two classic problems. The first is the problem of competing descriptions. Simplifying somewhat, we can say that neuroscientists describe human behaviour from the bottom-up, beginning with chemical and electrical signals between individual nerve cells and working up to the functional processing that takes place within and between different brain regions. These descriptions are mechanistic, deterministic and reductive. By way of contrast, theorists of ...

Direct assessment of organ specific sympathetic nervous system activity in normal and cardiovascular disease states

Direct assessment of organ specific sympathetic nervous system activity in normal and cardiovascular disease states

Anatomical Variations of the Lumbar Plexus: A Descriptive Anatomy Study with Proposed Clinical Implications

This study used dissection of 34 lumbar plexes to look at the prevalence of anatomical variations in the lumbar plexus and the six peripheral branches from the origin at the ventral roots of (T12) L1-L4 to the exit from the pelvic cavity. Prevalence of anatomical variation in the individual nerves ranged from 8.8–47.1% with a mean prevalence of 20.1%. Anatomical variations included absence of the iliohypogastric nerve, an early split of the genitofemoral nerve into genital and femoral branches, an aberrant segmental origin for the lateral femoral cutaneous nerve, bifurcation of the lateral femoral nerve prior to exiting the pelvic cavity, bifurcation of the femoral nerve into two to three slips separated by psoas major muscle fibers, the presence of a single anterior femoral cutaneous nerve rather than the normal presentation of two separate anterior femoral cutaneous branches, and the presence of an accessory obturator nerve. Comparison with relevant research literature showed a wide variation in reported prevalence of the anatomical variations noted in this study. Clinical implications and directions for future research are proposed.