Nerve In Man Research Articles

The biological role of galanin in normal and neuropathic states

Publisher Summary This chapter discusses the biological role of galanin in normal and neuropathic states. Injuries to peripheral nerves in man are associated with a range of debilitating consequences, the most severe of which is the emergence of chronic neuropathic pain. The etiology of such pain is poorly understood and existing clinical treatment is largely ineffective. There have been intense efforts over the last decade to characterize the changes that take place in the somatosensory system, particularly in primary sensory neurons, in a variety of animal models of nerve damage. It is now clear that many aspects of primary sensory neuron function are altered following injury or disease of peripheral axons. One important change is a mobilization of repair mechanisms within the damaged neurons, such as an up-regulation of a number of structural proteins. This regenerative response may be adaptive in the peripheral axon but it also seems to affect the anatomy of central terminations of damaged sensory afferents in the dorsal horn and here it may be maladaptive.

Neurotrophic factors in the auditory periphery.

Many of the neurotrophic factors promote the survival of developing peripheral sensory neurons, and they might be useful as therapeutic agents in the adult neuronal systems. During development, neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) mRNAs are expressed in the auditory sensory epithelium, which composes the peripheral target field of the cochlear (spiral) neurons. NT-3 mRNA is also expressed in the inner hair cells of the mature organ of Corti. mRNAs encoding their signal-transducing receptors, TrkC and TrkB, respectively, are expressed in the cochlear neurons. In addition to neurotrophins, which seem to have an important role during development, another neurotrophic factor, glial cell-line-derived neurotrophic factor (GDNF), seems to be involved in the maintenance of postnatal auditory neurons. In the present work, the cellular distribution of neurotrophins and GDNF in the developing and adult rat inner ear are compared. The effects of recombinant neurotrophins and GDNF on dissociated cochlear neurons in vitro are also compared. Recently, NT-3 and BDNF were used in vivo as therapeutic agents to protect guinea pig cochlear neurons from aminoglycoside-induced degeneration and GDNF from noise-induced degeneration. These data demonstrate that NT-3, BDNF, and GDNF might be potential candidates for prevention of degeneration of the auditory nerve in man.

Section of the vagal celiac branch in man reduces glucagon-stimulated insulin release

The purpose of this study was to determine whether section of the celiac branch of the vagus nerve in man affects the insulin response to intravenous glucagon injection. Patients who received a subtotal gastrectomy with lymph node dissection for gastric carcinoma were divided into two groups: the celiac-preserved group ( n=16) and the celiac-sectioned group ( n=13). The hepatic branches of the vagus were preserved in both groups. The glucagon test was performed twice in each patient during the operation; before and after manipulation of the celiac branch. Blood samples were collected just before and 6 min after the injection. No difference in the mean increases in blood glucose, insulin and C-peptide levels were seen between the two groups before the nerve manipulation. In the celiac-preserved group, the glucagon stimulated glucose-related C-peptide ratio (×10 −3) was 0.5±0.7 before the nerve manipulation and 3.5±3.0 after it, a significant difference ( p<0.01). In the celiac-sectioned group, this increase was not observed, the ratio was 0.7±0.6 before the nerve manipulation and 0.8±3.4 after. These results indicate that the vagal celiac branch in man may also be involved in the control of pancreatic insulin release.

Tongue motor responses following transcranial magnetic stimulation of the motor cortex and proximal hypoglossal nerve in man

Surface recordings of EMG responses were performed bilaterally from the tongue following transcranial magnetic cortex (TCS) and nerve stimulation (TNS) to characterize the activated corticonuclear pathways and to obtain normative data for a diagnostic use. TCS over the face-associated motor cortex with 1.3 times the response threshold for relaxed muscles produced bilateral tongue responses with similar latencies and amplitudes for ipsi- (8.3±1.1 ms, 1.3±0.7 mV) and contralateral responses (8.5±1.0 ms, 1.7±0.8 mV, n=20, 10 subjects). In individual subjects maximal ipsilateral and contralateral responses were elicited by stimulation over about the same cortex area which lay 2–4 cm lateral and 0–2 cm anterior to the center of the hand motor representation area. Magnetic stimulation of the hypoglossal nerve with 70% of the maximal stimulator output and a circular coil placed over the posterior lateral skull produced a more proximal nerve excitation than electrical stimulation at the mandible, as reflected by the response latencies (3.4±0.9 ms vs. 2.1±0.7 ms). The effect of magnetic TNS was independent of the direction of the coil currents. Central motor latencies as calculated by subtracting the response latencies after TNS from the overall latency after TCS were 4.8±1.2 ms and 5.0±1.1 ms for ipsi- and contralateral responses, respectively. The findings suggest the existence of a direct and fast conducting connection between motor cortex and brainstem tongue motor nuclei on both sides in man.

Intracranial recording of trigeminal evoked potentials from the brainstem and the trigeminal nerve in man

Event-related potentials and cued-recall performance were used to compare dyslexic and control adult subjects. Sentences that ended either congruously or incongruously were presented visually, one word at a time, at fast (stimulus-onset-asynchrony (SOA)=100 ms) or slow (SOA=700 ms) rates of presentation. Results revealed (1) a large effect of presentation rate that started with the N1–P2 components and lasted for the entire recording period, (2) larger N400 components for dyslexic than control subjects, at slow presentation rates, to both congruous and incongruous endings and (3) a large ERPs difference related to memory (Dm effect) that did not differentiate controls from dyslexics but was larger at slow than at fast rates of presentation. These findings indicate that the reading impairment observed in the present group of adult dyslexics is more likely to result from difficulties integrating the meaning of words within a sentence context than from pure sensory processing deficits.

Quadriceps strength and fatigue assessed by magnetic stimulation of the femoral nerve in man.

There is no nonvolitional method of assessing quadriceps strength which both supramaximally activates the muscle and is acceptable to subjects. In 10 normal subjects and 10 patients with suspected muscle weakness we used magnetic stimulation of the femoral nerve to elicit an isometric twitch and measured twitch tension (TwQ), surface electromyogram in addition to the maximum voluntary contraction force (MVC). Supramaximality was achieved in all subjects at a mean of 83% of maximum stimulator output. When supramaximal, TwQ was reproducible (mean coefficient of variation 3.6%, range 0.7-10.9) and correlated well with MVC (r2 = 0.83, P<0.001). In 7 normal subjects we measured TwQ before and after a fatiguing protocol; after 20 min TwQ was a mean of 55% (range 29-77%) of baseline and remained substantially reduced at 90 min. Magnetic femoral nerve stimulation is a painless, supramaximal method of assessing quadriceps strength and fatigue which is likely to be of value in clinical and physiological studies.

Collateral sprouting of cutaneous nerves in man.

Cutaneous nerve collateral sprouting was studied in 20 adults in whom a forearm cutaneous nerve had been resected from the upper arm, such that any recovery of cutaneous nerve function could not be accounted for by nerve regeneration. Ten patients entered the study immediately following surgery and the remainder at intervals thereafter, permitting a longitudinal study covering a 27-month period. Modality-specific stimuli were used to study light touch, sharp pain, cooling, warming and heat pain sensation. Efferent sympathetic C fibre function was determined by measuring sweating in response to total body heating. Though the patients described considerable subjective reduction in the sensory defect within 2 months, by 10-15 months the objective sensory tests showed encroachment at the margin by only 6 mm (P < 0.05) for light touch, 7 mm (P < 0.01) for sharp pain and 11.5 mm (P < 0.001) for heat pain, with no significant change for warming or cooling. By 24 months, recovery of sweating was evident within the zone of persistent sensory loss, for > or = 3 cm beyond the initial light touch margin (P < 0.005). This finding has important clinical implications as it calls into question the reliance placed on the recovery of sweating as evidence of nerve regeneration.

Magnetic Stimulation of the Femoral Nerve in Man

Magnetic Stimulation of the Femoral Nerve in Man

An anatomical analysis of the dorsoventral relationship between the sacral plexus and the pudendal nerve in man by use of computer aided three-dimensional reconstruction.

In order to investigate the dorsoventral relationship between the sacral plexus and the pudendal nerve in man, morphological examination was performed on one pelvic half of a male cadaver. The second and third spinal nerves were removed en bloc and sectioned serially for three-dimensional reconstruction imaging of the selected sections. Comparison of the sequential images revealed that the root of the pudendal nerve is first situated ventral to the caudal root of the sacral plexus, and that the former and the latter are shifted cranialward and caudalward, respectively, at the point of exit from the second anterior sacral foramen.

3D neuro-electronic interface devices for neuromuscular control: Design studies and realisation steps

In order to design the shape and dimensions of new 3D multi-microelectrode information transducers properly, i. e. adapted to the scale of information delivery to and from peripheral nerve fibres, a number of studies were, and still are, being performed on modelling and simulation of electrical volume conduction inside and outside nerves, on animal experiments on stimulation and recording with single wires and linear arrays, and on new technologies for 3D micro-fabrication. This paper presents a selection of the results of these ‘Neurotechnology’ studies at the University of Twente. The experimental and simulation results apply primarily to the peripheral motor nerves of the rat, but are also of interest for neural interfacing with myelinated nerves in man, as fascicles in man are about the same size as in the rat.

Airway effects of direct left-sided cervical vagal stimulation in patients with complex partial seizures

Airway nerves have been implied in obstructive lung diseases for many years. In experimental animals, vagal stimulation produces several features of asthma, including airflow obstruction and airway plasma exudation. Vagal stimulation is a novel and effective therapy in patients with refractory epilepsy. We evaluated the airway response to left-sided cervical electrical stimulation using 1 Hz (low stimulation: 30 s, once every 90 min) and 30 Hz (high stimulation: 30 s, every 5 min) in a randomized double-blinded fashion for 3 months in epileptic patients participating in a phase two efficacy study. In eight patients with high stimulation and six with low stimulation, no effect on FEV1 (forced expiratory volume in 1 s) was seen over 3 months chronic stimulation. In a follow-up, up to 9 months, no further deterioration of lung function was observed. Of five patients without concomitant lung disease who consented to more extended experiments, one patient produced a reduction of FEV1 with variable frequency and current stimulation (10–87 Hz and 0.5–2.5 mA respectively). In one patient with obstructive lung disease, however, increased frequency and current stimulation led to a stimulation-dependent decrease in FEV1. After the addition of inhaled ipratropium bromide (160 μg, dry powder) to this patient, there was a clear improvement of baseline FEV1, but only a slight improvement of the stimulation-induced deterioration of FEV1. We conclude that long-term vagal stimulation in patients without concomitant lung disease does not induce any significant changes in FEV1. However, in patients with obstructive lung disease, intense vagal stimulation can cause a deterioration of lung function. To our knowledge, this may be the first observation of the involvement of bronchoconstrictive vagal nerves in man.

Collateral Sprouting of Cutaneous Nerves in Man

Collateral Sprouting of Cutaneous Nerves in Man

Neurocardiac responses to vagoafferent electrostimulation in humans.

To determine if cardiac vagal tone is enhanced by vagal electrostimulation (VES), we examined the heart rate autospectrum (HRA) in eight patients with implanted stimulators for complex partial seizures. In four patients the VES was activated at 30 Hz and 500-msec pulse (HiStim group) compared to 2 Hz and 130-msec pulse for the LoStim group (n = 4). Continuous ECG and respiratory waveforms were recorded for 45 minutes every 8 hours (7-8 AM; 3-4 PM 11-12 PM) during resting supine wakeful epochs both before and 15 days after surgical implantation. From the HRA cardiac sympathovagal balance was expressed as the ratio of the low frequency (LF) power to the high frequency (HF) power. There were no presurgical differences between the groups in heart rate, its variance, or the energies contained in any autospectral band. The LoStim group showed no significant change in heart rate (HR), HF peak power, or LF:HF ratios during 2 weeks of VES. Conversely, in the HiStim group, the LF:HF peak power ratio (an expression of sympathetic dominance) decreased from 2.5 +/- 1.5 preimplant to 1.5 +/- 0.49 (P < 0.02) with VES. During VES there was a significantly higher HF power in the HiStim compared to LoStim group. No diurnal variations in HRA values were seen for either group. (1) A relationship exists between selective vagal nerve electrostimulation and the HRA; and (2) high stimulation frequency of the vagus nerve in man is associated with sustained augmentation of cardiac vagal tone throughout a 24-hour cycle.

Morphometric analysis of the cochlear nerve in man.

Fiber diameters were analyzed in the meatal segment of the cochlear nerve from 7 temporal bones obtained from 7 patients. Two patients had normal hearing for their age. Two had sustained noise exposure and one had presbyacusis of predominantly neural type. The cochleae displayed characteristic degeneration patterns. The other two manifested hearing loss of unspecified type. The fiber diameters ranged from 0.5 to 11 microns. The diameter distribution was unimodal in all seven nerves. The means of the diameters ranged from 4.2 to 5.5 microns. They were significantly different between patients with age-related normal hearing on the one hand and patients with noise induced hearing loss and neural presbyacusis on the other. The findings are discussed in relation to changes in nerve conduction speed and hearing loss; a possible correlation between the fiber diameter distribution and the tonotopical arrangement of the cochlea is suggested.

Multichannel measurements of magnetic compound action fields of the median nerve in man

Magnetic compound action fields (CAFs) evoked by electrical stimulation of the median nerve at the wrist were recorded with 7-channel 2nd-order SQUID gradiometers. CAFs measured over the elbow and upper arm were biphasic with field patterns and polarities corresponding to the depolarization and repolarization fronts of the action potential volley.

Is adrenaline released by sympathetic nerves in man?

Radiotracer methods were used to measure the rates of regional release of adrenaline and noradrenaline into plasma in man. This was done as a partial test of a theory of essential hypertension pathogenesis which envisages an important cotransmitter function for neuronally released adrenaline. In healthy resting men no release of adrenaline could be detected from the heart, lungs or liver. Adrenaline was released into the right renal vein but an adrenal medullary source is suspected. With the relatively limited activation of the cardiac sympathetic outflow which accompanied mental challenge and isometric exercise, cardiac adrenaline release remained undetectable. During supine bicycle exercise, which increased cardiac noradrenaline release 10-30 fold, to a mean value of 197 ng/min, cardiac adrenaline release averaged 2.36 ng/min. In two clinical conditions associated with persistently elevated plasma adrenaline concentrations, cardiac failure and adrenaline-secreting phaeochromocytoma, regional release of adrenaline was clearly evident. Thus, in normal man during exercise, and in patients with cardiac failure at rest, adrenaline is released from non-adrenal sources, and probably from sympathetic nerves. Whether neuronal adrenaline release of the degree found would be sufficient to facilitate noradrenaline release, augment sympathetically-mediated cardiovascular responses and contribute to the development of arterial hypertension remains to be tested.

Compound Action Potentials Recorded from the Intracranial Portion of the Auditory Nerve in Man: Effects of Stimulus Intensity and Polarity

Compound action potentials (CAP) were recorded from the intracranial portion of the eighth nerve in patients with normal hearing who were undergoing neurosurgical operations for cranial nerve disorders (trigeminal neuralgia and hemifacial spasm). Brain-stem auditory-evoked potentials were recorded intraoperatively to ensure that no noticeable changes occurred in conduction in the auditory nerve as a result of surgical dissections. The CAP recorded from the middle portion of the exposed intracranial portion of the eighth nerve in response to clicks of high intensity (100-110 dB peak equivalent SPL, or pe SPL) had a triphasic shape, as is commonly seen in monopolar recordings from long nerves. A second negative peak (N2) could be identified in some patients. There was little difference in the waveform of the CAP in response to condensation and rarefaction clicks, and in some patients the waveform of the CAP remained the same over a range of stimulus intensities (from 105 to 75 dB pe SPL), whereas in others the negative peak of the CAP became much broader in response to stimuli with intensities of less than 85 dB. In some patients the N2 peak became dominant as the stimulus intensity was decreased. At low stimulus intensities, the response consisted of a single, broad negativity. The latency-intensity curves for the N1 peak had different slopes in different patients. In those individuals in whom there was a noticeable difference between the latency of the N1 peak in response to clicks of opposite polarity, the latency-intensity curves of the responses to rarefaction clicks were steeper than those of the responses to condensation clicks, and the latency of the N1 peak to condensation clicks became shorter than that to rarefaction clicks at intensities below 85-90 dB pe SPL. The latency-intensity curves for the N2 peak were usually less steep than those of the N1 peak, but in some patients the curves for these two peaks had similar slopes. The amplitude of the N1 peaks showed a steep increase in click intensities at 95 and 105 dB, and a much less steep course for intensities below 95 dB. The amplitudes of the N2 peak reached a plateau in the range 95-105 dB, and decreased more rapidly than the N1 peak below 95 dB.

A comparison of magnetic and electrical stimulation of facial nerve at the cerebello-pontine angle in the dog

Magnetic stimulation is a painless, non-invasive technique which allows an alternative method for testing cranial nerves which were previously inaccessible. We compared the latency of muscle responses obtained by electrical stimulation of the facial nerve at the cerebello-pontine angle (CPA) to high intensity transcranial magnetic stimulation (TMS) in 6 dogs. Evoked muscle response from the levator nasolabialis during electrical stimulation had a mean latency of 6.24 ± 0.42 msec, compared with a mean of latency of 6.13 ± 0.50 msec obtained by magnetic stimulation. Orbicularis oculi had a mean latency of 3.65 ± 0.34 msec compared with a mean latency of 3.53 ± 0.36 msec for magnetic stimulation. This suggests that high intensity TMS results in direct activation of the facial nerve as it exits the brain-stem in dogs. This observation is in accord with previous clinical studies that magnetic stimulation results in activation of the intracranial segment of the facial of the facial nerve in man.

Late components in the compound action potentials (CAP) recorded from the intracranial portion of the human eighth nerve

The compound action potential (CAP) that can be recorded from the exposed intracranial portion of the eighth nerve in man to stimulation with broadband clicks of about 100 dB Pe SPL normally has an initial (small) positivity followed by a sharp negative peak with a latency of about 3 to 3.5 ms. The negative peak is usually followed by another positive-negative deflection with a latency of about 4 ms. Usually, no stimulus-related potential can be discerned at latencies longer than 5 ms. However, in a few patients we found a series of waves that occurred between 4 and 12 ms after the stimulation. The polarity of these waves reversed precisely (180° phase shift) when the polarity of the sound was reversed. Thus, these waves appeared clearly when the responses to clicks of opposite polarity were subtracted. These late waves were quasiperiodic with intervals between 1 and 2 ms. The waveform and duration differed between patients, but were remarkably constant in each patient. The timing of these late peaks was nearly independent of the stimulus intensity in the range studied (between 105 and 70 dB Pe SPL); in this respect the late waves differ fundamentally from the initial peaks, which showed a monotone decrease in latency with increasing stimulus intensity over this intensity range. Although the origin of these late waves is not known, the similarities between these waves and stimulated otoacoustic emissions indicate that the late waves may be the result of active cochlear processes similar to those that produce the cochlear echo.

Some Aspects of the Communicating Branch between the Musculocutaneous and Median Nerves in Man

Fascicular arrangement of the human brachial plexus is examined on 2 common cases and 3 peculiar cases in which a communicating branch was observed between the median and the musculocutaneous nerve. The musculocutaneous nerve consitss of spinal nerves from C.5, 6 and 7. The branch to the coracobrachialis receives its fibers from C.7 before it leaves the musculocutaneous nerve in 3 cases and after it leaves the musculocutaneous nerve in one case. In one case, C.7 does not send a branch to the coracobrachialis. The median nerve arises by two roots, one from the lateral cord, and the other from the medial cord of the brachial plexus. In a case in which a communicating branch was observed from the median nerve to the musculocutaneous, the fibers from C.7 join to the median nerve via the medial cord. Thus the median nerve involved all elements of the spinal nerve from C.5 to T.1. The elements of the median and the musculocutaneous nerves, therefore, are not affected by appearance of the communicating branch. The communicating branch between the median and the musculocutaneous nerves, consists of the fibers arose from C.5 and C.6, in all examined cases.