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Results for “sensory function”

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PubMed2005

Abnormalities of axon growth in human olfactory mucosa.

OBJECTIVES/HYPOTHESIS: Random biopsies of the human adult olfactory mucosa often demonstrate degenerative changes in the olfactory epithelium (OE) in both dysosmic and normosmic patients and, consequently, have limited diagnostic usefulness. However, detailed analysis of the subepithelial tissue with specific attention to the fascicles of the olfactory nerve and abnormalities of axonal growth may improve the correlation of histopathology with sensory function. STUDY DESIGN: Retrospective review of human OE biopsies. METHODS: Mucosal biopsies from the olfactory area obtained from 27 subjects were examined by light and electron microscopy, with particular attention to the olfactory nerve fascicles; results were correlated with clinical status. Immunohistochemical analysis was used to characterize the extent of axonal depletion, relative maturity of the parent population, and aberrant axonal growth. RESULTS: As expected, there are areas of respiratory metaplasia and neuronal depletion in normosmic as well as dysosmic patients. The degree of axon degeneration within the fascicles correlates better with individual olfactory status. Immature neurons predominate, and re-entrant neuromas develop in patients with olfactory loss caused by disconnection from the olfactory bulb. Individuals with olfactory loss caused by epithelial damage as with chronic rhinosinusitis display evidence of nerve fascicle degeneration and intraepithelial neuromas. CONCLUSION: The status of olfactory axons provides useful information on the overall condition of the olfactory periphery and improves the diagnostic usefulness of mucosal biopsies. In addition to an assessment of the epithelium per se, the fascicles of the olfactory nerve need to be characterized for a complete analysis of the olfactory mucosa.

Adult↗

PubMed2006

Understanding pathogenic mechanisms in polycystic kidney disease provides clues for therapy.

PURPOSE OF REVIEW: Polycystic kidney diseases are a group of inherited disorders that result in tubular dilatation and/or the development of fluid-filled cysts in the kidney. Identification and analysis of the primary defective protein in many of these diseases are providing insights into a common pathogenesis to polycystic kidney disease. This review explores this pathogenesis and determines the role that this knowledge is playing in the development of potential therapies. RECENT FINDINGS: Study of simple and syndromic forms of polycystic kidney disease has revealed that the defective proteins are localized to the primary cilia/basal body and that the pleiotropic phenotypes are often associated with defective ciliogenesis. Data indicating that the polycystins are involved in ciliary mechanosensation, and cellular changes in intracellular Ca and cAMP, have provided clues for possible therapeutic approaches that have proved highly effective in pre-clinical trials. SUMMARY: Polycystic kidney diseases are associated with defects to proteins involved in developing functional, sensory cilia in the kidney. While the primary defects in these disorders cannot be corrected at present, downsteam cellular changes can be targeted. Potential therapeutic agents are now being tested in patients, moving polycystic kidney disease research into a new and exciting phase.

Animals↗

PubMed2006

Magnetic stimulation of the quadriceps femoris muscle: comparison of pain with electrical stimulation.

OBJECTIVE: The objective of this study was to compare pain induced by magnetic stimulation of the quadriceps femoris (QF) muscle with that induced by transcutaneous neuromuscular electrical stimulation (NMES). DESIGN: Magnetic stimulation and transcutaneous NMES were applied to QF muscles of 17 normal volunteers. The intensity of each mode of stimulation was increased in a stepwise manner. Peak torque values of isometric contractions of QF muscles and visual analog scale (VAS) scores were recorded at each intensity level. The VAS scores of the two stimulating modalities were compared at the intensity-generating same peak torque values. RESULTS: The median VAS scores for electrical and magnetic stimulation were 5.7 and 0.3, respectively. The median difference between the VAS scores for electrical and magnetic stimulation was 3.7 (range, 1.7-8.5). The mean of the maximum peak torque obtained from each subject was higher in magnetic stimulation than in electrical stimulation (9.5 +/- 4.8 vs. 4.4 +/- 2.9 Nm). CONCLUSIONS: Magnetic stimulation of the QF muscle produced less pain at the same level of isometric peak torque than did transcutaneous NMES. Magnetic stimulation is a potential alternative to transcutaneous NMES, especially for persons with intact or residual sensory function.

Adult↗

PubMed2003

Tacrolimus, a potential neuroprotective agent, ameliorates ischemic brain damage and neurologic deficits after focal cerebral ischemia in nonhuman primates.

Tacrolimus (FK506), an immunosuppressive drug, is known to have potent neuroprotective activity and attenuate cerebral infarction in experimental models of stroke. Here we assess the neuroprotective efficacy of tacrolimus in a nonhuman primate model of stroke, photochemically induced thrombotic occlusion of the middle cerebral artery (MCA) in cynomolgus monkeys. In the first experiment, tacrolimus (0.01, 0.032, or 0.1 mg/kg) was intravenously administered immediately after MCA occlusion, and neurologic deficits and cerebral infarction volumes were assessed 24 hours after the ischemic insult. Tacrolimus dose-dependently reduced neurologic deficits and infarction volume in the cerebral cortex, with statistically significant amelioration of neurologic deficits at 0.032 and 0.1 mg/kg and significant reduction of infarction at 0.1 mg/kg. In the second experiment, the long-term efficacy of tacrolimus on neurologic deficits and cerebral infarction was assessed. Vehicle-treated monkeys exhibited persistent and severe deficits in motor and sensory function for up to 28 days. A single intravenous bolus injection of tacrolimus (0.1 or 0.2 mg/kg) produced long-lasting amelioration of neurologic deficits and significant reduction of infarction volume. In conclusion, we have provided compelling evidence that a single dose of tacrolimus not only reduces brain infarction but also ameliorates long-term neurologic deficits in a nonhuman primate model of stroke, strengthening the view that tacrolimus might be beneficial in treating stroke patients.

Animals↗

PubMed2006

Animal models of inherited neuropathies.

PURPOSE OF REVIEW: Mutations in a number of genes have been associated with inherited neuropathies (Charcot-Marie-Tooth or CMT disease). This review highlights how animal models of demyelinating CMT have improved our understanding of disease mechanisms. Transgenic CMT models also allow therapies to be developed in a preclinical setting. RECENT FINDINGS: Rodent models for the most common subtypes of human CMT disease are now available, and two mouse mutants modeling the rare CMT4B subform have lately extended this repertoire. In a peripheral myelin protein 22 kDa (Pmp22) transgenic rat model of CMT1A, administration of a progesterone receptor antagonist reduced Pmp22 overexpression, axon loss and clinical impairments. Dietary ascorbic acid prevented dysmyelination and premature death in a Pmp22 transgenic mouse line. Neurotrophin-3 promoted small fiber remyelination in CMT1A xenografts and sensory functions in CMT1A patients. Gene expression profiling in rodent models of CMT may identify further therapeutical targets. While original classifications distinguish the demyelinating and axonal forms of CMT, recent findings emphasize that axon loss is a common feature, possibly caused by Schwann cell defects rather than demyelination per se. This supports our model that myelination and long-term axonal support are distinct functions of all myelinating glial cells. SUMMARY: Animal models have opened up new perspectives on the pathomechanisms and possible treatment strategies of inherited neuropathies.

Animals↗

PubMed1996

Auditory temporal coding in dyslexia.

Developmental dyslexia is generally believed to result from impaired linguistic processing rather than from deficits in low-level sensory function. Challenging this view, we studied the perception of non-verbal acoustic stimuli and low-level auditory evoked potentials in dyslexic adults. Compared with matched controls, dyslexics were selectively impaired in tasks (frequency discrimination and binaural unmasking) which rely on decoding neural discharges phase-locked to the fine structure of the stimulus. Furthermore, this ability to use phase-locking was related to reading ability. In addition, the evoked potential reflecting phase-locked discharges was significantly smaller in dyslexics. These results demonstrate a low-level auditory impairment in dyslexia traceable to the brainstem nuclei.

Adult↗

PubMed2006

Acclimation to chronic constant-rate peripheral stimulation provided by a vestibular prosthesis.

We are developing two types of vestibular prosthetics that electrically stimulate afferent neurons. One type replaces absent sensory function by providing stimulation that modulates above and below a baseline established with the head stationary. The other type provides constant stimulation and is turned on only when necessary, for example, to override unnatural variations like those experienced by patients suffering from Ménère's syndrome; this prosthesis does not provide motion information. Both prostheses require neural plasticity, which we investigated by providing chronic constant-rate stimulation to semicircular canal neurons in three guinea pigs. The stimulation was alternately switched on or off for eight consecutive weeks before being switched daily. A brisk horizontal nystagmus was measured when the stimulation was first turned on and then dissipated over the course of a day. The nystagmus demonstrated an after-effect in the opposite direction when the stimulation was turned off. The nystagmus that we measured after just a few (2 to 5) off-to-on transitions returned to baseline more rapidly than when first turned on. In fact, after many such off-to-on or on-to-off transitions, little nystagmus was evoked by turning the stimulation on or off. These findings show that the brain acclimates to constant-rate stimulation.

Acclimatization↗

PubMed2004

Evaluation of topiramate as an anti-hyperalgesic and neuroprotective agent in the peripheral nervous system.

Abstract Topiramate (TPM), a novel anti-convulsant currently approved for the treatment of epileptic disorders, has been shown to possess neuroprotective effects in models of cerebral ischemia, status epilepticus, and facial nerve lesion. Furthermore, pilot studies showed an effect of TPM in neuropathic pain models. Here, we studied the anti-hyperalgesic and neuroprotective efficacy of TPM in rat models of peripheral nerve lesions. Rats with a unilateral chronic constrictive injury (CCI) or a crush lesion of the sciatic nerve were treated with a twice-daily dose of 20 mg/kg of TPM. Behavioral and neurophysiological tests were used to measure pain-related behavior, motor, and sensory function. Morphometry was performed to evaluate sciatic nerves. In CCI, treatment with TPM attenuated mechanical hyperalgesia and cold allodynia. In sciatic nerve crush, TPM reduced cold allodynia and attenuated thermal hyperalgesia at the early and late phase of the observation. There was no difference in the numbers of surviving or regenerating nerve fibers between saline- and TPM-treated rats in either model. Electrophysiological studies carried out over a period of 3 months after sciatic nerve crush did not show major differences between TPM- and saline-treated rats. In conclusion, we could show moderate anti-hyperalgesic effects but could not prove a neuroprotective effect of TPM in these two rat nerve injury models using electrophysiological and morphometric methods.

Animals↗

PubMed2005

A critical review of interfaces with the peripheral nervous system for the control of neuroprostheses and hybrid bionic systems.

Considerable scientific and technological efforts have been devoted to develop neuroprostheses and hybrid bionic systems that link the human nervous system with electronic or robotic prostheses, with the main aim of restoring motor and sensory functions in disabled patients. A number of neuroprostheses use interfaces with peripheral nerves or muscles for neuromuscular stimulation and signal recording. Herein, we provide a critical overview of the peripheral interfaces available and trace their use from research to clinical application in controlling artificial and robotic prostheses. The first section reviews the different types of non-invasive and invasive electrodes, which include surface and muscular electrodes that can record EMG signals from and stimulate the underlying or implanted muscles. Extraneural electrodes, such as cuff and epineurial electrodes, provide simultaneous interface with many axons in the nerve, whereas intrafascicular, penetrating, and regenerative electrodes may contact small groups of axons within a nerve fascicle. Biological, technological, and material science issues are also reviewed relative to the problems of electrode design and tissue injury. The last section reviews different strategies for the use of information recorded from peripheral interfaces and the current state of control neuroprostheses and hybrid bionic systems.

Animals↗

PubMed1991

Accidental injection of ether into the epidural space.

Five ml diethyl ether was accidentally injected into the epidural space via an epidural catheter at the end of a Caesarean section. Immediately the patient felt a hot and burning pain in her legs that led to paraparesis, with a sensory level to T8. The patient showed bilateral recovery of both motor and sensory functions 4 hours after the accident.

Accidents↗

PubMed2004

Opioids and the gut: pharmacology and current clinical experience.

This article reviews the pharmacology and physiology of opiate receptors and the current and potential uses of opioid agonists and antagonists in clinical gastroenterology. Mu-receptors are involved in motor and sensory functions, and their modulation is established for treatment of diarrhea. Mu-antagonists have potential to reverse endogenous (e.g., postoperative ileus) or iatrogenic dysmotility (e.g., opioid bowel dysfunction). Modulation of the function of kappa-receptors may be a novel approach to control visceral pain in functional gut disorders. Results of formal testing of novel opioid modulators are keenly awaited.

Animals↗

PubMed2005

Hypothalamic-pituitary gonadal axis and immune response imbalance during chronic filarial infections.

Bi-directional relationships operate between the hypothalamic-pituitary-gonadal axis and the immune system. Cytokines, peptide hormones and their shared receptors/ligands are used as a common biological language for communication within and between the immune and neuroendocrine systems. Such communication suggests an immunoregulatory role for the brain and a sensory function for the immune system. We used a radioimmunoassay to measure the concentrations of steroid hormones (cortisol, testosterone, estradiol and progesterone) and pituitary hormones [follicle stimulating hormone (FSH), luteinizing hormone (LH) human chorionic gonadotropin (HCG) and prolactin] in peripheral blood plasma from 78 young Gabonese women with chronic filarial infections. We used an enzyme-linked immunosorbent assay to determine the concentrations of four proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), gamma interferon (IFN-gamma), interleukin-1 (IL-1) and IL-6] in the same plasma samples. Progesterone was unchanged and all other steroid hormone plasma concentrations were lower in microfilaremic women than in amicrofilaremic women. The concentration of LH was higher in amicrofilaremic women, whereas the prolactin concentration was higher in microfilaremics. The plasma concentrations of TNF-alpha, IFN-gamma, IL-1 and IL-6 were higher in microfilaremic women. A strong negative correlation was found between the steroid and pituitary hormones and the pro-inflammatory cytokines. Conversely, a strong positive correlation was found between prolactin and the same cytokines. These data provide first evidence of immune system and hormonal system disturbance during chronic filarial infections and suggest that the observed imbalance should be taken into account in the diagnosis and treatment of filarial infections.

Adolescent↗

PubMed1995

Inadvertent epidural injection of potassium chloride. Report of two cases.

Two patients underwent thoracotomy for resection of pulmonary or esophageal carcinoma. Postoperatively, epidural catheters were inserted for pain management. Complaints of severe injection pain over the abdomen or lower extremities were made during one administration of pain medication. Progressive weakness and numbness developed over the lower trunk and lower extremities, with subsequent respiratory difficulties. Potassium chloride (KCl) was suspected to have been mistaken for normal saline as the diluent for morphine. In addition to endotracheal intubation and ventilatory support, steroids were administered both intravenously and epidurally to suppress spinal cord irritation. The two patients regain motor and sensory functions 14 and 18 hours later, respectively, without sequelae.

Humans↗

PubMed1997

[Intraepithelial nerve endings in the lingual marginal papillae of newborn piglets].

The structure and occurrence of nerve fibres and nerve terminals in the lingual marginal papillae of newborn piglets are investigated by means of the osmium-zinc-iodate method and by transmission-electron microscopy. Subepithelial nerve fibres primarily accompany the blood vessels. They cross the epithelium with an almost vertical course to terminate in the stratum superficiale or the stratum corneum. Due to rows of varicosities, the axons look like a 'string of pearls'. As a result of the superficial localization and the typical ultrastructure, they seem to have a sensory function. Therefore, the papillae marginales are considered to function as mechanoreceptors.

Animals↗

PubMed1996

Silent afferents: a separate class of primary afferents?

1. In recent years, fine sensory nerve fibres have been detected that are not excited by physiological stimuli, even at potentially tissue damaging intensities. These silent afferents are known to supply knee joint, skin and viscera; in the last case, silent afferents seem to be particularly numerous. 2. When an artificial inflammation is induced, many silent afferents develop spike activity, others remain quiescent. Silent afferents that do respond probably have a nociceptive sensory function. Under inflammatory conditions some silent afferents are sensitized to physiological stimuli, others are probably chemospecific. 3. Orthodromic activity in silent afferents may sum spatially and temporally in second order neurons with other nociceptive information and may thereby contribute to different pain states. Furthermore, there is evidence that the activation of chemospecific silent afferents may lead to sensitization of nociceptive dorsal horn neurons. 4. Some silent afferents probably contain neuropeptides that may be liberated under pathophysiological conditions, such as inflammation. 5. Whether certain pathological states can be exclusively attributed to the activation of silent afferents or whether silent afferents sustain the functions of 'conventional' nociceptors remains to be clarified.

Animals↗

PubMed1980

Second-toe to hand transplantation: a clinical experience of 25 cases.

Twenty-five cases of second-toe transplantation to replace the thumb and other fingers are reported. There were 20 toal successes, four partial successes and one total failure. A total of eight patients had circulatory complications at some stage after operation. The overall motor and sensory functions of the transplanted toes were highly satisfactory. The donor foot did not suffer functionally despite the absent second toe.

Adolescent↗

PubMed1990

On the Role of Galanin, Substance P and Other Neuropeptides in Primary Sensory Neurons of the Rat: Studies on Spinal Reflex Excitability and Peripheral Axotomy.

The interaction of intrathecally (i.t.) applied galanin (GAL) with substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), somatostatin (SOM) and C-fibre conditioning stimulation (CS) with regard to their effects on the spinal nociceptive flexor reflex was studied in decerebrate, spinalized, unanaesthetized rats with intact or sectioned sciatic nerves. SP, CGRP, VIP and SOM applied onto the surface of lumbar spinal cord or a brief CS train (1 Hz, 20 s) to the sural nerve facilitated the flexor reflex for several minutes in animals with intact or sectioned nerves. Pretreatment with GAL, which by itself had a biphasic effect on the flexor reflex in a dose-dependent manner, antagonized the reflex facilitation induced by sural CS before and after sciatic nerve section. SP-induced facilitation of the flexor reflex was antagonized by GAL in rats with intact sciatic nerves, but not after nerve section. In contrast, VIP-induced reflex facilitation was antagonized by GAL only after sectioning of the sciatic nerve. GAL was effective in antagonizing the facilitatory effect of CGRP under both situations, but had no effect on SOM-induced facilitation. A parallel immunohistochemical study revealed that after sciatic nerve section GAL-like immunoreactivity (LI) and VIP-LI are increased in the dorsal root ganglia and that these two peptides coexist in many cells. The present results indicate that GAL antagonizes the excitatory effect of some neuropeptides which exist in the spinal cord. This antagonism could explain the inhibitory effect of GAL on C-fibre CS-induced facilitation of the flexor reflex, which is presumably due to the release of some of these neuropeptides from the terminals of primary afferents. Furthermore, the interaction between GAL and other neuropeptides is altered by sciatic nerve section, paralleling changes in the levels of these neuropeptides in primary afferents and their pattern of coexistence after nerve section. It is proposed that SP and CGRP are important mediators of the spinal flexor reflex in intact rats. However, after axotomy VIP may replace SP in this capacity, paralleling the decrease in SP and marked increase in VIP levels. In general the study provides further support for involvement of peptides in sensory function.

Journal Article↗

PubMed1994

Auditory localization behaviour in visually deprived cats.

The ability to localize sounds in azimuth was tested in five cats that had been binocularly deprived of vision from birth for several months and in three normal age-matched controls. Brief tone bursts were presented in an eight-choice apparatus along 360 degrees of the azimuthal plane at constant elevation. Using positive reinforcement techniques, the cats were trained to walk from the centre of the 3 m diameter circular enclosure to the hidden loudspeakers. The distribution of sound localization error from 55 trials per cat at each speaker position was measured, and its standard deviation was used to assess the precision of sound localization. All cats localized tones straight ahead of them most precisely; performance at lateral and rear positions was gradually less precise. When the sound localization ability of normal and binocularly deprived cats was compared across speakers, a significantly enhanced precision was found for binocularly deprived cats overall (P < 0.002; two-way analysis of variance). An improvement was found at each individual speaker position, but it was greatest at lateral and rear positions. In two sets of control experiments normal cats were retested (i) in the dark with the aid of an infrared camera and (ii) after 3 months of binocular lid suture. Normal cats in the dark did not show any differences in their sound localization behaviour. Late-deprived cats showed a tendency for better performance, which fell short of statistical significance. Our results in visually deprived cats agree well with some reports on the sound localization ability of blind humans, but disagree with others. Our data provide support for a hypothesis of compensatory plasticity, in which sensory functions get sharpened with the loss of another modality. They seem to rule out the necessity for vision to play a role in the postnatal calibration of auditory space.

Acoustic Stimulation↗