PubMed Health⌕ Search

Biomedical subjects

L Kruger

Publications and source records attributed to L Kruger.

At least 55 records · Page 3Linked to original sources
PubMed1987

An interpretation of dental innervation based upon the pattern of calcitonin gene-related peptide (CGRP)-immunoreactive thin sensory axons.

Calcitonin gene-related peptide (CGRP) is a recently characterized neuroactive substance that is expressed in a large proportion of small- to medium-diameter sensory ganglion neurons whose central terminals lie in the superficial spinal and medullary dorsal horn. This restricted distribution within the peripheral nervous system suggests a prominent role for the peptide in nociceptive processing. The mammalian tooth pulp, which receives a relatively homogeneous afferent input from thin (putative nociceptive) fibers originating from this subpopulation of trigeminal ganglion cells, thus affords an ideal target zone in which to examine peripheral nociceptive mechanisms. The large percentage of these neurons displaying CGRP-like immunoreactivity (CGRP-LI) furthermore provides a valuable tool to study its thin-fiber afferent innervation. CGRP-LI has been localized within intact, decalcified specimens of rat, cat, monkey, and human teeth and associated dental structures. A remarkably robust CGRP-LI innervation of molar pulp and dentin was revealed in all species, with fibers coursing both in fascicles and individually, in variable relation to blood vessels and pulpal stroma. Our methods enabled tracing of a large number of axons through Raschkow's plexus and odontoblast layer into dentinal tubules. Paralleling anterograde axonal transport studies, a greater share of fibers was found in coronal vis-à-vis radicular dentin. In the rat, this fiber pattern stood in contrast both to incisor dentin, which appeared devoid of CGRP-LI, and to the abundant labeled axons in gingiva and periodontal tissues. Surgical deafferentation of rat mandible resulted in widespread depletion of CGRP-LI, while superior cervical ganglionectomy was without effect, confirming the sensory nature of the CGRP-LI fibers. Neonatal capsaicin treatment greatly attenuated the immunostaining, providing evidence for CGRP-LI localization in chemosensitive unmyelinated afferents. The great density of CGRP-LI axons demonstrated is considered in contrast to the restricted range and extent of sensory stimuli to which teeth are presumably subjected, and in relation to the diverse ongoing trophic, regulatory, and reparative processes in tooth structures. It is therefore suggested that these fibers may be subserving prominent efferent roles in dental pulp not directly related to nociception.

Animals↗
PubMed1986

Peptidergic nociceptive axon visualization in whole-mount preparations of cornea and tympanic membrane in rat.

A whole-mount preparation is described for visualizing unmyelinated peptide immunoreactive axons in two specialized tissues, thin enough for tracing axons to their terminal knobs. These tissues, the cornea and the mucosal surface of the tympanic membrane, are known to possess specialized nociceptor innervation and can be used for selecting sensory endings labeled by peroxidase reaction product and embedded in plastic for more detailed analysis. Rat calcitonin gene-related peptide antibody proved a particularly robust primary antibody found in a substantial proportion of sensory unmyelinated axons in a variety of fixation and preparative conditions.

Animals↗
PubMed1986

Localization of specific binding sites for atrial natriuretic factor in peripheral tissues of the guinea pig, rat, and human.

Specific, high affinity atrial natriuretic factor (ANF) binding sites were identified and localized by autoradiographic techniques in peripheral tissues of the guinea pig, rat, and human. In the guinea pig kidney, high concentrations of ANF binding sites were located in the glomerular apparatus, outer medulla, and small renal arteries. Other peripheral tissues containing ANF binding sites included the zona glomerulosa of the adrenal cortex, the smooth muscle layer of the aorta and gallbladder, the lung parenchyma, the posterior lobe of the pituitary, the ciliary body of the eye, and the leptomeninges and choroid plexus of the brain. The distribution of ANF binding sites in the rat and human kidney was nearly identical to those seen in the guinea pig kidney; high concentrations were present in the glomerular apparatus, outer medulla, and small renal arteries. These results are consistent with earlier physiological and pharmacological studies that suggested that ANF plays a functional role in the regulation of extracellular fluid volume and blood pressure. There appears to be little species variation in the location and concentration of renal ANF binding sites, suggesting that, at least in the kidney, the results in experimental animals are relevant to the actions of ANF in humans. The finding that ANF binding sites were stable and present in high concentrations in human postmortem kidneys further suggests that these tissues may be amenable to testing for the involvement of ANF receptor dysfunction in diseases such as hypertension and congestive heart failure.

Adrenal Glands↗
PubMed1985

Projections of the rat trigeminal sensory nuclear complex demonstrated by multiple fluorescent dye retrograde transport.

The fluorescent dyes True Blue, Fast Blue, Nuclear Yellow and SITS were used to examine the connections of the rat brainstem sensory trigeminal nuclear complex (nV). Particular attention was paid to the following questions: do individual trigeminal neurons project to multiple targets via axon collaterals; and do primary afferent inputs to the various regions of nV arise from individual cells? Pairs of injections, using contrasting dyes, were made into the following target area combinations: ventrobasal thalamus-ipsilateral superior colliculus, cerebellum-contralateral thalamus, nucleus principalis of nV-contralateral thalamus, and nucleus principalis of nV-subnucleus caudalis of spinal nV. In general, numerous neurons throughout all subdivisions of nV and within the trigeminal ganglion were labeled by a single dye following the injections. In addition, many cells in a similar distribution were found to be doubly-labeled following such injection combination. These data demonstrate the existence of significant subpopulations of first- and second-order neurons that project to multiple targets via divergent axonal ramifications throughout the rat sensory trigeminal system.

Animals↗
PubMed1985

The response of single guard and down hair mechanoreceptors to moving air-jet stimulation.

The response properties of single guard (G) and down (D) hair afferent nerve fibers innervating the hairy skin of the hindlimb were studied in acute barbiturate-anesthetized cats. The purpose of the study was to identify and analyze the relative contribution of those stimulus features determining the discharge patterns evoked in single afferents by a fine air-jet stimulus moving across the skin and varying in force, velocity, position, direction and orientation. The response of single G hair afferents to moving air-jet stimuli reveals that the responsiveness of each fiber to stimuli with arbitrary orientation, direction and position within the receptive field (RF) displays an optimum velocity sensitivity which is not predictable from punctate data. Although the response pattern is remarkably consistent for each moving stimulus condition, there are significant differences in response as a function of stimulus orientation, direction and velocity. RF 'maps' constructed from the responses evoked as the air-jet traverses the skin reveal multiple zones of high and low sensitivity. The distribution of sensitive zones is remarkably consistent for maps constructed with stimuli varying in orientation, direction and velocity. It is apparent that the principal determinant of the response for a given stimulus traverse is the spatial distribution of sensitive spots throughout the RF. Although noticeably more uniform in sensitivity, the RFs of D hair afferents demonstrate similar properties. These findings indicate that G and D hair afferent nerve fibers respond more vigorously to moving stimuli than to stationary displacement and display complex RF inhomogeneities which must be taken into account for the study of central neuronal information processing and feature extraction.

Animals↗
PubMed1985

Excitation of dorsal column nucleus neurons by air-jet moving across the skin.

Single unit recordings from dorsal column neurons were made during application of mechanical somatic stimuli moving at controlled velocities across the neuron's receptive field. The neurons responded in stereotypic patterns which changed with altered stimulus parameters of velocity, direction and intensity. Spatial analysis of the response patterns indicates that the neurons generate action potentials when the stimulus probe activated particular discrete locations within the receptive field.

Afferent Pathways↗
PubMed1985

Thin-fiber cutaneous innervation and its intraepidermal contribution studied by labeling methods and neurotoxin treatment in rats.

Sensory nerves innervating rat distal limb skin were labeled by axonal transport of an enzyme-lectin conjugate injected into lumbar dorsal root ganglia (DRG), with emphasis on tracing the course of the thin axons. Selective neonatal neurotoxin destruction of most unmyelinated sensory or sympathetic axons was achieved by treatment with capsaicin (CAP) and 6-hydroxydopamine (6-OHDA), respectively. The relationship of substance P-immunoreactive (SPI) axons to the patterns of axonal transport-labeled thin axons was compared in normal and neurotoxin-treated animals. SPI is restricted to a limited population of unmyelinated axons, and electron-microscopic observation reveals its total absence in myelinated axons. SPI fibers of sensory origin, as determined by CAP susceptibility, can be traced into the epidermal stratum spinosum, in relation to guard hair follicles, mast cells, and a specific class of small blood vessels. These morphological features are not eliminated by neurotoxin sympathectomy, and some are inferred to contribute to the initial events associated with the neurogenic vasodilation and plasma extravasation associated with the inflammatory response. A re-evaluation of the concept of "free nerve endings" is suggested in the context of the variety of afferent and efferent patterns displayed by sensory peptidergic unmyelinated axons, their putative nociceptive role, and the functional diversity of sensory C fibers.

Animals↗
PubMed1984

Deafferentation in animals as a model for the study of pain: an alternative hypothesis.

The notion that post-deafferentation autonomy is a pain response is unsupported by the results of studies with neurotoxins. The selective massive destruction of a fiber system considered essential to normal nociception--unmyelinated primary afferent axons--prior to deafferenting nerve lesions did not stop or even significantly impede post-denervation DI despite massive evidence from humans and animals that pain following nerve lesions originates in the periphery and is generated by abnormal discharges in the injured nerve. In addition, when a reduction in abnormal impulse discharges of both large and small injured sensory axons could be inferred following neonatal sympathectomy, DI was not reduced in incidence or severity. This latter observation (1) provides further support for a dissociation between DI and pain, since any contribution of myelinated primary afferent axons to painful pathology probably was substantially reduced by sympathectomy and (2) suggests that DI also may be unrelated to non-painful sensory pathology attributable to abnormal activity in the thick-diameter fiber population. These findings and an evaluation of other relevant observations suggest that DI may not be a manifestation of deafferentation pain and perhaps this animal model for the experimental study of pain should be discarded. An alternative view of DI, reconcilable with known properties of this behavior, is that it reflects a proclivity in some species and circumstances to shed a functionally-impaired insensate appendage.

Afferent Pathways↗
PubMed1984

Absence of intraspinal sprouting in dorsal root axons caudal to a partial spinal hemisection: a horseradish peroxidase transport study.

Primary afferent sprouting in the spinal cord was evaluated by comparing the central projection of horseradish peroxidase (HRP)-labeled sciatic nerve afferent axons in nonlesioned control rats, and in rats subjected to acute or chronic partial spinal hemisections as adults. The lesions were performed at various levels from T10 to L3, and removed supraspinal and varying amounts of descending propriospinal afferents to lumbar segments receiving the maximal sciatic projection. The hemisections typically involved all but the dorsal column, although in some cases a portion of the dorsal column, including the corticospinal tract, was also transected. The distribution pattern and density of spinal HRP reaction product was not significantly different in experimental and control preparations in any segment below the lesion, regardless of the quantity of denervation, or the density of the normal sciatic projection in a given terminal region. These results, together with our previous finding concerning an absence of primary afferent sprouting following long-term dorsal root ganglionectomies, suggest that current concepts concerning collateral sprouting as a factor in functional plasticity in the mature mammalian spinal cord warrant re-evaluation.

Afferent Pathways↗
PubMed1984

Fine-structural characterization of the somatic innervation of the tympanic membrane in normal, sympathectomized, and neurotoxin-denervated rats.

The pars tensa of the rat tympanic membrane (TM) consists largely of a lamina propria of specialized unbanded collagen bounded on the outer surface by an unusually thin epidermal layer and on the inner surface by a flat, single-cell mucosal layer. The mucosal layer is innervated solely by unmyelinated (C) axons, whereas the cutaneous layer is supplied by both myelinated and C axons. The outer surface differs from general body skin, lacking dermal papillae, hairs, sweat glands, and distinctive dermal corpuscular structures. Epidermal innervation includes distinctive terminals in the basal layer, unassociated with Merkel cells, and deeper intraepidermal smaller endings containing accumulations of mitochondria and vesicles. The sensory nature of these endings can be inferred by their extensive, but not total, elimination following neonatal capsaicin treatment (a potent neurotoxin for thin sensory fibers) and their preservation following surgical or neurotoxin sympathectomy. The thin mucosal epithelium displays capillaries and beaded axons close to the free surface of the middle ear. The unmyelinated terminals contain predominantly large, dense-core vesicles (LDCVs). Capsaicin treatment results in extensive elimination of terminals containing LDCVs in surface epithelia. A possible small trophic influence of sensory thin-fiber supply was noted on the development of the epidermal layers. The sensory modalities elicited by natural stimulation of the TM is considered in relation to the pattern of innervation.

Animals↗
PubMed1983

An examination of intraspinal sprouting in dorsal root axons with the tracer horseradish peroxidase.

Postdeafferentation reorganization in the central terminal fields of spared dorsal root axons was evaluated by examining the intraspinal distribution of horseradish peroxidase-labeled sciatic nerve afferent fibers at various intervals following the removal of several lumbar dorsal root ganglia. The sciatic projection to the spinal cord, as determined by the pattern and density of intraspinal reaction product, was remarkably stable following the ganglionectomies. For as long as 3 months later, there was no evidence that sciatic afferent fibers had formed anomalous connections either with new spinal segments or in denervated areas within normal segments of entry. These findings cast doubt upon the existence of anatomic reorganization within the spinal cord following its partial deafferentation and suggest that physiological processes other than new axonal growth underlie observations such as postdenervation alterations in the response properties of dorsal horn neurons and the recovery of behavioral function.

Animals↗
PubMed1983

Spatial properties of receptive fields of mechanosensitive primary afferent nerve fibers.

Tactile sensation is rich and varied, requiring input from a variety of mechanoreceptors whose spatiotemporal aspects deserve careful study. Recent data for virtually every class of sensitive mechanoreceptor have revealed spatial inhomogeneities in sensitivity reflecting the distribution of sense organ terminals and the complexity of gradients in the complex spatial organization of receptive fields. Controlled surface parallel stimulation provides a means for examining sensitivity in a manner that may shed light on active tactile exploration and allow quantitative analysis of orientation, direction, and velocity properties underlying some aspects of feature extraction by the central nervous system.

Acclimatization↗
PubMed1981

Fine structure of myelinated mechanical nociceptor endings in cat hairy skin.

High-threshold mechanoreceptors (mechanical nociceptors) with myelinated axons were electrophysiologically identified in hairy skin of the cat as described by Burgess and Perl ('67). Such elements possess receptive fields consisting of a number of punctate areas from which maximal firing can be elicited by intense (skin-damaging) mechanical stimuli. The spots of the receptive field are separated from each other by unresponsive regions, i.e., by skin areas from which responses cannot be evoked by stimuli effective at the spots. Fine steel pins were inserted to bracket closely a number of the spotlike responsive areas for each of several units. After aldehyde perfusion of the animal, osmification of the tissue and embedding in plastic, the marked skin zones were examined in semithin and ultrathin sections at the light and electron microscopic level. Near each delineated area, a thinly myelinated axon was found that could be traced to the papillary layer where it loses its myelin sheath. Unmyelinated axons accompanied by thin Schwann cell processes were then traced and found to penetrate the epidermal basal lamina in one of the papillae. At the epidermal penetration site, the axons contained both clear round, and large, dense core vesicles; at this level, the surrounding Schwann cell cytoplasm exhibited numerous pinocytotic vesicles. The zone of penetration may constitute the receptive apparatus. Some of these axons have been traced within the basal epidermal layer where they become surrounded by keratinocytes, lose their Schwann sheath, and apparently terminate. This overall morphological pattern was consistently present in the demarked areas of focal responsiveness, and was rare in the surrounding skin; this and its difference from other cutaneous neural endings suggest that the intraepidermal axon-Schwann cel complex constitutes the receptive structure for myelinated mechanical nociceptors. It is suggested that such complexes are the sense organs responsible for initiating the sensation of pricking pain produced by localized mechanical injury of the skin.

Afferent Pathways↗
PubMed1981

Properties of velocity-mechanosensitive neurons of the cat ventrobasal thalamic nucleus with special reference to the concept of convergence.

Neurons in the ventrobasal (VB) thalamic nucleus of lightly anesthetized cats were studied in order to analyze their discharge properties in response to controlled mechanical stimuli. Properties of the vast majority of the neuronal population largely resemble those of peripheral sensitive mechanoreceptors in their response to the velocity and, to a more limited extent, the amplitude component, of skin and hair displacement within restricted receptive fields. Detailed examination reveals some 'complex' characteristics suggestive of central integration in about 11% of VB neurons. Complex properties appear to indicate convergent input reflecting receptive field organization, the variety of velocity-related discharges and patterns of inhibition. The rarity of isolated 'surround' inhibition and the definition of what constitutes 'lemniscal' properties are discussed in the context of these and other related findings.

Afferent Pathways↗
PubMed1981

Polysaccharide and cytoplasmic changes in motoneurons during "chromatolysis" in the opossum spinal cord.

Following axotomy, motoneurons of the opossum spinal cord display an early "axon reaction" or "chromatolysis" characterized by a redistribution of ribosomes accounting for a widespread basophilia and an apparent reduction in the size of two distinct varieties of Nissl bodies. This alteration is accompanied by zones of increased extracellular glycocalyx demonstrable in light and electron microscopy. In addition, large intracellular periodic acid-Schiff-positive vacuolated zones in the neuron periphery possess numerous free ribosomes, glycogen, lipids, and huge vacuolated sacs containing a flocculent matrix material similar to that found within the sacs of granular endoplasmic reticulum. "Artifacts" in the neuronal periphery associated with chromatolysis seen in light microscopy are probably related to polysaccharide alterations and redistribution of granular endoplasmic reticulum.

Animals↗
PubMed1981

Axonal transport studies of the trigeminal nerve roots of the cat. With special reference to afferent contributions to the portio minor.

The transport of protein molecules by axoplasmic flow has been used to trace axonal projections in the trigeminal system of the cat. Autoradiography with tritiated amino acid labeling of synthesized proteins and the transport of the enzyme horseradish peroxidase have been employed. The latter method has enabled demonstration of afferent axons within the portio minor, some of which are of cutaneous origin. The trigeminal "motor root" thus appears to be homologous with spinal ventral roots in possessing a potentially significant sensory function. The presence of such afferent fibers in nerve roots thought previously to have an exclusively motor function may explain instances of preserved sensation or failure to relieve pain following rhizotomy of the trigeminal portio major.

Afferent Pathways↗
PubMed1981

Cellular localization of 2-[3H]deoxy-D-glucose from paraffin-embedded brains.

Results of experiments in which regional neuronal activity is revealed by a 2-[3H]deoxy-D-glucose (3H-2-DG)-paraffin section-emulsion autoradiography method are described. The trigeminal pathway of freely behaving mice was activated differentially by selective patterns of whisker removal. One hour after injection of concentrated 3H-2-DG, the animals were perfused systemically with a periodate/lysine/paraformaldehyde mixture (McLean, I. W., and P. K. Nakane (1974) J. Histochem. Cytochem. 22: 1077-1083), the brains were embedded in paraffin, and serial sections were taken and coated with emulsion for autoradiography. Diffusion of the isotope out of the tissue was assessed visually and by liquid scintillation counting. While substantial loss of 3H isotope into the embedding fluids (about 95%) was found, the scintillation counts and the autoradiograms showed good fixation of the isotope in situ, no evidence of isotope movement into the emulsion, and no gradients of diffusion in the sectioned material. Patterns of regional labeling were similar to those reported from brains prepared by conventional 2-[14C]deoxy-D-glucose (14C-2-DG) autoradiography; for instance, auditory and vestibular pathways in the brainstem were heavily and specifically labeled. Trigeminal structures associated with the intact (stimulated) whiskers were labeled relatively heavily, indicating that label uptake is specific with respect to neuronal activity. In the cortex, the patterns of label corresponded directly and precisely to those barrels known to receive inputs from the intact whiskers. Distribution of silver grains in the cortex and in the brainstem was correlated directly with neuronal profiles, including processes, some of which were identified by means of a Nissl counterstain. Clearly, this approach offers considerable technical advantages, in particular, the ease with which the histological material is prepared. The resolution of the autoradiograms and the quality of the histology are excellent.

Animals↗