Neurophysiologic aspects of allogeneic skin and upper extremity composite tissue transplantation in primates.
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Animals↗
Biomedical subjects
B L Munger
Publications and source records attributed to B L Munger.
Neural modulation of cutaneous differentiation: epidermal hyperplasia and precocious hair development following partial neuralectomy in opossum pups.
The original intent of the present study was to evaluate the compensatory response of the nervous system to areas of denervation. A portion of the spinal cord in the lumbosacral region of one-day opossum pups (Monodelphis domesticus) was removed by cauterization. This partial neuralectomy produced an expected compensatory response of neurons in the dorsal root ganglia, but in addition produced unexpected abnormalities of cutaneous differentiation. At 4-6 days following surgery, an increase in the thickness of the epidermis resembling glabrous palmar or plantar skin was seen. This hyperplastic epidermis appeared to be associated with an abnormally dense innervation of the dermis and epidermis. Eight days following partial neuralectomy most animals showed areas of precocious hair development. Nerve fibers were always seen in the dermis associated with these precocious hairs and were seen to penetrate the basal lamina in the region of the epidermal-hair shaft boundary. These results imply a critical role for afferent nerves in the normal development of the skin and its appendages.
Animals↗
The enigma of sensitivity in Pacinian corpuscles: a critical review and hypothesis of mechano-electric transduction.
The present report reviews the physiological and morphological specializations of Pacinian corpuscles and other mechanoreceptors that are present in the skin and connective tissues of the body as well as the cochlea. The remarkable sensitivity of Pacinian corpuscles is such that the only form of mechanical energy that could be perceived by a Pacinian corpuscle is a sound wave. In fact the human finger as demonstrated by Munger and Ide (1987) can perceive sound waves when water is the coupling agent. The structural specializations are equally remarkable with extensive membrane specializations of both the inner core and inner portion of the outer core. The halves of the inner core are each coupled with gap junctions and the inner portion of the outer core joined with numerous tight junctions. The cleft regions have specializations involving the axolemma that consist of numerous axonal spines containing bundles of filaments projecting into the cleft of the inner core. These structural specializations are thought to represent specializations for mechano-electric transduction analogous in many respects to the hair cells of the cochlea. A hypothesis for mechano-electric transduction is presented that may account in part for the extreme sensitivity of Pacinian corpuscles and other mechanoreceptors.
Animals↗
The cytology of human Pacinian corpuscles: evidence for sprouting of the central axon.
During the course of the studies on non-traumatized Pacinian corpuscles from normal human adults, we have frequently encountered corpuscles which have an 'apparently multiple' innervation in both light and electron microscopic preparations. On closer inspection of serial sections for both light and electron microscopy, these 'apparently multiple' axon terminals have been found in fact to be branches of the main central axon within the inner core of the corpuscle. Sprouting occurred at the trunk or at the extreme tip of the main axon, and such sprouts extended in various directions from the central axon throughout the inner core, producing tortuous and complex patterns of this 'multiple' innervation. These axonal sprouts do not have separate inner cores separated from one another, but rather are embedded in a common inner core. The presence of a common inner core thus differentiates normal axonal sprouts from the experimentally or pathologically produced multiple innervation that results form regeneration of axons in a previously denervated corpuscle. We conclude that the inner core of Pacinian corpuscles is a unique micro-environment promoting sprouting of sensory axon in the normal human adult as well as juvenile Pacinian corpuscles.
Adolescent↗
Neuroanatomical evidence of reinnervation in primate allografted (transplanted) skin during cyclosporine immunosuppression.
Histological evidence is presented documenting the reinnervation of sensory mechanoreceptors across major histocompatibility barriers in allografted primate (baboon) skin. Meissner and pacinian corpuscles, as well as hair follicles, showed a spectrum of reinnervation by host axons. Our light and electron microscopic evidence to date has suggested that allografted Merkel cells did not survive transplantation. This, and other instances of tissue and receptor destruction resulting from histoincompatibility, indicated marked differences when skin allografts were compared to autografts with respect to the ability of host axons to locate and reinnervate sensory mechanoreceptors.
Animals↗
Successive waves of differentiation of cutaneous afferents in rat mystacial skin.
The present study has traced the sequence of maturation of sensory receptors in the mystacial pad of postnatal rats. At birth the follicle-sinus complexes (F-SC) are well innervated by deep vibrissal nerves although the number of axons entering the sinus is less than that in the adult. The innervation of the F-SC by the conus or superficial vibrissal nerves derived from skin nerves that form the superficial dermal nerve plexus is limited to the Merkel rete ridge collar at birth, and the innervation to the inner conical body is conspicuously absent. The inner conical body innervation begins to appear 3-4 days after birth and rapidly matures over the week. By 3 weeks of age the F-SCs have a mature sensory innervation. At birth small guard hairs are present in the intervibrissal pelage and are associated with scant axons of the superficial dermal nerve plexus, but no mature sensory terminals are present. The sensory innervation of the intervening pelage begins to differentiate during the second week and mature piloneural complexes can be recognized by 3 weeks of age. Innervation to vellus hairs is still developing at 3-4 weeks of age. These maturational changes in peripheral sensory innervation correlate with gradual changes in the structure of barrels in the first somatosensory cortex (SI). Sequential waves of differentiation of sensory receptors appear to be a general feature of neural development.
Animals↗
A comparative light microscopic analysis of the sensory innervation of the mystacial pad. I. Innervation of vibrissal follicle-sinus complexes.
This comparative study was conducted to provide a detailed, comprehensive description of the innervation to the follicle-sinus complex (F-SC) of mystacial vibrissae and to determine if interspecies variability in the innervation of the F-SCs may be related to differences in the structure or existence of barrels in the primary somatosensory (SI) cortex. Two silver techniques (Winkelmann on 100 micron-thick-frozen sections and Sevier-Munger on 8 micron-thick paraffin sections) were applied to comparable mystacial skin samples from adult hamsters, mice, rats, gerbils, rabbits, guinea pigs and cats. The basic structure and innervation of the F-SCs is the same in all species. Six distinct populations of sensory receptors are identified at consistent locations: Merkel endings in the epidermal rete ridge collar at the mouth of the follicle; circularly disposed presumptive lanceolate, Ruffini, and free nerve endings (FNE) in the inner conical body; longitudinal lanceolate endings in a dense palisade in the mesenchymal sheath at the level of the ring sinus; Merkel endings in the external root sheath at the level of the ring sinus; scattered corpuscular and FNEs (possibly lanceolate or Ruffini endings) in the cavernous sinus; and a few FNEs in the dermal papilla. In each F-SC, the first two locations are supplied by several superficial vibrissal nerves that arise from several small nerves that also innervate the skin between the vibrissae. These superficial nerves may innervate more than one F-SC. The next three locations are supplied by a single large deep vibrissal nerve that is derived directly from a row fascicle of the infraorbital nerve. Each deep nerve innervates a single F-SC. The source of the papilla innervation was not found. The ring sinus locations are consistently the most heavily innervated in all species. The number of axons in comparable deep vibrissal nerves is similar among the rodents, higher in the cat, and lower in the rabbit. Innervation of the inner conical body varies considerably, being dense in species that vigorously whisk their vibrissae (hamster, mouse, rat, and gerbil) and sparse or absent in species that minimally or never whisk (guinea pig, rabbit, and cat). Innervation to the cavernous sinus is sparse particularly in hamsters and gerbils. The innervation to the rete ridge is uniquely absent in the rabbit.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
A comparative light microscopic analysis of the sensory innervation of the mystacial pad. II. The common fur between the vibrissae.
The innervation to the common fur between the vibrissae was examined in the hamster, mouse, rat, gerbil, rabbit, guinea pig, and cat. Samples were taken from central locations among the more caudal vibrissae in the mystacial pad and processed with Richardson's variant of the Bielschowsky silver technique or with Winkelmann's silver technique to selectively stain peripheral axons and terminals. Additional samples were taken among the rostral vibrissae in the rat. We found major unpredictable species-related variations in the distribution of receptor types, innervation density, and the quantity of innervation in the skin between neighboring vibrissae. The common fur is composed of numerous larger guard hairs and even more numerous smaller vellus hairs. The guard hairs usually are richly innervated with fully developed piloneural complexes composed primarily of a pallisade of lanceolate endings and a circumferential array of Ruffini and free nerve endings. The vellus hairs are usually innervated by individual or shared free nerve endings. The piloneural complexes in the cat, rat, and mouse are usually complete, whereas those in the other species were usually incomplete and lacked Ruffini endings. There is considerable interspecies variation in the relative quantity of innervation between homologous neighboring vibrissae. The quantity of innervation is related to a combination of receptor completeness, innervation density, and distance between vibrissae. The quantity of intervibrissal fur innervation is by far highest in the cat, relatively high in the rabbit, relatively low in the hamster and caudal mystacial pad of the rat, and lowest in the mouse, gerbil, guinea pig, and rostral mystacial pad of the rat. The differences in the innervation between the cat and the rabbit correlate well with published physiologic data on types of receptor units. Also, barrels are most prominent in species having relatively low quantities of intervibrissal innervation and are less prominent or absent in species having high quantities of intervibrissal innervation.
Animals↗
Degeneration and regeneration of peripheral nerve in the rat trigeminal system. II. Response to nerve lesions.
The course of vibrissa sensory receptor denervation and subsequent reinnervation was studied following transection or crush of the rat infraorbital nerve. Eighteen hours after nerve lesion, the large-diameter myelinated nerves supplying the lanceolate receptors of the intermediary zone and the Merkel cells of the stratum basale contained areas of focal axoplasmic abnormalities, and some of the nerve terminals exhibited vacuolization, mitochondrial swelling, and disruption of the neurofilament pattern. The Merkel cells and lanceolate receptors of the intermediary zone were completely deafferented by 24 hours after the nerve injuries. The Ruffini complex, free nerve endings and lanceolate receptors of the inner conical body, as well as the free nerve endings and lanceolate receptors of the connective tissue below the Ringwulst, were completely normal 24 hours after crush or transection of the nerve. These receptors underwent progressive degeneration from days 2 through 6 and the vibrissa was totally denervated by day 7. Regenerating axons were first seen entering the vibrissae 2 weeks after the crush lesion and 1 month following nerve transection. Except for a slight decrease in the percentage of Merkel cells innervated, vibrissae from post-crush animals were virtually indistinguishable from normal by 3 months. In contrast, vibrissae from rats subjected to the transection lesion exhibited evidence of misdirected axons and abnormally reinnervated receptors throughout the course of regeneration. Axons entering the hairs with the main vibrissal nerve were observed contributing to the innervation of the inner conical body, an area normally supplied exclusively by the conus nerve. Many of the lanceolate receptors contained multiple unmyelinated axons, and the usually highly ordered circular innervation of the inner conical body was markedly abnormal. It is suggested that these results may help explain the faulty sensory localization and abnormal sensations reported by patients suffering a peripheral nerve injury.
Animals↗
The neuroanatomical basis for the protopathic sensibility of the human glans penis.
The human glans penis is covered by stratified squamous epithelium and a dense layer of connective tissue equivalent to the dermis of typical skin. Rete ridges of the epidermis are irregular and vary in height depending on location, age, and presence or absence of a foreskin. The papillary layer of the dermis blends into and is continuous with the dense connective tissue forming the tunica albuginea of the corpus spongiosum of the glans penis. The most numerous nerve terminals are free nerve endings (FNEs) present in almost every dermal papilla, as well as scattered throughout the deeper dermis. FNEs are characterized by an incomplete Schwann cell investment, and contain irregularly scattered neurofilaments and neurotubules, clusters of mitochondria, vesicles of variable size and various inclusions. The ratio of FNEs to corpuscular receptors is approximately 10:1 and a similar ratio of small to large axons is seen in dermal nerves. Genital end bulbs are present throughout the glans, but are most numerous in the corona and near the frenulum. The unique corpuscular receptor of the glans penis consists of axon terminals that at an ultrastructural level resemble a tangled skein of FNEs. Simple, Pacinian and Ruffini corpuscles were occasionally identified predominantly in the corona glandis. Epidermal Merkel nerve endings and other types of mechanoreceptors typically found in primate glabrous skin (lip or digit) are not present. Rarely, dermal Merkel cells have been identified associated with genital end bulbs. The abundance of FNEs in isolated as well as corpuscular form can be correlated with the embryogenesis and known neurophysiologic and psychophysical parameters of sensory function of the glans penis. Finally, the divergence in reported values for the threshold of tactile and painful stimuli when applied to glabrous skin of fingertip and glans penis can be considered as an example of dissociated sensibility. The anatomical basis for this dissociation is the abundance of FNEs and absence of Merkel terminals and typical Meissner corpuscles in the covering of the glans, and the converse in glabrous skin of the digit.
Adolescent↗
Degeneration and regeneration of peripheral nerve in the rat trigeminal system. I. Identification and characterization of the multiple afferent innervation of the mystacial vibrissae.
Light and electron microscopic techniques were utilized to examine the sensory innervation of the rat mystacial vibrissa. Each vibrissa is innervated by a large nerve bundle that enters the hair below the level of the Ringwulst and a smaller bundle (conus nerve) that pierces the capsule at the top of the hair. The main nerve bundle innervates four types of sensory receptors: (1) free nerve endings (FNEs), (2) lanceolate receptors in the connective tissue below the Ringwulst, (3) Merkel cell-neurite complexes in the outer root sheath, and (4) lanceolate receptors in the intermediary zone. The smaller nerve bundle innervates the area of the sinus hair referred to as the conical body and supplies (1) a Ruffini corpuscle, (2) FNEs, and (3) lanceolate receptors in the inner conical body. The Ruffini complex of the inner conical body and the FNEs of the dense connective tissue below the Ringwulst have not been identified in previous morphological studies of the rat sinus hair. The Ruffini corpuscle, characterized by the compartmentalization of collagen bundles by Schwann cells and fibroblasts (septal cells), encircles the hair shaft in a manner analogous to the Ruffini complexes of nonsinus hairs. Identification of this receptor in the rat vibrissa provides an anatomic explanation for physiological recordings of mystacial primary afferents with slowly adapting type II properties in the rat.
Animals↗
The early embryogenesis of papillary (sweat duct) ridges in primate glabrous skin: the dermatotopic map of cutaneous mechanoreceptors and dermatoglyphics.
The present study documents the early innervation of the epidermis prior to the onset of differentiation of the papillary (sweat duct) ridge in glabrous digital skin of rhesus monkey embryos measuring 45, 50 and 55 mm (crown-rump) length. We observed small papillary ridges, spaced at a distance of approximately 40 microns, projecting into the dermis in the center of the distal glabrous digital pad of digits 2-5 in the 55-mm embryo. The other digital pads lacked any sign of ridge formation. A two-dimensional, approximately hexagonal grid of afferent nerves was present in the superficial dermis of all digital and palmar pads. At regular intervals of approximately 40 microns, afferent nerves ascended from the superficial dermal nerve plexus and innervated the overlying epidermis. By electron microscopy, axonal growth cones were identified contacting Merkel cells that projected several microns down into the superficial dermis in the digital pad of digit 3. Thus, the earliest wave of differentiated dorsal root ganglion neuroblasts innervates Merkel cells. Schwann cells partially encircled these growing axon tips and could be identified by the presence of rough endoplasmic reticulum and free ribosomes. The youngest embryo studied had no sign of ridge formation; however, axons ascended from the superficial dermal nerve net at 30-40-microns intervals to innervate the epidermis. We conclude that afferent nerve fibers provide a two-dimensional grid that could modulate the spacing and arrangement of the papillary or sweat duct ridges of successive digits. Such an interaction is possible between digits based on the overlapping dermatotopic maps of each rete ridge. An abnormal fingerprint could thus reflect abnormal dorsal root ganglion neuroblasts expressed through mesenchyme and epidermis.
Afferent Pathways↗
The sensory innervation of the rat rhinarium.
The present study documents the characteristics of innervation of the rhinarium or hairless rat snout skin by light and electron microscopy. The outer glabrous surface is covered with a stratified squamous epithelium that forms both rete pegs and rete ridges, the latter on the inferior border near the philtrum. The glabrous skin contains numerous presumptive epidermal and dermal free nerve endings (FNE's), Merkel terminals at the base of the rete ridges and pegs, and simple, nonencapsulated corpuscles. A second region of dense innervation, found on an elevation of the inner wall of the vestibule, contains similar components of innervation, with the exception that no Merkel terminals were identified. Since no Merkel terminals were present in this area of the vestibule, intraepidermal as well as dermal FNE's could be identified with certainty. This skin is covered by a thin squamous epithelium overlying dense connective tissue. The simple corpuscles are similar to those in the rhinarium, as well as resembling those described in other species. FNE's were frequently observed intimately associated with simple corpuscles. Several examples of large FNE's with two to three layers of cytoplasmic lamellae were found, suggestive of transitional forms between FNE's and simple corpuscles. Thus, the pattern of sensory innervation in the glabrous rat snout skin is similar to that found in other furred species described to date, but in addition, the sensory innervation of ridged skin in the rat also resembles that of epidermis organized into rete pegs. This dense sensory innervation may be correlated with whisking behavior of the predominantly nocturnal rat.
Animals↗
The terminal myelin segments of afferent axons to cutaneous mechanoreceptors.
The present study documents reductions in thickness of the myelin sheath without change in axonal diameter in a series of fortuitous longitudinal sections of axons innervating mechanoreceptors. These findings are interpreted to mean that we must indicate that caution should be expressed in the evaluation of quantitative data on myelinated axons in close proximity to their termination as sensory receptors.
Animals↗
The innervation of the primate fungiform papilla--development, distribution and changes following selective ablation.
The development of the terminal parts of the chorda tympani nerve, lingual nerve and cranial sympathetics in the macaque fungiform papillae were studied by light- and electron microscopy. Their respective distributions in the intra- and extragemmal compartments of papillae from adult macaques were examined following selective ablation of each nerve. Prior to midgestation, a single bundle of unmyelinated axons which contained numerous axoaxonic synapses passed through the subepithelial connective tissue and ramified in the single nascent chemosensory corpuscle and surrounding non-gustatory epithelium. Following midgestation, additional chemosensory corpuscles appeared, possibly by division of existing corpuscles, myelination of axons was begun, axoaxonic synapses were eliminated, and nerve terminals appeared in the subepithelial connective tissue as free nerve endings and coiled simple nerve endings. In the perinatal period, coiled simple endings, corpuscular receptors and Meissner corpuscles were present in the papilla core. Large numbers of intra-epithelial nerve endings were present in the extragemmal epithelium throughout development. Tonofilament collars ensheathed intra-epithelial axons and 80-100 nm dense core granules, occupying adjacent epithelial cells, appeared to be sequestered near such axons. Experimental selective ablation indicated that the terminal parts of chorda tympani fibers were present only within chemosensory corpuscles. In contrast, lingual nerve endings were present both in the extragemmal epithelium and chemosensory corpuscles and also were the sole supply of corpuscular receptors. Sympathetics appeared to be sparsely distributed in the papilla core. Intra-epithelial axons degenerated within 24 h following transection, while axons with Schwann or lamellar cell sheaths or myelin persisted for at least 3 days.
Animals↗
Early differentiation of the afferent nervous system in glabrous snout skin of the opossum (Monodelphis domesticus).
Early differentiation of afferent fibers innervating the snout skin of Monodelphis domesticus was studied by electron microscopy and by light-microscopic silver staining techniques. This study was undertaken to investigate the relationship between dermal and epidermal innervation in the neonate opossum while correlating these findings with behavioral responses. The advantage of using this species is that the neonate is born in a very immature stage and has a rostrocaudal development of the peripheral nervous system. Glabrous snout skin from young opossums was studied at birth (0 day) and postnatal days 1, 3, and 5. Neurite bundles were seen within the dermis, with axons and growth cones approaching the epidermis. Some axons penetrated the dermal-epidermal junction in newborn pups. Merkel cells were consistently numerous during the time spanned by this study. Mature Merkel cells had granules polarized toward an associated neurite and were often located in the base of the rete pegs. Immature Merkel cells were characterized by a lack of polarization of granules and absence of an apposed neurite, suggesting that these cells can differentiate without an associated neurite. Contiguous Merkel cells had junctional complexes in 0- and 1-day animals. Schwann cells, identified by their contact with neurite bundles, were present in large numbers, especially in the superficial dermis. Melanocytes could be identified in the epidermis in 5-day pups only. Developing rete pegs could be recognized in 0-day animals and became prominent in 5-day pups. These observations suggest that afferent fibers are present at a very early age and that some of these fibers are anatomically mature. These findings support the concept that the ability of the neonate to locate a teat and suckle requires only the presence of mature epidermal innervation, while dermal receptors appear later during postpartum development.
Afferent Pathways↗
The sensorineural apparatus of the human eyelid.
The present study describes a complex array of sensory nerve terminals in the human eyelid. In many respects this pattern of innervation resembles that previously described in the rhesus monkey, but in other respects it is unique to man. The most prominent nerve terminals are a complex array of lanceolate and circular Ruffini and free nerve endings that envelop the eyelashes. In addition, Merkel cells have not been conclusively identified to date in other nonhuman primate nonsinus hairs. The external root sheath collar contains Merkel cells, and dermal Merkel cells have also been identified close to the collar. The anterior cutaneous surface of the eyelid contains small vellus hairs with typical lanceolate, Ruffini, and free nerve endings resembling those of primate facial skin. Scattered Meissner and scant simple corpuscles as well as scattered free nerve endings (FNEs) can be identified on the occlusal surface of the eyelid. Intraepithelial as well as dermal FNEs were most easily identified in this region in areas lacking other corpuscular receptors. Corpuscular receptors are especially common at the occlusal/conjunctival angle. The inner or conjunctival surface of the eyelid appears to be a glandular epithelium, whereas in the rhesus monkey it is stratified squamous epithelium. This epithelium needs additional study. In summary, the present study confirms the unique sensory neural status of the human eyelid and verifies the presence of Ruffini nerve terminals by light and electron microscopy and of free nerve ending terminals at least by light microscopy, as well as a unique pattern of innervation of the human eyelash.
Adolescent↗
Effects of insulin on cardiac lysosomes and protein degradation.
Hearts perfused in the absence of added insulin had 1) accelerated rates of protein degradation, as assessed by release of phenylalanine and tyrosine; 2) increased rates of release of seven other amino acids; 3) decreased lysosomal latency and sedimentable lysosomal enzyme activity; 4) increased numbers of autophagic vacuoles in cardiac muscle cells; and 5) decreased activity of beta-N-acetylglucosaminidase in dense lysosomes (1.06-1.09 g/ml), as compared to hearts perfused in the presence of the hormone. After 3 h of perfusion in the absence of insulin, the changes that developed in protein degradation, lysosomal latency, and sedimentability, and in enzyme activity in dense lysosomes, were reversed by insulin addition during 90 min of subsequent perfusion. These studies suggest a role for insulin in controlling the activity of the lysosomal system and the involvement of this system in protein degradation, particularly in insulin-deprived tissue.
Acetylglucosaminidase↗