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PubMed1996

Evolution of morphological and histochemical changes in the adult cat cuneate nucleus following forelimb denervation.

Morphological and histochemical changes were studied in the ipsilateral cuneate nucleus between one and 52 weeks after forelimb denervation in adult cats. The deafferented nucleus and neighboring fasciculus were noticeably reduced in size within four weeks and decreased further by 13 weeks. The intensity of acetylcholinesterase staining decreased within one week and was further reduced one month after nerve transections. This reduction in acetylcholinesterase staining was transient, approaching control levels within one year. Parvalbumin immunostaining was also altered by the nerve transections; on the deafferented side, the neuropil staining in the cuneate nucleus and fasciculus decreased, but the number of parvalbumin-positive cells was consistently greater than in the contralateral side. These cell counts returned to normal levels within one year. One month after the injury, cytochrome oxidase activity was reduced. This reduction persisted and was even more apparent after one year. In parallel, the cell clusters of the nucleus became progressively less distinct. These observations in an adult mammal indicate that peripheral nerve injury imposes molecular and morphological changes on second-order sensory neurons which evolve differentially with time. Although some changes developed rapidly after deafferentation, the onset of others was slower; and whereas some seemed irreversible, others eventually regressed. Taken together with the functional studies of others, these findings suggest that early molecular changes observed in cuneate neurons reflect adaptive reactions to lesion-induced alterations in afferent activity. Permanent deprivation of the normal input, however, would eventually lead to chronic, and perhaps irreversible, degenerative changes.

Acetylcholinesterase↗

PubMed1996

Quantitative analysis of anatomical changes in the cuneate nucleus following forelimb denervation: a stereological morphometric study in adult cats.

The consequences on the cuneate nucleus of the transection of the major nerves of the forelimb in adult cats were studied quantitatively with stereological procedures on celloidin-embedded material. The cell cluster region of the normal cuneate was 2.93 +/- 0.41 (mean +/- SD) mm3. This volume decreased significantly 4.5 weeks after the injury. The decrease amounted to 11-23%, and persisted until the longest survival studied (36 weeks). Despite this reduction in nuclear volume, there was no significant loss of neurons. The normal cell cluster region contained 48.8 +/- 7.3 (mean +/- SD) x 1000 neurons. Neuronal density showed a significant 16.8% mean increase between 4 weeks and 36 weeks of deafferentation. Perikaryal volume decreased by an average of 15.2%, between 1 and 36 weeks, but since cell bodies make only a small fraction of the total volume, much of the overall volume reduction observed must be attributed to a concomitant reduction of the neuropil. The distribution of cell size suggested that there are two populations of neurons, presumably corresponding to interneurons and projection neurons. This bimodal distribution was maintained after deafferentation, but after 4 weeks it shifted to the left, showing an increase in small cells and a decrease of large cells. These findings demonstrate that peripheral deafferentation causes a substantial and persistent decrease of cytoplasmic mass in the cuneate nucleus, involving both neuropil and neuronal cell bodies, but does not lead to neuron loss, at least up to 36 weeks after injury. These effects suggest that the altered synaptic input and trophic support subsequent to deafferentation leave the cuneate nucleus in a permanently compromised, albeit seemingly stable, state.

Animals↗

PubMed2000

Rostrocaudal branching within the climbing fibre projection to forelimb-receiving areas of the cerebellar cortical C1 zone.

The inferior olive climbing fibre projection to two somatotopically corresponding regions of the paravermal C1 zone in lobule V of the anterior lobe and the rostral folia of the paramedian lobule (PML) in the posterior lobe were investigated in cats by using a combined electrophysiological and retrograde double-labelling technique. In each experiment (n = 7), a small injection of rhodamine-tagged beads was made into the forelimb-receiving part of the C1 zone in one region of the cortex, and an injection of fluorescein-tagged beads was made into the other region. The two regions were found to receive olivary input from cells located in a partially overlapping territory within the rostromedial dorsal accessory olive (DAO). At progressively more rostral levels of DAO, the territory providing climbing fibres to the anterior lobe was centred more laterally than the territory projecting to the rostral PML. Where overlaps occurred, cells that provided climbing fibres to one or the other region were intermingled with a smaller population of double-labelled cells that had axons that branched to supply climbing fibres to both regions of the zone. The double-labelled cells represented on average 26% of the smaller total population of labelled cells within the area of overlap and 7% of the total population of neurones projecting to both regions of the zone. Overall, the findings suggested that the C1 zone within spatially separate but somatotopically corresponding regions of the paravermal cerebellar cortex receives at least partially independent olivary inputs, consistent with the presence of distinct microzones at different rostrocaudal levels of the zone.

Afferent Pathways↗

PubMed2001

Functional-adaptive anatomy of the forelimb in the Didelphidae, and the paleobiology of the Paleocene marsupials Mayulestes ferox and Pucadelphys andinus.

An attempt to determine the locomotor activities of Mayulestes ferox (Borhyaenoidea) and Pucadelphys andinus (Didelphoidea) from the early Paleocene site of Tiupampa (Bolivia) is presented. The functional anatomy of the forelimbs of these South American marsupials is compared to that of some living didelphids: Caluromys philander, Micoureus demerarae, Marmosa murina, Didelphis marsupialis, Monodelphis brevicaudata and Metachirus nudicaudatus. Deductions from bone morphology to myology and locomotor behavior in the fossils are inferred from the comparisons with living forms. Some features of the postcranial skeleton, indicative of arboreal adaptations, are found in the extinct marsupials: anteriorly projected acromion, hemispherical head of the humerus, extended humeral lateral epicondylar ridge, medially protruding humeral entepicondyle, proximal ulnar posterior convexity, and deep flexor fossa on the medial side of the ulna. But other features are related to a more terrestrial pattern: the well-developed tubercles of the humeral head, the elongated olecranon process of the ulna, and the oval shape of the radial head. Mayulestes had clear arboreal abilities, but, as a predaceous mammal, probably hunted on the ground. Pucadelphys was less specialized, close to the living Monodelphis, a terrestrial insectivorous form with some skeletal features related to arboreal locomotion that are probably plesiomorphic for marsupials.

Adaptation, Physiological↗

PubMed1990

Effects of speed on forelimb joint angular displacement patterns in vervet monkeys (Cercopithecus aethiops).

Shoulder, elbow and wrist joint angular displacement patterns were analyzed for five vervet monkeys across increasing speed. Within symmetrical gaits, the peak positions of the pattern for each joint tended to decrease with increasing speed as did the yield angle of the elbow (more "yielding"). Across the walk(run)-gallop transition there were no notable changes in the displacement patterns, but there was a consistent decrease in the range of elbow movements and an increase in the yield angle. Across symmetrical gaits, there was also a tendency for some of the peak positions to decrease. These results are compared with those available for cats and dogs, and are interpreted relative to functional and neurological aspects of forelimb movements in primates.

Animals↗

PubMed1975

Morphogenesis of the carpal elements in the regenerating forelimb of adult Notophthalmus viridescens viridescens.

This study is concerned with the morphogenesis of the carpal elements in the regenerating forelimb of the adult newt. Blastema cells surrounding the remnant bony stumps begin to differentiate into cartilage on the twentieth post-amputation day. Subsequently, masses of carilage build up from the radial and ulnar stumps. The radial mass is larger and differentiates more rapidly than the ulnar mass. By the fifty-fifth post-amputation day, the eight basic carpal elements are formed, with fusion of two of the units, intermedium with ulmare, occurring by the seventieth day. The completed regenerate possesses the seven carpal elements characteristic of the normal adult limb. The present results show that during limb regeneration in the adult newt the carpal elements are restored to their original number and position and that the pattern of such carpal differentiation proceeds in a proximodistal direction influenced by the stump remnants of the radius and ulna.

Animals↗

PubMed1985

Fine structure of the forelimb regenerate of the African clawed toad, Xenopus laevis.

Forelimb regenerates from postmetamorphic Xenopus froglets were examined at various stages postamputation by light microscopy and scanning and transmission electron microscopy. The outside surface of the wound epithelium was found to exhibit progressive changes following amputation with a distinct difference in appearance between stump epidermis and wound epithelium at all stages examined. The internal structure of the wound epithelium is characterized by loosely arranged cells with numerous cell junctions and abundant intracellular filaments. The wound epithelium is separated at an early stage from the underlying cells by a thick band of extracellular matrix. Cells accumulating beneath the wound epithelium were morphologically similar to blastemal cells from completely regenerating limbs in other species but no evidence of myogenesis or abortive myogenesis was seen. Blastemal cells from the central portion of the regenerate were observed at varius stages of chrondrogenesis with those immediately beneath the wound epithelium least advanced in this respect. Those located more laterally appear not to be directly involved in chondrogenesis. Although the usual explanation for lack of complete regeneration in this species is inadequate innervation of the regenerate, the fine structure of the regenerating spikes noted here is markedly different than that of denervated, amputated newt limbs.

Animals↗

PubMed1986

Nomenclatural review of long digital forelimb flexors in carnivores.

A hitherto-unknown atavistic muscle in the dog initiated a review of the literature on the homologies and nomenclature of the forelimb flexors in carnivores and man. A consequence is that we recommend a revision of the nomenclature in the Nomina Anatomica Veterinaria (Ithaca, New York, 1983) so that it is in agreement with the Nomina Anatomica (Wilkins, Baltimore, 1983). This revision mainly consists of the incorporation of the terms M. palmaris longus and Mm. flexores breves manus.

Animals↗

PubMed1994

Embryological development of the arterial system of the forelimb in Tupaia.

BACKGROUND: The arterial system of the upper extremities in man shows drastic developmental changes and many individual variations related to interspecific variations in primates. The ontogenetic development in Tupaia was examined from the viewpoint of comparative embryology. METHODS: Histological specimens of 39 embryos were observed and reconstructed in three dimensions using a computer program. Four adult animals were dissected and examined with angiography to ascertain the end stage of development. RESULTS: At the proximal end of the upper arm the deep brachial artery appears first as a concomitant vessel with the radial nerve. It becomes reduced in size and is succeeded by the posterior circumflex humeral artery, which is accompanied initially by the axillary nerve and finally by the radial nerve. The main arterial passageway to the fingers consists of the brachial and interosseous arteries during early development. The superficial brachial artery and median artery are formed later, and their connection becomes the main route of blood supply for the finger arteries up to the adult stage. The ulnar artery is formed at the end of arterial development to form the ulnar end of the superficial palmar arch. The superficial antebrachial arteries are also recognized. CONCLUSIONS: All the arterial elements of the forelimb in Tupaia are observed in a variety of primates, including man, and the characteristics of Tupaia are thought to represent the primitive conditions of the common ancestor of tree shrews and primates.

Angiography↗

PubMed1981

Postnatal histogenetic death of rat forelimb motoneurons.

Previous workers have reported a five fold decrease in motoneuron numbers occurring from birth to adulthood in the rat. It has also been reported that forelimb muscles receive connections from motoneurons in both ventral horns prior to day 14 of life in the rat and that the contralateral cells subsequently degenerate completely by day 21. In the present study, postnatal changes in motoneuron number and distribution within the ventral horn were studied in the rat using the technique of retrograde horseradish peroxidase (HRP) transport following intramuscular infusion of HRP into biceps brachii (BB). Peripheral nerves other than those to BB were sectioned and ligated to control for HRP diffusion. The spatial organization of BB motoneurons was compared in animals 9-14 days old and adult animals using computer 3-D reconstruction. This allowed observations of the BB motoneurons from a variety of perspectives in relationship to a number of spinal cord landmarks and avoided the necessity for transverse and horizontal sectioning of the cords in alternate animals. A decrease of 50-75% in the number of HRP filled motoneurons number was found from birth to adulthood (adults 98-150, neonates 172-243). The spatial arrangement of the BB motoneurons with regard to the root entry zones and other landmarks such as the dorsolateral convexity of the ventral horn, remains constant from birth to adulthood. No evidence was found to support the existence of inappropriate connections from motoneurons in either the ipsi or contralateral ventral horns of neonate rats. It is suggested that the comparatively small decreases in motoneurons postnatally could be a continuation of the histogenetic processes of cell death begun in utero and is related to the postnatal development of the central and peripheral connections of motoneurons.

Aging↗

PubMed1982

Electrophysiologic studies of cutaneous nerves of the forelimb of the cat.

The cutaneous innervation of the forelimb was investigated in 20 barbiturate-anesthetized cats by using electrophysiological techniques. The cutaneous area (CA) innervated by each cutaneous nerve was delineated in at least six cats by brushing the hair in the CA with a small watercolor brush while recording from the nerve. Mapping of adjacent CA revealed larger overlap zones (OZ) than were noted in the dog. Remarkable findings were that the brachiocephalic nerve arose from the axillary nerve and the CA comparable to that supplied by the cutaneous branch of the brachiocephalic nerve in the dog was supplied by a cutaneous branch of the suprascapular nerve. The CA supplied by the communicating branch from the musculocutaneous to the median nerve was similar in both species except that the communicating branch arose proximal to any other branches of the musculocutaneous nerve in the cat, whereas it was a terminal branch in the dog. The superficial branch of the radial nerve gave off cutaneous brachial branches in the cat proximal to the lateral cutaneous antebrachial nerve. The CA of the palmar branches of the ulnar nerve did not completely overlap the CA of the palmar branches of the median nerve as occurred in the dog; thus an autonomous zone (AZ) for the CA of the palmar branches of the median nerve is present in the cat, whereas no AZ existed for the CA of this nerve in the dog.

Animals↗

PubMed1983

The growth of nerves in relation to the formation of premuscle cell masses in the developing chick forelimb.

A description is given of the growth of segmental nerves 13 to 16 (SN13 to SN16) from the brachial myotomes into the ventral and dorsal premuscle cell masses of the chick forelimb. At stage 25 (Hamburger and Hamilton, '51), segmental nerves have converged to form two nerve trunks which enter the ventral and dorsal premuscle cell masses. These nerves grow into the limb, parallel to its proximodistal axis. The nerve trunk in the ventral compartment, the brachialis longus inferior (bli n), grows on the brachial artery as far as the metacarpals. The nerve trunk in the dorsal compartment, the brachialis longus superior (bls n), grows on the precartilage adjacent to a dorsal premuscle density as far as the metacarpals. The brachialis longus inferior and superior nerve trunks give rise to a number of nerves during their growth to the metacarpals. Each of these nerves appears at the time of formation of a new premuscle cell density. At late stage 25, a posterior and ventral premuscle density forms in the middle of the stylopodium; posterior fascicles of the bli n diverge at this level and grow toward this new density to form the ulnar nerve. By stage 26 a posterior and ventral premuscle density is prominent over the bli n, at the junction of the stylopodium and the zeugopodium; ventral fascicles of the bli n grow into this density to form the flexor digitorum profundus nerve. At this stage a posterior and dorsal premuscle density forms just beyond the junction of the stylopodium and zeugopodium. Posterior fascicles of the bls n diverge at this level and grow toward this density to form a nerve from which the extensor metacarpi ulnaris, extensor digitorum communis, and radialis laterialis nerves are destined to form. At stage 29 the premuscle cell masses of the autopodium have formed. The remaining nerve fascicles comprising the bls n (the radialis profundus nerve) grow into the autopodium and branch to innervate each of the dorsal premuscles. The remaining nerve fascicles comprising the bli n (the middle nerve) grow into the autopodium and branch to innervate each of the ventral premuscles.

Animals↗

PubMed1985

The somatotopic organization of forelimb cutaneous nerves in the brachial dorsal horn: an anatomical study in the cat.

The projection of forelimb cutaneous nerves to the brachial dorsal horn was studied in the cat by the transganglionic transport method. The results demonstrate a precise somatotopic termination pattern. Afferent nerves from the paw occupy the largest area, with the palm represented most medially in the dorsal horn, followed progressively more laterally by the representations for the palmar and dorsal surfaces of the digits and the dorsum of the paw. The digits are represented in a longitudinal sequence, with the first digit in the caudal part of C6 and the fifth in the caudal part of C8. The projections of the wrist and arm are split, with the line of discontinuity located along the ventral surface of the limb, so that the radial side is represented rostral to the paw and the ulnar side caudal to the paw, with the dorsal surface of the arm represented lateral to the paw. Nerves innervating the skin of the back project to the lateralmost part of the dorsal horn. The degree of overlap or separation of the terminal fields of the nerves along the mediolateral axis of the dorsal horn seems to correspond to the degree of overlap or separation of the peripheral innervation fields. However, along the rostrocaudal axis there appears to be an overlap for which there is no counterpart peripherally.

Afferent Pathways↗

PubMed1995

Evolution of cortical responsiveness subsequent to multiple forelimb nerve transections: an electrophysiological study in adult cat somatosensory cortex.

Multiunit recordings along mediolateral rows in the primary somatosensory cortex of the animals described by C. Avendaño, D. Umbriaco, R.W. Dykes, and L. Descarries (1995, J. Comp. Neurol. 354:321-332) provided information about the functional status of the regions in and near the deafferented cortex. Responses changed along this axis from normally organized receptive fields in the hindlimb representation through a transition zone of unusually small receptive fields into the clearly deafferented forelimb representation, where receptive fields were uncommon and often had unusual characteristics. The most abrupt change along this axis was the appearance of a repetitive, bursting discharge pattern in the multiunit activity near the border of the deprived cortex. The appearance of this pattern was used as a reference to describe differences between normal and deprived cortices. The nature of these differences evolved with time. Much of the deprived cortex lacked identifiable receptive fields for months after the nerve transections and, 1 year later, still only about half of the recording sites within the deprived region displayed organized receptive fields. Some sites within the deprived region lacking definable receptive fields could be excited at long latencies by somatic stimuli anywhere on the body. With time, regions of normal cortex near the border with the deprived zone became more involved in these processes. Spontaneous activity and thresholds also changed with time in both normal and deprived cortices.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

PubMed2003

Bone formation during forelimb regeneration: a microtomography (microCT) analysis.

In our study of bone regeneration in the forelimbs of mature newts (Notophthalmus viridescens), we used noninvasive X-ray microtomography (microCT) to image regenerating limbs from 37 to 85 days and matching (contralateral) controls. We compared the patterns of regenerated and existing (nonregenerated) bone, investigating in particular the onset of mineralization of specific bones, the level of mineral present, and the lengths of the different bones. Overall, we find that the missing limb skeletal elements are restored in a proximal-to-distal direction, which reiterates the developmental patterning program. However, in contrast to this proximal-distal sequence, the portion of the humerus distal to the amputation site fails to ossify in synchrony with the regenerating radius and ulna. This finding suggests that the replacement of cartilage with mineralized bone close to the amputation site is delayed with respect to other regenerating skeletal elements.

Animals↗

PubMed2005

Identification of cDNAs associated with late dedifferentiation in adult newt forelimb regeneration.

Epimorphic limb regeneration in the adult newt involves the dedifferentiation of differentiated cells to yield a pluripotent blastemal cell. These mesenchymal-like cells proliferate and subsequently respond to patterning and differentiation cues to form a new limb. Understanding the dedifferentiation process requires the selective identification of dedifferentiating cells within the heterogeneous population of cells in the regenerate. In this study, representational differences analysis was used to produce an enriched population of dedifferentiation-associated cDNA fragments. Fifty-nine unique cDNA fragments were identified, sequenced, and analyzed using bioinformatics tools and databases. Some of these clones demonstrate significant similarity to known genes in other species. Other clones can be linked by homology to pathways previously implicated in the dedifferentiation process. These data will form the basis for further analyses to elucidate the role of candidate genes in the dedifferentiation process during newt forelimb regeneration.

Aging↗

PubMed2006

Newt orthologue of Growth arrest-specific 6 (NvGas6) is implicated in stress response during newt forelimb regeneration.

Red-spotted newts are capable of regenerating various structures and organs through the process of epimorphic regeneration. Receptor tyrosine kinases (RTKs) and their ligands are important for normal cellular development and physiology but most have not yet been characterised during regeneration. We have isolated a newt orthologue of Growth arrest-specific 6 (NvGas6), and examined its expression during forelimb regeneration and within a blastema cell line (B1H1). During limb regeneration, NvGas6 expression increases upon amputation, peaks during maximal blastema cell proliferation, and is subsequently downregulated during redifferentiation. Transcripts are localised to the wound epithelium and distal mesenchymal cells during dedifferentiation and proliferative phases, and scattered within redifferentiating tissues during later stages. In B1H1 cultures, NvGas6 is upregulated under reduced serum conditions and myogenesis. Treatment with mimosine and colchicine or exposure to heat shock or anoxia results in upregulation of NvGas6 expression. Taken together, our findings suggest that during regeneration, NvGas6 expression may be upregulated in response to cellular stress.

Amino Acid Sequence↗

PubMed1975

Disruption of normal forelimb regeneration in adult Notophthalmus viridescens by sublethal concentrations of trypan blue.

The effects of the vital dye trypan blue (TpB) on the regeneration of amputated newt forelimbs were examined. Administration of the dye (10 mug/g body weight) via IP injection during the early wound healing and dedifferentiation phases of regeneration inhibited the normal regenerative response. The accumulation phases of regeneration are similarly halted but only by greater concentrations of TpB (50 mug/g body weight) while redifferentiation and morphogenesis are only affected by still greater concentrations of the dye (100 mug/g body weight). In addition to abolishing the regenerative response, low levels of TpB were also capable of inducing skeletal abnormalities in the regenerates as might be expected from previous reports on the teratogenicity of the dye. The in vitro action of newt hyaluronidase (as well as purified testicular hyaluronidase) on hyaluronate was diminished by TpB, with virtually complete inhibition observed at initial reaction mixture concentrations of 100 mug/ml. The results of this study suggest that TpB acts to disrupt the normal regenerative response by preventing dedifferentiation and remodeling, perhaps by inhibition of various necessary lytic enzyme functions or by interference with normal intercellular communications.

Animals↗