RA regulation of keratin expression and myogenesis suggests different ways of regenerating muscle in adult amphibian limbs.
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Formation of a regeneration blastema following limb amputation is believed to occur through a process of dedifferentiation. It has been suggested, however, that the cells contributed to the blastema by the stump muscle are satellite-like cells, rather than cells originated by dedifferentiation. We have previously shown that simple epithelial keratins 8 and 18 are expressed in the mesenchymal progenitor cells of the regenerating amphibian limb and in cultured cells with myogenic potential, and that their expression appears to be causally related to changes in proliferation and differentiation. We show here that retinoic acid (RA) affects the expression of these keratins differently in myogenic cells originated from normal limb and limb blastema. Furthermore, we find that the effects of RA on proliferation, myogenic differentiation and adhesion of these cells also differ. In fact, whereas RA does not affect keratin expression, proliferation or myogenic differentiation in blastemal cells, it does decrease keratin levels and thymidine incorporation and increase myogenesis in cells from normal limb. Conversely, RA increases cell adhesion only in blastemal cells. Significantly, these effects of RA on cultured cells are consistent with those observed in vivo. Overall the results presented here suggest that in the urodele limb there are two distinct cell populations with myogenic potential, one originating from dedifferentiation and one equivalent to the satellite cells of the mammalian muscle, which are likely to be primarily involved in blastema formation and muscle repair, respectively. (+info)
Lengthening of congenital below-elbow amputation stumps by the Ilizarov technique.
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Patients with short congenital amputations below the elbow often function as if they have had a disarticulation of the elbow. We have reviewed the results in six patients who had lengthening of such stumps by the Ilizarov technique to improve the fitting of prostheses. The mean lengthening was 5.6 cm (3.4 to 8.4), and in two patients flexion contractures of the elbows were corrected simultaneously. Additional lateral distraction was used in one patient to provide a better surface on the stump. There were no major complications. All six patients were able to use their prosthesis at the latest follow-up after 39 to 78 months. (+info)
Thalamic and cortical contributions to neural plasticity after limb amputation.
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Little is known about the substrates for the large-scale shifts in the cortical representation produced by limb amputation. Subcortical changes likely contribute to the cortical remodeling, yet there is little data regarding the extent and pattern of reorganization in thalamus after such a massive deafferentation. Moreover, the relationship between changes in thalamus and in cortex after injuries of this nature is virtually unexplored. Multiunit microelectrode maps were made in the somatosensory thalamus and cortex of two monkeys that had long-standing, accidental forelimb amputations. In the deprived portion of the ventroposterior nucleus of the thalamus (VP), where stimulation to the hand would normally activate neurons, new receptive fields had emerged. At some recording sites within the deprived zone of VP, neurons responded to stimulation of the remaining stump of the arm and at other sites neurons responded to stimulation of both the stump and the face. This same overall pattern of reorganization was present in the deprived hand representation of cortical area 3b. Thus thalamic changes produced by limb amputation appear to be an important substrate of cortical reorganization. However, a decrease in the frequency of abnormal stump/face fields in area 3b compared with VP and a reduction in the size of the fields suggests that cortical mechanisms of plasticity may refine the information relayed from thalamus. (+info)
Suppression of hindlimb inputs to S-I forelimb-stump representation of rats with neonatal forelimb removal: GABA receptor blockade and single-cell responses.
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Neonatal forelimb removal in rats results in the development of inappropriate hindlimb inputs in the forelimb-stump representation of primary somatosensory cortex (S-I) that are revealed when GABA(A) and GABA(B) receptor activity are blocked. Experiments carried out to date have not made clear what information is being suppressed at the level of individual neurons. In this study, three potential ways in which GABA-mediated inhibition could suppress hindlimb expression in the S-I stump representation were evaluated: silencing S-I neurons with dual stump and hindlimb receptive fields, silencing neurons with receptive fields restricted to the hindlimb alone, and/or selective silencing of hindlimb inputs to neurons that normally express a stump receptive field only. These possibilities were tested using single-unit recording techniques to evaluate the receptive fields of S-I forelimb-stump neurons before, during, and after blockade of GABA receptors with bicuculline methiodide (for GABA(A)) and saclofen (for GABA(B)). Recordings were also made from normal rats for comparison. Of 92 neurons recorded from the S-I stump representation of neonatally amputated rats, only 2.2% had receptive fields that included the hindlimb prior to GABA receptor blockade. During GABA receptor blockade, 54.3% of these cells became responsive to the hindlimb, and in all but two cases, these same neurons also expressed a stump receptive field. Most of these cells (82.0%) expressed only stump receptive fields prior to GABA receptor blockade. In 71 neurons recorded from normal rats, only 5 became responsive to the hindlimb during GABA receptor blockade. GABA receptor blockade of cortical neurons, in both normal and neonatally amputated rats, resulted in significant enlargements of receptive fields as well as the emergence of receptive fields for neurons that were normally unresponsive. GABA receptor blockade also resulted in increases in both the spontaneous activity and response magnitudes of these neurons. These data support the conclusion that GABA mechanisms generally act to specifically suppress hindlimb inputs to S-I forelimb-stump neurons that normally express a receptive field on the forelimb stump only. (+info)
Reorganization of primary motor cortex in adult macaque monkeys with long-standing amputations.
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The organization of primary motor cortex (M1) of adult macaque monkeys was examined years after therapeutic amputation of part of a limb or digits. For each case, a large number of sites in M1 were electrically stimulated with a penetrating microelectrode, and the evoked movements and levels of current needed to evoke the movements were recorded. Results from four monkeys with the loss of a forelimb near or above the elbow show that extensive regions of cortex formerly devoted to the missing hand evoked movements of the stump and the adjoining shoulder. Threshold current levels for stump movements were comparable to those for normal arm movements. Few or no sites in the estimated former territory of the hand evoked face movements. Similar patterns of reorganization were observed in all four cases, which included two monkeys injured as adults, one as a juvenile, and one as an infant. In a single monkey with a hindlimb amputation at the knee as an infant, stimulation of cortex in the region normally devoted to the foot moved the leg stump, again at thresholds in the range for normal movements. Finally, in a monkey that had lost digit 5 and the distal phalanges of digits 2-4 at 2 yr of age, much of the hand portion of M1 was devoted to movements of the digit stumps. (+info)
The use of bone bridges in transtibial amputations.
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We sought to describe the bone bridge technique in adults, and present a variation for use in children, as well as to present its applicability as an option in elective transtibial amputations. This paper presents a prospective study of 15 transtibial amputations performed between 1992 and 1995 in which the bone bridge technique was employed. The patients' ages ranged from 8 to 48 years, with an average of 22.5 years. This technique consisted of the preparation of a cylinder of periosteum extracted from the tibia and with cortical bone fragments attached to it to promote a tibiofibular synostosis on the distal extremity of the amputation stump. We noted that the cortical bone fragments were dispensable when the technique was employed in children, due to the increased osteogenic capacity of the periosteum. This led to a variation of the original technique, a bone bridge without the use of the cortical bone fragments. RESULTS: The average time spent with this procedure, without any significant variation between adults and children, was 171 minutes. The adaptation to the definitive prosthesis was accomplished between 20 and 576 days, with an average of 180 days. Revision of the procedure was necessary in 3 amputations. CONCLUSIONS: This technique may be employed in transtibial amputations in which the final length of the stump lies next to the musculotendinous transition of the gastrocnemius muscle, as well as in the revision of amputation stumps in children, where the procedure has been shown to be effective in the prevention of lesions due to excessive bone growth. (+info)
Intracortical pathway involving dysgranular cortex conveys hindlimb inputs to S-I forelimb-stump representation of neonatally amputated rats.
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Reorganization of the primary somatosensory cortex (S-I) forelimb-stump representation of rats that sustained neonatal forelimb removal is characterized by the expression of hindlimb inputs that are revealed when cortical GABA receptors are pharmacologically blocked. Recent work has shown that the majority of these inputs are transmitted from the S-I hindlimb representation to the forelimb-stump field via an, as yet, unidentified pathway between these regions. In this study, we tested the possibility that hindlimb inputs to the S-I forelimb-stump representation of neonatally amputated rats are conveyed through an intracortical pathway between the S-I hindlimb and forelimb-stump representations that involves the intervening dysgranular cortex by transiently inactivating this area and evaluating the effect on hindlimb expression in the S-I forelimb-stump representation during GABA receptor blockade. Of 332 S-I forelimb-stump recording sites from six neonatally amputated rats, 68.3% expressed hindlimb inputs during GABA receptor blockade. Inactivation of dysgranular cortex with cobalt chloride (CoCl(2)) resulted in a significant decrease in the number of hindlimb responsive sites (9.5%, P < 0.001 vs. cortex during GABA receptor blockade before CoCl(2) treatment). Results were also compiled from S-I forelimb recording sites from three normal rats: 14.1% of 136 sites were responsive to the hindlimb during GABA receptor blockade, and all of these responses were abolished during inactivation of dysgranular cortex with CoCl(2) (P < 0.05). These results indicate that the S-I hindlimb representation transmits inputs to the forelimb-stump field of neonatally amputated rats through a polysynaptic intracortical pathway involving dysgranular cortex. Furthermore the findings from normal rats suggest that this pathway might reflect the amplification of a neuronal circuit normally present between the two representations. (+info)
Spinal cord atrophy and reorganization of motoneuron connections following long-standing limb loss in primates.
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Primates with long-standing therapeutic amputations of a limb at a young age were used to investigate the possibility that deefferented motor nerves sprout to new muscle targets. Injections of anatomical tracers into the muscles proximal to the amputated stump labeled a larger extent of motoneurons than matched injections on the intact side or in normal animals, including motoneurons that would normally supply only the missing limb muscles. Although the total numbers of distal limb motoneurons remained normal, some distal limb motoneurons on the amputated side were smaller in size and simpler in form. These results suggest that deprived motoneurons survive and retain function by reinnervating new muscle targets. The sprouted motor efferents may account for some of the reorganization of primary motor cortex that follows long-standing amputation. (+info)