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Corticostriatal projections from distal and proximal forelimb representations of the monkey primary motor cortex.

Corticostriatal projections from one distal and two proximal subregions in the forelimb representation of the primary motor cortex (MI) were examined in the macaque monkey. The distal and proximal subregions in the anterior bank of the central sulcus (distal and proximal-bank subregions) and the proximal subregion in the surface of the precentral gyrus (proximal-surface subregion) of the MI were identified using intracortical microstimulation. Different anterograde tracers were then injected into two of these three forelimb subregions of the MI. In the ipsilateral putamen, the distribution areas of corticostriatal fibers from the distal, proximal-bank and proximal-surface subregions were arranged from ventrolateral to dorsomedial in this order. These corticostriatal input zones were largely segregated from one another.

Animals↗

The effects of forelimb deafferentation on the post-natal development of synaptic plasticity in the hippocampus.

The effects of partial deafferentation of the forelimb on the development of long-term potentiation in the hippocampus of rats aged 13-18 days were studied. Long-term potentiation in hippocampus field CA1 was of greater amplitude and duration in control rats at 16-18 days of post-natal ontogenesis than in adult animals. Partial deafferentation by section of the median nerve in the forelimb on the 13th day of life led to the disappearance of this excess at 16-18 days. The peak in synaptic plasticity occurred later in operated animals--on day 17--and was much less marked than in controls. The decreases in the amplitude and duration of long-term potentiation in hippocampal field CA1 in operated animals provides evidence for a decrease in the sensitivity and/or number of NMDA receptors. This suggests that partial deafferentation of one limb may lead not to a decrease but to an increase in spike and synaptic activity in the hippocampus, which in normal conditions may affect the maturation of the plastic properties of synaptic transmission associated with the expression and positions of NMDA receptors. The level of long-term potentiation in sham-operated rats was significantly greater than in controls of the same age. This significant increase in NMDA-dependent long-term potentiation may be explained by a decrease in the level of activation due to anesthesia. It is suggested that the decrease in the spike activity of cells receiving signals from the median nerve may be compensated for by activation of other specific and non-specific inputs.

Aging↗

Dantrolene diminishes forelimb force-related tremor at doses that do not decrease operant behavior in the rat.

A behavioral preparation that affords concurrent measurement of forelimb force and tremor in rats was used to assess the effects of dantrolene sodium, a muscle relaxant and potential neuroprotective drug. Rats that were trained to press downward on an isometric force transducer while simultaneously licking water reinforcement were administered dantrolene (5.0 mg/kg, 7.5 mg/kg, and 10.0 mg/kg). Dantrolene diminished force output at the 7.5 mg/kg and 10.0 mg/kg doses and decreased tremor at all three doses. Dantrolene decreased the ratio of forelimb tremor to force output at all three doses. Dantrolene did not suppress operant behavioral output at these doses. These results suggest that dantrolene may affect fine motor control and decrease tremor at doses that do not produce behavioral suppression.

Animals↗

Inter-breed differences in equine forelimb kinematics at the walk.

Linear, temporal and angular biokinematic characteristics of the forelimb at the walk in different breeds were determined, highlighting inter-breed differences. Twenty-three healthy stallions were used: ten Andalusians (AN), seven Arabs (AR) and six Anglo-Arabs (AA). Height at the withers was significantly different between groups (P < 0.001). Six trials per horse were recorded using a levelled video camera (sampling frame rate 25 frames/s), digitized and analysed using a semi-automatic movement analysis system. No statistically significant differences in speeds were recorded between breeds (P > 0.05). The only temporal parameter which was similar in the three breeds was the moment at which the hoof reached the highest point in its trajectory. The variables presenting the most significant differences were the percentages of deceleration and propulsion within the stance phase. ANOVA for angular variables showed that the greatest difference was in the range of angular movement of the carpal joint, being higher in AN, due to a lower minimum value. In the fetlock joint, the greatest difference was observed in minimum values, which differed in all three breeds. Significant inter-breed differences were also observed for maximum limb retraction, being lowest in the AN group, followed by the AA and AR groups. This finding was reflected in the angular range of motion, despite smaller differences in the degree of limb protraction; very similar values were reported in all three breeds. As regards the elbow joint, no inter-breed differences were observed in terms of minimum values, whereas differences were recorded for maximum and angular range of motion, higher values being displayed by the AR and AN groups than by AA animals. In conclusion, inter-breed differences may be determined in equine forelimb biokinematics at the walk. This study distinguished between AN, AR and AA horses.

Animals↗

Effects of peripheral nerve implants on the regeneration of partially and fully innervated urodele forelimbs.

This study addresses the cellular mechanism of the nerve requirement for regeneration of the urodele forelimb. Others have suggested that only the Schwann cell lineage of the blastema requires nerves for regeneration and that upon limb denervation, Schwann cells arrest in the cell cycle and produce a factor that inhibits the cycling of the remaining blastema cells. Our objective was to test this Schwann cell inhibitor model. First, pieces of peripheral nerve were implanted into partially denervated (one third of the nerve supply cut) axolotl forelimbs in an attempt to provide sufficient additional Schwann cells to increase the threshold nerve requirement above that provided by the remaining nerves. These limbs showed delayed regeneration in 68% of the cases and mild deformities, as seen by Victoria Blue staining, in 10% of the cases, as compared with control, partially denervated contralateral limbs that received grafts of muscle or frozen/thawed nerve. Second, when pieces of peripheral nerve were implanted into fully innervated newt limbs, blastema formation was limited, and regeneration was delayed in 80% of experimental cases when compared with control, contralateral newt limbs with muscle or frozen/thawed nerve implants. The results support the inhibition model and further link the need for nerves in regeneration to a possible specific requirement by Schwann cells.

Amputation, Surgical↗

The implication of repeated versus continuous strain on nerve function in a rat forelimb model.

We studied the effect of repeated and continuous nerve strain using a rat forelimb model to investigate whether an innocuous level of strain applied continuously affects nerve function when applied repeatedly. We used the rat medial cord of the brachial plexus and assessed the effects of strain by studying nerve histology (blood-nerve barrier), function (grasping strength), and electrophysiology. Continuous stretching was applied to the rat forelimb for 1 hour at 2 N. After this strain neither histologic analysis, grasping strength, nor electrophysiologic analysis revealed any effect. We then applied repeated strain at both 60 and 120 times per hour; after the latter strain abnormalities in histology, grasping strength, and nerve conduction were identified. There results suggest that a small nerve strain applied repeatedly results in nerve dysfunction. Our data may help explain the cause of nonspecific neural symptoms in the upper extremities of patients with no objective findings.

Animals↗

Effects of forelimb amputation and denervation on protein synthesis in spinal cord ganglia of the newt.

Analysis of the effects of forelimb amputation and denervation on [35S]methionine incorporation into the protein of newt brachial plexus nerve ganglia showed that amputation increases the level of protein synthesis about 4-fold as compared with that of control (nonamputated) animals. Denervation without amputation nearly doubles the level of protein synthesis as compared with controls. Analysis of labeled protein by means of two-dimensional gel electrophoresis and radioautogram revealed incorporation patterns that are similar to controls; this observation suggests that amputation affects nerve cells quantitatively rather than qualitatively, in influencing the production of putative neurotrophic agents. A group of basic proteins ranging in Mr from 15,000 to 31,000 are prominently expressed in these radioautograms from experimental ganglia and may be important in promoting forelimb regeneration in the newt.

Amputation, Surgical↗

Growth of forelimb allografts in young rabbits immunosuppressed with cyclosporine.

Seventeen forelimbs were transplanted orthotopically from young Dutch rabbits to young New Zealand rabbits treated with cyclosporine. The transplanted limbs demonstrated significant bone growth. The growth in the transplanted limbs was about 75 to 80% of that observed in the unoperated limb. The long bones of the 3 longest surviving rabbits (133 days, 150 days, 150 days) studied radiographically demonstrated increases in length over their original lengths (humerus 22%, ulna 26%, and radius 31%). Hair and nail growth were noted at about day 10. Response to pain stimuli (withdrawal of forelimb) and functional use (ambulation with 50% weight bearing) was seen at two to three months. Permanent survival was not achieved because of a species-specific toxic wasting syndrome from cyclosporine.

Animals↗

Distribution of neurally activated postjunctional adrenoceptors in cat forelimb vasculature.

We assessed the relative contribution of postjunctional alpha-adrenoceptor subtypes in neurally evoked vasoconstrictor responses in the forelimb of anesthetized cats. Preganglionic stimulation of the thoracic sympathetic nerve trunk produced frequency-related decreases in blood flow of the entire forelimb as measured by ultrasonic flowmetry as well as vasoconstriction in the digital cutaneous bed as measured by laser-Doppler flowmetry. Vasoconstrictor responses were not altered significantly by intravenous (i.v.) treatment with propranolol (1 mg/kg) or atropine (1 mg/kg). In the entire limb, prazosin, (3-100 micrograms/kg i.v.) was a more potent antagonist of neurally evoked responses as compared with rauwolscine. In contrast, rauwolscine (10-300 micrograms/kg i.v.) was a more effective antagonist in the cutaneous bed. Combined treatment with both prazosin and rauwolscine was far more effective than either antagonist given alone in blocking vasoconstriction regardless of the measurement site. Moreover, basal cutaneous blood flow was increased by rauwolscine but not by prazosin. These results suggest that both subtypes of postsynaptic alpha-adrenoceptors are activated by sympathetic nerve stimulation. In the cutaneous bed, alpha 2-adrenoceptors appear to predominate. In addition, cutaneous vascular tone also appears to be regulated by hormonal alpha 2-adrenoceptor activation in cats.

Adrenergic alpha-Antagonists↗

Hand development and sequence of ossification in the forelimb of the European shrew Crocidura russula (Soricidae) and comparisons across therian mammals.

Hand development in the European shrew Crocidura russula is described, based on the examination of a cleared and double-stained ontogenetic series and histological sections of a c. 20-day-old embryo and a neonate. In the embryo all carpal elements are still mesenchymal condensations, and there are three more elements than in the adult stage: the 'lunatum', which fuses with the scaphoid around birth; a centrale, which either fuses with another carpal element or just disappears later in ontogeny; and the anlage of an element that later fuses with the radius. Carpal arrangement in the neonate and the adult is the same. In order to compare the relative timing of the onset of ossification in forelimb bones in C. russula with that of other therians, we built up two matrices of events based on two sets of data and used the event-pair method. In the first analysis, ossification of forelimb elements in general was examined, including that of the humerus, radius, ulna, the first carpal and metacarpal to ossify, and the phalanges of the third digit. The second analysis included each carpal, humerus, radius, ulna, the first metacarpal and the first phalanx to ossify. Some characters (= event-pairs) provide synapomorphies for some clades examined. There have been some shifts in the timing of ossification apparently not caused by ecological and/or environmental influences. In two species (Oryctolagus and Myotis), there is a tendency to start the ossification of the carpals relatively earlier than in all other species examined, the sauropsid outgroups included.

Alligators and Crocodiles↗

Assessment of the biological performance of the needle-free injector INJEX using the isolated porcine forelimb.

BACKGROUND: The development and utilization of novel needle-free injection devices in order to minimize needle stick injuries make increasing demands for suitable assay systems, which reflect the physiological situation in humans as close as possible. OBJECTIVES: It was therefore the goal of the present study to test the biological performance of a needle-free injector (INJEX) by the use of porcine skin as a model with a high predictive value for the feasibility in humans because of its close similarity to human skin. METHODS: In order to use porcine skin in the context of the underlying tissues, the isolated porcine forelimb was chosen as an assay model for use with the INJEX injector. Ink or the fluorescent dye fluorescein-isothiocyanate was injected and the penetration depth was determined metrically and dye distribution histologically. To assess the resorption of heparin, needle injection was compared with needle-free injection in a perfused limb model. RESULTS: Increasing amounts of ink increasingly penetrated into subcutaneous tissue layers in a cone-shaped manner mainly following lead structures. Penetration was hampered by skin thickness and by the deep muscle fascia, which served as a penetration barrier. Resorption of heparin was similar irrespective of injection by the use of a needle or the INJEX device. CONCLUSIONS: The isolated porcine forelimb serves as a versatile tool for the assessment of the biological performance of needle-free injection devices such as INJEX. Further studies are necessary to correlate the model for drug delivery in humans.

Absorption↗

Demonstration of congenital anomalies in the joints of the forelimbs and hindlimbs caused by several pharmacological agents.

In this study, fetal joint abnormalities caused by cytosine arabinoside, caffeine, sodium salicylate, and retinyl acetate administration during pregnancy, were investigated. In the cytosine-arabinoside-administered group, complete disappearance of joint spaces in the forelimbs, and narrowing or complete disappearance of joint spaces in the hindlimbs was highly noticeable. In the caffeine group, in all forelimb joints starting from art, humeri, there were abnormal fusions in bones, together with occasional disappearance of the joint space. In hindlimbs, similar findings were observed. In the sodium salicylate group, the complete disappearance of joint space and surfaces among humerus-radius and ulna was striking, and occasional fusions in tarsometatarsal joints were also present. Severe narrowing of the same joint space in the retinyl acetate group was striking. Total disappearance of the articulation manus and carpometacarpal joints was observed, together with hindlimb joint and bone findings.

Abnormalities, Drug-Induced↗

Treatment of forelimb growth plate deformity in 11 dogs by radial dome osteotomy and external coaptation.

Radial dome osteotomy and external coaptation were used to correct forelimb growth deformities with carpal valgus angles of 15 to 43 degrees in 11 dogs (12 forelimbs). Osteotomy sites were clinically healed by week 4. Appearance and function in 10 limbs was good to excellent. The angular deformity recurred in one dog by week 4 due to partial closure of the distal radial growth plate. Carpal valgus recurred in one dog by week 2 because the ulnar osteotomy healed before radial growth ceased.

Animals↗

Effect of heel elevation on forelimb conformation in horses.

OBJECTIVE: To determine the conformational changes in the distal forelimb of horses following heel elevation of 15 degrees and greater. An experimental study with repeated, within-horse measurements. PROCEDURE: Five clinically normal, mixed-breed horses were used to determine distal forelimb conformation following heel elevation from 0 to 45 degrees in 15 degree increments. Data were also compared to conformation of the limb in a Kimzey splint. Conformation was determined using lateral to medial radiographic projections. Conformation parameters assessed included measurement of apparent lengths of digital flexor tendons from the origin of their accessory ligaments to the points of insertion, and the joint angles of the distal limb. RESULTS: For angles of heel elevation from 15 to 45 degrees, the degree of joint angulation increased (increasing flexion) with heel elevation for the metacarpophalangeal, and proximal and distal interphalangeal joints. Conversely, the measured apparent lengths of the digital flexor tendons in the distal limb, decreased. CONCLUSION: The data supports the practice of elevating the heel (greater than 15 degrees) for conditions in which decreased fetlock extension may be desired such as with laceration or injury to the digital flexor tendons. Further study is required to determine whether heel elevation greater than 15 degrees reduces in vivo digital flexor tendon tension and also to ensure that the marked flexion of the distal interphalangeal joint with greater heel elevation is not detrimental over a prolonged period that may be required for the rehabilitation of flexor tendon injuries in the horse.

Animals↗

New in vitro procedures for experimental studies on the development of 11-day mouse embryo forelimb buds.

A new method has been developed for culturing 11-day mouse forelimb buds in vitro. In cultures performed with conventional procedures, skeletal pieces frequently appeared distorted and reduced in size. Moreover, forelimb buds explanted from embryos younger than a stage corresponding to 50 pairs of somites developed narrow hand plates devoid of radiated autopods. By contrast, in the new procedure using media supplemented with fetal calf serum and growth factors and enhancing distal feeding with carrier implants of catgut, enlarged pads were obtained that exhibited at least 4 digital rays in buds explanted from embryos with 40-44 pairs of somites. Compared with conventional procedures, the mean value of DNA content per limb bud was twice as great with use of our improved method. The ability of limb bud cells to proliferate and differentiate when cultured either in classical or in modified conditions, and the importance of the technical procedures, are discussed in the new prospect of in vitro developmental studies.

Animals↗

Ultrasonographic assessment of the proximal digital annular ligament in the equine forelimb.

Ultrasonography was used with 6 normal cadaver forelimbs of Dutch Warmblood horses to delineate the ultrasonographic anatomy of the palmar pastern region, with emphasis on the proximal digital annular ligament. Using a 5.5 MHz sector scanner, the thin proximal digital annular ligament was not visible on offset sonograms. Only if the digital sheath in the normal limb was distended was the distal border of this ligament outlined. In all normal limbs the palmarodistal thickness of the combined skin-proximal digital annular ligament layer in the mid-pastern region was 2 mm. The flexor tendons and distal sesamoidean ligaments were easily identified as hyperechoic structures. Distension of the digital sheath in the normal limbs clearly outlined the anechoic digital sheath pouches. In 4 lame horses ultrasonography aided the diagnosis of functional proximal digital annular ligament constriction. In all 4 diseased forelimbs ultrasonography demonstrated thickening of the skin-proximal digital annular ligament layer and distension of the digital sheath. In one of these limbs the distended digital sheath was also thickened. The flexor tendons and distal sesamoidean ligaments were normal. There was no radiographic evidence of additional bone or joint lesions.

Animals↗

Power flow in the equine forelimb.

A method is described for the estimation of segmental powers and power flow during the stance phase in the equine forelimb, to demonstrate the sources and paths of energy flow through the limb segments. S-VHS video and force platform data were collected for 5 walking trials in a sound Dutch Warmblood horse. Two camera views were combined using direct linear transformation and the resultant sagittal plane positional and angular data used together with the vertical and cranio-caudal ground reaction forces to calculate moments about the ends of the 4 lowermost segments of the forelimb, and the reaction forces at the segment ends. Power flows were calculated across the proximal and distal ends of each segment and total segmental power computed. During initial and terminal stance, power flowed into the cannon segment proximally, and out distally. For the rest of stance, the flow in the cannon was distal to proximal. At the pastern, power flowed in proximally during initial loading, and out distally. For most of the rest of stance, the pattern of flow was distal to proximal, except for terminal stance, when power flowed in through both ends. The largest effect at the hoof is a loss of energy in terminal stance as power flowed out proximally and into the pastern. The pastern appears to receive most of the energy during loading and pushoff and transfers this energy up the limb during midstance.

Animals↗

Kinematics in horses at the trot before and after an induced forelimb supporting lameness.

The aim of this study was to analyse the biokinematic alterations caused by an induced lameness in the right forelimb of Dutch Warmblood (DWB) horses using a system of computer-aided normal videography. Five mature DWB were recorded with a videocamera (frame rate 1/25) from a lateral view before and after an induced lameness. Before videotaping, passive markers were placed on the skin, over easily identifiable anatomical references to determine the joint angles in the forelimb (always on the flexor side). Lameness was induced using special horseshoes. The lameness was evident at the trot and mild at walk. The images were analysed using a real time digitalising system combined with a previously designed spreadsheet. Linear, temporal and angular parameters (maximum, minimum and angular range of motion) along the stride were calculated as well as the moments of highest extension (Pmax) and flexion (Pmin), expressed as a percentage of the whole stride. Results before and after the induced lameness were compared by a paired Student's t test at a significance level of P<0.05. No differences in speeds before and after the induced lameness were found. Stride length was significantly shorter in the lameness condition. Stride duration was slightly shorter in lameness. The diagonal stance phase increased, while the swing phase decreased. Angular parameters changed mainly in elbow, carpus, fetlock and retraction-protraction angles. This indicated that the angular range of motion in the elbow and carpal joints decreased, and the elbow Pmin occurred later in the stride. The results are useful in the development of video-based equine lameness diagnostics.

Animals↗