Arthur Eberstein

Neuromuscular plasticity following limb immobilization.

SummaryThe effects of immobilization on the ultrastructure of the rat neuromuscular junction of type I and type II muscle fibres were studied both qualitatively and quantitatively. Muscle fibre areas were measured as well The plantaris muscle was immobilized in a shortened position by applying a plaster cast for three weeks. Immobilized muscles were then compared to normal litter mates. Both type I and type II immobilized muscle fibres atrophied. Endplates from type II muscle fibres exhibited greater amounts of degeneration than type I endplates. Degeneration consisted of nerve terminal disruption, exposed junctional folds, postsynaptic areas which contained little or no postjunctional folds, and subjunctional sarcoplasmic masses. In addition to degeneration, the type II endplates also exhibited regeneration in the same endplate consisting of small terminals associated with large expanses of junctional folds, several small terminals occurring within the same primary synaptic cleft, and several axons wrapped by the same Schwann cell. These observations suggest terminal axonal regeneration. Our results demonstrate that limb immobilization produces muscle atrophy as well as denervation-like changes at the neuromuscular junctions which leads to terminal axonal sprouting and an ultrastructural remodelling.

The effect of electrical stimulation on reinnervation of rat muscle: contractile properties and endplate morphometry

Denervated extensor digitorum longus muscles of Wistar rats were electrically stimulated in vivo for 4 days (2h per day) after peroneal nerve crush 1 cm from the muscle. Isometric contractile properties and endplate ultrastructure were measured on days 11 and 18. On day 11, the time to peak (116% of control) and 1/2-relaxation time (136% of control) for the twitch tensions of stimulated muscles measured in vivo were significantly less than those (127% and 157% of controls, respectively) of non-stimulated muscles. Peak twitch and tetanic tensions were not significantly different. The postsynaptic area of endplates for stimulated muscles were closer in size to controls than those for the non-stimulated ones. On day 18, no difference was found in the contractile responses between stimulated and non-stimulated groups. Similarly, the postsynaptic areas were the same for both groups. These results demonstrate that denervated muscle stimulated electrically for 4 days prior to reinnervation can preserve the structure of the endplate as well as accelerate recovery of normal function in reinnervated muscle fibers after 11 days of denervation.

Passive Exercise and Reinnervation of the Rat Denervated Extensor Digitorum Longus Muscle after Nerve Crush

Denervated extensor digitorum longus muscles of Wistar rats were passively exercised for 4 days (2 h/day) after peroneal nerve crush 1 cm from the muscle. Isometric contractile properties and end plate ultrastructure were measured 11 days post crush. No significant differences were observed in tension characteristics between the exercised and non exercised muscles on day 11. However, the postsynaptic area of end plates for exercised muscles were closer in size to controls than those for the non exercised ones. In addition, the end plates from the exercised muscles exhibited increased numbers of axonal sprouts and terminals than non exercised muscles. These results demonstrate that denervated muscles exercised 4 days before reinnervation can preserve the structure of the end plate as well as enhance reinnervation and sprouting at these end plates after 11 days of denervation.

Myotonic muscle in mouse. A light and electron microscopic study in serial sections.

Abstract The EDL muscle of the Bar Harbor Strain C57BL 6Jdy 2j mouse was studied in serial section by light and electron microscopy. Phase contrast microscopy of 15 μm epon sections revealed fiber abnormalities such as central nucleation, atypical fiber diameter and regions of focal fiber necrosis; fiber splitting detected in such sections was a prominent feature of the myotonic muscle. Ultrathin resectioning of selected 15 μm sections showed additional alterations such as dilation of the sarcoplasmic reticulum, mitochondrial conglomerations and disruptions, sarcolemmal infolding and breakdown, and myofibrillar degeneration. The most notable neuropathic changes included distortion in shape and decrease in numbers of synaptic vesicles as well as axonal retraction, reduplication of the basement membrane, and the presence of dense bodies between axon and junctional sarcolemma. These data indicate the involvement of both muscle fiber and motor end plate in mouse myotonic dystrophy.

An electromyographic study of induced myotonia in rats.

Abstract A systemic electromyographic study has been made of myotonia in rats induced by the subcutaneous injection of 25-azacholesterol. The myotonia was characterized by trains of discharges continuously varying in frequency and amplitude (myotonic potentials) and spontaneous random bursts of short duration potentials. The mean duration of the myotonic motor unit action potentials were 1.6 ± 0.2 msec compared to 2.6± 0.4 msec for the normal action potentials. It was found that the fast muscles (anterior tibialis and gastrocnemius) became profoundly myotonic whereas the slow muscle (soleus) was virtually unaffected.

A noninvasive technique to assess completeness of spinal cord lesions in humans

The effect of scalp stimulation delivered through electrodes overlying the motor cortex was evaluated in five healthy subjects and six patients with traumatic spinal cord injury. The latency to the onset of the electromyographic response was measured in the biceps brachii and abductor pollicis brevis muscles. In all the patients, latencies to the muscle (biceps brachii) whose innervation originated above the lesion were in the normal range; whereas, latencies to the muscle (abductor pollicis brevis) whose innervation originated below the lesion were prolonged. Electromyographic signals were recorded in muscles which showed no voluntary motor activity. No lateral differences in latencies were found in healthy subjects; however, in the patients, significant differences were obtained between the right and left abductor pollicis brevis muscles. The results of this study demonstrate that the spinal cord of patients with a lesion deemed to be clinically complete, contains nerve fibers which descend through the lesion and are capable of conveying impulses leading to muscle contraction.

Long-term effects of partial denervation on sprouting and muscle fiber area in rat plantaris

The long-term effects of partial denervation on the muscle fiber cross-sectional area, degree of axonal sprouting, and end-plate morphology were examined 1, 3, 6, 9, and 12 months postsurgery in rat plantaris muscle. After 1 month of partial denervation, mean cross-sectional areas of type I and type II myofibers were significantly lower than that of sham-operated controls; fiber atrophy and hypertrophy was observed. After 3 months, we found no statistical difference in the mean cross-sectional fiber area between the two experimental groups. After 6 months, the fiber areas were now significantly larger than controls, possibly the result of compensatory work hypertrophy, due to the overuse of remaining hyperexpanded motor units. Preterminal, intranodal, and intraterminal sprouting were found to significantly increase from 1 to 6 months following partial denervation. While sprouting was enhanced, the number of terminal branch points per end plate did not change. Following 9 months of partial denervation and overuse, the mean fiber areas significantly decreased as compared to controls. The former muscles were found to contain angulated fibers, group atrophy, and increased levels of axonal sprouting. The number of terminal branches per end plate was now significantly increased over control values, possibly a compensatory response to reduced synthesis of neurotrophic factor(s) and/or transmitter-related components. At 12 months, fiber areas, axonal sprouting, and the number of terminal branches per end plate have all decreased. Degenerating end plates, denervated myofibers, angulated fibers, and group atrophy were observed. It would appear that aging-like changes are occurring earlier in chronically stressed, partially denervated muscles.

Clofibrate-induced myotonia in the rat

Clofibrate induced electromyographic and contractile responses in rats consistent with myotonia.

Transmembrane potentials of human muscle cells in vivo

Abstract A system was designed and constructed which permits recording the resting and action potential of muscle fibers in man in vivo . The procedure involves passing a cannula containing a microelectrode through the skin into the muscle. No anesthesia is required. An average resting potential of 77.5 mv (with a standard deviation of 11.3 mv and a standard error of 1.2 mv) was observed for the anterior tibial muscle in normal subjects.

Nerve sprouting and endplate growth induced in normal muscle by contralateral partial denervation of rat plantaris

The incidence of motor nerve and terminal sprouting was quantitatively analyzed in normal unoperated muscles, in homologous muscles contralateral to muscles which have been partially denervated, in partially denervated muscles, and in sham-operated muscles. Muscles were studied by light microscopy after staining motor endplates by a combined silver-cholinesterase stain. In addition, the incidence of endplates containing terminal sprouts, the number of terminal branch points per endplate, and endplate, and endplate size were also assessed in the various groups examined. We observed that following section of the L4 spinal nerve, the incidence of sprouting (preterminal and intranodal) in the contralateral muscle exhibited a 2-fold increase over sham-operated controls. We also found a correlation between nerve terminal sprouting, terminal branch point number and endplate size. All of these parameters were significantly increased in the contralateral muscles as compared to the sham-operated control muscles. These findings suggest that normal muscles undergo sprouting which can be enhanced by contralateral partial denervation. The possible underlying mechanism may be the transneuronal induction of sprouting.