Biomedical subjects

Arthur W English

Publications and source records attributed to Arthur W English.

9 recordsLinked to original sources

PubMed2006

Recovery of electromyographic activity after transection and surgical repair of the rat sciatic nerve.

The recovery of soleus (SOL), gastrocnemius (GAS), and tibialis anterior (TA) electromyographic activity (EMG) after transection and surgical repair of the sciatic nerve was studied in Sprague-Dawley rats using chronically implanted stimulation and recording electrodes. Spontaneous EMG activity in SOL and GAS and direct muscle (M) responses to posterior tibial nerve stimulation persisted for < or =2 days after sciatic nerve transection, but SOL and GAS H-reflexes disappeared immediately. Spontaneous EMG activity began to return 2-3 wk after transection, rose nearly to pretransection levels by 60 days, and persisted for the duration of the study period (120 days). Recovery of stimulus-evoked EMG responses began about 30 days after sciatic nerve transection as multiple small responses with a wide range of latencies. Over time, the latencies of these fractionated responses shortened, their amplitudes increased, and they merged into a distinct short-latency component (the putative M response) and a distinct long-latency component (the putative H-reflex). The extent of recovery of stimulation-evoked EMG was modest: even 100 days after sciatic nerve transection, the responses were still much smaller than those before transection. Similar gradual development of responses to posterior tibial nerve stimulation was also seen in TA, suggesting that some regenerating fibers sent branches into both tibial and common peroneal nerves.

Animals↗

PubMed2005

Enhancing axon regeneration in peripheral nerves also increases functionally inappropriate reinnervation of targets.

The specificity of reinnervation of peripheral targets by regenerating motor axons was studied in mice by using retrograde fluorescent tracers applied to the cut ends of the tibial and common fibular nerves after transection and surgical repair of the sciatic nerve. When the nerve ends were aligned and secured with fibrin glue, more motoneurons labeled after application of tracer to the common fibular nerve were found in regions of the spinal cord that normally contain only tibial motoneurons. The magnitude of such inappropriate reinnervation did not change at different times after repair. Intentional misalignment of the cut nerve stumps at the time of repair resulted in more extensive inappropriate reinnervation of the different peripheral targets. If the proximal stump of the cut nerve was electrically stimulated at the time of repair, if the distal stump was treated with chondroitinase ABC, or if both protocols were applied, the number of motoneurons labeled was increased. This increase was accompanied by more extensive reinnervation of inappropriate targets than found after untreated nerve repair. Although alterations in the caudorostral distributions of labeled motoneurons observed were not as great as observed after purposeful misalignment of the cut nerve ends, the topographic relationship between the spinal locations of motoneuron somata and the peripheral targets of their axons is disrupted. Enhancement of motor axon regeneration by induction of growth-promoting signaling pathways, reduction in growth inhibition in the environment of regenerating axons, or both, is accompanied by an increase in the amount of functionally inappropriate reinnervation of peripheral targets.

Animals↗

PubMed2005

Axon regeneration in peripheral nerves is enhanced by proteoglycan degradation.

Regeneration of axons in the peripheral nervous system is enhanced by the removal of glycosaminoglycan side chains (GAGs) of chondroitin sulfate proteoglycans. However, some axons regenerate poorly despite such treatment, suggesting the existence of additional inhibitors. We compared the effects of enzymatic removal of GAGs from chondroitin sulfate proteoglycans versus two other proteoglycan species, heparan sulfate and keratan sulfate proteoglycans, on the regeneration of peripheral axons. Common fibular (CF) nerves of thy-1-YFP-H mice were cut and repaired using short segments of CF nerves harvested from wild-type littermates and pre-treated with a GAG-degrading enzyme for 1 h prior to nerve repair. Axonal regeneration was assayed by measuring the lengths of profiles of YFP+ axons in optical sections of the grafted nerves 1 week later. Except for grafts treated with keratanase, more and longer axon profiles were encountered in enzyme-treated grafts than in control grafts. Heparinase III treatments induced the greatest number of axons to enter into the graft. The proportions of axon profiles longer than 1000 microm were greater in grafts treated with chondroitinase ABC or heparinase I, but not with either keratanase or heparinase III. More regenerative sprouts were observed after treatment with heparinase I than any other enzymes. Treatment with a mixture of all four enzymes resulted in an enhancement of axon regeneration which was greater than that observed after treatment with any of the enzymes individually. The effects of chondroitinase ABC and heparinase III were correlated with specific GAG degradation. We believe that enzymatic removal of GAGs is especially effective in promoting the ability of regenerating axons to select their pathway in the distal stump (or nerve graft) and, in the case of chondroitinase ABC or heparinase I, it may also promote growth within that pathway.

Analysis of Variance↗

PubMed2005

Neurotrophin-4/5 is required for the early growth of regenerating axons in peripheral nerves.

The requirement of the trkB ligand, neurotrophin-4/5 (NT-4/5), for the growth of regenerating axons in the peripheral nervous system (PNS) is not well established. We studied regenerating axon growth in transected peripheral nerves of thy-1-YFP-H mice that had been repaired using allografts obtained from brain-derived neurotrophic factor (BDNF) or NT-4/5 knockout mice. Lengths of profiles of YFP+ axons measured in these grafts were compared with those measured in grafts obtained from wild-type donors. When compared with axon profiles measured in grafts from wild-type donors, axon profile lengths measured in grafts from homozygous (NT-4/5(-/-)) or heterozygous (NT-4/5(+/-)) mice were significantly shorter. In contrast, the lengths of axon profiles measured in grafts from BDNF(+/-) mice were not significantly different from those measured in grafts from wild-type mice. A reduced amount of BDNF, but not NT-4/5, is sufficient to promote the elongation of regenerating axons in the PNS. When grafts from wild-type or NT-4/5(-/-) mice were treated acutely at the time of surgical repair either with exogenous BDNF or NT-4/5, the lengths of axon profiles measured in the grafts were significantly longer than those measured in grafts from untreated wild-type mice. These findings are consistent with a requirement for NT-4/5 from within the pathway used by regenerating axons for the successful growth of those axons in peripheral nerves.

Animals↗

PubMed2003

Sex differences in rabbit masseter motoneuron firing behavior.

To evaluate whether sex differences in the proportions of fibers of different phenotypes in the masseter muscle might be the result of differences in the behavior of their motoneurons, we studied the firing patterns of masseter motoneurons in adult male and female rabbits. Activity in individual motoneurons was determined from high spatial resolution EMG recordings made during cortically evoked rhythmic activation of the masticatory muscles. Although some motoneurons could be said to fire according to slow-tonic or fast-phasic patterns, most did not. In both sexes a substantial range of median firing rates and median firing durations was found. In adult males, masseter motoneurons fired more rapidly than those recorded from adult females. No significant sex differences in motoneuron firing duration were found. These results are consistent with the hypothesis that androgen-induced differences in rabbit masseter muscle fiber phenotype are a reflection of differences in motoneuron firing rate. Whether this effect of androgen is directly upon the motoneurons or is the result of a response of muscle fibers to androgen remains to be investigated.

Action Potentials↗

PubMed2003

Sex differences in rabbit masseter muscle function.

The proportions of fibers of different phenotypes in the rabbit masseter muscle differ strikingly in adult males and females. Muscles from females contain similar proportions of small fibers that express both the slow/beta and cardiac alpha myosin heavy chain (MyHC) isoforms and larger fibers containing the IIa MyHC isoform. In muscles from males, nearly 80% of fibers are of the IIa phenotype. To evaluate the functional significance of these sex differences, we used finely graded intramuscular microstimulation to study the contractile properties of masseter motor units in >6-month-old male and female rabbits. Twitch forces and torques in males were significantly greater in magnitude than those of females. Greater proportions of units that produced larger forces/torques were encountered in the males. The same motor units produced force or torque more rapidly in males than in females, principally because units in which twitch rise times were >22 ms were found only in females. The forces applied to the mandible and the torques generated about the right mandibular condyle were studied during cortically evoked rhythmic activation of the masticatory muscles. The overall range of torque rise times and the magnitudes of the peak torques did not differ between sexes. The mean rise time was significantly shorter and the mean peak torque was significantly greater in males. We conclude that sex differences in fiber phenotype proportions are reflected in sex differences in motor unit properties and in the function of these motor units during rhythmic activation.

Animals↗

PubMed2003

Neurotrophin 4/5 is required for the normal development of the slow muscle fiber phenotype in the rat soleus.

During normal postnatal development, rat soleus (SOL) muscle fibers undergo a dramatic fast-to-slow myosin heavy chain (MyHC) isoform transformation. We exploited this phenomenon to evaluate the role of neurotrophin 4/5 (NT-4/5) in the regulation of muscle fiber phenotype. Intramuscular injections of recombinant NT-4/5 into the SOL muscle of rat neonates significantly accelerated the normal fast-to-slow MyHC isoform transformation. Sequestration of endogenous NT-4/5 with TrkB-IgG prevented this transformation from occurring. Administration of the other TrkB ligand, brain-derived neurotrophic factor (BDNF), did not affect the normal course of the MyHC isoform transformation in this muscle, indicating that the observed effect is NT-4/5 specific. Botulinum toxin blockade of synaptic transmission significantly disrupted the normal fast-to-slow MyHC isoform switch. Because administration of NT-4/5 to paralyzed muscles failed to restore the normal course of this MyHC transformation, we believe that the effect of NT-4/5 is not directly on the muscle fibers but that it probably activates or forms a type of retrograde signal to motoneurons. The developmental upregulation of NT-4/5 mRNA in rat SOL muscle fibers occurred earlier than the upregulation of MyHC I/b mRNA associated with muscle fiber transformation. This timing is consistent with the idea that NT-4/5 is involved in early events that lead to the upregulation of the slow MyHC isoform in this muscle.

Animals↗

PubMed2002

Development of sex differences in the rabbit masseter muscle is not restricted to a critical period.

The proportions of muscle fibers of different phenotype in the adult rabbit masseter differ greatly in different sexes. These sex differences are not apparent in young adults, but arise under the influence of testosterone in the males. We examined whether this switch occurred during a critical period of postnatal development. Testosterone was administered to young adults 1, 2, or 4 mo after castration, and also to adult females. Samples of masseter muscle were taken at four monthly intervals after the onset of treatment and examined for the expression of different myosin heavy chain (MyHC) isoforms by using a panel of monoclonal antibodies. Despite the length of androgen deprivation, treatment with testosterone produced a marked MyHC isoform switch from alpha-slow/beta to IIa. This male proportion of fibers of different phenotypes persisted well beyond the return of serum testosterone levels to pretreatment levels. Thus brief exposure to testosterone produces a permanent change in the proportions of masseter muscle fibers of different phenotypes, and the capacity for this change is not restricted to a critical period.

Animals↗

PubMedDate not supplied

Cytokines, growth factors and sprouting at the neuromuscular junction.

The formation of neuronal sprouts, either from synaptic terminals or nearby nodes of Ranvier, is a widely known form of plasticity of motoneurons. Sprouts form in response to several stimuli, but most notably in partially denervated or paralyzed muscle. In search of the cellular or molecular basis of this phenomenon, several largely parallel lines of investigation have been pursued. Strong evidence is presented that at least four cytokines or growth factors may be involved in motoneuron sprouting, each of which uses a distinctive signaling pathway. Three of the different proposed sprouting molecules: neuroleukin, insulin-like growth factor, and neural cell adhesion molecules can be viewed as muscle-derived retrograde signaling molecules of roughly equal potency to induce motoneurons to sprout. A fourth molecule, ciliary neurotrophic factor (CNTF) is likely to form an essential anterograde signal, from Schwann cells to muscle fibers, that ultimately produces sprouting. Other cytokines and growth factors such a neurotrophins or GDNF family members are discussed, but their role in motoneuron sprouting is less clear. These cytokines and growth factors could represent redundant mechanisms for self-repair of the neuromuscular junction or they could interact at different levels of their cellular pathways.

Animals↗