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Biomedical subjects

B M Carlson

Publications and source records attributed to B M Carlson.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Power measurement of denervated muscle isografts with neurorrhaphy and nerve-implantation in rats].

The hypothesis was tested in this experiment that after 7 months of predencervation, the reinnervation of muscle grafts with neurorrhaphy results in greater recovery of force and power than with nerve-implantation. In a highly inbred strain of rats, soleus muscles were isografted. The donor muscles were either immediately denervated at the time of isografting or denervated 2, 4, 7 months prior to isografting. Soleus muscles from each donor group were transplanted into the right legs of hosts with either epineurial anastomosis (NR group) or nerve implantation (NI group). The contralateral soleus muscles of hosts served as controls. Sixty days after transfer, both right and left soleus grafts/muscles were evaluated for force and power measured in situ. The absolute force values were significant higher in NR group (61% of normal) than in NI group (40% of normal) in 2-month group but the result invenrsted in 7-month group, less than 20% and more than 20% of normal in NR and NI groups respectively. The reduced ability of grafts to generate force and power resulted from the different ways of reinnervation in denervated muscles and the period of predenervation. Maybe the nerve-implantation is better than the neurorrhaphy for reinnervating a long-term denervated muscle.

Anastomosis, Surgical↗
PubMed1997

Skeletal muscle regeneration during aging and after long-term denervation.

Data accumulated in recent years strongly suggest that the basis for at least part of the muscle atrophy seen in old age is related to the diminution of motor innervation in normal muscle and a decreased effectiveness of reinnervation of regenerating muscle fibers. Thus, attempts to stabilize reverse the decline of the skeletal musculature during aging must take into account both the effects of aging on the peripheral nervous system and the presence of populations of denervated muscle fibers in the aging muscles. Of considerable importance is the question of how long muscle fibers in old animals can remain denervated before they begin to lose their capacity for restoration if they ultimately become reinnervated. The experimental studies reviewed here have shown that normal muscles in old animals are capable of a high degree of restoration as long as their motor nerve supply remains undamaged. After a certain period of time, denervated muscle in young animals steadily loses the capacity to restore or repair itself. To date, so little information is available on the properties of denervated muscle in old animals that meaningful comparisons cannot be made. Ultimately, ensuring that normal or injured muscle in old individuals is supplied by an effective motor innervation may be a real key to the problems of muscle loss in old age, but if such could be provided, it will be important that the old musculature, whether normal or injured, is capable of adequately responding to the innervation.

Aging↗
PubMed1996

The recovery of long-term denervated rat muscles after Marcaine treatment and grafting.

Disruption of the nerve supply results in the rapid loss of mass and contractile force in skeletal muscles. These losses are reversible to a high degree in short-term denervated muscles with grafting and nerve implantation. However, return is much poorer in long-term denervated muscles. This study examined the basis for the differences in the recovery of non-denervated and 7-month denervated rat extensor digitorum longus (EDL) muscles after grafting and nerve implantation. We found that the level of recovery is related to the ability of muscle fibers to degenerate and regenerate after grafting. Fibers within long-term denervated muscles do not degenerate and regenerate as well as those within muscles which are not denervated prior to grafting. The functional recovery of the denervated muscles is significantly improved when their fibers are induced to degenerate with the myotoxic anesthetic, Marcaine, Degeneration of these fibers is followed by massive regeneration. The finding that denervated muscles are capable of being restored to a significant level by inducing regeneration may be useful in the clinical treatment of denervated muscles.

Analysis of Variance↗
PubMed1996

The regeneration of noninnervated muscle grafts and marcaine-treated muscles in young and old rats.

Free grafts of the extensor digitorum longus (EDL) muscle in 4-month-old rats regenerate 2-3 times better than in 24-month-old rats. Based on these data, we formulated the working hypothesis that deficient reinnervation is one of the most important age-related environmental factors within the host that might account for the poor regeneration. In the present experiments, we compared the regeneration of EDL muscles in two groups of young and old rats: (a) 21-day grafts, with fibers regenerating in the absence of nerves, and (b) Marcaine-treated muscle with fibers regenerating in the presence of uninterrupted innervation. The specific hypothesis was that, under each of these circumstances, reinnervation was not involved and age-related differences in regeneration would not be seen. Differences were assessed by measurements of mass and maximum isometric force normalized to values for age-matched control muscles. In the absence of nerves, the degree of regeneration in 21-day noninnervated EDL grafts was not significantly different between young and old rats. Similarly, when EDL muscles were damaged by Marcaine and regenerated in the presence of uninterrupted innervation, no differences were noted between young and old rats. These data support the working hypothesis that a deficiency in reinnervation with increasing age accounts, at least in part, for the poorer success of muscle regeneration in grafts in old compared with young rats.

Aging↗
PubMed1995

Adaptation of nicotinic acetylcholine receptor, myogenin, and MRF4 gene expression to long-term muscle denervation.

Muscle activity alters the expression of functionally distinct nicotinic acetylcholine receptors (nAChR) via regulation of subunit gene expression. Denervation increases the expression of all subunit genes and promotes the expression of embryonic-type (alpha 2 beta delta gamma) nAChRs, while electrical stimulation of denervated muscle prevents this induction. We have discovered that the denervation-induced increases in alpha, beta, gamma, and delta subunit gene expression do not persist in muscles that have been denervated for periods extending beyond a couple of months. However, expression of RNA encoding the epsilon-subunit remains elevated suggesting a return to expression of predominantly adult-type (alpha 2 beta delta epsilon) nAChR in long-term denervated muscles; a finding confirmed by single channel patch-clamp analysis. Since the nAChR subunit genes are regulated by the MyoD family of muscle regulatory factors, and the genes encoding these factors are also induced following short-term muscle denervation, we determined their level of expression in long-term denervated muscle. Although MyoD and myf-5 RNA levels remained elevated, myogenin and MRF4 RNAs were induced only transiently by muscle denervation. Surprisingly, Id-1, a negative regulator of transcription, was gradually induced in denervated muscle with RNA levels peaking about two months after denervation. It is likely that this maintained level of increased Id expression, in conjunction with the returning levels of myogenin and MRF4 expression, account for the reduced level of embryonic receptors in long-term denervated muscle. These changing patterns of gene expression may have important consequences for the ability of muscle to recover function after denervation.

Adaptation, Physiological↗
PubMed1995

Factors influencing the repair and adaptation of muscles in aged individuals: satellite cells and innervation.

From the standpoint of structure, the loss of muscle mass could be attributed to the loss of muscle fibers, the reduction of volume of persisting muscle fibers, or both. This review will concentrate upon factors that could contribute to the presence of thin muscle fibers in old muscles. One mechanism that could account for the presence of a population of thin muscle fibers is the loss of innervation due to the death or the remodeling of motor units in aging muscles. If the denervated muscle fibers fail to become reinnervated, or if they are unable to respond to reinnervation by new nerve terminals, they would undergo a progressive atrophy. If muscle fibers are damaged through exercise, direct trauma or other causes, they would degenerate and regenerate. Early regenerating muscle fibers are thinner than normal. If the regenerating muscle fibers are non-innervated, regeneration will not be complete; instead the regenerating muscle fibers will atrophy. All of the above mechanisms could contribute to an overall reduction in muscle mass. This review ends with an enumeration of outstanding questions concerning muscle atrophy and its reversal in old individuals.

Adaptation, Physiological↗
PubMed1992

Formation of the peripheral nervous system during tail regeneration in urodele amphibians: ultrastructural and immunohistochemical studies of the origin of the cells.

In the regenerating newt tail, epimorphic regeneration--which recapitulates morphologically normal embryonic development--proceeds along a rostrocaudal differentiation gradient. Innervation of the new myomeres results from the spinal roots of segments rostral to the amputation plane and from ventral roots emerging from the lateroventral region of the regenerating spinal cord, in which motor neurons are differentiating. Electron microscopy and an indirect immunofluorescence study with anti-glial fibrillary acid protein (GFAP) confirm that the ventrolateral part of the regenerated ependymal tube gives rise to cells of the ventral root sheath and the spinal ganglia. Anti-GFAP and anti-neurofilament antibodies showed that ependymoglial cells and Schwann cells may play a role in neuronal pathfinding by helping guide and stabilize pioneering axons as they extend toward the myomeres. The carbohydrate epitope NC-1 is expressed in the spinal cord, in sheath cells of the spinal ganglia and in the non-myelin-forming Schwann cells of the peripheral nervous system. L1, a Ca++ independent neural cell adhesion molecule, was detected in the axonal compartments of the regenerating spinal cord, on immature and/or non-myelin-forming Schwann cells within the peripheral nervous system (PNS), and on nerve fibers within the regenerate. These immunohistochemical observations collectively support the hypothesis that Schwann cells already present in the blastema could be involved in organizing neural pathways.

Animals↗
PubMed1992

Expression of alpha-cardiac and alpha-skeletal actin mRNAs in relation to innervation in regenerating and non-regenerating rat skeletal muscles.

The expression of alpha-cardiac and alpha-skeletal actin mRNA in regenerating muscle was examined. Changes in mRNA levels were analyzed in autografted extensor digitorum longus (EDL) muscles in rats using alpha-isoform specific synthetic oligonucleotides and beta-actin cDNA as probes. After autografting, the expression of alpha-cardiac actin mRNA was induced; concomitantly that of alpha-skeletal actin mRNA was reduced. The pattern of alpha-actin mRNA expression appeared to be similar to that seen in embryonic skeletal muscle. In order to evaluate the effects of innervation on alpha-actin mRNA expression in regenerating muscle, nerveless, standard, and nerve-intact autografted muscles were examined. More complete innervation facilitated the recovery of alpha-skeletal actin mRNA to control levels, but had little effect on the amount of alpha-cardiac actin mRNA. We found that regenerating muscle shows that embryonic pattern of alpha-actin mRNAs in the early stage and concluded that the recovery of alpha-skeletal actin mRNA expression to the adult pattern is influenced by innervation, while alpha-cardiac actin mRNA expression is nerve independent.

Actins↗
PubMed1992

Extraocular muscle regeneration in primates. Local anesthetic-induced lesions.

Retrobulbar administration of several local anesthetics (0.75% bupivacaine, 2.0% mepivacaine or 2.0% lidocaine plus 1:100,000 epinephrine) in monkeys resulted in a low incidence of muscle fiber lesions in the extraocular muscles closest to the site of injection. Most lesions resulted in the degeneration and regeneration of muscle fibers on the surface of the muscles, but occasionally a massive internal lesion was seen. In contrast, large lesions were common in rectus muscles that received direct injections of local anesthetics in both monkeys and humans. The morphology and temporal sequence of muscle fiber degeneration and regeneration was similar to that seen in primate thumb muscles injured by anesthetic agents.

Adult↗
PubMed1992

Morphologic characteristics of muscles grafted in rabbits with neurovascular repair.

In 34 female white rabbits, rectus femoris (RFM) muscles were grafted with immediate anastomoses of the vasculature (VA) and with nerves either left intact (NI-VA) or with nerves repaired (NR-VA). The purpose of the study was to compare the morphologic changes that occur in NI-VA grafts and NR-VA grafts from 8 to 120 days after grafting. After 8 days, nearly complete survival of all muscle fibers was found. The muscle mass and single fiber cross-sectional area (CSA) of the NI-VA group remained near control values for the first 30 days and then declined to 82 percent and 62 percent of the control values, respectively. Little evidence of morphologic disruption was observed. The NR-VA grafts displayed a significant denervation atrophy within the first 15 days, with relative values 67 percent of the control value for mean mass and 53 percent for single fiber CSA. By 120 days, mass and CSA recovered to 80 percent and 62 percent of control values. Although the similarity of the deficits in the nerve-intact and nerve-repaired grafts suggest that tenotomy and repair, rather than innervation, were the major limitations, the mechanism was not resolved.

Adipose Tissue↗
PubMed1991

A method for preparing skeletal muscle fiber basal laminae.

Previous attempts to prepare skeletal muscle basal laminae (BL) for ultrastructural analyses have been hampered by difficulties in successfully removing skeletal muscle proteins and cellular debris from BL tubes. In the present study we describe a two phase method which results in an acellular muscle preparation, the BL of which are examined by light, transmission electron, and scanning electron microscopy. In the first phase, excised rat extensor digitorum longus muscles are subjected to x-radiation and then soaked in Marcaine to inhibit muscle regeneration and to destroy peripheral muscle fibers. The muscles are then grafted back into their original sites and allowed to remain in place 7-14 days to allow for maximal removal of degenerating muscle tissue with minimal scar tissue formation. In the second phase, the muscle grafts are subjected sequentially to EDTA, triton X-100, DNAase, and sodium deoxycholate to remove phagocytizing cells and associated degenerating muscle tissue. These procedures result in translucent, acellular muscle grafts which show numerous empty tubes of BL backed by endomysial collagenous fibers. These preparations should be useful for morphological analyses of isolated muscle BL and for possible in vitro studies by which the biological activity of muscle BL can be examined.

Animals↗
PubMed1991

Early innervation of skeletal muscle during tail regeneration in urodele amphibians.

The innervation pattern of skeletal muscles was studied in the normal and regenerating tail of Notophthalmus viridescens. Silver staining for nerve endings and histochemical localization of acetylcholinesterase (AChE) were used for light microscopy. In In normal musculature, AChE positive reactions were localized at the ends of the muscle fibers where they are anchored on connective tissue septa by myotendinous junctions. At this level, silver staining shows nerve terminals forming endplates. During regeneration, positive reactions for AChE appear de novo as dense plates localized at the ends of the newly formed myotubes. The mechanisms involved in the localization of AChE on this surface seem to operate before previous local contacts by nerve terminals. From the ultrastructural data and immunohistochemical results with anti-laminin antibody, these observations suggest that regenerating muscle fibers determine a region of post-synaptic specialization in close relation with the organization of myotendinous regions and basement membrane formation. Nerve-muscle contacts appear at these levels at stage IV (15-20 days after amputation) in the stump and in the rostral part of the regenerate (transition zone). These nerve terminals are provided by the disorganized peripheral nervous system of the injured segment. In the regenerate a similar pattern of AChE reaction can be seen in every myotube, differentiating according to a rostro-caudal gradient. Innervation at the ends of the muscle fibers is in spatiotemporal relation with the exists of the ventral roots from the regenerating nerve cord as the regenerate continues to grow in length.

Animals↗
PubMed1991

Muscle fiber branching--difference between grafts in old and young rats.

Large numbers of branched muscle fibers occur in the freely grafted rat extensor digitorum longus muscle. The ratio of branched/non-branched muscle fibers in grafts is much higher in old (24 months) than in young (4 months) host rats. Cross-age transplants show that the proportion of branched muscle fibers is related to the age of the grafted muscle and not to the age of the host. This is in contrast to mass and maximum isometric tension, in which the age of the host, rather than the age of the grafted muscle, is the determinant of the success of the muscle graft.

Aging↗
PubMed1991

Induction of adult-type nicotinic acetylcholine receptor gene expression in noninnervated regenerating muscle.

Expression of adult-type nicotinic acetylcholine receptors at the neuromuscular junction is thought to result from selective induction of their genes in endplate-associated nuclei due to local neurotrophic control. However, denervation studies indicate that endplate-specific expression can be maintained in the absence of the nerve. We investigated the role played by the basal lamina in this expression by assaying for the adult-type-specific epsilon RNA in noninnervated regenerating muscle. We found that this RNA is locally expressed beneath the old endplates after 10 days of regeneration. At earlier times epsilon RNA is also found in areas other than the endplate region. These results indicate that in adult muscle the basal lamina contains all the components necessary to direct nicotinic acetylcholine receptor gene expression to the endplate.

Animals↗