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PubMed1995

Periodontal regeneration in class III furcation defects of beagle dogs using guided tissue regenerative therapy with platelet-derived growth factor.

We developed an effective regenerative therapy, referred to as platelet-derived growth factor-BB (PDGF-BB)-modulated guided tissue regenerative (GTR) therapy (P-GTR), capable of achieving periodontal regeneration of horizontal (Class III) furcation defects in the beagle dog. To determine its efficacy, repair and regeneration of horizontal furcation defects by P-GTR therapy and GTR therapy were compared. Chronically inflamed horizontal furcation defects were created around the second (P2) and fourth mandibular premolars (P4). After demineralization of the root surfaces with citric acid, the surfaces of left P2 and P4 were treated with PDGF-BB (P-GTR therapy) and those of contralateral teeth were treated with vehicle only (GTR therapy). Periodontal membranes were placed and retained 0.5 mm above the cemento-enamel junction for both groups. The mucoperiosteal flap was sutured in a coronal position and plaque control was achieved by daily irrigation with 2% chlorhexidine gluconate. At 5, 8, and 11 weeks, two animals each were sacrificed by perfusion with 2.5% glutaraldehyde through the carotid arteries, and the lesions were sliced mesio-distally, demineralized, dehydrated, and embedded. Periodontal healing and regeneration after GTR and P-GTR therapy were compared by histomorphometric as well as morphological analysis. Morphometric analysis for each time period was performed on the pooled samples of P2 and P4. Five weeks after both therapies, the lesions were filled primarily by tissue-free area, epithelium, inflamed tissue, and a small amount of newly formed fibrous connective tissue. At 8 and 11 weeks after P-GTR therapy, there was a statistically greater amount of bone and periodontal ligament formed in the lesions. The newly formed bone filled 80% of the lesion at 8 weeks and 87% at 11 weeks with P-GTR therapy, compared to 14% of the lesion at 8 weeks and 60% at 11 weeks with GTR therapy. Also, with P-GTR therapy there was less epithelium and tissue-free area, less inflamed tissue, and less connective tissue. Morphological analysis indicated that the defects around P2 revealed faster periodontal repair and regeneration than those around P4. While the lesions around P2 were effectively regenerated by 11 weeks even after GTR therapy, those around P4 failed to regenerate. On the other hand, P-GTR therapy further promoted periodontal repair and regeneration so that at 8 weeks the lesions around P2 and P4 demonstrated complete and nearly complete regeneration, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Alveolar Process↗
PubMed1996

[An experiment study of the guided bone regeneration].

During the process of wound healing, different cellular components have varied speeds of migrating. By implanting a membrane, a space was created for selected cells, that is so called guided tissue regeneration. Since bone had the potential of regeneration, the concept of guided tissue regeneration was used in the process of bone regeneration in the present study, namely, guided bone regeneration. Defects of 10 mm-long were produced on bilateral radii of 10 adult New Zealand rabbits by surgery. The defects on experimental sides were bridged with silicone tube. The opposite side served as the control. Radiography of forearms of rabbits was taken weekly. Samples were treated with 3-point bending test and histology respectively. On experimental sides, by 3-4 weeks, new bone from the fractured ends grew into bone defect, seven of ten healed within 6-8 weeks. The other 2 only had a gap less than 1 mm left. No one healed on the control sides. The maximum value of 3-point bending test on experimental sides was 11.7 times greater than that of the control sides. It was shown that bone regenerated in the tube, and no callus formed out the tube by both gross samples and histologic examinations. On histology, the gap less than 1 mm on X-ray films was fibrocartilage zone, which connected regenerated bone from both distal and proximal bone ends. The defects on the control were occupied by connective tissue. In conclusion, guided bone regeneration also presents in long bone, that may provide a new method in the treatment of bone defect and promote fracture healing.

Animals↗
PubMedDate not supplied

Ridge augmentation with guided bone regeneration and GTAM case illustrations.

The principle of Guided Bone Regeneration (GBR) can be used for Ridge Augmentation. These case illustrations describe the technique using Autogenous Cortico-Cancellous Bone Grafts and stabilization with Miniscrews and placement of a GTAM Barrier Membrane. Nyman et al (1990) published the first report of enlargement of a reduced alveolar ridge. Becker & Becker, Jovanovic, Buser et al have documented successful regeneration of such ridges. A study by Lang et al established that: 1. An undisturbed healing period of at least six months is required for optimal bone regeneration. 2. Smaller defects (less than 70 mm.3) regenerate almost completely. 3. Larger defects (greater than 90 mm.3) regenerate 90-93 percent and bone grafts may enhance success in larger defects. 4. Premature membrane removal will result in incomplete regeneration. Buser et al have described the technique of GBR in detail. They found the creation and maintenance of a secluded space is essential for successful outcome with GBR procedures. This space allows for the in growth of osteogenic cells so that bone regeneration is undisturbed by competing non-osteogenic soft tissue cells. Space-making defects such as extraction sockets are simple to treat, but localized ridge augmentation may be difficult because the membrane is not supported by bony walls. E-PTFE membranes have been reinforced with titanium struts and mini screws have been developed as a way of dealing with membrane collapse. Buser et al began to utilize autogenous bone grafts to support the membrane and to act as an osseoinductive scaffold for bone regeneration. They utilized a cortico-cancellous block graft in the centre of the augmentative area with smaller chips to fill in the periphery. The cortical portion of the graft re-establishes the buccal cortex and the cancellous portion is placed against the host bone. The host bone is perforated to open the marrow spaces. Placement of membrane protects the bone graft (up to 50 percent of grafted bone is lost through resorption in augmentation procedures where membrane is not used).

Alveolar Ridge Augmentation↗
PubMed2000

Age-related changes in muscle fiber regeneration in the human thyroarytenoid muscle.

BACKGROUND: Muscle fiber regeneration is essential to maintain normal muscle fiber populations and muscle mass by continuous replacement of fibers lost to acute muscle injury or overuse. However, the extent of ongoing muscle fiber regeneration in the laryngeal muscles is unknown. OBJECTIVE: The present study provides statistically unbiased, quantitative estimates of the content of regenerating fibers in the human thyroarytenoid muscle over the adult lifespan. DESIGN: In the adult, only regenerating muscle fibers express the developmental myosin isoform. Therefore, regenerating fibers were identified using immunohistochemical techniques. The content of regenerating muscle fibers in the entire muscle volume was then estimated using stereological techniques. Through the use of a computer-automated sampling protocol, stereological data were collected from sets of isotropic uniform random cryostat sections. Overprojection error was minimized by using a confocal laser-scanning microscope to image thin optical sections for use as sample fields. SUBJECTS: Eight autopsy cases, subjects ranging in age from 19 to 81 years. RESULTS: The summed length of fibers expressing developmental myosin increased significantly (P=.02) with age when compared with the overall muscle fiber length. CONCLUSIONS: This finding indicates that muscle fibers maintain the capability for spontaneous regeneration, and that the proportion of regenerating fibers increases as the thyroarytenoid muscle ages. This increase is possibly a compensatory response to an age-related increase in muscle fiber injury or death.

Adult↗
PubMed1990

Segmental mandibular regeneration by distraction osteogenesis. An experimental study.

We report the use of distraction osteogenesis for segmental mandibular regeneration. This technique has been used in thousands of patients in the Soviet Union to regenerate as much as 30 cm of tubular bone in the extremities. However, we are unaware of previous experimental or clinical reports of segmental mandibular regeneration by distraction osteogenesis. In a canine model, 2.5-cm segmental mandibular defects were filled with regenerate bone in 25 days at a rate of 1.0 mm/d using bifocal distraction osteogenesis. The diameters of the regenerate segments were comparable with preexisting mandible, and all animals resumed normal oromandibular function following regeneration. The regenerate bone was evaluated radiographically, angiographically, and histologically. In the control group without distraction osteogenesis, the segmental defects failed to fill with regenerate bone. The theoretical basis for distraction osteogenesis, a detailed description of the technique, and a review of previous studies on experimental mandibular lengthening are presented.

Animals↗
PubMed1999

Characteristics of regenerating horizontal semicircular canal afferent and efferent fibers in the toadfish, Opsanus tau.

The horizontal semicircular canal nerve of the toadfish, Opsanus tau, was transected and allowed to regenerate. The time course, morphometrics, and projection patterns of regenerating afferent and efferent vestibular fibers were determined. Nerve transections were performed both pre- and postganglionically, and regeneration was assessed in afferent and efferent fibers by bulk labeling the peripheral axons of the horizontal semicircular canal nerve with biocytin after nerve regrowth. Afferent fibers regrew through the transection site within 14 days and projected to all vestibular nuclei within 3 weeks. Bouton and branch number, axon length, surface area, volume, fiber diameter, and internodal distance were quantified for afferent fibers from eight sites within the vestibular nuclei, and axon number and soma size was quantified for the efferent fibers. Extensive regeneration was seen within 5 weeks of transection in all nuclei, and most morphometric parameters approached or exceeded control levels within 10 weeks. Regeneration appeared to recapitulate morphogenesis with an initial overproduction of boutons and branch points followed by elimination of presumably superfluous structures. Internodal distance remained significantly shorter in regenerating afferent axons than in control fish throughout the 15-week observation period. Efferent fibers also were observed to regenerate. Efferent axon number, diameter, and soma size were indistinguishable from those in controls from 3 weeks posttransection through week 15. Electrophysiological recordings from the horizontal canal nerve during mechanical stimuli of the canal confirmed that the regenerated axons transmitted normal signals. The return of normal equilibrium and behavior coincided with the projection of afferent fibers into the central vestibular nuclei, indicating that functional connections had been reestablished.

Afferent Pathways↗
PubMed2000

Marking zebrafish, Danio rerio (cyprinidae), using scale regeneration.

Tagging or marking small laboratory-bred fish species is not an easy task. This also holds for the zebrafish, Danio rerio, which is widely used throughout the world as a model organism for genetics, developmental biology, etc. We present a simple marking technique based on scale regeneration. A comparative morphological study of various types of zebrafish scales indeed shows that regenerated scales are easily distinguishable from nonregenerated ones. We propose to take advantage of this typical morphology to mark a single or several individuals. This technique, based on a natural biological process, is easy to perform and does not enhance fish mortality in laboratory breeding conditions. It permits assembly of several specimens in a single tank with the possibility of identifying each of them by regenerated-scale coding. Nevertheless, a prerequisite is that the species does not lose and regenerate scales in large numbers in laboratory breeding conditions. To check this, 5,200 scales were removed from a large region of the left flank in 100 zebrafish and the number and position of regenerated scales were statistically analysed. Our results indicate that (1) laboratory-bred zebrafish have only a few regenerated scales (7.48%), (2) the probability of finding a regenerated scale is similar whatever its position in a row (antero-posterior axis), but (3) it differs from one row to another (scales from the back are more frequently lost than those from the pectoral region). This paper presents a procedure to mark small breeding colonies of zebrafish using scale regeneration with the number and position of the scales to be removed with high probability of marking success. J. Exp. Zool. 286:297-304, 2000.

Animal Identification Systems↗
PubMed2000

Apical epithelial cap morphology and fibronectin gene expression in regenerating axolotl limbs.

Urodele amphibians (salamanders) are unique among adult vertebrates in their ability to regenerate limbs. The regenerated structure is often indistinguishable from the developmentally produced original. Thus, the two processes by which the limb is produced - development and regeneration - are likely to use many conserved biochemical and developmental pathways. Some of these limb features are also likely to be conserved across vertebrate families. The apical ectodermal ridge (AER) of the developing amniote limb and the larger apical epithelial cap (AEC) of the regenerating urodele limb are both found at the limb's distalmost tip and have been suggested to be functionally similar even though their morphology is quite different. Both structures are necessary for limb outgrowth. However, the AEC is uniformly smooth and thickly covers the entire limb-tip, unlike the AER, which is a protruding ridge covering only the dorsoventral boundary. Previous data from our laboratory suggest the multilayered AEC may be subdivided into separate functional compartments. We used hematoxylin and eosin (H+E) staining as well as in situ hybridization to examine the basal layer of the AEC, the layer that lies immediately over the distal limb mesenchyme. In late-stage regenerates, this basal layer expresses fibronectin (FN) message very strongly in a stripe of cells along the dorso-ventral boundary. H+E staining also reveals the unique shape of basal cells in this area. The stripe of cells in the basal AEC also contains the notch/groove structure previously seen in avian and reptilian AERs. In addition, AEC expression of FN message in the cells around the groove correlates with previous amniote AER localization of FN protein inside the groove. The structural and biochemical analyses presented here suggest that there is a specialized ridge-like compartment in the basal AEC in late-stage regenerates. The data also suggest that this compartment may be homologous to the AER of the developing amniote limb. Thus, the external differences between amniote limb development and urodele limb regeneration may be outweighed by internal similarities, which enable both processes to produce morphologically complete limbs. In addition, we propose that this basal layer of the AEC is uniquely responsible for AEC functions in regeneration, such as secreting molecules to promote mesenchymal cell cycling and dictating the direction of limb outgrowth. Finally, we include here a clarification of existing nomenclature to facilitate further discussion of the AEC and its basal layer.

Ambystoma↗
PubMed1998

Regeneration and myogenic cell proliferation correlate with taurine levels in dystrophin- and MyoD-deficient muscles.

This study coupled proton magnetic resonance spectroscopy (1H-NMR) and in situ hybridization plus autoradiography in a novel examination of different phenotypes of adult myogenesis that arise from genetic disruptions in mice. Study of muscle extracts from normal and dystrophin-deficient mdx limb and diaphragm muscles confirmed our previous findings linking taurine and muscle regeneration at the peak of damage and repair. 1H-NMR distinguished biochemical differences in regenerating muscles that were consistent with the extent of repair in three strains: mdx dystrophic mice; MyoD(-/-) mice that lack expression of the early myogenic regulatory gene MyoD; and a double-mutant mdx:MyoD(-/-) strain lacking expression of both MyoD and dystrophin. We tested the hypothesis that differences in spectra according to genotype and the regeneration phenotype are related specifically to proliferation by committed myogenic precursor cells. 1H-NMR distinguished the three mutant strains: Taurine was highest in mdx muscles, with the phenotype of most effective regeneration; lowest in MyoD(-/-) muscles, with the least effective formation of new muscle in repair, as reported previously; and intermediate in double-mutant muscles, now reported to show an intermediate repair phenotype. The early and late muscle precursors (mpcs) expressing myf5 and myogenin were examined for proliferation. Eighteen percent of mdx myf5-positive mpcs were proliferative, whereas myf5-positive mpcs did not proliferate in regenerating muscles that lacked MyoD expression. By contrast, whereas 30% of myogenin-positive mpcs were proliferative in mdx muscles, almost none were proliferative in MyoD(-/-) muscles, and 12% were proliferative in double-mutant muscles. Therefore, the extent of accumulated structural regeneration, taurine levels, and proliferation of late mpc (expressing myogenin) were congruent across genotypes. Proliferation by early mpc (expressing myf5) was inhibited by the lack of MyoD expression during muscle regeneration. These studies indicate the potential for 1H-NMR monitoring of muscle status in disease, regeneration, and treatment.

Animals↗
PubMed2000

Activity-induced fiber regeneration in rat soleus muscle.

In an attempt to understand why muscle recovery is limited following atrophy due to limb immobilization, satellite cell activity and muscle fiber regeneration were analyzed in rat soleus muscles. Adult rat hindlimbs were immobilized in plaster casts for a period of two to ten weeks. Soleus muscles were examined by electron microscopy for evidence of fiber degeneration or regeneration, and to quantify satellite cell nuclei. Immunocytochemical localization of embryonic myosin was used to identify regenerating myofibers. Soleus muscle wet weight to body weight ratios for the casted muscles significantly decreased over the 10-week immobilization period. The casted muscles displayed ultrastructural evidence of minor fiber damage, including myofibrillar atrophy, Z-disc disruption, and abnormal triadic junctions. No ultrastructural evidence of regeneration was seen in the casted animals. The number of satellite cells in the casted muscles significantly decreased from 6.4% to 3. 3% by eight to 10 weeks of immobilization. Approximately 1.0% of extrafusal fibers in the control soleus muscles appeared to be regenerating since they expressed embryonic myosin and were of a small diameter, while in casted muscles, only 0.1% of the fibers were embryonic myosin-positive. Following release from immobilization, a reappearance of embryonic myosin-positive fibers was noted within four days of renewed activity. In contrast to control muscles, embryonic myosin-positive fibers in the recovery muscles included both small and large diameter fibers. Subtle changes in functional activity influence muscle damage and subsequent myofiber regeneration. Reduced activity reduces muscle fiber regeneration, while increased activity, as seen by increased hindlimb weight bearing and return to normal activity following immobilization, increase regenerating fibers and also the expression of embryonic myosin in adult fibers.

Aging↗
PubMed2000

Pathfinding, target recognition, and synapse formation of single regenerating fibers in the adult grasshopper Schistocerca gregaria.

After lesion of the peripheral tympanal nerve of the adult locust (Schistocerca gregaria), sensory axons regenerate into their original target areas. We examined the individual behavior of single regenerating auditory afferents during pathway and target selection by intracellularly recording and labeling them at different times postlesion. During axotomy, spontaneous activity is not increased in either the distal or proximal part of the cells. Stimulus response properties of lesioned cells with or without regenerating axons are not influenced. Surprisingly, only 55% of sensory neurons regenerate through the lesion site and often give rise to more than one axonal fiber. Within the central nervous system, 70% of regenerated axons consistently follow an incorrect pathway to reach the correct target region. Often, one of two processes formed by a cell chooses the correct pathway, and the other the incorrect one. In the target region, regenerated axons reconstitute somatotopically ordered projections and form synapses that resemble those of intact fibers in number and structure. The regeneration process does not induce a detectable expression of antigens that are known to be expressed during neural development in these neurons. Our study clearly demonstrates that precise synaptic regeneration is possible in adult animals within a completely differentiated central nervous system, although pathfinding and formation of arborizations are disturbed in a particular and probably system-related manner. The results strongly suggest that accurate pathfinding is unlikely to be a decisive factor in target area recognition and synaptogenesis.

Animals↗
PubMed2000

Extent of ossification at the amputation plane is correlated with the decline of blastema formation and regeneration in Xenopus laevis hindlimbs.

Xenopus laevis larvae gradually lose the ability to regenerate lost hindlimb structures as they progress through metamorphosis. Previous studies have suggested that this loss of regenerative capacity occurs in a proximal-to-distal fashion. We assessed the quality of overall regeneration and early bud blastema formation in order to evaluate previous explanations for this loss of regenerative ability in Xenopus. We further examined the extent to which epidermis, basement membrane, dermis, cartilage, bone, periosteum, and accumulated mesenchyme within the blastema are involved in the decline of regenerative abilities during mid-metamorphic stages of development. Each tissue was scored based on its contributions to the regeneration blastema, in accordance with previously reported blastemal descriptions. Tadpoles amputated at the ankle and tarsal-metatarsal joints scored objectively higher within the overall regeneration and blastema quality rating systems. Both joint sites met more criteria associated with regeneration-capable blastemas than tadpoles amputated through the middle of the tarsus, especially at later stages of metamorphosis. The three amputation sites studied began to vary in their ability to regenerate skeletal elements and to generate productive blastemas during the same stages at which we initially observed ossification of the tarsus. These results suggest that the decline of Xenopus hindlimb regeneration does not occur in a strictly proximal-to-distal fashion but rather is dependent at later stages on the state of ossification of the structure through which amputation occurs. Our morphological and cellular observations reveal specific times and places during Xenopus hindlimb development at which further investigations into tissue-specific molecular events during early regeneration should be focused.

Amputation, Surgical↗
PubMed2000

Effects of short- and long-term Schwann cell denervation on peripheral nerve regeneration, myelination, and size.

Poor functional recovery after peripheral nerve injury has been generally attributed to inability of denervated muscles to accept reinnervation and recover from denervation atrophy. However, deterioration of the Schwann cell environment may play a more vital role. This study was undertaken to evaluate the effects of chronic denervation on the capacity of Schwann cells in the distal nerve stump to support axonal regeneration and to remyelinate regenerated axons. We used a delayed cross-suture anastomosis technique in which the common peroneal (CP) nerve in the rat was denervated for 0-24 weeks before cross-suture of the freshly axotomized tibial (TIB) and chronically denervated CP nerve stumps. Motor neurons were backlabeled with either fluoro-ruby or fluorogold 12 months later, to identify and count TIB motor neurons that regenerated axons into chronically denervated CP nerve stumps. Number, size, and myelination of regenerated sensory and motor axons were determined using light and electron microscopy. We found that short-term denervation of < or =4 weeks did not affect axonal regeneration but more prolonged denervation profoundly reduced the numbers of backlabeled motor neurons and axons in the distal nerve stump. Yet, atrophic Schwann cells retained their capacity to remyelinate regenerated axons. In fact, the axons were larger and well myelinated by long-term chronically denervated Schwann cells. These findings demonstrate a progressive inability of chronically denervated Schwann cells to support axonal regeneration and yet a sustained capacity to remyelinate the axons which do regenerate. Thus, axonal interaction can effectively switch the nonmyelinating phenotype of atrophic Schwann cells back into the myelinating phenotype.

Animals↗
PubMed1992

Retinoic acid-induced change in anteroposterior positional identity in regenerating axolotl limbs is dose-dependent.

Retinoic acid (RA) induces pattern duplication in the proximodistal (PD) axis of axolotl limb regenerates. The effect is dose-dependent, with the maximum extent of duplication being evoked at a dose of 150 micrograms RA/g body weight. The same dose of RA induces maximum pattern completion in the anteroposterior (AP) axis of regenerating anterior half or double anterior half limbs. RA inhibits the regeneration of posterior half or double posterior half limbs (Kim, W.S., and Stocum, D.L. [1986] Dev Biol 114:170-179). The effects of lower doses of RA on the AP axis of limb regenerates have not been tested and thus it is not known whether the effects of RA on positional identity in this axis are dose-dependent or are all-or-none. To answer this question, we examined the effects of a range of doses of RA on AP positional identity in regenerating double anterior and double posterior axolotl forelimbs and hindlimbs constructed by exchanging the anterior and posterior halves of right and left zeugopodia as either autografts or homografts. Ten days after the exchange, the double half zeugopodia were amputated through their distal ends. At 4 days postamputation, the animals were injected intraperitoneally with 20, 50, 75, or 100 micrograms RA/g body weight and the constructs allowed to regenerate for at least 6 weeks. Control double anterior forelimbs and hindlimbs formed symmetrical regenerates with an average of two and 1.8 anterior digits, respectively. RA treatment induced the blastema of double anterior zeugopodia to regenerate missing posterior structures in mirror-image patterns and to duplicate zeugopodial and stylopodial elements in the PD axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambystoma↗
PubMed1995

Retinoic acid-induced cell death in the wound epidermis of regenerating zebrafish fins.

Previous work has shown that treatment with retinoic acid (RA) can induce malformations in regenerating pectoral and caudal fins. RA-treated regenerates are narrower than unamputated and regenerated control fins because of a decrease in the distance between rays, and either partial or total fusion of some of them. In order to tackle the issue of how RA induces its teratogenic effects on regenerating fins, and which cell types may be specifically affected by RA, we have examined the cellular changes occurring in early regenerates following treatment with retinoids. The work presented here shows for the first time that RA induces significant apoptosis in the wound epidermis, but not in the mesenchyme, of a regenerating appendage, besides inhibiting blastema development as reported in other species. We also show that RA does not retard regeneration by inhibiting accumulation of blastemal cells, but probably by impairing their ability to migrate distal to the amputation plane. This effect is rapidly reversed by discontinuing the treatment, and within 24 hr of removing the drug, blastema development is well advanced. By this time the teratogenic effects induced by RA are already apparent. A correlation between the length of the apical ectodermal ridge (AER) and the number of digits formed has been demonstrated in developing limb buds. We therefore suggest that RA-induced patterning abnormalities in regenerating fins are the consequence of a reduction in the size of the wound epidermis, due to increased cell death, which would affect patterning of the underlying mesenchyme.

Animals↗
PubMed1995

Regeneration pattern of cardiac and skeletal muscle after transplantation into a skeletal muscle bed in rats.

BACKGROUND: The ability of skeletal muscle to regenerate after injury is well established. In contrast, cardiac muscle is incapable of regeneration and recovery after injury. The aim of the present study was to evaluate and compare the regeneration pattern of cardiac and skeletal muscle after transplantation into a skeletal muscle bed in rats. METHODS: The following group of transplants were performed at the site prepared by removing the host extensor digitorum longus (EDL) muscle. The first group consisted of cardiac muscle transplanted as one piece or after mincing into 1-mm pieces. The second group included cotransplants of cardiac and skeletal muscle minces that were intermixed. Entire EDL muscle or minced EDL muscle were also transplanted for comparison. Rats were sacrificed 3-30 days after transplantation for morphological analysis. RESULTS: The results demonstrated that skeletal muscle transplants underwent rapid regeneration, and by 30 days the entire muscle was filled with regenerated myofibers. In transplants of cardiac muscle significant inflammation, myocardial degeneration and necrosis were observed. In spite of the necrosis and fibrosis, the presence of a few regenerated myotubes in the outer region was observed. In cardiac and skeletal muscle cotransplants, the inflammation was restricted to cardiac tissue; however, by 30 days the entire cotransplant was filled with regenerated myotubes and myofibers. CONCLUSIONS: These results show that skeletal muscle is capable of growth, regeneration, and integration with the cardiac muscle after cotransplantation. Combination of skeletal and cardiac muscle may prove useful in defining the cellular processes necessary for enhancing cardiac repair after injury.

Animals↗
PubMed2002

Synaptic protein expression by regenerating adult photoreceptors.

Regeneration of functionally normal synapses is required for functional recovery after degenerative central nervous system insults and requires proper expression and targeting of presynaptic proteins by regenerating neurons. The reconstitution of presynaptic terminals by regenerating adult neurons is poorly understood, however. We examined the intrinsic ability of regenerating adult retinal photoreceptors to reconstitute properly differentiated presynaptic terminals in the absence of target contact. The expression and localization of vesicle-associated membrane protein (VAMP), synaptic vesicle protein 2 (SV2), synaptophysin, synapsin I, and synaptosomal-associated protein of 25 kDa (SNAP-25) was assessed immunocytochemically. Photoreceptor terminals in the intact retina contain VAMP, SV2, synaptophysin, and SNAP-25, but not synapsin I. Isolated, regenerating adult photoreceptors intrinsically expressed the proper complement of synaptic vesicle proteins in the absence of target contact: VAMP, SV2, and synaptophysin were present at all stages of regenerative growth; synapsin I was never expressed. At early stages of regenerative growth, VAMP, SV2, and synaptophysin were diffusely localized in the cell, with prominent VAMP labeling distributed along the plasma membrane. SV2 and synaptophysin rapidly localized to regenerated terminals, but VAMP accumulated much more slowly, indicating that these proteins are trafficked independently. In contrast, labeling for SNAP-25, which is associated with the presynaptic plasma membrane, was undetectable in regenerating photoreceptors, suggesting that SNAP-25 expression is target-regulated. Thus, regenerating photoreceptors can intrinsically regulate the expression of the proper set of synaptic vesicle proteins. Proper expression of other presynaptic proteins, such as SNAP-25, and proper subcellular localization of synaptic proteins such as VAMP, however, may require extrinsic cues such as target contact.

Age Factors↗
PubMed2003

Axonal sprouting in the optic nerve is not a prerequisite for successful regeneration.

Axonal sprouting, the production of axons additional to the parent one, occurs during optic nerve regeneration in goldfish and the frog Rana pipiens, with numbers of regenerate axons exceeding normal values four- to sixfold (Murray [1982] J. Comp. Neurol. 209:352-362; Stelzner and Strauss [1986] J. Comp. Neurol. 245:83-103). To determine whether axonal sprouting is a prerequisite for regeneration, the frog Litoria moorei was examined, a species that undergoes successful optic nerve regeneration but with a different time course compared with R. pipiens. Sprouting was assessed, as in goldfish and R. pipiens, from electron microscopic counts between the lesion and chiasm. However, disconnected axons that persist after axotomy would have falsely elevated the counts. The suspected overlap of these two axon populations was confirmed by labeling regenerate axons anterogradely with DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) and disconnected ones retrogradely with DiA (4-4-dihexadecylaminostyrl 1-N methylpyridinium iodide). Numbers of disconnected axons were estimated after preventing regeneration and subtracted from numbers in regenerate nerves. Throughout, the total number of regenerate axons was approximately one third lower than normal (P < 0.05) supporting a previous finding of minimal axonal sprouting in L. moorei (Dunlop et al. [2002] J. Comp. Neurol. 446:276-287). The validity of the subtractive electron microscopic method was confirmed by retrograde labeling to estimate numbers of retinal ganglion cells whose axons had crossed the lesion; values were approximately one third lower than normal. The data suggest that sprouting is not essential for either axon outgrowth or topographic map refinement.

Animals↗