Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “REGENERATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,621 records · Page 90Linked to original sources
PubMed2001

Distribution of the phosphorylated form of microtubule associated protein 1B in the fish visual system during optic nerve regeneration.

Microtubule associated proteins are a heterogeneous group of proteins that have been implicated in regulating microtubule stability. They play an important role in the organisation of the neuronal cytoskeleton during neurite outgrowth, plasticity and regeneration. The fish visual system presents a considerable degree of plasticity. Thus, the retina grows continually throughout life and the optic nerve regenerates after crush. In the present study, we compared the distribution of the microtubule associated protein 1B in its phosphorylated form (MAP1B-phos) in the normal adult fish visual system with that observed during optic nerve regeneration after adult optic nerve crush using a specific monoclonal antibody mAb-150. Expression of MAP1B-phos was observed in some ganglion cell somata and in developing, growing axons within the control optic nerve. Few immunoreactive terminals were seen in the control optic tectum. After optic nerve crush, we found additional MAP1B-phos expression in regenerating axons throughout the visual system. Our results demonstrate that MAP1B-phos is present in growing and regenerating axons of fish retinal ganglion cells, which suggests that the phosphorylated form of MAP1B may play an important role in developmental and regeneration processes within the fish central nervous system.

Animals↗
PubMed2001

Hair cell regeneration and recovery of auditory thresholds following aminoglycoside ototoxicity in Bengalese finches.

Birds regenerate auditory hair cells when original hair cells are lost. Regenerated hair cells become innervated and restore hearing function. Functional recovery during hair cell regeneration is particularly interesting in animals that depend on hearing for vocal communication. Bengalese finches are songbirds that depend on auditory feedback for normal song learning and maintenance. We examined the structural and functional recovery of the Bengalese finch basilar papilla after aminoglycoside ototoxicity. Birds were treated with the ototoxic aminoglycoside, amikacin, daily for 1 week. Treatment resulted in hair cell loss across the basal half of the basilar papilla and corresponding high frequency hearing loss. Hair cell regeneration and recovery of auditory brainstem responses were compared in the same animals. Survival times following treatment were between 1 day and 12 weeks. Analysis of structural recovery at weekly intervals indicated that hair cells in the Bengalese finch papilla require a maximum of 1 week to regenerate and appear with immature morphology at the epithelial surface. An additional 6 days are required for adult-like morphology to develop. Repopulation of the damaged region was complete by 8 weeks. Recovery of auditory thresholds began 1 week after treatment and reached asymptote by 4 weeks. Slight residual threshold shifts at 2.0 kHz and above were observed up to 12 weeks after treatment. Direct comparison of structural and functional recovery indicates that auditory thresholds recover maximally before a full complement of hair cells has regenerated.

Amikacin↗
PubMedDate not supplied

The quest for better recovery from peripheral nerve injury: current status of nerve regeneration research.

The author reviews relevant nerve regeneration research in the past half-century to give the reader familiarity with the background of current research efforts. Recent research has been aided by newer knowledge of the biology of nerve regeneration. Early efforts to improve nerve regeneration centered on improvements in technical or surgical repairs, with only modest gains. Although current technical improvements with lasers or fibrin glue to repair nerves may show promise, the approach of deMedinaceli et al. combines several new ideas with some improvement experimentally. With the discovery of nerve growth factors and a host of newer nerve growth promoting factors, the biochemical arena has explored. Special tubes to repair nerves enable easy manipulation of the environment to study the effects of various factors on nerve regeneration. Silastic and bioresorbable tubes show the most promise to enhance nerve regeneration by tubulization. Because of the explosion of knowledge and high levels of activity of research, it is apparent that further improvements of nerve regeneration are on the horizon.

Axons↗
PubMed1999

Nutritional modulation of liver regeneration by carbohydrates, lipids, and amino acids: a review.

The survival of patients after a life-threatening hepatic injury of varying etiology depends on the ability of the remaining hepatocytes to regenerate. Thus, the stimulation of hepatic regeneration can have tremendous therapeutic relevance. Experimental studies--performed mostly on a model of regenerating rat liver after partial hepatectomy--indicate that glucose administration inhibits, whereas infusion of a lipid emulsion can enhance, the rate of liver regeneration. However, the inhibitory effect of glucose on liver regeneration is not observed when glucose is administered together with other nutrients. The results further indicate that administration of a standard amino acid mixture without energy substrate has an inhibitory effect and that development of liver regeneration can be favorably influenced by branched-chain amino acids (valine, leucine, and isoleucine) and glutamine.

Amino Acids↗
PubMed1997

Bile acid secretion during synchronized rat liver regeneration.

One major difficulty in interpreting the changes occurring during liver regeneration is the co-existence of non-activated cells and proliferating hepatocytes at all stages of differentiation. The aim of this study was to investigate bile acid (BA) secretion into bile during normal (NLR) and synchronized (SLR) liver regeneration in rats. Regeneration was synchronized by reversible inhibition of ribonucleotide reductase by 10 h treatment with hydroxyurea (HU) shortly after two-third partial hepatectomy. Total BA output as measured by GC-MS increased immediately after partial hepatectomy. This was followed by a further transient enhancement during the next day in the NLR. HU treatment did not significantly modify total BA output, but after releasing synchronized regeneration a marked reduction was observed. This was followed by a recovery to reach values close to those of NLR on day 7 of the regenerative process in SLR. Amidated BA output as measured by HPLC analysis revealed an early enhancement in the proportion of non-conjugated BAs in bile in NLR. However, the profile of conjugated BAs, which was not affected by HU treatment, matched that of total BAs during the first stage of SLR. By contrast, the increase in BA output observed on day 3 of the regenerative process in this group was accounted for by an enhancement in non-conjugated BA secretion. On day 7 of the regenerative process, the proportion of conjugated BA in bile was restored to approximately 100% in this group. Most BA molecules were conjugated with taurine rather than with glycine in all experimental groups, during both NLR and SLR. GC-MS determinations indicated that the magnitude of the cholic acid predominance in all bile samples was significantly modified during liver regeneration. This was increased early after partial hepatectomy and declined toward control values after few (2-3) days. Enhancement in the cholic acid predominance was due to a reduction in the proportion of all other major BAs, above all ursocholic acid and omega-muricholic acid. By contrast, minor BAs in normal control rat bile such as allo-cholic acid were increased during both NLR and SLR, and remained at detectable levels up to day 7. Changes in the proportion of secreted BA species were similar in SLR and NLR except that the early reduction in the proportion of BAs other than cholic acid was more pronounced in SLR and the quantitative importance of the diversity in BA species was recovered earlier in SLR than in NLR. In summary, these results indicate that profound changes in BA secretion during rat liver regeneration do occur. Most of them are probably related to the existence of retro-differentiation/re-differentiation processes which are speeded up by hydroxyurea-induced synchronization of the wave of hepatocyte proliferation.

Animals↗
PubMed2000

Integrin and dystrophin associated adhesion protein complexes during regeneration of shearing-type muscle injury.

In shearing injury both the myofibres and connective tissue framework are breached and the muscle tendon continuity is disrupted. During regeneration the firm myofibre to extracellular matrix (ECM) adhesion must be re-established. We have analysed the expression of selected molecules implementing this adhesion in regenerating myofibres 2-56 days after transection of rat soleus muscle using quantitative immunohistochemistry and Northern blotting. Beta1 integrin mRNA level and alpha7 integrin and vinculin immunoreactivities were transiently increased in both the intact and regenerating parts of the transected myofibres by day 5-7 with normalization by day 10-14. After day 14, alpha7 integrin and vinculin accumulated at the tips of the regenerating myofibres, indicating formation of new mini-myotendinous junctions (mMTJ). Immunoreactivities for dystrophin and associated proteins as well as merosin appeared in regenerating myotubes by day 3-4 reaching control levels by day 56. Our results suggest that integrin and dystrophin associated molecules are complementary in myofibre-ECM adhesion. During regeneration, ruptured myofibres temporarily reinforce their integrin mediated lateral adhesion until mMTJs are formed. Thereby the load on the newly formed scar and the risk of rerupture are reduced. Dystrophin associated molecules appear later and replace integrin on the lateral aspects, while both complexes are abundant at the mMTJs. These molecular events correspond to our previous results on tensile strength.

Animals↗
PubMed2000

Molecular mechanisms of augmenter of liver regeneration as immunoregulator: its effect on interferon-gamma expression in rat liver.

BACKGROUND: We have shown that the administration of exogenous Augmenter of Liver Regeneration protein in intact rats i) regulates mitochondrial gene expression by inducing the transcription and translation of the nuclear-encoded mitochondrial transcription factor A, and ii) inhibits the lytic activity of liver-resident Natural Killer cells. AIMS: The present investigation was carried out to study the effect, in intact rats, of exogenous administration of Augmenter of Liver Regeneration protein on Interferon-gamma, a cytokine produced by activated Natural Killer cells and known to control the expression of mitochondrial transcription factor A, a nuclear gene responsible for mitochondrial metabolism. METHODS: Interferon-gamma was measured as messenger RNA in liver-derived mononuclear leukocytes and as protein in liver-derived Natural Killer cells after a single injection of Augmenter of Liver Regeneration protein. RESULTS: The data obtained demonstrate that: i) in intact rats, Augmenter of Liver Regeneration protein administration induces a reduction of Interferon-gamma in the liver-resident Natural Killer cells and ii) the administration of Interferon-gamma in 70% hepatectomized rats is followed by a significant reduction both of the mitochondrial transcription factor A expression and of liver regeneration. CONCLUSIONS: These data demonstrate the pivotal role of Augmenter of Liver Regeneration as Growth Factor and as immunoregulator by controlling, through Interferon-gamma levels, the mitochondrial transcription factor A expression and the lytic activity of liver-resident Natural Killer cells.

Animals↗
PubMed2004

Canadian Association of Neuroscience review: axonal regeneration in the peripheral and central nervous systems--current issues and advances.

Injured nerves regenerate their axons in the peripheral (PNS) but not the central nervous system (CNS). The contrasting capacities have been attributed to the growth permissive Schwann cells in the PNS and the growth inhibitory environment of the oligodendrocytes in the CNS. In the current review, we first contrast the robust regenerative response of injured PNS neurons with the weak response of the CNS neurons, and the capacity of Schwann cells and not the oligodendrocytes to support axonal regeneration. We then consider the factors that limit axonal regeneration in both the PNS and CNS. Limiting factors in the PNS include slow regeneration of axons across the injury site, progressive decline in the regenerative capacity of axotomized neurons (chronic axotomy) and progressive failure of denervated Schwann cells to support axonal regeneration (chronic denervation). In the CNS on the other hand, it is the poor regenerative response of neurons, the inhibitory proteins that are expressed by oligodendrocytes and act via a common receptor on CNS neurons, and the formation of the glial scar that prevent axonal regeneration in the CNS. Strategies to overcome these limitations in the PNS are considered in detail and contrasted with strategies in the CNS.

Animals↗
PubMedDate not supplied

Regeneration of the dopamine-cell mosaic in the retina of the goldfish.

A fundamental anatomical feature of retinal neurons is that they form planar mosaics. Each mosaic can be described by its density, pattern, and regularity (non-randomness). As part of ongoing studies to quantitatively describe the anatomy of regenerated retina in the goldfish, we determined the planimetric density and regularity of the mosaic of dopaminergic interplexiform cells in patches of regenerated retina and compared this to the mosaic generated de novo. In addition, we selectively ablated dopaminergic neurons with the neurotoxin 6-hydroxydopamine (6-OHDA) before inducing local regeneration and determined whether or not the absence of the extant dopaminergic neurons modulated the planimetric density or number of regenerated ones. The results showed that dopaminergic neurons are regenerated at higher planimetric densities and in less orderly arrays than normal. Furthermore, there was no statistical difference in the density or number of regenerated cells in normal retinas and retinas treated with 6-OHDA.

Animals↗
PubMed1992

A breakdown of the blood-brain barrier is associated with optic nerve regeneration in the frog.

We have examined the integrity of the blood-brain barrier during optic nerve regeneration in the frog Litoria (Hyla) moorei using rhodamine B-labeled bovine serum albumin (RBA). A transient localized breakdown of the blood-brain barrier was observed between 1 and 5 weeks after extracranial optic nerve crush. The zone of breakdown progressed along the experimental optic nerve, ascended the opposite optic tract, and swept rostro-caudally across the tectum contralateral to the crushed nerve. By 7 weeks, the blood-brain barrier was once again intact along the length of the optic pathway. In a concurrent series of frogs, regenerating optic axons were visualized by anterograde transport of horseradish peroxidase (HRP). At each stage examined, the region reached by the front of regenerating axons corresponded to that in which the blood-brain barrier had been shown to break down. In contrast to the results after nerve crush, the blood-brain barrier remained intact along the length of the optic pathway following optic nerve ligation to prevent regeneration. We conclude that the breakdown of the blood-brain barrier which occurs during optic nerve regeneration in the frog is triggered by the regenerating axons.

Animals↗
PubMed2001

Transgenic zebrafish for studying nervous system development and regeneration.

Alpha1 tubulin gene expression is induced in the developing and regenerating CNS of vertebrates. Therefore, alpha1 tubulin gene expression may serve as a good probe for mechanisms underlying CNS development and regeneration. One approach to identify these mechanisms is to work backwards from the genome. This requires identification of alpha1 tubulin DNA sequences that mediate its developmental and regeneration-dependent expression pattern. Therefore, we generated transgenic zebrafish harboring a fragment of the alpha1 tubulin gene driving green fluorescent protein expression (GFP). In these fish, and similar to the endogenous gene, transgene expression was dramatically induced in the developing and regenerating nervous system. Although transgene expression generally declined during maturation of the nervous system, robust GFP expression was maintained in progenitor cells in the retinal periphery, lining brain ventricles and surrounding the central canal of the spinal cord. When these cells were cultured in vitro they divided and gave rise to new neurons. We also show that optic nerve crush in adult fish re-induced transgene expression in retinal ganglion cells. These studies identified a relatively small region of the alpha1 tubulin promoter that mediates its regulated expression pattern in developing and adult fish. This promoter will be extremely useful to investigators interested in targeting gene expression to the developing or regenerating nervous system. As adult transgenic fish maintain transgene expression in neural progenitors, these fish also provide a valuable resource of labeled adult neural progenitor cells that can be studied in vivo or in vitro. Finally, these fish should provide a unique in vivo system for investigating mechanisms mediating CNS development and regeneration.

Animals↗
PubMed2001

MRF4 protein expression in regenerating rat muscle.

The myogenic transcription factors of the MyoD family are not expressed in normal adult skeletal muscle. They are upregulated at the transcript and protein levels in a precisely coordinated manner during regeneration. While the cellular distribution of MyoD, myf-5, and myogenin expression in regenerating muscle is well documented, little is known about the exact localization of MRF4. It was the aim of this study to monitor the cellular distribution of MRF4 protein during regeneration. The soleus muscle of 6-week-old male Wistar rats was devascularized and allowed to regenerate for 2, 5, 10 or 14 days. Immunostaining revealed the presence of MRF4 throughout the time periods studied. Expression was detected in the nuclei of myofibers which had survived the devascularization procedure 2 days after necrosis was induced. In nuclei of newly formed myotubes and young myofibers, MRF4 was co-expressed with MyoD and myogenin. MRF4 protein was absent from satellite cells (SC), with anti-M-cadherin being used as a SC marker. Taken together, our results demonstrate that MRF4 protein expression in regenerated fibers is restricted to the time around and after fusion. The absence of MRF4 protein in SC suggests that the role of MRF4 during regeneration is distinct from myf-5, MyoD, and myogenin.

Animals↗
PubMed2002

The Nogo receptor, its ligands and axonal regeneration in the spinal cord; a review.

At least three proteins present in CNS myelin, Nogo, MAG and OMgp are capable of causing growth cone collapse and inhibiting neurite outgrowth in vitro. Surprisingly, Nogo and OMgp are also strongly expressed by many neurons (including neocortical projection cells). Nogo expression is increased by some cells at the borders of CNS lesion sites and by cells in injured peripheral nerves, but Nogo and CNS myelin are largely absent from spinal cord injury sites, which are none the less strongly inhibitory to axonal regeneration. Nogo is found on growing axons during development, suggesting possible functions for neuronal Nogo in axon guidance. Although Nogo, MAG and OMgp lack sequence homologies, they all bind to the Nogo receptor (NgR), a GPI-linked cell surface molecule which, in turn, binds p75 to activate RhoA. NgR is strongly expressed by cerebral cortical neurons but many other neurons express NgR weakly or not at all. Some neurons, such as DRG cells, respond to Nogo and CNS myelin in vitro although they express little or no NgR in vivo which, with other data, indicates that other receptors are available for NgR ligands. NgR expression is unaffected by injury to the nervous system, and there is no clear correlation between NgR expression by neurons and lack of regenerative ability. In the injured spinal cord, interactions between NgR and its ligands are most likely to be important for limiting regeneration of corticospinal and some other descending tracts; other receptors may be more important for ascending tracts. Antibodies to Nogo, mainly the poorly-characterised IN-1 or its derivatives, have been shown to enhance recovery from partial transections of the spinal cord. They induce considerable plasticity from the axons of corticospinal neurons, including sprouting across the midline and, to a limited extent, regeneration around the lesion. Regeneration of corticospinal axons induced by Nogo antibodies has not yet been demonstrated after complete transections or contusion injuries of the spinal cord. It is not clear whether antibodies against Nogo act on oligodendrocytes/myelin or by binding to neuronal Nogo, or whether they can stimulate regeneration of ascending axons in the spinal cord, most of which express little or no NgR. Despite these uncertainties, however, NgR and its ligands offer important new targets for enhancing plasticity and regeneration in the nervous system.

Animals↗
PubMedDate not supplied

Regeneration of adult axons in white matter tracts of the central nervous system.

It is widely accepted that the adult mammalian central nervous system (CNS) is unable to regenerate axons. In addition to physical or molecular barriers presented by glial scarring at the lesion site, it has been suggested that the normal myelinated CNS environment contains potent growth inhibitors or lacks growth-promoting molecules. Here we investigate whether adult CNS white matter can support long-distance regeneration of adult axons in the absence of glial scarring, by using a microtransplantation technique that minimizes scarring to inject minute volumes of dissociated adult rat dorsal root ganglia directly into adult rat CNS pathways. This atraumatic injection procedure allowed considerable numbers of regenerating adult axons immediate access to the host glial terrain, where we found that they rapidly extended for long distances in white matter, eventually invading grey matter. Abortive regeneration correlated precisely with increased levels of proteoglycans within the extracellular matrix at the transplant interface, whereas successfully regenerating transplants were associated with minimal upregulation of these molecules. Our results demonstrate, to our knowledge for the first time, that reactive glial extracellular matrix at the lesion site is directly associated with failure of axon regrowth in vivo, and that adult myelinated white matter tracts beyond the glial scar can be highly permissive for regeneration.

Aging↗
PubMed1995

Clusterin expression and apoptosis in tissue remodeling associated with renal regeneration.

To analyze the role of clusterin in renal diseases involving a regenerative process, we have used a novel rodent model to compare temporal and spatial expression of clusterin mRNA. Thus, renal artery stenosis was used to induce unilateral non-infarctive renal atrophy. After several weeks, when cellular pathology of atrophic kidneys involved minimal apoptosis or inflammatory response and mitosis was at normal levels, regeneration of atrophic kidneys was stimulated by removal of the contralateral healthy kidneys. The regrowth response was very rapid and involved renal hyperplasia rather than hypertrophy. Regenerating kidneys were studied 0, 4, 8, 24 hours and 2, 3, 5, 7, and 14 days after contralateral nephrectomy. Several parameters were compared: level and localization of clusterin mRNA; cell proliferation; cell dedifferentiation and redifferentiation and apoptosis. During the acute regenerative phase (first 24 hr) clusterin expression was markedly increased, decreasing to untraceable levels by five days of regeneration. Clusterin mRNA was localized in dilated or collapsed atrophic tubules that had lost identifying surface structures of normal tubular epithelium (termed dedifferentiated). Clusterin was also localized in the periphery of some blood vessel walls. Cell proliferation peaked at three to five days of regeneration, and was also localized in dedifferentiated tubules. Despite the regenerative stimulus, an unexpected result was a transient but marked increase in apoptotic cell death in atrophic tubules in the first 24 hours of regeneration. Our results provide evidence of a temporal association between increased clusterin expression and apoptosis, but in situ localization showed clusterin mRNA over apparently viable, as well as apoptotic, cells in the epithelium of tubules showing clusterin expression. Clusterin mRNA was rarely identified over epithelial cells in foci of non-atrophic (non-dedifferentiated) nephrons that responded to the regenerative stimulus by cellular hypertrophy. The dramatic response after initiation of regeneration, especially the initiation of apoptosis in the tubular epithelium, may have applications for the study of genetic changes leading to renal oncogenesis.

Animals↗
PubMed2001

A role of tensin in skeletal-muscle regeneration.

Regeneration of skeletal muscle requires the activation, proliferation, differentiation and fusion of satellite cells to generate new muscle fibres. This study was designed to determine the role of tensin in this process. Cardiotoxin was used to induce regeneration in the anterior tibial muscles of tensin-knockout and wild-type mice. From histological analysis, we found that the regeneration process lasted longer in knockout than in wild-type mice. To investigate the mechanism involved in this delay, we examined each regeneration step in animals and cultured primary cells. We found fewer proliferating myogenic cells identified by bromodeoxyuridine and desmin double labelling in knockout mice on the first 2 days after injury. Expression of myosin, paxillin, dystrophin and dystrophin-associated proteins were delayed in knockout mice. Withdrawal from the cell cycle was less efficient in isolated knockout myoblasts, and the fusion capacity was reduced in these cells as well. These defects in regeneration most likely contributed to the 9-fold increase of centrally nucleated fibres occurring in the non-injected knockout mice. Our results demonstrated clearly that tensin plays a role in skeletal-muscle regeneration.

Animals↗
PubMed1967

Protein synthesis by microsomal particles from regenerating rat liver.

1. Washed microsome particles from regenerating liver were shown to incorporate [(14)C]leucine into protein more actively than similar preparations from normal liver. 2. The total incorporation in the preparations from regenerating liver increased linearly with the amount of protein incubated, whereas this was not so with preparations from normal liver. 3. The greater activity of regenerating-liver microsomes appeared to be associated with the bound polysomes. 4. The size distribution of polysomes obtained after removal of membrane with deoxycholate was the same in normal and regenerating liver. 5. In general the activity of polysome preparations from normal and regenerating liver was similar. 6. It is concluded that the greater activity of the particles in the microsome fraction from regenerating liver is to be attributed to the ribosomes bound to membrane and that their activity is controlled by factors present in the membrane.

Animals↗
PubMed1972

The conversion of orotic acid into uridine 5'-monophosphate by isolated perfused normal and regenerating rat livers.

The release of (14)CO(2) from [7-(14)C]orotic acid was measured in isolated perfused normal and regenerating rat livers. With some limitations, the release of (14)CO(2) from [7-(14)C]orotic acid can be used to estimate UMP synthesis in perfused livers. Isolated perfused livers rapidly pick up labelled orotic acid added to perfusate and convert most of it into UMP. Perfused regenerating livers produce approx. 2.5 times as much UMP/g of liver as do perfused normal livers. However, the absolute amount of orotic acid converted into UMP is higher in perfused normal livers than in perfused regenerating livers. Perfused regenerating livers do not differ in their orotic acid uptake and UMP synthesis from livers of comparable size in which regeneration is not taking place. The total amount of orotic acid taken up by the liver (rather than the rate of uptake) and the size of the liver appear to be the determining factors in UMP production. The results suggest that the decrease in liver size caused by partial hepatectomy may be in itself sufficient to account for an increase in the flow of metabolites in the pyrimidine pathway at the early stages of liver regeneration.

Animals↗