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PubMed1990

The initial period of peripheral nerve regeneration and the importance of the local environment for the conditioning lesion effect.

The aim of this study was to investigate the early period of neurite outgrowth in the regenerating rat sciatic nerve and to determine if the non-neuronal cells were important for the conditioning lesion effect. Regeneration distance was evaluated with the pinch-reflex test 6 h to 5 days after a test crush lesion. The regeneration velocity accelerated during approximately 3 days, whereupon outgrowth continued with a constant velocity. In unconditioned nerves the initial delay was 2.8 h and the constant rate of regeneration was 3.2 mm/day. In nerves with a distal conditioning lesion the initial delay was 2.4 h and the rate of regeneration increased by 52%. When the test crush was applied at the same place as the conditioning crush the initial delay was 1.9 h and the rate of regeneration increased by 61%. The conditioning lesion effect was not influenced by the distance between the cell body and the conditioning crush lesion. Furthermore, the conditioning lesion effect could not be expressed if conditioned axons grew into a freeze injured nerve section. Incorporation of [3H]thymidine increased in the regenerating nerve segment. The increase occurred earlier if this segment had been subjected to a conditioning crush lesion. The results of these experiments showed that peripheral neurites start to regenerate within a few hours after an injury, suggesting that growth cone formation is independent of the cell body reaction. A conditioning crush lesion increases the regeneration velocity and its acceleration, and the conditioning lesion effect cannot be expressed in the absence of living Schwann and other non-neuronal cells.

Animals↗
PubMed1984

Cell death of asynaptic neurons in regenerating spinal cord.

The weakly electric fish Sternarchus albifrons possesses a unique class of asynaptic neurons, the electromotor neurons, whose axons constitute the electric organ. The cell bodies of origin of the electrocyte axons are located in the spinal cord. Both spinal cord and electromotor neurons ( electrocytes ) regenerate after amputation of the tail. Sternarchus spinal cords which have regenerated for 1 or more years show a progression in number of perikarya of electromotor neurons along the rostro-caudal axis. The most recently regenerated region of the cord is at the caudal end, which consists of a tube of ependyma. Progressing rostrally along regenerated spinal cord from the caudal end, numerous cells are generated and large numbers of electromotor neurons differentiate. The maximum number of electromotor neurons per transverse section of regenerated cord is five times higher than in normal mature cord. Rostral to this, the number of electromotor neurons decreases gradually to the normal number near the transition zone (the border with unregenerated cord). As the more rostral regenerated cord has presumably had a longer period of regeneration, we conclude that excess numbers of electromotor neurons are generated initially, and that subsequently the number of these neurons is decreased by cell death. This conclusion is supported by the fact that younger regenerates (2-4 months) have larger-than-normal numbers of perikarya of electromotor neurons extending up to the transition zone (Anderson and Waxman , 1981). No evidence of migration or depletion of electromotor neurons from unregenerated cord rostral to the amputation has been observed. Since the axons of the electromotor neurons in Sternarchus do not normally form any synapses, this study provides evidence that factors other than synaptic competition must be responsible for determining cell death during regeneration of these spinal neurons.

Animals↗
PubMed1991

Stimulation of regeneration of the rat sciatic nerve by 50 Hz sinusoidal magnetic fields.

The effect of sinusoidal magnetic field stimulation on regeneration of the rat sciatic nerve was studied. Rats were exposed, after crush lesioning of the nerve, between a pair of Helmholtz coils to a 50 Hz magnetic field of 0.2 mT or 0.4 mT, respectively. Regeneration of the sciatic nerve was measured by the "pinch test," or by immunocytochemical staining for neurofilaments 1 to 6 days after the crush lesion. Intermittent stimulation (4 h/day) at 0.2 mT did not affect regeneration, while continuous stimulation with the same field enhanced regeneration distances measured at Days 1, 2, and 3. Intermittent stimulation with 0.4 mT increased regeneration distances in 3-day regenerated nerves. In the rats exposed continuously to 0.4 mT regeneration was higher in all groups (1, 2, 3, 4, and 6 days). This field enhanced the regeneration velocity by 21%. Pretreatment for 7 days with continuous stimulation either at 0.2 mT or at 0.4 mT did not affect regeneration of the sciatic nerve after a crush lesion.

Animals↗
PubMed1989

Neurofilament elongation into regenerating facial nerve axons.

Immunocytochemistry was used to show that neurofilaments advance into regenerating facial nerve axons at 2.5 mm/day, which is less than the rate of axonal elongation (4.3 mm/day), measured from the transport of radiolabeled protein into the axons. Thus, the distal region of the newly-regenerated axons is deficient in neurofilaments, and this was confirmed by electron microscopy. These neurofilament-free regenerating axons could also be detected by immunocytochemistry using antibody to protein B50 (GAP43), a component of growth-cones. Immunoblots of nerve segments, incubated with monoclonal antibodies against the three neurofilament proteins, showed that all three proteins were present in the neurofilaments elongating into the regenerating axons, and confirmed the more distal extensions of B50 immunoreactivity. These results show that neurofilament immunocytochemistry underestimates the extent of axonal regeneration, and it is suggested that this technique should be employed with caution in regeneration studies. When the facial nerve received a conditioning lesion 7 days prior to a test lesion, axonal regeneration rate increased to 6.0 mm/day, and there was a proportional increase in neurofilament elongation rate to 4.4 mm/day. This occurred in spite of the reduction in cell body neurofilament protein synthesis induced by the lesions. It is concluded that the rate of neurofilament extension into regenerating axons is not governed by cell body synthesis but by local interactions with other cytoskeletal materials which support the increased regeneration rate of conditioned axons.

Animals↗
PubMed1994

Regeneration of rat sciatic nerves in silicone tubes: characterization of the response to low intensity d.c. stimulation.

Endogenous d.c. electric fields have been postulated to play a role in normal development and repair functions of a variety of living systems. The corollary hypothesis, that exogenous electric fields can alter development and repair mechanisms, has led to the use of d.c. electric fields as a means to enhance mammalian peripheral nerve regeneration. This study investigates the response of transected rat sciatic nerves within silicone tubes to low intensity d.c. stimulation. In 40 rats, the right sciatic nerves were transected and sutured into silicone tubes, leaving a 5.0 mm gap between the stumps. The nerves were either treated with 10 microA d.c., with the cathode at the midpoint of the tube and the anode distant, or received no exogenous current. Three weeks later, transverse sections from the center of the tissue bridging the two segments were analysed by sampling approximately 12% of the cross sectional area, using x 1000 magnification on the light microscope. All non-stimulated (control) nerves showed regeneration of myelinated axons at the center of the bridge, while only 35% of the nerves stimulated with 10 microA had such a response. Of the nerves with regeneration of myelinated axons at the center of the tube, the control nerves had significantly more myelinated axons (P = 0.0028) than treated nerves. Stimulated nerves showed bizarre regeneration responses, including formation of multiloculated cysts and neuroma-like formations. In control nerves there was a gradual tapering of axon number from proximal to distal in the regeneration bridge, while in the stimulated nerves there was a sharp decrease in the number of axons proximal to the cathode. We hypothesize that this effect is due to the accumulation of electrolysis products at the cathode, which inhibit regeneration through this region. Regeneration of transected rat sciatic nerves is not enhanced by electric currents applied in this manner. Previous work interpreted the increased number of axonal cross-sections in the tube as an increase in the absolute number of regenerating fibers. Our data suggest that the increased number of axonal cross-sections is due to neuroma formation, probably in response to the accumulation of electrolysis products at the cathode. This work brings into question claims of an enhancement of peripheral nerve regeneration by applied electric fields.

Animals↗
PubMed2006

Endocrine cell and nerve regeneration in autologous in situ tissue-engineered small intestine.

BACKGROUND: The purpose of this study was to regenerate a larger size of small intestinal tissue than that of our previous study and to evaluate the regeneration of the endocrine cells (ECC) and nerve system of autologous tissue-engineered small intestine. The effect of implantation of large numbers of smooth muscle cells (SMC) for the regeneration of small intestine was also investigated. METHODS: Two types of scaffolds with different cell densities were fabricated: low density (LD) of SMC in the scaffold and high density (HD) of SMC in the scaffold. Both scaffolds were implanted into defects of isolated ileum in a canine model. Animals were sacrificed at 8, 12, 18, and 24 weeks. RESULTS: The area of engineered small intestine in the HD group was four times larger than that in the LD group, although that was smaller in size than the original size of the defect. There were no significant changes in the thickness of regenerated smooth muscle layer (SML) in the LD and HD groups. The numbers of endocrine cells gradually increased after implantation. At 18 weeks of regeneration, the number of ECC reached levels comparable to that of normal mucosa. The nerve fibers extended to the center of the graft area and were observed in regenerated SML and regenerated villi at 24 weeks. CONCLUSIONS: The ECC and nerve fibers were regenerated in autologous in situ tissue-engineered small intestine. Seeding a large number of SMC was not sufficient for the regeneration of the small intestine in a tubular configuration.

Animals↗
PubMed2003

Regeneration of transgenic skeletal muscles with altered timing of expression of the basic helix-loop-helix muscle regulatory factor MRF4.

In regenerating muscle cells, muscle regulatory factor (MRF) 4 is normally the last of the four MRFs to be expressed. To analyze how the timing of MRF4 expression affects muscle regeneration, we compared regeneration after local freeze injury of muscles from wild-type mice with muscles from transgenic mice in which MRF4 expression was under control of an approximately 1.6-kb fragment of the myogenin promoter. Three days after injury, masseter and tibialis anterior (TA) muscles in wild-type mice expressed little or no MRF4 mRNA; whereas these muscles in transgenic mice expressed abundant MRF4 mRNA from both the transgene and the endogenous gene. Thus, MRF4 up-regulation was accelerated in transgenic compared to wild-type regenerating muscles, and expression of the transgene appeared to activate, perhaps indirectly, expression of the endogenous MRF4 gene. At 11 days after injury, regeneration, as measured by cross-sectional area and density of regenerated fibers, was significantly impaired in transgenic TA compared to wild-type TA, whereas at 19 days after injury both transgenic and TA muscle fibers had fully recovered to preinjury values. Regeneration of masseter muscles, which normally regenerate much less completely than TA muscles, was unaffected by the transgene. Thus, the timing of MRF4 up-regulation, as well as additional muscle-specific factors, can determine the progress of muscle regeneration.

Animals↗
PubMed1999

Changes in hepatic venous oxygen saturation related to the extent of regeneration after partial hepatectomy in rats.

BACKGROUND: Changes in hepatic oxygen metabolism in relation to the extent of liver regeneration are expected after partial hepatectomy. There are few reports, however, about hepatic oxygen metabolism during liver regeneration. In this study, we evaluated changes in hepatic oxygen metabolism related to the regeneration rate, and the relationship between hepatic venous oxygen saturation (Shvo2) and liver regeneration after partial hepatectomy. METHODS: The work was done using 50% hepatectomized rats with continuous infusion of octreotide for inhibition of liver regeneration or with saline as control. The hepatic hemodynamics, oxygen metabolism, and Shvo2 levels as well as the regenerating liver status were evaluated for 3 days after hepatectomy. RESULTS: Administration of octreotide resulted in a significant reduction of the regenerating liver weight on days 1 and 3 after hepatectomy compared with the control group. Significantly decreased DNA synthesis and proliferating cell nuclear antigen labeling index were also found on day 1. Meanwhile, hepatic oxygen consumption (HVO2) and oxygen extraction ratio were significantly decreased in the octreotide-treated group on day 1. In contrast, the Shvo2 levels in the octreotide-treated group were significantly higher than those in the control group, and were inversely correlated with the HVO2. CONCLUSION: The remnant liver demands an increased amount of oxygen in relation to the extent of regeneration, and changes in the Shvo2 are inversely correlated with the HVo2. Therefore, monitoring the Shvo2 could be useful for estimating liver regeneration after partial hepatectomy.

Animals↗
PubMed2000

Effects of neonatal injury of the inferior alveolar nerve on the development and regeneration of periodontal nerve fibers in the rat incisor.

Our previous study showed that the migration of terminal Schwann cells occurred in the periodontal ligament of the rat lower incisor following transection of the inferior alveolar nerve (IAN) in the adult animals [Y. Atsumi, K. Matsumoto, M. Sakuda, T. Maeda, K. Kurisu, S. Wakisaka, Altered distribution of Schwann cells in the periodontal ligament of the rat incisor following resection of the inferior alveolar nerve: An immunohistochemical study on S-100 proteins, Brain Res. 849 (1999) 187-195]. The aim of the present study was to investigate the effects of neonatal transection of the IAN on the regeneration of axon elements and Schwann cells in the periodontal ligament of the rat lower incisor. Following transection of IAN at post-natal day 5 (PN 5d), when the numbers of both axon elements and the terminal Schwann cells were very small, regenerating nerve fibers appeared between post-injured days 7 (PO 7d) and PO 14d, and increased in number thereafter gradually. Although the terminal morphologies of regenerated Ruffini endings became identical to those of the adult animals by PO 54d, the number of regenerated PGP 9.5-IR nerve fibers did not recover the adult levels even by PO 56d. A small number of Schwann cells migrated into the shear zone, the border between the alveolus-related part (ARP) and the tooth-related part (TRP), but did not enter into the TRP. Following transection of the IAN at PN 14d or PN 28d, when clusters of apparent terminal Schwann cells could be recognized, axon regeneration started around PO 5d. Individual axon terminals of the regenerating Ruffini endings ramified and became identical to those of the adult animals around PO 28d, but the number of regenerated Ruffini endings was smaller than that of the adult animals. Similar to the adult animals, the migration of Schwann cells into the shear zone and TRP occurred, and disappeared prior to the completion of the axonal regeneration. The present results indicate that the migration of the Schwann cells into TRP during the regeneration of the periodontal nerve fibers following nerve injury to the IAN depends on the maturation of the terminal Schwann cells of the periodontal Ruffini endings, not on post-operative time.

Age Factors↗
PubMed1998

Calretinin-like immunoreactivity in the regenerating periodontal ruffini endings of the rat incisor following injury to the inferior alveolar nerve.

Regeneration of calretinin (CR)-like immunoreactive (IR) nerve fibers was investigated in the periodontal ligament of the rat lower incisor following resection of the inferior alveolar nerve (IAN). In addition, the degeneration and regeneration processes of periodontal nerve fibers were examined by immunohistochemistry for protein gene product 9.5 (PGP 9.5), a general neuronal marker. In normal animals, the periodontal nerve fibers showing PGP 9.5-like immunoreactivity (LI) formed either periodontal Ruffini endings with expanded arborization and thin free nerve endings in the alveolar half of the ligament. Thick CR-IR nerve fibers also appeared in a dendritic fashion in the same region, but thin CR-IR nerve fibers were rarely observed. Five days following resection of the IAN, a major population of PGP 9.5-IR and all CR-IR nerve fibers disappeared except for some thin PGP 9.5-IR nerves in the periodontal ligament. Regenerated PGP 9.5-IR nerve fibers appeared around 7 days following resection, in contrast to a very small number of regenerated CR-IR nerve fibers. Around 14-21 days following resection, the number and terminal morphology of regenerated PGP 9.5-IR nerve fibers were comparable to those observed in normal animals, but the number of regenerated CR-IR nerve fibers was still smaller than that of normal animals. The number of regenerated CR-IR nerve fibers increased to return to normal by 56 days following injury. The delay of expression of CR-LI in the regenerated periodontal Ruffini endings suggests that functional recovery of periodontal Ruffini endings occurred after the completion of the regeneration of periodontal nerve fibers.

Animals↗
PubMed1996

Evidence for multiple satellite cell populations and a non-myogenic cell type that is regulated differently in regenerating and growing skeletal muscle.

We have performed studies to determine if different populations of satellite cells provide nuclei to growing and regenerating skeletal muscle fibers. Satellite cells were isolated from regenerating or growing anterior tibialis muscles, and their phenotypic properties were compared in vitro. Isolates from regenerating muscle contained 31% satellite cells, and those from control muscle contained 66% satellite cells, as determined by their expression of desmin. Among the desmin-positive satellite cells present from each preparation, two distinct populations of satellite cells were evident. Approximately 28% of satellite cell colonies were composed of only large cells, contained less than 50 cells/colony, and were designated as type 1 colonies. The remainder of satellite cell colonies isolated from either regenerating or control muscles were primarily composed of small cells, contained from 60 to 150 cells/colony, and were designated as type 2 colonies. Despite dramatic differences in the ratio of myogenic to non-myogenic cell types, satellite cells from regenerating and control muscles formed myotubes and expressed myosin heavy chain at similar levels. Treatment of regenerating cultures with dexamethasone resulted in a 16% increase in the number of desmin-positive colonies and dramatically decreased the proliferation of non-myogenic cells. These results suggest that at least two distinct populations of satellite cells can be isolated from regenerating and control skeletal muscles, and that non-myogenic cells are differentially regulated in regenerating versus non-regenerating environments.

Animals↗
PubMed1986

Muscular dystrophy and muscle regeneration.

An animal model of muscular dystrophy, the dystrophic (129ReJ dy/dy) mutant mouse, was used to evaluate the regenerative phenomenon in dystrophic muscle. The effect of age on "spontaneous" regeneration (i.e., regeneration in the absence of secondary trauma) was assessed by quantitative morphometric analysis and evaluation of myosatellite cell dynamics (i.e., myosatellite cell frequency, proliferative activity, and fusion capability). Spontaneous regeneration ceased by the time the mice were 8 weeks old. The findings suggested that the small "regenerating" myofibers found in older dystrophic muscle had been formed earlier in the time course of the disease and were growth-inhibited. To determine the cause of the cessation of regeneration, dystrophic muscle was subjected to the severe trauma of whole-muscle transplantation, a trauma that results in total myofiber necrosis followed by de novo myotube formation. When young dystrophic muscle (from 4- to 6-week-old dystrophic mice) was orthotopically transplanted, the time course of degeneration-regeneration was similar to that seen in age-matched normal muscle. Moreover, the regenerated dystrophic myofibers were capable of long-term survival (200 days or longer after transplantation), and they failed to show evidence of histologic changes consistent with murine dystrophy. When older dystrophic muscle (from 17-week-old dystrophic mice), muscle that failed to display spontaneous regeneration, was transplanted, it displayed remarkable regenerative capacity. It was suggested that the cessation of spontaneous regeneration in older dystrophic murine muscle is due not to exhaustion of myosatellite cell proliferative capacity, but rather to age-related loss of the mitogenic effect of dystrophy on the myosatellite cells of dystrophic muscle.

Aging↗
PubMed2002

Changes in mRNA content of developing opossum spinal cord at stages when regeneration can and cannot occur after injury.

The molecular mechanisms responsible for regeneration in the mammalian central nervous system (CNS) are poorly understood. Unlike the situation in adults, in the neonatal opossum, as in other immature mammals, the CNS shows successful regeneration after injury. We have used the isolated opossum CNS as a preparation for studying regeneration. An advantage of the opossum is that its developing spinal cord exhibits a gradient of regeneration in time and space. Thus, the potential for repair becomes lost in the cervical spinal cord when animals reach an age of 12 days or more. Animals up to 17 days of age still show regeneration in less mature lumbar segments of the spinal cord. To identify genes that underlie the process of regeneration we are studying mRNA changes in spinal cords at various stages of development. We have developed techniques for narrowing down the number of candidate genes by performing different gene subtraction experiments and by cross-hybridizing their results. This allowed us to select sequences differentially expressed in regeneration and to eliminate genes unrelated to that process. Our results reveal a number of novel sequences that could be important for spinal cord regeneration, as well as genes already supposed to play a role in regeneration.

Animals↗
PubMed2003

Diabetic neuropathy and nerve regeneration.

Diabetic neuropathy is the most common peripheral neuropathy in western countries. Although every effort has been made to clarify the pathogenic mechanism of diabetic neuropathy, thereby devising its ideal therapeutic drugs, neither convinced hypotheses nor unequivocally effective drugs have been established. In view of the pathologic basis for the treatment of diabetic neuropathy, it is important to enhance nerve regeneration as well as prevent nerve degeneration. Nerve regeneration or sprouting in diabetes may occur not only in the nerve trunk but also in the dermis and around dorsal root ganglion neurons, thereby being implicated in the generation of pain sensation. Thus, inadequate nerve regeneration unequivocally contributes to the pathophysiologic mechanism of diabetic neuropathy. In this context, the research on nerve regeneration in diabetes should be more accelerated. Indeed, nerve regenerative capacity has been shown to be decreased in diabetic patients as well as in diabetic animals. Disturbed nerve regeneration in diabetes has been ascribed at least in part to all or some of decreased levels of neurotrophic factors, decreased expression of their receptors, altered cellular signal pathways and/or abnormal expression of cell adhesion molecules, although the mechanisms of their changes remain almost unclear. In addition to their steady-state changes in diabetes, nerve injury induces injury-specific changes in individual neurotrophic factors, their receptors and their intracellular signal pathways, which are closely linked with altered neuronal function, varying from neuronal survival and neurite extension/nerve regeneration to apoptosis. Although it is essential to clarify those changes for understanding the mechanism of disturbed nerve regeneration in diabetes, very few data are now available. Rationally accepted replacement therapy with neurotrophic factors has not provided any success in treating diabetic neuropathy. Aside from adverse effects of those factors, more rigorous consideration for their delivery system may be needed for any possible success. Although conventional therapeutic drugs like aldose reductase (AR) inhibitors and vasodilators have been shown to enhance nerve regeneration, their efficacy should be strictly evaluated with respect to nerve regenerative capacity. For this purpose, especially clinically, skin biopsy, by which cutaneous nerve pathology including nerve regeneration can be morphometrically evaluated, might be a safe and useful examination.

Animals↗
PubMed2000

Axonal regeneration from CNS neurons in the cerebellum and brainstem of adult rats: correlation with the patterns of expression and distribution of messenger RNAs for L1, CHL1, c-jun and growth-associated protein-43.

Some neurons in the brain and spinal cord will regenerate axons into a living peripheral nerve graft inserted at the site of injury, others will not. We have examined the patterns of expression of four molecules thought to be involved in developmental and regenerative axonal growth, in the cerebellum and brainstem of adult rats, following the implantation into the cerebellum of peripheral nerve grafts. We also determined how the expression patterns observed correlate with the abilities of neurons in these regions to regenerate axons. Three days to 16 weeks after insertion of living tibial nerve autografts, neurons which had regenerated axons into the graft were retrogradely labelled from the distal extremity of the graft with cholera toxin conjugated to horseradish peroxidase, and sections through the cerebellum and brainstem were processed for visualization of transported tracer and/or hybridized with riboprobes to detect messenger RNAs for the cell recognition molecules L1 and CHL1 (close homologue of L1), growth-associated protein-43 and the cellular oncogene c-jun. Retrogradely labelled neurons were present in cerebellar deep nuclei close to the graft and in brainstem nuclei known to project to the cerebellum. Neurons in these same nuclei were found to have up-regulated expression of all four messenger RNAs. Individual retrogradely labelled neurons also expressed high levels of L1, CHL1, c-jun or growth-associated protein-43 messenger RNAs (and vice versa), and every messenger RNA investigated was co-localized with at least one other messenger RNA. Purkinje cells did not regenerate axons into the graft or up-regulate L1, CHL1 or growth-associated protein-43 messenger RNAs, but there was increased expression of c-jun messenger RNA in some Purkinje cells close to the graft. Freeze-killed grafts produced no retrograde labelling of neurons, and resulted in only transient and low levels of up-regulation of the tested molecules, mainly L1 and CHL1. These findings show that cerebellar deep nucleus neurons and precerebellar brainstem neurons, but not Purkinje cells, have a high propensity for axon regeneration, and that axonal regeneration by these neurons is accompanied by increased expression of L1, CHL1, c-jun and growth-associated protein-43. Furthermore, although the patterns of expression of the four molecules investigated are not identical in regenerating neuronal populations, it is probable that all four are up-regulated in all neurons whose axons regenerate into the grafts and that their up-regulation may be required for axon regeneration to occur. Finally, because c-jun up-regulation is seen in Purkinje cells close to the graft, unaccompanied by up-regulation of the other molecules investigated, c-jun up-regulation alone cannot be taken to reliably signify a regenerative response to axotomy.

Animals↗
PubMed1998

Cell population changes during atrophy and regeneration of rat parotid gland.

Limited data exist regarding the changes in number and location of myoepithelial cells during salivary gland atrophy and regeneration. Through the use of double immunohistochemical labeling for muscle-specific actin and amylase coupled with morphometric analysis, this study investigated the changes in distribution and proportion of cell types during salivary gland atrophy/regeneration phases in a model previously used to study proliferation in rat parotid gland. The double immunohistochemical labeling clearly showed the changes in proportion of cell types in the atrophying and regenerating glands. The morphometric analysis showed that the relative myoepithelial area increased (as did the intercalated duct and striated duct areas) as the gland atrophied. Myoepithelial cells occupied 19.0% of the total epithelial area by day 7 of atrophy, up from 2.7% in the resting gland. Regeneration of acinar cells was obvious 1 day after duct release. The myoepithelial cell area decreased to 4.3% of the total epithelial area by day 14 of regeneration; this value was higher than the percentage of area in the resting gland (p = 0.02). The relative areas of acinar, striated duct, and intercalated duct cells returned to resting levels after 14 days of regeneration. The morphometric and histologic results of this study show that the parotid gland is capable of regenerating to essentially normal anatomic condition after 7 days of gland atrophy and then 14 days of regeneration. Each type of cell, however, responded to the atrophy and regeneration differently. Atrophy of salivary glands from radiation therapy. Sjögren's syndrome, or sialadenitis is an important clinical problem. Study of the salivary gland response to atrophy and regeneration may provide a framework for designing strategies for the radioprotection of salivary glands or methods by which to treat or reverse the effects of gland atrophy.

Actins↗
PubMed2000

Role of Schwann cells in retinal ganglion cell axon regeneration.

It is a well known fact that the injured PNS can successfully regenerate, on the other hand, the CNS such as retinal ganglion cell (RGC) axons of adult mammals is incapable of regeneration. After injury, RGC axons rapidly degenerate and most cell bodies go through the process of cell death, while glial cells at the site of injury undergo a series of responses which underlie the so-called glial scar formation. However, it has become apparent that RGCs do have an intrinsic capacity to regenerate which can be elicited by experimental replacement of the inhibitory glial environment with a permissive peripheral nerve milieu. Schwann cells are a major component of the PNS and play a role in regeneration, by producing various kinds of functional substances such as diffusible neurotrophic factors, extracellular matrix and cell adhesion molecules. RGC regeneration can be induced by cooperation of these substances. The contact of RGC axons to Schwann cells based upon the structural and molecular linkages seems to be indispensable for the stable and successful regeneration. In addition to cell adhesion molecules such as NCAM and L1, data from our laboratory show that Schwann cells utilize short focal tight junctions to provide morphological stabilization of the contact with the elongating axon, as well as a small scale of gap junctions to facilitate traffic of substances between them. Moreover, our results show that modifications of functional properties in neighboring glial cells of optic nerve are induced by transplantation of Schwann cells. Astrocytes usually considered to form a glial scar guide the regenerating axons in cooperation with Schwann cells. A decrease of the oligodendrocyte marker O4 and migration of ED-1 positive macrophages is observed within the optic nerve stump. Accordingly, RGC regeneration is not a simple phenomenon of axonal elongation on the Schwann cell membrane, but is based on direct and dynamic communication between the axon and the Schwann cell, and is also accompanied by changes and responses among the glial cell populations, which may be partly associated with the mechanisms of optic nerve regeneration.

Animals↗
PubMed1990

Persistent effects of a serotonin depletor (p-chlorophenylalanine) in regenerated planaria (Dugesia dorotocephala).

p-Chlorophenylalanine (pCPA) caused an increase in looping and locomotion speed in planaria (Dugesia dorotocephala). These effects dissipated quickly after treatment, except in animals that regenerated from worms surgically sectioned after treatment. Planaria that regenerated from head sections showed more looping 6 and 11 days later than tail regenerates, regenerates from untreated worms, and uncut worms. After the initial acceleration, pCPA animals, especially regenerates from tail sections, slowed down compared with untreated controls. Tail regenerates showed reduced speed 6 and 11 days later in comparison with head regenerates, regenerates from untreated animals, and uncut animals. The speed effect may have been due to pathogenesis in the eye spots in pCPA animals. The looping effect, however, may have been due to persisting serotonin depletion in the head regenerates. It is suggested that research on this problem might profitably be pursued with sexually reproducing planaria, to examine the possibility of genetic recoding due to serotonin depletion.

Animals↗