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PubMed2000

Effects of different types of injury to the inferior alveolar nerve on the behavior of Schwann cells during the regeneration of periodontal nerve fibers of rat incisor.

The present study reports on different regeneration patterns of axons and Schwann cells in the periodontal ligament of the rat incisor using immunohistochemistry of protein gene product 9.5 (PGP 9.5) and S-100 protein. Three kinds of injury (transection, crush and segmental resection) were applied to the inferior alveolar nerve. In normal animals, PGP 9.5- and S-100-immunoreactivities were detected in the axons and Schwann cell elements of periodontal Ruffini endings, respectively. They were restricted to the alveolus-related part, occurring only rarely in the tooth-related part and in the shear zone (the border between the alveolus-related and tooth-related parts). Both transection and segmental resection caused the complete disappearance of PGP 9.5-immunoreactive nerve fibers in the periodontal ligament, while a small number of them could be found following the crush injury. Regenerating PGP 9.5-reactive nerve fibers appeared at 5 days and 21 days following the transection and segmental resection, respectively. The regeneration of periodontal nerve fibers completed in a period of 21-28 days and 14-21 days following the transection and crush, respectively, but was not completed even at 56 days following the segmental resection. The behavior of Schwann cells during regeneration was similar after the different nerve injuries; spindle-shaped S-100-immunoreactive cells, presumably Schwann cells, appeared in the shear zone and the tooth-related part. These cells disappeared 5-7 days prior to the completion of the regeneration of axonal elements of the periodontal ligament following the transection and crush. Following the segmental resection, in contrast, spindle-shaped S-100-positive cells disappeared from the tooth-related part at 42 days, although the axonal regeneration of periodontal Ruffini endings proceeded even until 56 days. We thus conclude that the duration of the migration of Schwann cells depends on the state of the regeneration of axons.

Animals↗
PubMed2005

Oxidized galectin-1 is an essential factor for peripheral nerve regeneration.

Although many factors have been implicated in the regenerative response of peripheral axons to nerve injury, the signals that prompt neurons to extend processes in peripheral nerves after axotomy are not well-understood. As shown in the first chapter, oxidized recombinant human galectin-1 (rhGAL-1/Ox), which lacks lectin activity, promotes initial axonal growth in an in vitro peripheral nerve regeneration model at low concentrations (pg/ml). At a similarly low concentration, rhGAL-1/Ox has also been shown to be effective in enhancing axonal regeneration using in vivo experiments. Moreover, the application of functional anti-rhGAL-1 antibody strongly inhibited axonal regeneration in vivo as well as in vitro. Since galectin-1 (GAL-1) is expressed in the regenerating sciatic nerves as well as in both sensory and motoneurons, these results indicate that GAL-1, which is secreted into the extracellular space, is subsequently oxidized and then may regulate initial repair after axotomy. This possibility was confirmed by Western blot analysis, which revealed that both reduced and oxidized forms of GAL-1 are present in culture media of DRG neurons and immortalized adult mouse Schwann cells (IMS32). Externalized GAL-1/Ox has been found to stimulate macrophages to secrete an axonal regeneration-promoting factor. From these results, we propose that axonal regeneration occurs in axotomized peripheral nerves as a result of cytosolic reduced GAL-1 being released from Schwann cells and injured axons, which then becomes oxidized in the extracellular space. GAL-1/Ox in the extracellular space stimulates macrophages to secrete a factor that promotes axonal growth and Schwann cell migration, thus enhancing peripheral nerve regeneration and functional recovery. These results suggest that rhGAL-1/Ox may be a novel factor for functional restoration of injured peripheral nerves.

Animals↗
PubMed1989

Ultrastructural investigation of nerve regeneration in vivo--comparison with in vitro neurite formation.

The process of regeneration of rat dorsal root ganglion cells was investigated by scanning and transmission electron microscopy and compared with the process of in vitro neurite formation. After disruption of the granular reticulum, numerous microtubules appeared in the perinuclear cytoplasm. Many thin, regenerating nerve fibers were found at the suture line adjacent to collagen fibers. Subsequently, the number of cytoplasmic neurofilament bundles increased and many of the regenerated nerves attached to the suture line. By the eighth week after experimental injury, the granular reticulum had reconstituted in the cytoplasm and the regenerated nerves resembled those of control animals, although the fiber arrangement was somewhat irregular. The process was almost identical to that of in vitro neurite formation, although the time course was much slower. Structural proteins, such as actin, tubulin, and neurofilament triplet, appeared to form similarly in neuronal regeneration and in vitro neurite formation. The results also suggest that microtubules are essential for nerve regeneration as well as neurite formation and that components of the neuronal microenvironment, such as collagen fibers and migrating cells, play crucial roles in nerve regeneration.

Animals↗
PubMed1989

[Study of regeneration in periodontal tissue after implantation of bone ceramic and collagen gel compound materials. Evaluation of histopathological finding and autoradiography].

The aim of this study is to determine the process of periodontal tissue regeneration and the metabolic activity of osteoblasts after implantation of bone ceramic and collagen gel compound materials (BC). Bone defects were artificially prepared in the alveolar septa of the bilateral upper first and second molars of Wistar rats. Subsequently, BC were implanted into the defective sites on the left side, and the gingival flaps were closed. At the defective sites on the right side, as a control, gingival flaps were closed without implantation. Rats were sacrificed 1, 3, 5, 7 or 14 weeks after implantation, and prepared tissue sections were observed both pathologically and autoradiographically using 3H-Proline. The results obtained were as follows: Pathological Findings One week after BC implantation, inflammatory cellular infiltration of the surrounding gingival connective tissue was relatively mild. Three weeks after implantation, BC were present in fibrous connective tissues, and some directly bound to the marices of regenerated bone. Observation 5 weeks after implantation revealed that BC had become embedded in the regenerated bone matrices and that there was giant cell reaction to foreign bodies at the margin of BC located in connective tissue. BC were directly bound to the regenerated bone matrices without intermediary fibrous tissues 7 and 14 weeks after implantation. Connective tissues showed high grade regeneration of collagen fiber bundles, in an arrangement that tended to be fixed in mesial and distal directions. Autoradiographic Findings There was no uptake of 3H-Proline into the regenerated bone matrices or the gingival connective tissue surrounding BC, while uptake of 3H-Proline into the entire area around the root apex and in the vicinity of the alveolar septum was observed with time (weeks) after BC implantation. These results suggest that BC provide nuclei for bone regeneration through inclusion in newly-generated periodontal bone tissue, although it is difficult to produce definite induction of bone tissue by BC alone. It is also apparent that these are useful bone implantation materials for restoration of the physiological morphology of alveolar bone in periodontal surgical treatment.

Animals↗
PubMed1987

Proteoglycan synthesis during intramembranous bone regeneration following avulsive wounding in guinea pig long bones.

Information on proteoglycan synthesis by bone cells and tissue is largely limited to studies of developing fetal bone. The present investigation focuses on proteoglycan synthesis during the intramembranous type of bone regeneration seen within avulsive (puncture-type) defects placed in guinea pig tibiae. [35S] Sulfate-labeled proteoglycans were extracted from tissue within regenerating tibial avulsive defects seven days following surgical wounding and also from xiphisternal cartilage utilized as an internal control. Labeled proteoglycans in 4M guanidine HCl extracts of regenerating bone and cartilage were purified by DEAE-Sephacel chromatography and further analyzed by chromatography and appropriate enzyme digestions. Regenerating bone tissue contained a proteoglycan relatively small in size (Kav = 0.56 following chromatography on Sepharose CL-2B) compared to proteoglycan from xiphisternal cartilage (Kav = 0.17). Alkaline borohydride treatment degraded this bone proteoglycan (Kav = 0.4 on Sepharose CL-6B), indicating an average molecular weight of glycosaminoglycan chains approximating 50,000. Enzymatic digestions followed by Sepharose CL-6B chromatography showed that glycosaminoglycan side chains of regenerating bone proteoglycan contained dermatan sulfate, with 60% chondroitinase AC II-resistant but chondroitinase ABC-sensitive material. This bone proteoglycan did not interact with hyaluronic acid to form aggregates under conditions where such aggregates were formed by xiphisternal cartilage proteoglycan. The regenerating bone proteoglycans are therefore similar to other bone proteoglycans in hydrodynamic size and glycosaminoglycan chain size, but differ in the per cent of iduronic acid within glycosaminoglycan side chains. This guinea pig bone proteoglycan may be associated with the large mesenchymal cell population noted histologically within the bone defects at seven days of regeneration.

Animals↗
PubMed1985

Muscle regeneration induced by cells autografted in adult rats.

Right triceps surae of 3-week-old Wistar rats were minced and devitalized with liquid nitrogen, a treatment which completely inhibits their ability to regenerate when they are orthotopically autografted. In a first series of experiments, cells were isolated from the left triceps surae, mixed with the devitalized right mince and autografted; in a second series, cells were moreover allowed to proliferate in vitro for a few weeks before being grafted. The regenerates were examined 60 days after surgery. In the first series, all the regenerates were contractile and developed a maximal isometric tetanic force of 18 +/- 6 mN (n = 5); they contained 152 +/- 80 muscle fibres located proximally, the number of which decreased along the proximo-distal axis, being 24 +/- 24 in the median part of the regenerate. The muscle fibres appeared histologically normal except for their shortness (less than 10 mm) and narrowness (mean luminal diameter: 30 microns). In the second series, 2 out of 5 regenerates were comparable with those of the first series except that their fibres were shorter; the 3 other regenerates were unexcitable. These experiments demonstrate that cells isolated from an adult striated muscle are able to regenerate striated muscle fibres in an adult animal and that these cells can retain this property if they are grown in culture.

Animals↗
PubMed2003

Growth factor enhancement of peripheral nerve regeneration through a novel synthetic hydrogel tube.

OBJECT: The authors' long-term goal is repair of peripheral nerve injuries by using synthetic nerve guidance devices that improve both regeneration and functional outcome relative to an autograft. They report the in vitro processing and in vivo application of synthetic hydrogel tubes that are filled with collagen gel impregnated with growth factors. METHODS: Poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (PHEMA-MMA) porous 12-mm-long tubes with an inner diameter of 1.3 mm and an outer diameter of 1.8 mm were used to repair surgically created 10-mm gaps in the rat sciatic nerve. The inner lumen of the tubes was filled with collagen matrix alone or matrix supplemented with either neurotropin-3 at 1 microg/ml, brain-derived neurotrophic factor at 1 microg/ml, or acidic fibroblast growth factor (FGF-1) at 1 or 10 microg/ml. Nerve regeneration through the growth factor-enhanced tubes was assessed at 8 weeks after repair by histomorphometric analysis at the midgraft level and in the nerve distal to the tube repair. The tubes were biostable and biocompatible, and supported nerve regeneration in more than 90% of cases. Nerve regeneration was improved in tubes in which growth factors were added, compared with empty tubes and those containing collagen gel alone (negative controls). Tubes filled with 10 microg/ml of FGF-1 dispersed in collagen demonstrated regeneration comparable to autografts (positive controls) and showed significantly better regeneration than the other groups. CONCLUSIONS: The PHEMA-MMA tubes augmented with FGF-1 in their lumens appear to be a promising alternative to autografts for repair of nerve injuries. Studies are in progress to assess the long-term biocompatibility of these implants and to enhance regeneration further.

Animals↗
PubMed1998

Regeneration of graft liver in adult-to-adult living donor liver transplantation using a left lobe graft.

Graft size-matching is one of the critical concerns in adult-to-adult living donor liver transplantation (ATALDLT). In this study, we evaluated regeneration of a small-for-size graft less than 50% of the standard liver volume (SLV). We reviewed nine patients of united network of organ sharing (UNOS) status 2 or 3 who had undergone ATALDLT with a left lobe graft. For the comparison of liver regeneration, 20 hepatectomized patients for biliary malignancy were selected as non-transplant control group. In the ATALDLT group, graft size ranged from 30 to 49% of the SLV of recipients and their regeneration rates were 158%, 182%, 200% and 185% after 1,2, 3 and 4 weeks following transplantation, respectively. In the control group, preoperative volume of left lobe to whole liver volume ranged between 40 and 54% and their regeneration rates were 145%, 156%, 163% and 177% after 1,2, 3 and 4 weeks following extended right lobectomy, respectively. There was no statistical difference in regeneration rates between two groups. In the ATALDLT group, serum aspartate aminotransferase showed the median peak level of 198 IU/L on the first postoperative day and it was normalized within one week. Recovery of bilirubin clearance lagged behind rapid volume regeneration by about one week. Two patients died of sepsis. We postulate that the regenerative power of small-for-size grafts from living donors is preserved, although time-lag between volume regeneration and metabolic capability occurs in small-for-size grafts, when the initial graft volume meets metabolic demands during the early postoperative days.

Adult↗
PubMed2003

Relationship between utrophin and regenerating muscle fibers in duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a dystrophinopathy, and its associated gene is located on Xp21. Moreover, utrophin, a recently identified structural homologue of dystrophin is reported to be up-regulated in DMD. In order to investigate the association between utrophin and muscle regeneration in DMD, an immunohistochemical study using antibodies to utrophin, dystrophin, vimentin and desmin was carried out in 17 cases of DMD, 3 cases of polymyositis and 1 case of dermatomyositis. Dystrophin was negative in almost all cases of DMD, but positive in all cases of inflammatory myopathy (IM). Utrophin was positive in 94.0% of DMD and in 75.0% of IM. 36.4% of the myofibers were positive in DMD, as compared to 10.5% in IM (p=0.001). In both groups, utrophin positivity was present most commonly in small regenerating fibers (p=0.001, 0.013). Vimentin and desmin were intensely positive in regenerating fibers in all cases of DMD and IM. 34.4% and 35.4% of myofibers were positive for vimentin and desmin in DMD, as compared to 21.8% and 20.9% in IM (p=0.001, 0.001). In both groups, vimentin and desmin positivity were present most commonly in small regenerating fibers (p=0.001, 0.001). The staining intensities of utrophin, vimentin and desmin were also higher in small regenerating fibers. These results show that utrophin up-regulation is regeneration-associated, and that it is proportional to the quantity of regenerating myofibers, but is not specific for DMD.

Adolescent↗
PubMed2007

Expression patterns and action analysis of genes associated with inflammatory responses during rat liver regeneration.

AIM: To study the relationship between inflammatory response and liver regeneration (LR) at transcriptional level. METHODS: After partial hepatectomy (PH) of rats, the genes associated with inflammatory response were obtained according to the databases, and the gene expression changes during LR were checked by the Rat Genome 230 2.0 array. RESULTS: Two hundred and thirty-nine genes were associated with liver regeneration. The initial and total expressing gene numbers found in initiation phase (0.5-4 h after PH), G(0)/G(0) transition (4-6 h after PH), cell proliferation (6-66 h after PH), cell differentiation and structure-function reconstruction (66-168 h after PH) of liver regeneration were 107, 34, 126, 6 and 107, 92, 233, 145 respectively, showing that the associated genes were mainly triggered at the beginning of liver regeneration, and worked at different phases. According to their expression similarity, these genes were classified into 5 groups: only up-regulated, predominantly up-, only down-, predominantly down-, up- and down-, involving 92, 25, 77, 14 and 31 genes, respectively. The total times of their up- and down-regulated expression were 975 and 494, respectively, demonstrating that the expressions of the majority of genes were increased, and that of a few genes were decreased. Their time relevance was classified into 13 groups, showing that the cellular physiological and biochemical activities were staggered during liver regeneration. According to gene expression patterns, they were classified into 33 types, suggesting that the activities were diverse and complex during liver regeneration. CONCLUSION: Inflammatory response is closely associated with liver regeneration, in which 239 LR-associated genes play an important role.

Animals↗
PubMed2003

Gene and protein expressions of p28GANK in rat with liver regeneration.

AIM: To observe the gene and protein expression changes of p28GANK in regenerating liver tissues, and to reveal the biological function of p28GANK on the regulation of liver regeneration. METHODS: One hundred and thirty two adult male Sprague-Dawley rats were selected, weighing 200-250 g, and divided randomly into sham operation (SO) group and partial hepatectomy (PH) group. Each group had eleven time points: 0, 2, 6, 12, 24, 30, 48, 72, 120, 168 and 240 h, six rats were in each time point. The rats were undergone 70% PH under methoxyflurane anesthesia by resection of the anterior and left lateral lobes of the liver. SO was conducted by laparotomy plus slight mobilization of the liver without resection. Liver specimens were collected at the indicated time points after PH or SO. The expression level of p28GANK mRNA was determined by Northern blot as well as at protein level via immunohistochemical staining. The expressions of p28GANK mRNA in these tissues were analyzed by imaging analysis system of FLA-2000 FUJIFILM and one way analysis of variance. The protein expressions of p28GANK in these tissues were analyzed with Fromowitz' method and Rank sum test. RESULTS: The expression of p28GANK mRNA in the regenerating liver tissues possessed two transcripts, which were 1.5 kb and 1.0 kb. There was a significantly different expression patterns of p28GANK mRNA between SO and PH groups (P<0.01). The expression of p28GANK mRNA increased 2 h after PH, the peak time was 72 h (SO group: 163.83+/-1.4720; PH group: 510.5+/-17.0499, P<0.01). There was a significant difference in the 1.5 kb transcript, which decreased gradually after 72 hours. The protein expression of p28GANK was mainly in the cytoplasm of regenerating hepatocytes, and increased near the central region 24 h after PH, and became strongly positive at 48 h (+++, vs the other time points P<0.05), but decreased 72 h after PH. CONCLUSION: The expression of p28GANK mRNA increases in the early stage of rat liver regeneration, the protein expression of p28GANK is mainly in the cytoplasm of regenerating liver cells. It suggests that the gene of p28GANK may be an important regulatory and controlled factor involved in hepatocyte proliferation during liver regeneration.

Animals↗
PubMed2002

Inhibition of protein kinase C prevents Purkinje cell death but does not affect axonal regeneration.

In organotypic cultures, mouse Purkinje cells regenerate their axons from embryonic day 18 (E18) to postnatal day 0 (P0), die of apoptosis between P1 and P7, and survive but do not regenerate at P10. This particular behavior of Purkinje cells did not allow us to find out when the developmental switch between regeneration and lack of regeneration occurs. This work was undertaken to suppress Purkinje cell apoptosis and to investigate whether the same molecules that prevent apoptosis could also influence axonal growth, regeneration, or both. We show that brain-derived neurotrophic factor, neurotrophin 3, and insulin-like growth factor I have marginal effects on P3 Purkinje cell death. The use of Gö6976 [a protein kinase C (PKC) inhibitor] or a transgenic mouse line, in which a pseudosubstrate PKC inhibitor has been specifically targeted to Purkinje cells, prevents the massive Purkinje cell death in P3 organotypic cultures. In addition, Gö6976 promotes axotomized Purkinje cell survival up to P7. Thus, the inhibition of PKC activity is able to prevent Purkinje cell apoptosis in organotypic cultures. Furthermore, Gö6976 increases the outgrowth of dendrites and axon collateralization, as shown after gene gun enhanced green fluorescent protein transfection. In contrast, PKC inhibitors do not influence the axonal regenerative capability of Purkinje cell during development; the latter decreases between E18 and P7 after the same time course in control and Gö6976-treated slices. Thus, because inhibition of PKC prevents Purkinje cell death but does not affect axonal regeneration, these two events (cell death and axonal regeneration) seem to be differentially regulated.

Animals↗
PubMed1999

CNTF, not other trophic factors, promotes axonal regeneration of axotomized retinal ganglion cells in adult hamsters.

PURPOSE: To investigate the in vivo effects of trophic factors on the axonal regeneration of axotomized retinal ganglion cells in adult hamsters. METHODS: The left optic nerve was transected intracranially or intraorbitally, and a peripheral nerve graft was apposed or sutured to the axotomized optic nerve to enhance regeneration. Trophic factors were applied intravitreally every 5 days. Animals were allowed to survive for 3 or 4 weeks. Regenerating retinal ganglion cells (RGCs) were labeled by applying the dye Fluoro-Gold to the distal end of the peripheral nerve graft 3 days before the animals were killed. RESULTS: Intravitreal application of ciliary neurotrophic factor substantially enhanced the regeneration of damaged axons into a sciatic nerve graft in both experimental conditions (intracranial and intraorbital optic nerve transections) but did not increase the survival of distally axotomized RGCs. Basic fibroblast growth factor and neurotrophins such as nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 failed to enhance axonal regeneration of distally axotomized RGCs. CONCLUSIONS: Neurons of the adult central nervous system can regenerate in response to trophic supply after injury, and ciliary neurotrophic factor is at least one of the trophic factors that can promote axonal regeneration of axotomized RGCs.

Animals↗
PubMed2000

[Optic nerve regeneration: contemporary views and perspectives of clinical use].

Recent extensive advances in neuroscience not only proved that optic nerve has a capacity for functional repair, but made its regeneration a reality in laboratory mammals. Today it is evident that optic nerve after axonotmesis displays signs of very active regeneration. Nevertheless, the regeneration is inhibited by a number of factors acting in the environment of normal CNS. Inhibitors secreted by oligodendrocytes and deposited in the layer of myelin attenuate migration of macrophages and process of phagocytosis, which is indispensable for axon regeneration. Astrocytes, which secrete substances supporting nerve regeneration, can not migrate to the injured axons. Glial scar formation prevent axon regrowth and revascularisation. Moreover, immediate expression of certain genes causes axotomised retinal ganglion cells to undergo process of programmed cell death--apoptosis. At present, regeneration of the optic nerve may be successfully promoted in laboratory set-up with substances which can slow down ganglion cells apoptosis and promote axon regrowth. Peripheral nerve bridges and embryonic transplants offer the regenerating axons more friendly environment than that of the normal, matured CNS. One problem, which can not yet be successfully addressed, is how to lead regrowing axons back appropriately to their original targets to reform patterned connections.

Humans↗
PubMed2000

Axonal regeneration of retinal ganglion cells depending on the distance of axotomy in adult hamsters.

PURPOSE: To examine the relationship between the distance of axotomy and axonal regeneration of injured retinal ganglion cells (RGCs) systematically and the effect of a predegenerated (pretransected or precrushed) peripheral nerve (PN) graft on axonal regeneration of RGCs axotomized at a definite distance (0.5 mm from the optic disc) in comparison with a normal PN graft. METHODS: The optic nerve (ON) was transected intraorbitally at 0.5, 1, 1.5, 2, or 3 mm or intracranially at 6 to 8 mm from the optic disc, and a PN graft was transplanted onto the ocular ON stump in adult hamsters. Four weeks after grafting, the number of RGCs regenerating their injured axons into the PN graft was investigated in all animals. RESULTS: The number of regenerating RGCs decreased significantly when the distance of axotomy increased from 0.5 to 7 mm. A precrushed PN graft was shown to enhance more injured RGCs to regenerate axons than a normal or pretransected PN graft. CONCLUSIONS: The distance of axotomy on the ON of adult hamsters is critical in determining the number of regenerating RGCs. Thus, experimental strategies to repair the damaged ON by PN transplantation is to attach a precrushed PN graft as close to the optic disc as possible to obtain optimal axonal regeneration of the axotomized RGCs.

Animals↗
PubMed2000

Cataractogenic lens injury prevents traumatic ganglion cell death and promotes axonal regeneration both in vivo and in culture.

PURPOSE: To examine and quantify neuroprotective and neurite-promoting activity on retinal ganglion cells (RGCs) after injury of the lens. METHODS: In adult albino rats, penetrating lens injury was performed by intraocular injection. To test for injury-induced neuroprotective effects in vivo, fluorescence-prelabeled RGCs were axotomized by subsequent crush of the optic nerve (ON) with concomitant lens injury to cause cataract. The numbers of surviving RGCs were determined in retinal wholemounts and compared between the different experimental and control groups. To examine axonal regeneration in vivo, the ON was cut and replaced with an autologous piece of sciatic nerve (SN). Retinal ganglion cells with axons that had regenerated within the SN under lens injury or control conditions were retrogradely labeled with a fluorescent dye and counted on retinal wholemounts. Neurite regeneration was also studied in adult retinal explants obtained either after lens injury or without injury. The numbers of axons were determined after 1 and 2 days in culture. Putative neurotrophins (NTs) were studied within immunohistochemistry and Western blot analysis. RESULTS: Cataractogenic lens injury performed at the same time as ON crush resulted in highly significant rescue of 746 +/- 126 RGCs/mm(2) (mean +/- SD; approximately 39% of total RGCs) 14 days after injury compared with controls without injury or with injection of buffer into the vitreous body (30 +/- 18 RGCs/mm(2)). When lens injury was performed with a delay of 3 days after ON crush, 49% of RGCs survived, whereas delay of 5 days still rescued 45% of all RGCs. In the grafting paradigm virtually all surviving RGCs after lens injury appeared to have regenerated an axon within the SN graft (763 +/- 114 RGCs/mm(2) versus 79 +/- 17 RGCs/mm(2) in controls). This rate of regeneration corresponds to approximately 40% of all RGCs. In the regeneration paradigm in vitro preceding lens injury and ON crush 5 days previous resulted in a maximum of regeneration of 273 +/- 39 fibers/explant after 1 day and 574 +/- 38 fibers/explant after 2 days in vitro. In comparison, in control retinal pieces without lens injury 28 +/- 13 fibers/explant grew out at 1 day, and 97 +/- 37 fibers/explant grew out at 2 days in culture. Immunohistochemical and Western blot analysis of potential NTs in the injured lens revealed no expression of ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), NT-4, nerve growth factor (NGF), and basic fibroblast growth factor (bFGF). CONCLUSIONS: The findings indicate that the lens contains high neuroprotective and neuritogenic activity, which is not caused by NT. Compared with the data available in the literature, this neuroprotection is quantitatively among the highest ever reported within the adult rat visual system.

Animals↗
PubMed1975

Liver regeneration after portacaval transportation in rats.

General recognition of the presence of a specific hepatotrophic factor in portal blood that is necessary for liver regeneration was delayed by two major problems. First, there was a long period of confusion regarding liver atrophy, liver hypertrophy, and cellular hyperplasia. Second, because only exposure to other liver tissue destroys the hepatotrophic activity, all of the studies that were based on bypassing the portal blood into the systemic circulation merely diluted the active substance, which still was available to the hepatocytes by recirculation through the hepatic artery. These problems have been resolved by the development of more sophisticated methods by which to assay liver regeneration and by the introduction of the double liver model to study regeneration. During the time when liver weight alone was used to assess regeneration, the regenerative capacity of the liver was reported to be much greater after portacaval transposition than after end-to-side portacaval shunt, a finding that is inconsistent with current knowledge of the hepatotrophic portal blood factor. To re-evaluate the effect on liver regeneration of providing a compensatory systemic venous inflow after complete portal diversion, 40 partially hepatectomized inbred rats which had previously undergone either a sham operation and end-to-side portacaval shunt or a portacaval transposition were compared on the basis of six separate criteria of regeneration. All of the livers actively regenerated and no significant advantage of providing a substitute systemic venous inflow to the liver could be detected by any of the criteria.

Animals↗
PubMed2001

Cones regenerate from retinal stem cells sequestered in the inner nuclear layer of adult goldfish retina.

PURPOSE: To determine whether retinal progenitor cells in the inner nuclear layer give rise to regenerated cones after laser ablation of photoreceptors in adult goldfish retina. METHODS: Using a technique developed previously in this laboratory, photoreceptors in the retina of adult goldfish were ablated with an argon laser. The mitotic marker, bromodeoxyuridine, was used to label proliferating and regenerated cells, which were identified with cell-specific markers. RESULTS: Cells proliferating locally within lesion included microglia, Müller glia, and retinal progenitors in the inner nuclear layer (INL). The nuclei of both Müller glia and associated retinal progenitors migrated from the inner to the outer nuclear layer. The proliferating retinal progenitors, which express Notch-3 and N-cadherin, regenerated cone photoreceptors and then rod photoreceptors. CONCLUSIONS: Previous work has demonstrated that photoreceptors in the goldfish retina regenerate selectively after laser ablation, but the source of regenerated cones has not been identified. The results reported here provide support for the existence of retinal stem cells within the adult fish retina that are capable of regenerating cone photoreceptors. The data also support the involvement of Müller glia in the production of regenerated cones.

Animals↗