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PubMed2002

Transplants of fibroblasts genetically modified to express BDNF promote axonal regeneration from supraspinal neurons following chronic spinal cord injury.

Transplants of fibroblasts genetically modified to express BDNF (Fb/BDNF) have been shown to promote regeneration of rubrospinal axons and recovery of forelimb function when placed acutely into the injured cervical spinal cord of adult rats. Here we investigated whether Fb/BDNF cells could stimulate supraspinal axon regeneration and recovery after chronic (4 week) injury. Adult female Sprague-Dawley rats received a complete unilateral hemisection injury at the third cervical spinal cord segment (C3). Four-five weeks later the injury site was exposed and rats received transplants of unmodified fibroblasts (Fb/UM) or Fb/BDNF. Four-five weeks after transplantation, locomotor recovery was examined on a test of forelimb usage and regeneration of supraspinal axons was studied following injection of the anterograde tracer biotin dextran amine (BDA). Rubrospinal tract (RST), reticulospinal tract (ReST), and vestibulospinal tract (VST) axons regenerated into transplants of either Fb/UM or Fb/BDNF but the length of axonal growth was significantly different in the two groups. The absolute distance of ReST growth was 1.8-fold greater in Fb/BDNF than in Fb/UM and the absolute distance of growth of RST and VST axons showed a statistically significant 4-fold increase. All three types of regenerated axons occupied a greater proportional length of Fb/BDNF transplants than of Fb/UM transplants. Only VST axons extended into the host spinal cord caudal to the Fb/BDNF grafts, but these axons were sparse. Rats receiving Fb/BDNF used both forelimbs together to explore walls of a cylinder more often than rats receiving Fb/UM, indicating partial recovery of forelimb usage. These results demonstrate that fibroblasts genetically modified to express BDNF promote axon regeneration from supraspinal neurons in the chronically injured spinal cord with accompanying partial recovery of locomotor performance.

Animals↗
PubMed1994

Effect of repeated portal-triad cross-clamping during partial hepatectomy on hepatic regeneration in normal and cirrhotic rats.

The effects of ischemia/reperfusion during 70% partial hepatectomy on hepatic regeneration was evaluated in normal rats and thioacetamide-induced cirrhotic rats. Total hepatic ischemia and reperfusion (15 min each) by portal-triad cross-clamping was repeated two times in normal rats and four times in cirrhotic rats during hepatectomy. The labeling index of hepatocytes on Day 1 after operation (POD) and hepatic regeneration ratio on POD 28 were measured. In normal rats, the repeated ischemia/reperfusion decreased the survival rate from 100 to 77% (P < 0.05), lowered the hepatocyte labeling index from 33.5 +/- 2.5 to 16.7 +/- 6.5%, and diminished the hepatic regeneration ratio from 199 +/- 17 to 137 +/- 12% (P < 0.01). However, portal-systemic shunt improved those levels to 100, 30.6 +/- 13.7, and 169 +/- 19%, respectively (P < 0.01). In cirrhotic rats, no portal congestion was observed and hepatic regeneration was not suppressed by ischemia/reperfusion. Thus, portal pooling and the reperfusion of pooled portal blood may be the cause of inhibition on hepatic regeneration and not ischemia/reperfusion of the liver itself. Therefore, repeated portal-triad cross-clamping for short periods of time during the resection of cirrhotic liver is not harmful for hepatic regeneration.

Animals↗
PubMed1995

Expression of cytokine genes during liver regeneration after partial hepatectomy in rats.

In the present study to demonstrate the relationship between cytokines and liver regeneration we investigated by Northern blot hybridization the cytokine gene induction in the regenerating liver and several other organs (spleen, lung, and kidney) in the rat after partial hepatectomy (PH). We also examined whether Kupffer cells and the spleen are involved in the induction of cytokine mRNA in the regenerating liver. Both IL-1 alpha and beta mRNA increased transiently 1/2 to 1 hr after PH in nonparenchymal cells (NPC) of the regenerating liver; they reached a maximum before the peak of hepatocyte DNA synthesis. PH also induced a slight, but significant, gene expression of IL-1 in lung and kidney in the early postoperative period. TNF-alpha mRNA increased gradually in the spleen, but not the liver, of partially hepatectomized rats at 3 to 12 hr and then reached a peak at 24 hr after PH. IL-6 transcripts were not detected in the regenerating liver, spleen, lung, or kidney during liver regeneration. In contrast, no cytokine gene expression was induced in any of these four organs during the first 3 days after sham operation or unilateral nephrectomy. When Kupffer cell activity was suppressed by gadolinium chloride pretreatment, or when splenectomy was performed 24 hr before PH, the constitutive IL-1 alpha and beta mRNA expressions in NPC of the normal rat liver were completely suppressed. In conclusion, the present study demonstrates, for the first time, the specific kinetics of cytokine gene expression in the liver, spleen, lung, and kidney after PH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Effect of subtotal pancreatectomy on the rate of liver regeneration: the role of hepatic stimulator substance.

The endogenous signals controlling liver regeneration are becoming rapidly defined. One of the key findings during liver regeneration following partial hepatectomy is the appearance of peripheral blood factors that stimulate DNA synthesis in the parenchymal cells. Hepatopoietin A, or hepatocyte growth factor, has been described as a complete mitogen for hepatocytes, one of its major tissue sources being the pancreas. The changes in the rate of DNA synthesis (incorporation of [3H] thymidine into DNA) in both subtotally pancreatectomized-partially hepatectomized (Group A) and partially hepatectomized (Group B) male rats were determined at different postoperation times. DNA synthesis in Group A was increased progressively, reaching a maximum at 40 hr after operation in contrast to the 24- and 32-hr peaks obtained in nonpancreatectomized rats (Group B). However, liver regeneration in Group A was significantly lower than in Group B. To evaluate the effects of hepatic stimulator substance (HSS) on liver regeneration, the time course of HSS biological activity during the liver regeneration process was determined in the livers of Group A rats. A concurrent change of HSS activity and rate of liver regeneration was observed. These results support the hypothesis that HSS biological activity may be delayed but not suppressed by subtotal pancreatectomy.

Alanine Transaminase↗
PubMed1999

Age-related changes on parameters of experimentally-induced liver injury and regeneration.

Age-dependent changes related to liver injury and regeneration were studied in rats aged 2, 12, and 30 months in a time period of 96 hr following a sublethal dose of thioacetamide (6.6 mmoles/kg body wt). Serum aspartate aminotransferase activity increased earlier in young rats, but the severity of injury was higher in those aged 12 months when compared to young and to old. Microsomal hepatocyte FAD monooxygenase activity was induced earlier in 2-month-old rats following intoxication and the increase was significantly lower both in the youngest and in the oldest groups when compared to adults. As a parameter of hepatocellular postnecrotic regeneration, DNA synthesis (2C --> 4C) was evaluated. The population of hepatocytes in S phase peaked more sharply and earlier in young rat hepatocytes, and was 8 to 12 times higher than the initial in hepatocytes from 2- and 12-month-old rats, while the rise was only 3 times in the oldest group. At 96 hr of intoxication the restoration towards normal in all these parameters was complete in young, incomplete in adult, and slightly detected in the oldest. Serum proliferative activity, assayed on mouse NIH 3T3 fibroblast cultures, increased preceding the necrosis and this increase was higher in 2- and 12-month-old (171% and 224%, respectively), while in the oldest the increase was only 110%. This mitogenic activity decreased in all groups during necrosis, showing a second peak, nondetectable in rats aged 30 months, parallel to regeneration. Serum TNFalpha level was absent in untreated animals and increased markedly following intoxication, the highest values being recorded at 72 hr of intoxication in serum from rats aged 12 months (347 +/- 30 pg/ml) and the lowest at 30 months (4.1 +/- 0.3 pg/ml). The serum ability to induce nitric oxide synthase activity on peritoneal macrophages ex vivo showed significant time- and age-dependent changes in nitric oxide release: a decrease throughout necrosis and an increase during regeneration. We conclude that the main age-related changes in the sequenced process of liver injury and regeneration are the delayed response in the development of cell killing and regeneration and the decreased regenerative ability, which significantly delays the restoration of liver function.

3T3 Cells↗
PubMed1992

Growth factor expression in normal and diabetic rats during peripheral nerve regeneration through silicone tubes.

The silicone tube model of regeneration has proved to be an invaluable tool for experimental studies aimed at understanding expression of growth factors during normal and abnormal metabolic states of regeneration. Since the morphological parameters of nerve growth and myelination are well-defined and easily identified in this model, the expression of both diffusible and intracellular-acting growth factors can be readily correlated with the occurrence of these cellular events. These studies facilitate the study of the cellular and molecular events that accompany regeneration. Further, because the sciatic nerve can be traced up to its corresponding neurons, growth factor gene expression can also be studied by in situ hybridization and Northern blotting techniques. This is particularly important in defining the cell source of extracellularly released growth factors. Finally, and most importantly, the regeneration process in the normal or diseased metabolic state (such as diabetes) can be manipulated via the administration of adjuncts to the tube that either promote or inhibit regeneration. Further studies in this regard, and in the identification of growth factors involved and their role during regeneration should shed some light on the pathogenesis and possible means of mitigating or reversing diabetic neuropathy.

Animals↗
PubMed2005

Facts and theories of induced organ regeneration.

Induced organ regeneration is de novo synthesis of a physiological, or nearly physiological, organ at the same anatomical site as the organ that is being replaced. Regeneration of skin, peripheral nerves and the conjunctiva, described in this chapter, have been accomplished using biologically active scaffolds (regeneration templates) seeded with epithelial cells; devices for regeneration of the first two organs are in clinical use. There is substantial empirical evidence that templates induce regeneration by blocking contraction, the major mechanism for closure of severe wounds in adults. Templates appear to function by interfering with normal myofibroblast function well as by acting as temporary configurational guides for synthesis of new stroma that resembles that of the organ under replacement. The combined evidence supports a theory which predicts that selective blocking of the adult healing response uncovers the latent fetal response to injury and leads to organ regeneration. An independent theory suggests that loss of regenerative potential during the mammalian fetal-adult transition is associated with simultaneous acquisition of individual immunocompetence.

Adaptation, Physiological↗
PubMed1995

Fast and slow rat muscles degenerate and regenerate differently after whole crush injury.

The whole-crush injured rat skeletal muscle was used as a model to explore the regenerating potentialities of fast and slow muscles. Laminin was chosen to follow changes in basal lamina and desmin to visualize new muscular elements; they were revealed by immunofluorescence on cryostat sections of either fast (extensor digitorum longus) or slow (soleus) regenerating muscle. Soleus myolysis was rapid, extensive and heterogeneous. Basal laminae were nearly destroyed. In contrast, extensor digitorum longus maintained its basal lamina framework during myolysis. Soleus reconstruction began early, following the pattern of remaining basal laminae as closely as possible, but regeneration stagnated from day 16 and the regenerated muscle was fibrotic. In extensor digitorum longus, reconstruction progressed slower than in soleus, but regularly from the periphery toward the centre of the muscle. The regenerated extensor digitorum longus showed a quasi-normal structure from day 16. At the end of the process, the elimination of old basal lamina was completed in extensor digitorum longus, but was not achieved in soleus. We propose that the old basal lamina should help the initiation of reconstruction. This new model also underlines the importance of the turnover of basal laminae in muscular regeneration, and will be useful to understand the background of the different regenerative response of both muscles.

Animals↗
PubMed1995

Critical period in muscle spindle regeneration in grafts of developing rat muscles.

Extensor digitorum longus (EDL) muscles from rats at various intervals after birth were grafted into EDL muscles of adult recipients. Three to twelve months after the operation, host muscles containing the grafts were removed and examined for the presence of muscle spindles in the graft. The aim of the study was to establish when muscle spindles become capable of regeneration during development. Regenerated muscles grafted during the first week after birth were virtually spindleless. Grafts of muscles transplanted 10 and 15 days postnatally contained only 5-8 muscle spindles on average. In contrast, the regenerated grafts originating from muscles of 24- and 28-day-old rats were spindle-rich as in mature muscle grafts; the number of spindles in the transplanted EDL muscles (25.0 +/- 2.3; mean +/- SE) attained values comparable to free standard autografts of these muscles in adult animals. Thus, the critical period after grafting, which also involves the loss of a vascular supply, is considerably longer than the critical period for muscle-spindle survival after nerve injury. Fifteen days after birth, when muscle spindles still survive denervation, only a few regenerated spindles were present in the individual muscle regenerates. We assume that the low resistance of immature spindle capsules to ischaemia accounts for their massive degeneration and abortive spindle regeneration in grafts from 10- to 15-day-old rats.

Adenosine Triphosphatases↗
PubMed1978

An ultrastructural study of regeneration of minced smooth muscle in the vas deferens of the guinea-pig.

Electron microscopic studies were made of the regeneration of minced smooth muscle of the vas deferens of the guinea-pig 3 days to 15 weeks after operation. At 3--5 days the mince contained degenerating smooth muscle cells and dedifferentiating cells showing characteristics of embryonic smooth muscle cells: numerous free ribosomes, well developed rough endoplasmic reticulum and Golgi apparatus with few peripherally placed myofilaments associated with dense bodies. During the first two weeks of regeneration, scattered cells surrounded by debris and collagen were separated by a large extra-cellular space. After three weeks, extracellular space was reduced to near normal values. Regenerating cells had a shorter length than normal cells, but during later stages of regeneration they showed an increase in diameter. Muscle effector bundles began to form after 2 to 3 weeks. Initially there were large gaps between the muscle cells, but at later stages of bundle formation, the extracellular space between the muscle cells was much reduced. From 3 weeks, arterioles appeared between the smooth muscle bundles in the regenerating areas. Regeneration of individual smooth muscle cells was complete by 15 weeks after the operation.

Animals↗
PubMed1976

Fate of 3H-thymidine labelled myogenic cells in regeneration of muscle isografts.

Intact and denervated extensor digitorum longus (EDL) muscles of 20-day-old inbred Lewis-Wistar rats were labelled with 3H-thymidine. Ninety minutes after the injection of the isotope 4.0% of the nuclei were labelled in the intact (i.e. innervated) and 9.6% in the muscles, denervated 3 days before administration of the isotope. The labelled EDL muscles were grafted into the bed of the previously removed EDL muscles of inbred animals and these isografts were studied 30 days later. In the EDL muscles, regenerated from innervated isografts only occasionally labelled endothelial cells were found whereas in the muscles regenerated from denervated isografts also parenchymal muscle nuclei were regularly labelled. The incidence of labelled nuclei in the regenerated EDL muscles was, however, about 20 times lower than in the donor EDL muscles. The presen experiments provide a direct proof of utilization of donor satelite cell nuclei for regeneration in grafted muscle tissue. With respect to the low incidence of labelled nuclei in regenerated EDL muscles, other sources of cells apparently also contribute to the regeneration process.

Animals↗
PubMed1977

Regeneration of soleus muscles of rat autografted in toto as studied by electron microscopy.

Rat soleus muscles were autografted from right to left legs, and regeneration following necrosis of all original myofibres was studied after 7 to 250 days. The best regenerates were from grafts replacing all calf muscles and sutured to the tendon stumps. After 30 days the size of such regenerates was equal to those from minced gastrocnemius muscles: the cross sectional area of muscle tissue was 30% (1.7 mm2) and the number of fibres was 180% (4500) of normal soleus muscles; the fibre diameters were 10 to 40mum. To increase the number of myoblasts before grafting some muscles were injured by Ringer solution of 70 degrees C and transplanted after 2 days. Nevertheless, this did not influence regeneration. After 7 days clusters of myotubes occurred in the periphery of the muscle. These myotubes originated from myoblasts growing like endothelial cells on the inner face of the persisting basal lamina tubes of necrotic fibres. After 30 days the muscles were vascularized. Fibres formed in a common basal lamina detached and so looked "split". Satellite cells of new fibres came from undifferentiated cells associated with myotubes, i.e. from myoblasts. After 30 days and more regenerates contained three sorts of fibres. 1. Thin (5 to 20 mum) fibres resembling fetal muscle fibres. They were most prominent after 30 days, and probably not yet innervated. 2. Thin (10 mum) degenerating fibres as in long-time denervated muscles. 3. Thick (more than 30 mum) mature looking fibres which were innervated and revealed end-plates. Half of the grafts studied after 30 and 60 days contained unmyelinated and myelinated axons which had grown along strands of surviving Schwann cells. After 250 days, only two muscles were studied which both lacked innervation. Almost all regenerates contained muscle spindles, which, however, were not innervated. Within the persisting spindle capsules new muscle fibres had been formed from satellite cells of the former intrafusal fibres.

Animals↗
PubMed1977

Responses in the hypoglossal nucleus to delayed regeneration of the transected hypoglossal nerve, a quantitative ultrastructural study.

Electron micrographs of the left hypoglossal nucleus of adult male albino rats were quantitatively analyzed from 9-70 days after allowing the transected left hypoglossal nerve to regenerate after an 84 day delay. Delay was achieved by implanting the proximal stump into already innervated sternomastoid muscle, where no regeneration occurred. Regeneration was then allowed by denervating the sternomastoid. During the regenerative period the initially high number of abnormally electron dense perikarya and dendrites decreased to almost normal values, but no cell removal was seen. This suggested that the degenerate appearance of many profiles after prolonged prevention of regeneration, was reversible. The neuropil bouton and dendrite counts, and the numbers of synapsing boutons per dendrite, increased steadily to normal values from the low values of suppressed regeneration. Somatic bouton frequencies, even though already low, decreased further at 32 days, and later increased but not to normal values. The decrease at 32 days coincided with the loss of many subsurface cisterns, and dispersion of Nissl substance, all suggestive of chromatolysis. Later the subsurface cisterns and Nissl substance returned. It was suggested that the delay of complete recovery of somatic bouton frequencies might be because of lack of sensory information from the denervated muscle into which the hypoglossal nerve was regenerating, or because of abnormally low starting values for the recovery phase. Astrocyte (or, occasionally microglial) sheaths persisted along bouton-free perikaryal surfaces.

Animals↗
PubMed1995

Regeneration and post-metamorphic development of the central nervous system in the protochordate Ciona intestinalis: a study with monoclonal antibodies.

In this study, we use three monoclonal antibodies that recognise antigens present in the central nervous system of the ascidian Ciona intestinalis to study regeneration and post-metamorphic development of the neural ganglion. We have also used bromodeoxyuridine labelling to study generation of the neuronal precursor cells. The first antibody, CiN 1, recognises all neurones in the ganglion, whereas the second, CiN 2, recognises only a subpopulation of the large cortical neurones. Western blotting studies show that CiN 2 recognises two membrane-bound glycoproteins of apparent Mr 129 and 100 kDa. CiN 1 is not reactive on Western blots. Immunocytochemical studies with these antibodies show that CiN 1-immunoreactive neurone-like cells are present at the site of regeneration as early as 5-7 days post-ablation, a sub-population of CiN 2-immunoreactive cells being detected by 9-12 days post-ablation. The third antibody, ECM 1, stains extracellular matrix components and recognises two diffuse bands on Western blots of whole-body and ganglion homogenates. The temporal and spatial pattern of appearance of CiN 1 and CiN 2 immunoreactivity both during post-metamorphic development and in regeneration occurs in the same sequence in both processes. Studies with bromodeoxyuridine show labelled nuclei in some neurones in the regenerating ganglion. Plausibly these originate from the dorsal strand, an epithelial tube that reforms by cell proliferation during the initial phases of regeneration. A second population of cells, the large cortical neurones, do not incorporate bromodeoxyuridine and thus must have been born prior to the onset of regeneration. This latter finding indicates a mechanism involving trans-differentiation of other cell types or differentiation of long-lived totipotent stem cells.

Animals↗
PubMed1982

Enhanced acceptance of regenerating bone marrow of random bred newborn mice by random bred adult mice.

Regenerating bone marrow of newborn random bred Sabra mice (9-13 days old) was obtained by the administration of two consecutive i.p. injections of hydroxyurea (HU) (2 x 100 mg/kg body wt), three days prior to collection of the marrow cells. The bone marrow of HU-treated newborn mice was assayed for CFU-S, CFU-C and plasma-clot-diffusion-chamber (PCDC) progenitor cells. A fourfold content of CFU-S was found in the regenerating bone marrow compared with that of the control marrow, while the level of CFU-C and PCDC progenitor cells was the same in treated and untreated newborn mice. In lethally irradiated adult, random bred Sabra recipient mice, transfused with regenerating bone marrow from newborn mice, the initial survival rate was greater than in irradiated animals receiving normal newborn marrow (75% as against 50%); marrow repopulation, 10-14 days after transfusion, was also greater in the former than in the latter group of animals (1.5-2x10(6) nucleated cells per femur as compared with 08.-2x10(5)). The bone marrow of these groups of mice was assayed for CFU-S, CFU-C and PCDC progenitor cells; with a cell inoculum of 5 x 10(4) i.v., 10(5) in vitro and 5 x 10(4) per DC, respectively, pluripotent and committed stem cells were detected in the experimental group and were lacking in control recipients. Regenerating bone marrow of newborn mice was also transfused into lethally irradiated splenectomized recipients. In this experimental group there was high mortality, low marrow repopulation and lack of CFU-S (5-10 x 10(4) cell inoculum). The results of this study indicate that, despite genetic differences among random bred Sabra mice, regenerating bone marrow of newborn mice "takes better" than normal marrow in lethally irradiated recipients. Improved marrow acceptance is possibly due to the increased content of activated CFU-S and/or pre-CFU-S in the regenerating bone marrow

Age Factors↗
PubMed1976

Time course of regeneration of minced frog muscles estimated by the level of energetic substrates.

1. Gastrocnemius muscles of frogs have been excised, chopped and put back into the leg. 2. The weight of the implanted muscles increases until the 8th day after the operation and then decreases to 1/3 of that of the control by the 30th day. 3. The inulin space is twice as high in regenerating muscle as in the unoperated controls. 4. Adenosine nucleotides are in an enzymatic equilibrium set by the ratio creatine/phosphorylcreatine during regeneration of the muscle. 5. Glycolytic intermediates (hexose monophosphate, fructose-1,6-diphosphate, alpha-glycerophosphate and lactate) have been measured during the course of muscle regeneration up to the 30th day. The results suggest that the glycolysis of regenerating muscle is very active. 6. The total creatine (sum of creatine and phosphorylcreatine) is very low after the operation: 5% of that of the controls; it rises sharply after the 8th day, and reaches 30% of that of the control on the 30th day. 7. The amount of total creatine seems proportional to the progress of the muscle regeneration. It is suggested to use this substance as a biochemical reference for biochemical works on muscle regeneration.

Adenine Nucleotides↗
PubMed1994

Regulating factors of liver regeneration after hepatectomy.

The factors regulating liver regeneration were studied by measuring changes in the liver volume and serum hepatocyte growth factor (HGF) levels after hepatectomy. Changes in the liver volumes were studied in 68 hepatectomized patients, including (A) hepatoma patients who had chronic hepatitis or liver cirrhosis (n = 44) and (B) metastatic liver cancer patients who had normal liver parenchyma (n = 24). The hepatic volume increased by 13.8% of the remnant hepatic volume in group A and by 49.1% in group B. The examined factors included the percentage of resected liver volume (%RLV) and the results of laboratory tests. Regression analysis showed that in group A, both %RLV (beta = 0.46) and the serum total bilirubin (T-Bil) level (beta = -0.33) correlated significantly with the extent of liver regeneration and that in group B, only %RLV (beta = 0.78) correlated significantly with the regeneration. Serum HGF levels after hepatectomy were studied in 21 hepatectomized patients, including 11 hepatoma patients and 10 patients with some types of metastatic liver cancer. Serum HGF levels increased significantly after surgery in all 21 patients. Regression analysis, however, showed that the change in HGF was related to liver cirrhosis (beta = 0.46) and to the maximal postoperative T-Bil level (beta = 0.51) but not to the extent of liver regeneration after hepatectomy. These results suggest that liver regeneration is regulated primarily by factors relating to the percentage of the resected liver parenchyma and that serum HGF levels do not directly relate to liver regeneration after surgery.

Aged↗
PubMed1975

Degeneration and regeneration of adrenergic nerves in mesenteric blood vessels, iris and atrium of the rat after 6-hydroxydopamine injection.

Degeneration of adrenergic axons after 6-hydroxydopamine (6-OH-DA), 2 times 68 mg kg-1 i.v. within 6h, and the subsequent regeneration process over the following 205 days were studied in rat mesenteric vessels, wight atria and irides, using the histochemical fluorescence method of Falck and Hillarp. The objective of the study was to determine why noradrenaline is less depleted and recovers much more rapidly in the mesentery than in other tissues after 6-OH-DA (Finch et al., 1973). The mesentery was further studied by electron microscopy and noradrenaline content analyses, until day 29 after 6-OH-DA treatment. Virtually all adrenergic terminal axons in these tissues were destroyed one day after 6-OH-DA. The large nonterminal axon bundles which occur along the mesenteric vessels and rarely in the heart survived and revealed an intensified catecholamine fluorescence; correspondingly, the mesenteric noradrenaline content was only reduced to 29% of control values. In contrast, such large nonterminal axon bundles were not observed in control iris preparations, and no adrenergic fibres survived in the irides, as suggested by fluorescence microscopy. Regenerating axons were observed in all organs after 3-8 days. The number of nerve terminals along the circumference of the external elastic lamina, as observed in ultrathin cross sections of mesenteric vessels, appeared virtually normal 4 weeks after treatment. Meanwhile, the noradrenaline content of the mesentery returned to approximately 85% of control values. As suggested by fluorescence microscopy, complete adrenergic regeneration occurred in mesenteric vessels between days 46 and 105, while regeneration in atrium and iris was incomplete even at day 205; The density of adrenergic axons in the iris, morphometrically determined, was only 76% and 88% of controls on days 160 and 205, respectively. The survival of the many large nonterminal axon bundles in the mesentery with increased NA content explains the relatively small NA depletion of the mesentery; The rapid recovery of the mesenteric NA content is due to faster regeneration of adrenergic terminal axons in the mesentery as compared with iris and atrium. This is tentatively explained in terms of sprouting from the large axon bundles surviving close to the destroyed terminal axons of the mesenteric vessels, whereas in the other tissues no (iris) or only a few (atrium) large nonterminal axon bundles occur and persist to act as a source of quickly regenerated terminal axons.

Animals↗