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At least 19 recordsLinked to original sources
PubMed1994

Topographic distribution of efferent fibers originating from homotopic or heterotopic transplants: heterotopically transplanted neurons retain some of the developmental characteristics corresponding to their site of origin.

The present study was undertaken to determine whether the topographical distribution of cortical efferents is exclusively dependent on environmental cues or is also controlled by intrinsic factors. For the purpose, we used a sensitive tract-tracing method (Phaseolus vulgaris leucoagglutinin) to compare the pattern of efferent fibers of homotopic and heterotopic transplants of embryonic (E16) neocortex. Our findings indicate that transplants of embryonic sensorimotor cortex placed homotopically in the sensorimotor cortex of newborn rats distribute a set of efferent projections not fundamentally different from that of normal sensorimotor cortex. The pattern of efferents arising from transplants of embryonic occipital cortex heterotopically placed in the sensorimotor cortex of newborns is strikingly different. Heterotopically transplanted neurons: (i) only rarely contact normal targets of the motor cortex; (ii) systematically project towards normal targets of the visual cortex (primary and secondary visual cortical areas, dorsal and ventral lateral geniculate nuclei, lateral dorsal and lateral posterior thalamic nuclei, anterior pretectal nucleus and superficial and intermediate layers of the superior colliculus); (iii) distribute fibers to structures normally receiving fibers from both motor and visual cortices (caudate-putamen, pontine nuclei), either exclusively into the visual cortico-recipient zone of the structure or into both visual and motor cortico-recipient zones. Taken together, these results seem to indicate that the heterotopically transplanted cells have retained certain anatomical characteristics of their locus of origin.

Animals↗
PubMed1995

Morphological alterations of hippocampal pyramidal neurons heterotopically transplanted into the somatosensory cortex of adult rats: a quantitative Golgi study.

A characteristic feature of hippocampal organization is the laminated termination of extrinsic and intrinsic afferents. At present, it is not known to what extent these layer-specific fiber projections modulate the development and final shape of the dendritic arbor of hippocampal target neurons. In the present study, pieces of late embryonic (E18) rat hippocampus were transplanted heterotopically into a cavity in the somatosensory cortex of 6-8 week-old recipient rats. Here, the transplanted neurons differentiated and survived up to several months in the absence of their specific extrinsic afferents. Moreover, tracing of transplant connections with the carbocyanine dye DiI revealed only a limited projection between the transplant and the host neocortex. Golgi-impregnated transplants were used to analyze the postsynaptic structures (dendrites and spines) of hippocampal pyramidal cells quantitatively. Compared with controls, the transplanted pyramidal neurons showed a significant reduction of apical primary dendrites and basal dendritic branches, i.e. of peripheral dendritic portions that originate farther from the soma. In contrast, the number of basal primary dendrites originating directly from the perikaryon was enhanced. Spine density on the main apical dendritic shaft was significantly lower in all peripheral dendritic segments in transplanted neurons. We conclude from our results that the absence of layer-specific extrinsic afferents that normally terminate on peripheral parts of the dendritic arbor of hippocampal pyramidal neurons caused a reduction of these peripheral dendrites and spines. In contrast, the increase of dendrites and spines near the cell body might be induced by intrinsic fibers that normally terminate on these proximal dendritic portions and are known to sprout under transplant conditions.

Animals↗
PubMed2003

Degenerative changes and cell death in long-living homo- and heterotopic transplants from embryonic germ layers of rat neocortex.

Morphological study of allotransplants of rat embryonic neocortex 14-18 months after transplantation into the neocortex, lateral cerebral ventricle, and sciatic nerve of adult animals revealed death of nerve and glial cells in the delayed postoperation period independently on the site of transplantation. After heterotopic transplantation the count of degenerated neurons was 2 times higher that after homotopic transplantation. In heterotopic transplants a considerable number of grafted neurons underwent reversible and irreversible degenerative changes accompanied by their premature aging. Neuronal death is probably determined by insufficiency of trophic influence from afferent structures and target tissues. We hypothesized that antiapoptotic preparations can be used for prevention of transplanted cell death. It was also found that degeneration of neurons was associated with impaired vascularization of transplants and pronounced immune reaction of the recipient in late posttransplantation period. Transplantation of embryonic brain structures can serve as a model system in studies concerning involutive and pathological processes in the central nervous system and in the search for factors improving survival of neurons.

Animals↗
PubMed2002

Dolichol levels in younger and older rat hearts heterotopically transplanted in younger recipients.

Dolichol (D) levels increase dramatically in older tissue. An understanding of the exchangeability of D between tissues may be essential in order to understand the mechanism of the abnormal accumulation associated with aging. The question was investigated by the use of organ transplantation. D-poor hearts donated by 3-mon-old and D-rich by 22-mon-old male Lewis rats were transplanted heterotopically in 3-mon-old syngenic recipients, whose peripheral tissues and liver were poor in D. Native and transplanted hearts were taken 7 and 21 d after surgery. Native hearts of 3-mon- and 22-mon-old male Lewis rats served as control. D concentration and quantity were higher in older than in younger native hearts as expected. In the transplanted hearts, the quantity of D was unchanged, irrespective of the age of the donor and of the time of transplantation, whereas D concentration increased because of the remarkable disuse atrophy. No changes in D were observed in recipients' tissues. It is concluded that dolichol is not redistributed via circulation from the transplanted heart to the tissues and liver of the younger recipient.

Aging↗
PubMed1996

Development of spinal cord projections from neocortical transplants heterotopically placed in the neocortex of newborn hosts is highly dependent on the embryonic locus of origin of the graft.

Previous experiments based on heterotopic transplantation paradigms have indicated that the distribution of efferents developed by layer V pyramidal cells seems to be related to where in the neocortex the cells develop and not to where they were generated. The present study was undertaken in an attempt to obtain a quantitative estimation of the weight of extrinsic factors in the development of neocortical efferents. Fragments of embryonic (E15-E19) frontal or occipital cortex were grafted homotopically or heterotopically into the frontal or occipital cortex of newborn rats. As adults, the hosts received an injection of a retrograde tracer into the pyramidal tract decussation, and the distribution of the subsequent cell labeling was examined in each category of transplant. The mean numbers of labeled cells were 725 in frontal-to-frontal transplants and 250 in frontal-to-occipital transplants. In occipital-to-frontal transplants, the numbers of labeled cells were extremely low, ranging from 0 to 14. Finally, as expected, practically no cell labeling was found in occipital-to-occipital transplants. Thus, transplants of presumptive frontal origin systematically develop and maintain in adulthood a spinal cord projection even though they are placed in the host occipital cortex. Conversely, transplants of presumptive occipital origin are practically incapable of maintaining a spinal cord projection in adulthood even though they are placed in the host frontal cortex. It seems, therefore, that the generation of regional differences in efferent connectivity found in the mature cortex depends on early regional specification within the neocortical neuroepithelium.

Animals↗
PubMed1996

A comparison of the patterns of migration and the destinations of homotopically transplanted neonatal subventricular zone cells and heterotopically transplanted telencephalic ventricular zone cells.

The cells arising in the anterior part of the subventricular zone (SVZa) migrate along a well-demarcated pathway which lacks radial glial fibers to the olfactory bulb where they differentiate into interneurons of the granule cell layer or glomerular layer (Luskin, 1993, Neuron 11, 173). To analyze the mechanisms underlying this highly directed migration, we have compared the migratory behavior of unmanipulated SVZa-derived cells to that of homotopically transplanted SVZa cells and of heterotopically transplanted telencephalic ventricular zone (VZ) cells that ordinarily migrate in association with radial glial fibers. To identify the phenotype of the SVZa progenitor cells prior to their transplantation, we characterized them in vitro using cell type-specific markers. After 1 day in culture nearly all the SVZa cells were stained with TuJ1, a neuron-specific marker; only an occasional cell exhibited a glial phenotype as judged by the presence of GFAP-immunoreactivity. This indicates that SVZa cells express a neuronal phenotype. To reveal the spatiotemporal distribution of homotopically transplanted neonatal SVZa cells in a host brain, dissociated SVZa cells from Postnatal Day 0 (P0)-P2 animals were labeled with the lipophilic dye PKH26 or the cell proliferation marker BrdU and implanted into the SVZa of host animals of the same age. Within the first week after transplantation there were vast numbers of labeled cells throughout the pathway. Over the next 2 weeks the labeled cells migrated into the overlying cellular layer of the olfactory bulb and began to differentiate, and within 4 weeks the transplanted cells had reached their final positions in the granule cell and glomerular layers of the olfactory bulb in the same proportions as for unmanipulated SVZa-derived cells. While en route to the olfactory bulb the homotopically transplanted cells never strayed from the migratory pathway. In contrast, heterotopically transplanted VZ cells from the embryonic telencephalon did not undergo migration although they did differentiate. These results demonstrate that the homotopically transplanted SVZa-derived cells adopt a mode of migration indistinguishable from that ordinarily utilized by SVZa-derived neurons and that the VZ cells are unable to decipher the same set of guidance cues.

Animals↗
PubMed1997

Heat shock protein 70 expression in native and heterotopically transplanted rat hearts.

Heat shock proteins (hsp) are intracellular proteins that are rapidly synthesized in response to a variety of stress factors. Recent studies in rats have shown that these proteins can elicit a lymphocyte response during cardiac allograft rejection. We studied the expression of the inducible (i) and constitutive (c) forms of hsp70 in rat cardiac allograft and isograft recipients to evaluate their utility as indicators of transplant rejection. Heterotopic transplantation of rat hearts was performed, using Lewis to Lewis isografts and ACI to Lewis allografts. Sham-operated rats were used as controls. Transplanted isograft, allograft, and native hearts of the transplant recipients and their livers and spleens were harvested at 5 days posttransplant and analyzed for hsp70 (i) and (c) expression by Western blots. Seven animals were studied in each group. Isografts at 3 and 60 days and allografts at 8 days were also studied. Quantification of band densities was carried out by laser densitometry. Physiological function of the native hearts of the transplant recipients was studied using Langendorff preparations. High levels of hsp70 (i) were noted in the transplanted and native hearts of the transplant recipients but not in their livers or spleens or in the hearts of the sham-operated control animals. Myocardial function of the native hearts of the transplant recipients was not significantly different from that of the controls. Significantly higher levels of hsp70 (c) were present in mild and severely rejecting allografts compared with controls and nonrejecting isografts. In the rat model of heterotopic cardiac transplantation, high levels of hsp70 (i) in the native hearts of the allograft and isograft recipients suggest a transplant-related, cardiac-specific stress process, not previously described. Heat shock protein 70 (c) expression is significantly increased during early and late allograft rejection and may serve as an indicator of transplant rejection.

Animals↗
PubMed1991

Isovolumic loading prevents atrophy of the heterotopically transplanted rat heart.

Heterotopically (infrarenal) transplanted cardiac isografts are histologically normal, spontaneously beating, hemodynamically unloaded hearts that undergo rapid and predictable atrophy. To study the factors that regulate cardiac growth we examined the effect of left ventricular (LV) isovolumic balloon placement on the weight, in vitro protein synthesis rate, and LV RNA content of the transplanted heart. At day 0 the donor LV weight was 367 +/- 8 mg, which decreased to 226 +/- 14 mg (p less than 0.001) after transplantation. Isovolumic loading with a latex balloon (volume, 111 +/- 10 microliters) significantly increased the LV weight of the transplanted heart to 397 +/- 13 mg when compared with that of the unloaded heart 14 days after surgery and prevented the atrophy when compared with the LV weight at day 0. Sham-loaded transplants had LV weights of 256 +/- 17 mg, which did not differ from the LV weight of unloaded transplanted hearts. Protein synthesis rates (nmol lysine/LV/hr) and total LV RNA and LV 18S RNA content were significantly greater in the balloon-loaded hearts when compared with the unloaded isografts and returned to levels similar to those measured in the in situ hearts. The ability of isovolumic loading of the LV to prevent atrophy via increased protein synthesis and the maintenance of LV RNA in the heterotopically transplanted heart further supports the important role of cardiac work in the regulation of cardiac growth.

Animals↗
PubMed1990

Intraoperative hemodynamics in liver transplantation comparing orthotopic with heterotopic transplantation in the pig.

The intraoperative hemodynamic changes and several graft function parameters were studied comparing orthotopic liver transplantation with auxiliary partial liver transplantation (APLT) in the pig. Thirty-one Yorkshire pigs (ca. 25 kg b.w.) were randomly allocated to OLT (n = 16) or APLT (n = 15). During the construction of portal anastomosis the median cardiac output dropped to 67% of the initial value in OLT and to 49% in APLT (P less than 0.02). Median duration of the portal flow interruption was shorter in APLT: 15 min versus 48 min in OLT (P less than 0.002). After unclamping of the aorta, the median systolic blood pressure dropped to 75 mmHg in OLT and to 90 mmHg in APLT (P less than 0.02). APLT is less time-consuming: median duration of transplantation was 128 min versus 165 min in OLT (P less than 0.002). SGOT levels were lower in APLT than in OLT (median SGOT on the first postoperative day 67 was IU/L versus 177 IU/L, P less than 0.002). It is concluded that APLT is a shorter procedure than OLT with a shorter portal flow interruption, being less offensive to the recipient.

Animals↗
PubMedDate not supplied

Membrane antigen expression of syngeneically but heterotopically transplanted hepatocytes in rats.

The expression of membrane antigens on rat hepatocytes transplanted syngeneically and heterotopically was analyzed immunohistochemically using monoclonal antibodies against rat hepatocytes. Isolated adult and fetal hepatocytes were able to survive in the spleen, salivary gland, thymus, or subcapsular region of the kidney for various periods after transplantation. Fairly clear expression of HAM2, 4, and 8 antigens was observed on hepatocytes transplanted into syngeneic spleen, suggesting that the cells might be functionally equivalent to hepatocytes in situ. HAM4 antigen was localized specifically on the newly formed bile-canalicular faces of hepatocytes. The expression of HAM2 (MHC class I) antigen on the transplanted hepatocytes appeared much stronger on the side facing lymphoid tissues, than on the other faces, suggesting that some immunological reactions may take place between hepatocytes and lymphoid tissue. HAM8 antigen, which is localized on gap junctions between neighboring hepatocytes in rat liver, was also recognized between transplanted hepatocytes. In salivary glands where hepatocytes were transplanted, bile-canaliculus-like structures were observed not only between neighboring hepatocytes but also between hepatocytes and salivary acinar cells, suggesting good interaction between the two different epithelial cell types. Hepatocytes transplanted into thymus appeared viable, but most showed fatty degeneration. Some healthy hepatocytes survived in the interlobular connective tissue and the thymic cortical tissue. When fetal hepatocytes were transplanted heterotopically, they formed a mass consisting of hepatocytes and bile duct-like structures 7 wk after transplantation. The inoculated hepatocytes possessed HAM4 antigen, which was not recognized on fetal hepatocytes at day 14 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The effects of long-term graft preservation and prostaglandin E1 on intraoperative hemodynamic changes in liver transplantation. A comparison between orthotopic and heterotopic transplantation in the pig.

The study aimed to compare the intraoperative hemodynamic changes during orthotopic liver transplantation (OLT) with those during heterotopic liver transplantation (HLT) after different durations of cold storage of the graft. The effect of prostaglandin E1 (PGE1) on these parameters was also studied. Sixty-nine female Yorkshire pigs underwent either OLT (n = 32) or HLT (n = 37) with a graft stored for 2 hr (n = 31), 24 hr (n = 16), 48 hr (n = 7), or 72 hr (n = 15). In 16 transplantations in the various groups, PGE1 was given intravenously to both donor and recipient animals and it was added to the preservation and flushing solutions. Univariate nonparametric tests (Mann-Whitney and Wilcoxon rank-sum) were used for analysis of cardiac output (CO), mean arterial pressure (MAP), left and right ventricular minute work (LVMW, RVMW), pulmonary capillary wedge pressure (PCWP), and systemic and pulmonary vascular resistance (SVR, PVR), at different intervals during the operative procedure. For the three main variables--i.e., the type of transplantation, the use of PGE1, and the preservation time, multiple regression analysis was performed. During HLT, portal vein clamping lowered MAP and CO, while during the anhepatic phase in OLT, SVR increased and CO dropped. After recirculation of the graft, an increase in PVR and a decrease in SVR were found in both OLT and HLT. At different stages of the surgical procedure, longer graft storage time diminished CO and MAP (P less than 0.001), especially in OLT. PGE1 appeared to reduce the cardiovascular reserves needed to compensate the changes after recirculation of the graft. The observed differences in intraoperative hemodynamics between OLT and HLT can partly be attributed to differences in operative techniques. Extension of the graft preservation period resulted in poor cardiac performance, more so in OLT than HLT. The native liver in HLT might be able to metabolize the presumed myocardial depressant factors, released by the graft upon reperfusion. Prostaglandin E1 did not protect against the reperfusion syndrome.

Alprostadil↗
PubMed1993

Reproduction of the obliterative bronchiolitis lesion after heterotopic transplantation of mouse airways.

Obliterative bronchiolitis, characterized histopathologically by airway inflammation and occlusion of small airways by vascularized fibrous tissue, constitutes an important threat to the long-term survival of lung and heart-lung transplant recipients. The pathogenesis of obliterative bronchiolitis is poorly understood, and successful preventative or treatment strategies are not available. We sought to develop a preclinical model system of obliterative bronchiolitis by transplanting murine airway grafts, consisting of tracheas and main bronchi, into the subcutaneous tissue of allogeneically mismatched recipient animals. By 10 days after transplantation, allografts demonstrated subepithelial and/or peritracheal inflammation, epithelial necrosis, and early fibroproliferation. Grafts harvested 21 days after transplantation demonstrated fibroproliferation in the airway wall or lumen in nine of 10 allografts versus 0 of 10 isografts (P = 0.0001). In addition, abnormal epithelium (ie, nonciliated cuboidal, squamous, or absent) was seen in all allografts, while nine of nine isografts demonstrated normal respiratory epithelium (P = 0.0003). Although differences exist between this model and the chronic rejection process in human lung transplant recipients, these findings reproduce the characteristic features of obliterative bronchiolitis and demonstrate that this lesion can result from allograft rejection. This model will be useful for studying the pathogenesis, prevention, and treatment of obliterative bronchiolitis after lung transplantation.

Animals↗