| 1. |
- Duan, W M, et al.
(författare)
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Quinolinic acid-induced inflammation in the striatum does not impair the survival of neural allografts in the rat
- 1998
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X. ; 10:8, s. 606-2595
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Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that inflammation related to intracerebral transplantation surgery can affect the survival of intrastriatal neural allografts. To test this hypothesis, we transplanted dissociated embryonic mesencephalic tissue from one of two rat strains, Lewis (allogeneic grafts) or Sprague-Dawley (syngeneic grafts), to the striatum of Sprague-Dawley rats. The target striatum was either intact or had received a local injection of quinolinic acid 9 days earlier, in order to induce a marked inflammation. At 6 or 12 weeks after transplantation, there was no significant difference between the different groups regarding the number of surviving grafted tyrosine hydroxylase immunoreactive neurons. However, the graft volume of both the syngeneic and allogeneic implants was significantly larger in the quinolinate-lesioned than in the intact striatum. There were dramatically increased levels of expression of major histocompatibility complex class I and II antigens, marked infiltrates of macrophages, activated microglia and astrocytes, and accumulation of large numbers of CD4 and CD8 positive T-lymphocytes in the quinolinate-lesioned striatum. In contrast, these immunological markers were much less abundant around both syngeneic and allogeneic grafts placed in intact striatum. We conclude that severe inflammation caused by quinolinic acid does not lead to rejection of intrastriatal neural allografts.
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| 2. |
- Duan, W M, et al.
(författare)
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Rat intrastriatal neural allografts challenged with skin allografts at different time points
- 1997
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 148:1, s. 47-334
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Tidskriftsartikel (refereegranskat)abstract
- The present study was designed to address two questions. First, can an intrastriatal neural allograft exhibit long-term survival (18 weeks) if the host is immunized by an orthotopic skin graft 6 weeks after neural transplantation (the 6w-Long group)? Second, can an intrastriatal neural allograft survive when the host is challenged by an orthotopic skin allograft either simultaneously (Sim) with the intracerebral graft surgery or 2 (2w) weeks later? Dissociated embryonic ventral mesencephalic tissue from Lewis rats was stereotaxically injected into the striatum of Sprague-Dawley rats with unilateral 6-hydroxydopamine lesions. Six weeks after neural grafting, no reduction in amphetamine-induced motor asymmetry was observed in the Sim and 2w groups. At 6 weeks after skin grafting, the mean motor asymmetry scores had returned to the initial pretransplantation levels in the 6w-Long group. All the neural allografts in the Sim group were completely rejected, and the mean number of tyrosine hydroxylase immunoreactivity neurons in the grafts was significantly reduced in the 2w and the 6w-Long group, when compared to the no-skin control group. There were very high levels of expression of MHC class I and II antigens, marked cellular infiltrates containing macrophages and T-lymphocytes, and several activated microglia and astrocytes in and around the surviving intracerebral transplants in the 2w and the 6w-Long groups. The results suggest that intrastriatal neural allografts are more likely to be rejected rapidly if the host is efficiently immunized with the same alloantigens simultaneously or soon after the neural transplantation than at a later time point. When established neural allografts are subjected to a strong immunological challenge, they undergo protracted rejection.
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| 3. |
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| 4. |
- Duan, M., et al.
(författare)
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Deposition of Scintillating Layers of Bismuth Germanate (BGO) Films for X-ray detector applications
- 1998
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Ingår i: IEEE Transactions on Nuclear Science. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9499 .- 1558-1578. ; 45:3, s. 525-527
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Tidskriftsartikel (refereegranskat)abstract
- Bi4Ge3O12 films were deposited by pulsed laser ablation on glass and SiO2/Si substrates. The crystal structures of the films depend on the deposition temperature. XRD patterns indicate that the films deposited at substrate temperature less than 400°C are amorphous. The as deposited amorphous films can be crystallized by post rapid thermal annealing (RTA) in the temperature window from 750°C to 800°C for 2 minutes in a oxygen ambient environment. RBS measurements confirm that the films have the same chemical composition as that of the target. The surface morphology of the films were characterized by atomic force microscopy (AFM)
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| 5. |
- Duan, W M, et al.
(författare)
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Addition of allogeneic spleen cells causes rejection of intrastriatal embryonic mesencephalic allografts in the rat
- 1997
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Ingår i: Neuroscience. - 0306-4522. ; 77:2, s. 599-609
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Tidskriftsartikel (refereegranskat)abstract
- To address the importance of antigen-presenting cells for the survival of intracerebral neural allografts, allogeneic spleen cells were added to the graft tissue before transplantation. Dissociated embryonic, dopamine-rich mesencephalic and adult spleen tissues were prepared from either inbred Lewis or Sprague-Dawley rats. A mixture of neural and spleen cells was sterotaxically transplanted into the right striatum of adult Sprague-Dawley rats. Controls were neural allografts without addition of allogeneic spleen cells and syngeneic neural grafts with or without the addition of syngeneic spleen cells. Six weeks after transplantation, brain sections were processed immunocytochemically for tyrosine hydroxylase, specific for grafted dopamine neurons, and a bank of markers for various components in the immune and inflammatory responses. The neural allografts which were mixed with allogeneic spleen cells were rejected. In these rats, there were high levels of expression of major histocompatibility complex class I and II antigens, intense cellular infiltration including macrophages and activated microglial cells, and a presence of cluster of differentiation 4- and 8-immunoreactive cells in the graft sites. Moreover, there were increased levels of intercellular adhesion molecule-1, tumour necrosis factor-alpha and interleukin-6 in and around the grafts which were undergoing rejection. In contrast, syngeneic neural grafts survived well regardless of whether they were mixed with syngeneic spleen cells or not, and control neural allografts also exhibited unimpaired survival. No significant difference was observed in the number of grafted dopamine neurons among these three latter groups. The levels of expression of the different markers for inflammation and rejection were generally lower in these grafts than in implants of combined allogeneic neural and spleen cells. In summary, intrastriatal neural allografts, which normally survive well in our animal model, were rejected if allogeneic spleen cells from the same donor were added to the graft tissue. The added spleen cells caused strong host immune and inflammatory responses. The study gave support to the notion that immunological privilege of the brain does not provide absolute protection to immunogenetically histoincompatible neural grafts.
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| 6. |
- Duan, W M, et al.
(författare)
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Immune reactions following systemic immunization prior or subsequent to intrastriatal transplantation of allogeneic mesencephalic tissue in adult rats
- 1995
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522. ; 64:3, s. 41-629
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Tidskriftsartikel (refereegranskat)abstract
- We have previously found that dissociated mesencephalic tissue, which differs from the host at both major histocompatibility complex and non-major histocompatibility complex gene loci, can survive stereotaxic transplantation to the striatum of adult rats. We have now studied the outcome of intrastriatal neural allografts in rats that were systemically immunized by an orthotopic skin allograft either prior or subsequent to intracerebral implantation surgery. Dissociated mesencephalic tissue from Lewis rat embryos was stereotaxically injected into the dopamine-depleted striatum of hemi-parkinsonian Sprague-Dawley rats. One group was immunized by an orthotopic allogeneic skin graft of the same genetic origin as the neural graft, six weeks before the neural transplantation (the pre-immunized group). Another group was post-immunized by an orthotopic skin allograft, six weeks after the neural transplantation (the post-immunized group). A control group of rats was not challenged by a skin allograft. Marked behavioural recovery was observed in six of seven rats in the control group, in six of eight rats in the post-immunized group, and in none of the pre-immunized rats. Tyrosine hydroxylase-immunopositive cells were found in rats from the two behaviourally compensated groups, but not in the pre-immunized group. The immune responses were evaluated by OX-18 (monoclonal antibody against major histocompatibility complex class I antigen), OX-6 (major histocompatibility complex class II antigen), OX-42 (microglia and macrophages), glial fibrillary acidic protein (astrocytes), OX-8 (cytotoxic T-lymphocytes) and W3/25 (helper T-lymphocytes) immunocytochemistry. All the neural allografts in the pre-immunized group were rejected, leaving scars only. There were more intense immune responses to the allografts in the post-immunized group than the control group, in terms of immunocytochemically higher expression of major histocompatibility complex class I and II antigens and more intense cellular reactions consisting of macrophages, activated microglia and astrocytes, in addition to CD8- and CD4-positive lymphocytes. In summary, the results show the following: (i) systemic pre-immunization leads to complete rejection of intrastriatal neural allografts, implying that the status of the host immune system before transplantation determines the outcome for intrastriatal neural allografts; (ii) established intrastriatal neural allografts can survive for at least six weeks after systemic immunization, in spite of increased host immune responses in and around the allografts; (iii) there are no marked immune reactions against intrastriatal neural allografts 13 weeks after implantation in rats which have not been systemically immunized by a skin allograft; (iv) pre-immunized rats may provide a very useful animal model to investigate the role of inflammatory lymphokines in immune rejection and to test alternative immunosuppressive drugs.
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| 7. |
- Duan, W M, et al.
(författare)
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Methylprednisolone prevents rejection of intrastriatal grafts of xenogeneic embryonic neural tissue in adult rats
- 1996
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 712:2, s. 199-212
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Tidskriftsartikel (refereegranskat)abstract
- We studied the effects of high-dose methylprednisolone on the survival of intrastriatal neural xenografts and the host responses against them. Dissociated mesencephalic tissue from inbred mouse (CBA-strain) embryos was transplanted to the intact striatum of adult Sprague-Dawley rats. The rats received either daily injections of methylprednisolone (30 mg/kg), or cyclosporin A (10 mg/kg), or no immunosuppressive treatment. Two or six weeks after transplantation, there was good survival of xenografts in both the methylprednisolone- and cyclosporin A-treated rats. In contrast, the xenografts in untreated control rats were all rejected by six weeks. There was no marked difference in the degree of expression of MHC class I and II antigens and the accumulation of activated astrocytes and microglial cells/macrophages between the three groups. However, both methylprednisolone and cyclosporin A reduced infiltration of T lymphocytes to the transplantation sites. The expression of pro-inflammatory cytokines (interferon-gamma, tumour necrosis factor-alpha, interleukin-6) in and around the grafts was lower in the methylprednisolone- and cyclosporin A-treated groups than in untreated control rats. Although high-dose methylprednisolone caused significant body weight loss, we conclude that this treatment can prevent rejection of intrastriatal grafts of xenogeneic embryonic neural tissue in the adult.
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| 8. |
- Duan, W M, et al.
(författare)
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Temporal pattern of host responses against intrastriatal grafts of syngeneic, allogeneic or xenogeneic embryonic neuronal tissue in rats
- 1995
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Ingår i: Experimental Brain Research. - 0014-4819. ; 104:2, s. 42-227
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Tidskriftsartikel (refereegranskat)abstract
- The host response to immunologically incompatible intrastriatal neural grafts was studied using immunohistochemical techniques. Dissociated ventral mesencephalic tissue from embryonic donors of either syngeneic, allogeneic or xenogeneic (mouse) origin was stereotaxically implanted into adult rats. The brains were analysed 4 days, 2 weeks or 6 weeks after grafting with antibodies against the following antigenic structures: major histocompatibility complex (MHC) class I antigens; MHC class II antigens; complement receptor (CR) 3 (marker for microglia and macrophages); helper T-lymphocyte antigen-cluster of differentiation (CD) 4; cytotoxic T-lymphocyte antigen-CD8; tyrosine hydroxylase (TH) (marker for transplanted dopaminergic neurons). The number of surviving TH-positive cells was not different at the various time points in either the syngeneic or allogeneic groups, whereas the xenogeneic cells were all rejected by 6 weeks. The host reactions were similar in character in the syngeneic and allogeneic groups. At 4 days after implantation, there were increased levels of expression of MHC class I and II antigens. In and around the grafts, there were cellular infiltrates consisting of activated microglia, macrophages, CD4- and CD8-positive lymphocytes. At 6 weeks, MHC expression was reduced and the cellular infiltrates had subsided with only low numbers of activated microglia cells and CD8-positive lymphocytes remaining. In the xenogeneic group, at 4 days, some grafts contained cavities, possibly reflecting acute rejection. At later stages, the xenografts were heavily infiltrated by macrophages, activated microglial cells and T-lymphocytes, and at 6 weeks all the xenografts were rejected. Taken together, the results suggest that there is an inflammation caused by the implantation process which leads to an accumulation of host defence cells. This, in turn, leads to increased MHC expression in and around the grafts. In syngeneic grafts, these reactions are short lasting and weak; for allografts slightly more pronounced and longer lasting than syngeneic grafts, but not sufficient to cause rejection. For xenografts, the reactions are more intense and lead to transplant rejection. Thus, a strong sustained inflammatory response may be an important determinator for the failure of histoincompatible neural grafts. It can be speculated that a short-term anti-inflammatory treatment of graft recipients may be a sufficient immunosuppressive regimen to allow long-term graft survival.
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| 9. |
- Larsson, L C, et al.
(författare)
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Discordant xenografts : different outcome after mouse and rat neural tissue transplantation to guinea-pigs
- 1999
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Ingår i: Brain Research Bulletin. - 0361-9230. ; 49:5, s. 76-367
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Tidskriftsartikel (refereegranskat)abstract
- Embryonic neural tissue obtained from other species has been considered as a donor tissue source in repair strategies for human neurodegenerative disorders. The neuro- and immunobiology of distantly related species combinations, discordant xenografts, need to be characterised. For this purpose, a small animal model would be an important research tool. Adult guinea-pigs, and adult rats as controls, received intrastriatal grafts of either mouse or rat embryonic ventral mesencephalic tissue. The survival rates and types of host immune response were assessed at 2 weeks after grafting using stereological techniques and semi-quantitative evaluations. In the mouse-to-guinea-pig group, all transplants were rejected and no tyrosine hydroxylase-immuno reactive (TH-IR) cells remained. In the rat-to-guinea-pig group, there was good survival of TH-IR cells (5050 SEM+/-1550), similar to that in the rat-to-rat group (4900 SEM+/-1540). In the mouse-to-rat group, half of the animals had no surviving TH-IR cells (520 SEM+/-230 for the whole group). These species combinations offer inexpensive, efficient, and suitable conditions to study important survival factors for discordant xenogeneic neural tissue transplants. The factors responsible for the divergent graft outcomes between the two combinations might provide clues on how to manipulate xenogeneic tissue to increase survival rates in the future.
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| 10. |
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