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Sequential intrastriatal grafting of allogeneic embryonic dopamine-rich neuronal tissue in adult rats : will the second graft be rejected?

Duan, W M LU ; Widner, H LU ; Björklund, A LU and Brundin, P LU (1993) In Neuroscience 57(2). p.74-261
Abstract

An important issue in clinical neural grafting is whether a second instriatial allograft can survive well in a patient who has received an allograft before. In this study, the survival, immunogenicity and function of intrastriatal grafts of allogeneic or syngeneic embryonic dopamine-rich tissue in rats which had previously received either an intrastriatal allo- or syn-graft or sham injections were examined. The first graft tissue was taken from inbred Lewis or Sprague-Dawley rat embryos and grafted into an intact striatum of adult Sprague-Dawley rats subjected to a unilateral 6-hydroxydopamine lesion on the contralateral side. Eight weeks after the first transplantation, either allogeneic or syngeneic tissue was grafted as dissociated... (More)

An important issue in clinical neural grafting is whether a second instriatial allograft can survive well in a patient who has received an allograft before. In this study, the survival, immunogenicity and function of intrastriatal grafts of allogeneic or syngeneic embryonic dopamine-rich tissue in rats which had previously received either an intrastriatal allo- or syn-graft or sham injections were examined. The first graft tissue was taken from inbred Lewis or Sprague-Dawley rat embryos and grafted into an intact striatum of adult Sprague-Dawley rats subjected to a unilateral 6-hydroxydopamine lesion on the contralateral side. Eight weeks after the first transplantation, either allogeneic or syngeneic tissue was grafted as dissociated tissue into the dopamine depleted striatum. The function of the second grafts was assessed by rotational asymmetry at two different time points, i.e. eight and 14 weeks after the second transplantation. There were significant reductions of rotational asymmetry in all groups over time, but no significant difference between groups. Tyrosine hydroxylase immunocytochemistry was used to assess dopamine cell survival and graft size. Statistical analysis revealed no significant differnce in the mean number of tyrosine hydroxylase immunoreactive cells or the mean volume of the second grafts placed on the right side (lesioned side) between groups. Monoclonal antibodies were used to evaluate cellular immune reactions and the major histocompatibility complex class I and class II expression in and around grafts. No major histocompatibility complex class I expression was seen in any of the graft combinations. The expression of the major histocompatibility complex class II antigens was generally higher in patches in and around the second allograft of rats which had previously received an allograft than that in and around any other type of grafts. However, the expression of the major histocompatibility complex class II antigens was low throughout the grafts and did not appear as marked perivascular infiltrates. All the major histocompatibility complex class II positive cells displayed a microglia-like morphology, supported by the parallel microglia and macrophage-specific OX-42 immunostaining. The results show that there is no marked on-going immune reactions in or around the implantation site in any group fourteen weeks after a second transplantation. It may be concluded, therefore, that sequential allografting, using stereotaxic implantation of dissociated embryonic neural tissue into the striatal parenchyma, is possible to perform without a major risk of graft rejection, provided that an atraumatic technique is used.

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keywords
Animals, Brain Tissue Transplantation, Dextroamphetamine, Dopamine, Female, Fetal Tissue Transplantation, Graft Rejection, Immunohistochemistry, Major Histocompatibility Complex, Movement, Neostriatum, Oxidopamine, Pregnancy, Rats, Rats, Inbred Lew, Rats, Sprague-Dawley, Stereotaxic Techniques, Stereotyped Behavior, Tyrosine 3-Monooxygenase, Journal Article, Research Support, Non-U.S. Gov't
in
Neuroscience
volume
57
issue
2
pages
74 - 261
publisher
Elsevier
external identifiers
  • scopus:0027489974
ISSN
0306-4522
DOI
10.1016/0306-4522(93)90061-J
language
English
LU publication?
yes
id
dad18992-7a62-4d08-8f16-f1ee396c2359
date added to LUP
2017-04-19 18:28:32
date last changed
2017-06-22 14:19:16
@article{dad18992-7a62-4d08-8f16-f1ee396c2359,
  abstract     = {<p>An important issue in clinical neural grafting is whether a second instriatial allograft can survive well in a patient who has received an allograft before. In this study, the survival, immunogenicity and function of intrastriatal grafts of allogeneic or syngeneic embryonic dopamine-rich tissue in rats which had previously received either an intrastriatal allo- or syn-graft or sham injections were examined. The first graft tissue was taken from inbred Lewis or Sprague-Dawley rat embryos and grafted into an intact striatum of adult Sprague-Dawley rats subjected to a unilateral 6-hydroxydopamine lesion on the contralateral side. Eight weeks after the first transplantation, either allogeneic or syngeneic tissue was grafted as dissociated tissue into the dopamine depleted striatum. The function of the second grafts was assessed by rotational asymmetry at two different time points, i.e. eight and 14 weeks after the second transplantation. There were significant reductions of rotational asymmetry in all groups over time, but no significant difference between groups. Tyrosine hydroxylase immunocytochemistry was used to assess dopamine cell survival and graft size. Statistical analysis revealed no significant differnce in the mean number of tyrosine hydroxylase immunoreactive cells or the mean volume of the second grafts placed on the right side (lesioned side) between groups. Monoclonal antibodies were used to evaluate cellular immune reactions and the major histocompatibility complex class I and class II expression in and around grafts. No major histocompatibility complex class I expression was seen in any of the graft combinations. The expression of the major histocompatibility complex class II antigens was generally higher in patches in and around the second allograft of rats which had previously received an allograft than that in and around any other type of grafts. However, the expression of the major histocompatibility complex class II antigens was low throughout the grafts and did not appear as marked perivascular infiltrates. All the major histocompatibility complex class II positive cells displayed a microglia-like morphology, supported by the parallel microglia and macrophage-specific OX-42 immunostaining. The results show that there is no marked on-going immune reactions in or around the implantation site in any group fourteen weeks after a second transplantation. It may be concluded, therefore, that sequential allografting, using stereotaxic implantation of dissociated embryonic neural tissue into the striatal parenchyma, is possible to perform without a major risk of graft rejection, provided that an atraumatic technique is used.</p>},
  author       = {Duan, W M and Widner, H and Björklund, A and Brundin, P},
  issn         = {0306-4522},
  keyword      = {Animals,Brain Tissue Transplantation,Dextroamphetamine,Dopamine,Female,Fetal Tissue Transplantation,Graft Rejection,Immunohistochemistry,Major Histocompatibility Complex,Movement,Neostriatum,Oxidopamine,Pregnancy,Rats,Rats, Inbred Lew,Rats, Sprague-Dawley,Stereotaxic Techniques,Stereotyped Behavior,Tyrosine 3-Monooxygenase,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {2},
  pages        = {74--261},
  publisher    = {Elsevier},
  series       = {Neuroscience},
  title        = {Sequential intrastriatal grafting of allogeneic embryonic dopamine-rich neuronal tissue in adult rats : will the second graft be rejected?},
  url          = {http://dx.doi.org/10.1016/0306-4522(93)90061-J},
  volume       = {57},
  year         = {1993},
}