Influence of chronic L-DOPA treatment on immune response following allogeneic and xenogeneic graft in a rat model of Parkinson’s disease
Brain, Behavior, and Immunity. 2017-03-01; 61: 155-164
DOI: 10.1016/j.bbi.2016.11.014
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1. Brain Behav Immun. 2017 Mar;61:155-164. doi: 10.1016/j.bbi.2016.11.014. Epub 2016
Nov 15.
Influence of chronic L-DOPA treatment on immune response following allogeneic and
xenogeneic graft in a rat model of Parkinson’s disease.
Breger LS(1), Kienle K(2), Smith GA(3), Dunnett SB(4), Lane EL(5).
Author information:
(1)School of Pharmacy & Pharmaceutical Sciences, Redwood Building, King Edward
VII Avenue, CF10 3NB Cardiff, UK; Brain Repair Group, Cardiff School of
Biosciences, Museum Avenue, CF10 3AX Cardiff, UK. Electronic address:
.
(2)School of Pharmacy & Pharmaceutical Sciences, Redwood Building, King Edward
VII Avenue, CF10 3NB Cardiff, UK. Electronic address: .
(3)Brain Repair Group, Cardiff School of Biosciences, Museum Avenue, CF10 3AX
Cardiff, UK. Electronic address: .
(4)Brain Repair Group, Cardiff School of Biosciences, Museum Avenue, CF10 3AX
Cardiff, UK. Electronic address: .
(5)School of Pharmacy & Pharmaceutical Sciences, Redwood Building, King Edward
VII Avenue, CF10 3NB Cardiff, UK. Electronic address: .
Although intrastriatal transplantation of fetal cells for the treatment of
Parkinson’s disease had shown encouraging results in initial open-label clinical
trials, subsequent double-blind studies reported more debatable outcomes. These
studies highlighted the need for greater preclinical analysis of the parameters
that may influence the success of cell therapy. While much of this has focused on
the cells and location of the transplants, few have attempted to replicate
potentially critical patient centered factors. Of particular relevance is that
patients will be under continued L-DOPA treatment prior to and following
transplantation, and that typically the grafts will not be immunologically
compatible with the host. The aim of this study was therefore to determine the
effect of chronic L-DOPA administered during different phases of the
transplantation process on the survival and function of grafts with differing
degrees of immunological compatibility. To that end, unilaterally 6-OHDA lesioned
rats received sham surgery, allogeneic or xenogeneic transplants, while being
treated with L-DOPA before and/or after transplantation. Irrespective of the
L-DOPA treatment, dopaminergic grafts improved function and reduced the onset of
L-DOPA induced dyskinesia. Importantly, although L-DOPA administered post
transplantation was found to have no detrimental effect on graft survival, it did
significantly promote the immune response around xenogeneic transplants, despite
the administration of immunosuppressive treatment (cyclosporine). This study is
the first to systematically examine the effect of L-DOPA on graft tolerance,
which is dependent on the donor-host compatibility. These findings emphasize the
importance of using animal models that adequately represent the patient paradigm.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.bbi.2016.11.014
PMCID: PMC5325122
PMID: 27864045