| Benefits and risks of intranigral transplantation of GABA-producing cells subsequent to the establishment of kindling-induced seizures. | |
| | |
MedLine Citation:
|
PMID: 18632280 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Neural transplantation has been investigated experimentally and clinically for the purpose of developing new treatment options for intractable epilepsy. In the present study we assessed the anticonvulsant efficacy and safety of bilateral allotransplantation of genetically engineered striatal GABAergic rat cell lines into the substantia nigra pars reticulata (SNr). Rats with previously-established seizures, induced by amygdala kindling, were used as a model of temporal lobe epilepsy. Three cell lines were transplanted: (1) immortalized GABAergic cells (M213-2O) derived from embryonic rat striatum; (2) M213-2O cells (CL4) transfected with human GAD67 cDNA to obtain higher GABA synthesis than the parent cell line; and (3) control cells (121-1I), also derived from embryonic rat striatum, but which did not show GAD expression. A second control group received injections of medium alone. Transplantation of M213-2O cells into the SNr of kindled rats resulted in significant but transient anticonvulsant effects. Neither control cells nor medium induced anticonvulsant effects. Strong tissue reactions were, however, induced in the host brain of kindled but not of non-kindled rats, and only in animals that received grafts of genetically modified CL4 cells. These tissue reactions included graft rejection, massive infiltration of inflammatory immune cells, and gliosis. The anticonvulsant effect of M213-2O cells emphasizes the feasibility of local manipulations of seizures by intranigral transplantation of GABA-producing cells. On the other hand, the present data suggest that kindling-induced activation of microglia in the SNr can enhance immune reactions to transplanted cells. In this case, under conditions of further immunological stimulation by CL4 cells, transfected with a human cDNA, substantial immune reactions occurred. Thus, it appears that the condition of the host brain and the production of foreign proteins by transplanted cells have to be considered in estimating the risks of rejection of transplants into the brain. |
| | |
Authors:
|
Marc W Nolte; Wolfgang Löscher; Christiane Herden; William J Freed; Manuela Gernert |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-07-15 |
Journal Detail:
|
Title: Neurobiology of disease Volume: 31 ISSN: 1095-953X ISO Abbreviation: Neurobiol. Dis. Publication Date: 2008 Sep |
Date Detail:
|
Created Date: 2008-08-19 Completed Date: 2008-12-15 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 9500169 Medline TA: Neurobiol Dis Country: United States |
Other Details:
|
Languages: eng Pagination: 342-54 Citation Subset: IM |
Affiliation:
|
Department of Pharmacology, Neuroscience Discovery Research, Abbott GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Brain Tissue Transplantation / adverse effects, methods* Cell Line, Transformed Disease Models, Animal Epilepsy / metabolism*, physiopathology, surgery* Female Gene Therapy / methods Glutamate Decarboxylase / genetics Graft Rejection / immunology, metabolism, prevention & control Humans Kindling, Neurologic / metabolism Microglia / immunology Neural Inhibition / physiology Neurons / cytology, metabolism, transplantation Rats Rats, Wistar Risk Assessment Stem Cell Transplantation / adverse effects, methods Substantia Nigra / metabolism*, physiopathology, surgery* Transfection / methods Treatment Outcome Up-Regulation / genetics gamma-Aminobutyric Acid / biosynthesis* |
| Chemical | |
Reg. No./Substance:
|
56-12-2/gamma-Aminobutyric Acid; EC 4.1.1.15/Glutamate Decarboxylase; EC 4.1.1.15/glutamate decarboxylase 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Interleukin Converting Enzyme inhibition impairs kindling epileptogenesis in rats by blocking astroc...
Next Document: A comparative study on in vitro and in vivo effects of topical vasodilators in human internal mammar...