Failure of neuroprotection by embryonic striatal grafts in a double lesion rat model of striatonigral degeneration (multiple system atrophy).

Details

Serval ID
serval:BIB_5852AB78A8ED
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Failure of neuroprotection by embryonic striatal grafts in a double lesion rat model of striatonigral degeneration (multiple system atrophy).
Journal
Experimental Neurology
Author(s)
Puschban Z., Waldner R., Seppi K., Stefanova N., Humpel C., Scherfler C., Levivier M., Poewe W., Wenning G.K.
ISSN
0014-4886 (Print)
ISSN-L
0014-4886
Publication state
Published
Issued date
2000
Peer-reviewed
Oui
Volume
164
Number
1
Pages
166-175
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
In the present experiment we studied the ability of embryonic striatal grafts to protect against striatal quinolinic acid (QA)-induced excitotoxicity in a previously established double lesion rat model of striatonigral degeneration (SND), the neuropathological substrate of parkinsonism associated with multiple system atrophy (MSA). Male Wistar rats received under halothane inhalation anesthesia a 6-hydroxydopamine 6-OHDA injection into the left medial forebrain bundle. Four to 5 weeks later apomorphine-induced rotation behavior was tested. Rats were divided into two treatment groups receiving either embryonic striatal cell suspensions or sham injections. Apomorphine-induced rotation behavior was retested 2 and 4 weeks after the grafting procedure. Following the rotation test animals of the striatal and sham graft group received a stereotaxic injection of 150 nmol QA. Again rotation behavior was assessed 2 and 4 weeks after lesioning. Brains were then processed to dopamine reuptake ([(3)H]mazindol), dopamine D1 ([(3)H]SCH23390), and D2 ([(3)H]spiperone) receptor autoradiography. Gliosis was detected using [(3)H]PK11195, a marker for peripheral benzodiazepine binding sites. Behavioral and autoradiographic analysis failed to show striatal protection in 6-OHDA prelesioned animals receiving embryonic striatal grafts. These findings indicate that beneficial protective effects of striatal grafts implanted into host striatum prior to excitotoxic insults are abolished in the presence of severe dopaminergic denervation. Our present results are relevant to future applications of neural grafting in MSA-SND.
Keywords
Animals, Apomorphine/pharmacology, Autoradiography, Binding, Competitive, Brain Tissue Transplantation, Corpus Striatum/embryology, Corpus Striatum/pathology, Disease Models, Animal, Dopamine/deficiency, Dopamine Agonists/pharmacology, Dopamine Plasma Membrane Transport Proteins, Fetal Tissue Transplantation, Male, Membrane Proteins/metabolism, Motor Activity/drug effects, Multiple System Atrophy/pathology, Multiple System Atrophy/surgery, Nerve Tissue Proteins/metabolism, Oxidopamine, Quinolinic Acid, Rats, Rats, Wistar, Receptors, Dopamine D1/metabolism, Receptors, Dopamine D2/metabolism, Striatonigral Degeneration/pathology, Striatonigral Degeneration/surgery, Treatment Failure
Pubmed
Web of science
Create date
20/01/2008 17:35
Last modification date
20/08/2019 14:12
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