Document Detail


Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging.
MedLine Citation:
PMID:  11918659     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated the microglial response to progressive dopamine neuron degeneration using in vivo positron emission tomography (PET) imaging and postmortem analyses in a Parkinson's disease (PD) rat model induced by unilateral (right side) intrastriatal administration of 6-hydroxydopamine (6-OHDA). Degeneration of the dopamine system was monitored by PET imaging of presynaptic dopamine transporters using a specific ligand (11)C-CFT (2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane). Binding of (11)C-CFT was markedly reduced in the striatum indicating dopaminergic degeneration. Parallel PET studies of (11)C-PK11195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3 isoquinoline carboxamide) (specific ligand for activated microglia) showed increased binding in the striatum and substantia nigra indicative of a microglial response. Postmortem immunohistochemical analyses were performed with antibodies against CR3 for microglia/macrophage activation. Using a qualitative postmortem index for microglial activation we found an initially focal, then widespread microglial response at striatal and nigral levels at 4 weeks postlesion. These data support the hypothesis that inflammation is a significant component of progressive dopaminergic degeneration that can be monitored by PET imaging.
Authors:
F Cicchetti; A L Brownell; K Williams; Y I Chen; E Livni; O Isacson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The European journal of neuroscience     Volume:  15     ISSN:  0953-816X     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2002-03-28     Completed Date:  2002-06-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  France    
Other Details:
Languages:  eng     Pagination:  991-8     Citation Subset:  IM    
Affiliation:
Neuroregeneration Laboratory, MRC119, McLean Hospital/Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD*
Antigens, CD147
Antigens, Neoplasm*
Antigens, Surface*
Antineoplastic Agents / pharmacology
Avian Proteins*
Blood Proteins*
Carbon Radioisotopes / diagnostic use
Dopamine / metabolism*
Encephalitis / pathology,  physiopathology,  radionuclide imaging*
Gliosis / pathology,  physiopathology,  radionuclide imaging
Isoquinolines / pharmacology
Membrane Glycoproteins / metabolism
Microglia / metabolism*,  pathology
Neostriatum / pathology,  physiopathology,  radionuclide imaging*
Neural Pathways / pathology,  physiopathology,  radionuclide imaging*
Neurons / metabolism*,  pathology
Oxidopamine / pharmacology
Parkinson Disease / pathology,  physiopathology,  radionuclide imaging
Rats
Substantia Nigra / pathology,  physiopathology,  radionuclide imaging*
Sympatholytics / pharmacology
Tomography, Emission-Computed
Tyrosine 3-Monooxygenase / metabolism
Grant Support
ID/Acronym/Agency:
NS 37654/NS/NINDS NIH HHS; NS 41263-02/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, Neoplasm; 0/Antigens, Surface; 0/Antineoplastic Agents; 0/Avian Proteins; 0/Blood Proteins; 0/Bsg protein, Gallus gallus; 0/Bsg protein, rat; 0/Carbon Radioisotopes; 0/Isoquinolines; 0/Membrane Glycoproteins; 0/Sympatholytics; 1199-18-4/Oxidopamine; 136894-56-9/Antigens, CD147; 85340-56-3/PK 11195; EC 1.14.16.2/Tyrosine 3-Monooxygenase

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