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Titolo:
The DaNeX study of embryonic mesencephalic, dopaminergic tissue grafted toa minipig model of Parkinson's disease: Preliminary findings of effect of MPTP poisoning on striatal dopaminergic markers
Autore:
Danielsen, EH; Cumming, P; Andersen, F; Bender, D; Brevig, T; Falborg, L; Gee, A; Gillings, NM; Hansen, SB; Hermansen, F; Johansen, J; Johansen, TE; Dahl-Jorgensen, A; Jorgensen, HA; Meyer, M; Munk, O; Pedersen, EB; Poulsen, PH; Rodell, AB; Sakoh, M; Simonsen, CZ; Smith, DF; Sorensen, JC; Ostergard, L; Zimmer, J; Gjedde, A; Moller, A;
Indirizzi:
Aarhus Univ Hosp, PET Ctr, DK-8000 Aarhus C, Denmark Aarhus Univ Hosp Aarhus Denmark C sp, PET Ctr, DK-8000 Aarhus C, Denmark Aarhus Univ Hosp, Dept Neuroradiol, DK-8000 Aarhus, Denmark Aarhus Univ Hosp Aarhus Denmark DK-8000 oradiol, DK-8000 Aarhus, Denmark Aarhus Univ Hosp, Dept Neurosurg, DK-8000 Aarhus C, Denmark Aarhus Univ Hosp Aarhus Denmark C t Neurosurg, DK-8000 Aarhus C, Denmark Aarhus Univ Hosp, Dept Neuroanaesthesia, DK-8000 Aarhus C, Denmark Aarhus Univ Hosp Aarhus Denmark C anaesthesia, DK-8000 Aarhus C, Denmark Aarhus Univ, Hosp Psychiat, Dept Biol Psychiat, DK-8000 Aarhus C, Denmark Aarhus Univ Aarhus Denmark C pt Biol Psychiat, DK-8000 Aarhus C, Denmark Odense Univ, Univ So Denmark, Dept Anat & Neurobiol, DK-5230 Odense M, Denmark Odense Univ Odense Denmark M Anat & Neurobiol, DK-5230 Odense M, Denmark Neuro Search, Glostrup, Denmark Neuro Search Glostrup DenmarkNeuro Search, Glostrup, Denmark
Titolo Testata:
CELL TRANSPLANTATION
fascicolo: 2, volume: 9, anno: 2000,
pagine: 247 - 259
SICI:
0963-6897(200003/04)9:2<247:TDSOEM>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
LIVING HUMAN-BRAIN; POSITRON EMISSION TOMOGRAPHY; VENTRAL MESENCEPHALON; SUBSTANTIA NIGRA; RE-INNERVATION; BINDING-SITES; PET; PIG; RECEPTORS; GLUCOSE;
Keywords:
Parkinson's disease; animal models; allografts; positron emission tomography (PET);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Danielsen, EH Aarhus Univ Hosp, PET Ctr, Norrebrogade 44, DK-8000 Aarhus C, Denmark Aarhus Univ Hosp Norrebrogade 44 Aarhus Denmark C , Denmark
Citazione:
E.H. Danielsen et al., "The DaNeX study of embryonic mesencephalic, dopaminergic tissue grafted toa minipig model of Parkinson's disease: Preliminary findings of effect of MPTP poisoning on striatal dopaminergic markers", CELL TRANSP, 9(2), 2000, pp. 247-259

Abstract

A multicenter study is under way to investigate the efficacy of allografting of embryonic mesencephalic neurons in a pig model of Parkinson's disease. We have first established that a stable parkinsonian syndrome can be established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicationof adult male Gottingen minipigs. We are now using positron emission tomography (PET) methods for testing the physiological responses to MPTP intoxication and the time course of the response to several treatment strategies. We now report preliminary results obtained in 11 pigs employed in the initial phase of the study; the completed study shall ultimately include 30 pigs. Animals were randomly assigned to one of five groups: 1) Control, 2) MPTPintoxication, 3) MPTP intoxication followed by allograft, 4) MPTP intoxication followed by allograft with immunosuppression, and 5) MPTP intoxicationfollowed by allograft with immunosuppression acid co-grafting of immoratized HiB5 cells, which had been manipulated to secrete glia cell line-derivedneurotrophic factor (GDNF) (approximate to 2 ng GDNF/h/10(5) cells). MPTP was administered (1 mg/kg/day, SC) for 7-10 days until the pigs had developed mild parkinsonian symptoms of muscle rigidity, hypokinesia, and impairedcoordination, especially of the hind limbs. Approximately 2 weeks after the last MPTP dose, animals received a T1-weighted magnetic resonance imaging(MRI) scan, and a series of dynamic PET recordings, After the First seriesof PET scans, four grafts of porcine embryonic mesencephalic tissue (E28 days) were placed in each striatum of some MPTP-intoxicated pigs, using MRI-based stereotactic techniques. Immunosuppression of some animals with cyclosporin and prednisolone began just prior to surgery. Two more series of PETscans were performed at 4-month intervals after surgery. After the last scans, pigs were killed and the blains were perfused for unbiased stereological examination of cytological and histochemical markers in striatum and substantial nigra. The behavioral impairment of the animals (the "Parkinson's score") had been evaluated throughout the 8-month period. Kinetic analysis of the first set of PET scans has indicated th;lt the rate constant for thedecarboxylation of FDOPA in catecholamine fibers was reduced by 33% in striatum of the mildly parkinsonian pigs. The rate of association of [C-11]NS-2214 to catecholamine uptake sites was reduced by 62% in the same groups ofpigs. No significant difference was found in the binding potential of [C-11]raclopride to the dopamine D-2-like receptors in striatum of the MPTP-intoxicated versus control pigs. These preliminary results are suggestive thatthe activity of DOPA decarboxylase may be upregulated in the partially denervated pig striatum.

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Documento generato il 31/10/20 alle ore 03:34:17