title: 6-Hydroxydopamine-induced lesions in a rat model of hemi-Parkinson's disease monitored by magnetic resonance imaging.
abstract: Injection with 6-hydroxydopamine (6-OHDA) into the nigrostriatal pathway results in loss of nigrostriatal dopaminergic neurons, which has been used widely as an animal model of Parkinson's disease. In the present study, location and extent of lesions 1 day after 6-OHDA injections (2, 4, 8, or 16 microg as a free base) in the substantia nigra (SN) were evaluated in rats by T(2)-weighted magnetic resonance imaging (MRI). The changes in MRI were also compared to immunohistochemical and behavioral changes. Hyperintense area in MRI was found at the region corresponding to 6-OHDA injection in a dose-dependent manner and was accompanied by a loss of tyrosine hydroxylase (TH)-positive cells. The shape of hyperintense area in the SN appeared to be composed of two components (i.e., circular and longitudinal regions). Administration of a larger dose of 6-OHDA (8-16 microg) was accompanied by an increase in hyperintense area and loss of TH-positive cells beyond the SN. The hyperintense area was observed on the first and third days after 6-OHDA injection, but the size and intensity declined to near normal levels on the ninth day. Rotational behavior induced by methamphetamine reached maximal levels at 4 microg 6-OHDA, and the behavior was maintained with doses up to 16 microg of 6-OHDA. Intrastriatal injection with 6-OHDA was less effective. These results suggest that MRI provides highly valuable information for verifying the size and location of intended lesions as well as for determining the optimal dose of neurotoxins in individual animals.
authors.affiliation: Institute of Life Sciences, Ajinomoto Co., Inc., Suzuki-cho 1-1, Kawasaki-ku, Kawasaki 210-8681, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondoh
authors.forename: Makoto
authors.initials: M
authors.lastname: Bannai
authors.forename: Hitoo
authors.initials: H
authors.lastname: Nishino
authors.forename: Kunio
authors.initials: K
authors.lastname: Torii
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D011237:Predictive Value of Tests; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D009498:Neurotoxins; D008694:Methamphetamine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine