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 μg 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 μg) 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 μg 6-OHDA, and the behavior was maintained with doses up to 16 μg 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.