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BioMed Research International
Volume 2013, Article ID 964034, 7 pages
http://dx.doi.org/10.1155/2013/964034
Research Article

In Vivo Evidence of Increased nNOS Activity in Acute MPTP Neurotoxicity: A Functional Pharmacological MRI Study

1Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529, Taiwan
2Department of Medical Imaging and Intervention, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan 33302, Taiwan
3School of Nursing, Queen’s University, Kingston, ON, Canada K7L 3N6
4Department of Microbiology and Immunology, Chang-Gung University, Taoyuan 33302, Taiwan

Received 13 January 2013; Revised 21 July 2013; Accepted 1 August 2013

Academic Editor: Tomio Inoue

Copyright © 2013 Tiing Yee Siow et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin commonly used to produce an animal model of Parkinson’s disease. Previous studies have suggested a critical role for neuronal nitric oxide (NO) synthase- (nNOS-) derived NO in the pathogenesis of MPTP. However, NO activity is difficult to assess in vivo due to its extremely short biological half-life, and so in vivo evidence of NO involvement in MPTP neurotoxicity remains scarce. In the present study, we utilized flow-sensitive alternating inversion recovery sequences, in vivo localized proton magnetic resonance spectroscopy, and diffusion-weighted imaging to, respectively, assess the hemodynamics, metabolism, and cytotoxicity induced by MPTP. The role of NO in MPTP toxicity was clarified further by administering a selective nNOS inhibitor, 7-nitroindazole (7-NI), intraperitoneally to some of the experimental animals prior to MPTP challenge. The transient increase in cerebral blood flow (CBF) in the cortex and striatum induced by systemic injection of MPTP was completely prevented by pretreatment with 7-NI. We provide the first in vivo evidence of increased nNOS activity in acute MPTP-induced neurotoxicity. Although the observed CBF change may be independent of the toxicogenesis of MPTP, this transient hyperperfusion state may serve as an early indicator of neuroinflammation.