Table of Contents
Cardiovascular Psychiatry and Neurology
Volume 2010, Article ID 506952, 16 pages
Research Article

Forebrain Ischemia Triggers GABAergic System Degeneration in Substantia Nigra at Chronic Stages in Rats

Department of Neurology (D4-5), Cerebral Vascular Disease Research Center, University of Miami Miller School of Medicine, P.O. Box 016960, Miami, FL 33101, USA

Received 20 January 2010; Revised 10 June 2010; Accepted 11 August 2010

Academic Editor: Héctor J. Caruncho

Copyright © 2010 B. Lin 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.


The long-term consequences of forebrain ischemia include delayed Parkinson's syndrome. This study revealed delayed neurodegeneration in the substantia nigra 8 weeks after 12.5 minutes of global ischemia in rat brain. Following neuronal loss of 30–40% in central and dorsolateral striatum at day 3, neuronal damage in the substantia nigra (SN) was assessed at 4–8 weeks using immunohistochemistry for glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (VGAT), and calretinin (CR). At day 56, the optical density of GAD67-, but not VGAT-, immunoreactivity in substantia nigra pars reticulata (SNR)—significantly decreased. CR-neurons concentrated in substantia nigra pars compacta (SNC) were reduced by 27% from day 3 ( ) to day 56 ( , ANOVA, ). Movement coordination was impaired at day 56, as evaluated using beam-walking test (time-to-traverse  sec versus  sec; sham versus ischemia, , , and 7, resp.). Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.