Forebrain ischemia triggers GABAergic system degeneration in substantia nigra at chronic stages in rats.
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 (n = 5) to day 56 (n = 7, ANOVA, p < .01). Movement coordination was impaired at day 56, as evaluated using beam-walking test (time-to-traverse 5.6 ± 1.2 sec versus 11.8 ± 5.4 sec; sham versus ischemia, p < .05, n = 5, and 7, resp.). Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.
Lin
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B
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.
Levy
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Raval
A P
AP
Perez-Pinzon
M A
MA
Defazio
R A
RA