神經保護藥物對粒線體功能異常時鼠腦病變的影響
Date Issued
2000
Date
2000
Author(s)
李旺祚
DOI
892314B002058
Abstract
Systemic injection of 3-nitropropionic
acid (3-NP), an irreversible inhibitor of
complex II in mitochondrial respiratory chain,
induces selective striatal lesions in rats and
non-human primates mimicking those in
Huntington’s disease. In recent studies,
dichloroacetate (DCA) was shown to have
protective effects in rat models of cerebral
ischemia and myocardial dysfunction.
However, its therapeutic effect on brain
lesions induced by mitochondrial dysfunction
is rarely investigated. In the past year, we
established an in vivo animal model to
evaluate the rat brain lesions in
mitochondrial dysfuction. In the present
study, we compared the therapeutic effect of
DCA and MK-801 by in vivo animal model.
Two-month-old Sprague-Dawley rats
were treated with 3-NP by continuous drug
release from mini-pump, implanted
subcutaneously. MK-801 (2mg/kg) and DCA
(100mg/kg) were given in the same way. The
rats were then evaluated by MRI (T2 maps)
and in vivo 1H-MRS at indicated time points.
We first evaluated the effect of chronic 3-NP
injection on rats, and then evaluated the
effect of DCA on the striatal lesions induced
by 5-day 3-NP injection. The results showed
that chronic 3-NP injection produced
behavioral change and selective striatal
lesions on rats. MRS also showed the decline
of NAA/Cr ratio, indicating the neuronal loss
or dysfunction. The simultaneous application
of DCA showed no attenuation of the striatal
lesions. The present results suggest that the application of DCA in brain lesions induced
by mitochondrial inhibitors need further
investigation.
Subjects
Huntington disease
SDGs
Publisher
臺北市：國立臺灣大學醫學院小兒科
Type
report
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