From the Department of Neuropsychiatry, Osaka University Medical School
(Japan).
Correspondence to Takashi Kudo, MD, PhD, Department of Neuropsychiatry, Osaka University Medical School, 2–2 Yamadaoda, Suita, Osaka 565, Japan. E-mail kudo{at}psy.med.osaka-u.ac.jp
Background and Purpose—An animal
model of chronic cerebral hypoperfusion was developed with coiled clips
applied to both carotid arteries of adult Mongolian gerbils for between
1 week and 2 months. In the brain of this animal model, rarefaction of
white matter with dilatation of the ventricles was frequently observed.
To better understand the mechanism of white matter alteration under
cerebral hypoperfusion, the chronological sequence of molecular changes
in the cerebral white matter of the animal model was
determined.
Methods—Specially designed coiled clips were placed around both
carotid arteries of Mongolian gerbils to create stenosis
without occlusion. Changes in levels of myelin basic protein (MBP) as a
marker of myelin, neurofilament H (NFH) as a marker of axonal proteins,
and glial fibrillary acidic protein (GFAP) in astroglia after 2 months
of cerebral hypoperfusion were analyzed with Western blotting
and enzyme-linked immunosorbent assay.
Results—Western blotting of the white matter after 2 months of
hypoperfusion showed that the levels of MBP and NFH decreased, whereas
that of GFAP increased. The time course of MBP and NFH changes
determined with enzyme-linked immunosorbent assay revealed that the
change of MBP preceded that of NFH.
Conclusions—In the present study it was shown that the damage
to myelin precedes that to the axon in the white matter in a chronic
cerebral hypoperfusion animal model, suggesting that the change in
myelin is the primary pathological event in the cerebral white matter
under chronic hypoperfusion. The present study may help in
understanding the mechanisms of white matter pathology in
leukoaraiosis.
Associate
Editor for Basic Science,
Medical College of Virginia,
Virginia Commonwealth University,
Richmond, Virginia
© 1998 American Heart Association, Inc.
Original Contributions
White Matter Changes in the Gerbil Brain Under Chronic Cerebral Hypoperfusion
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