H. Tomimoto et al., ALTERATIONS OF THE BLOOD-BRAIN-BARRIER AND GLIAL-CELLS IN WHITE-MATTER LESIONS IN CEREBROVASCULAR AND ALZHEIMERS-DISEASE PATIENTS, Stroke, 27(11), 1996, pp. 2069-2074
Background and Purpose The underlying cause of white-matter lesions, w
hich are frequent findings in cerebrovascular disease (CVD) and Alzhei
mer's disease (AD), remains uncertain. We performed immunohistochemica
l analysis of serum protein extravasation to investigate the function
of the blood-brain barrier in white-matter lesions. Methods White-matt
er lesions were estimated by use of Kluver-Barrera staining in patient
s diagnosed clinicopathologically as having ischemic CVD (n=14) and AD
(n=12) and from nonneurological control subjects (n=6). Axonal damage
s were investigated by use of immunohistochemistry for amyloid protein
precursor. Alteration of the blood-brain barrier was examined with fi
brinogen and immunoglobulins used as markers. The numbers of HLA-DR-po
sitive microglia and glial fibrillary acidic protein-positive astrogli
a were examined comparatively. Results White-matter lesions were grade
d as normal (grade 0) in 14 of the 32 cases (44%), slight (grade I) in
10 cases (31%), moderate (grade II) in 6 cases (19%), and severe (gra
de III) in 2 cases (6%). Amyloid precursor protein was accumulated mos
t frequently in grade II white-matter lesions. Immunohistochemistry fo
r serum proteins labeled astroglial cell bodies and their processes, w
hich seemed to have sequestered extravasated proteins. The groups with
detectable white-matter lesions had significantly higher grading scor
es for fibrinogen and immunoglobulins than the control group (P<.05).
Although the higher scores for serum protein extravasation were statis
tically significant in ischemic CVD cases (P<.05), there was no signif
icant increase in AD cases. Activated microglia and astroglia were mor
e numerous in the groups with white-matter lesions in both ischemic CV
D and AD cases, although this increase in the number of astroglia was
not evident in regions with clasmatodendrosis. Conclusions Dysfunction
of the blood-brain barrier is more prominent in white-matter lesions
seen in ischemic CVD than in AD and may have a role in the pathogenesi
s of cerebrovascular white-matter lesions.