(Stroke. 1997;28:1423-1429.)
© 1997 American Heart Association, Inc.
Articles |
Alterations in Glia and Axons in the Brains of Binswanger's Disease Patients
From the Department of Neurology, Faculty of Medicine, Kyoto University, Kyoto 606 Japan (I.A., H.T., T.S., H.W.), and the Institute of Neurology, University of Vienna, A-1097 Wien, Austria (H.B.).
Correspondence to I. Akiguchi, MD, Department of Neurology, Faculty of Medicine, Kyoto University, Kyoto 606 Japan.
Background and Purpose Although increasing attention is being paid to Binswanger's disease, a form of vascular dementia characterized by diffuse white matter lesions, only limited information is available on the pathological changes that occur in the glia and axons in the white matter. We therefore investigated the brains of patients with Binswanger's disease to gain further insight into its pathophysiology.
Methods Autopsied brains from patients with Binswanger's disease (group 3; n=17) were compared with those of non-neurological controls (group 1; n=5) and controls with large cortical infarcts but without significant white matter lesions (group 2; n=5). Glial fibrillary acidic protein (GFAP) was used as an immunohistochemical marker for astroglia, leukocyte common antigen (LCA) was used as a marker for microglia, and HLA-DR was used as a marker for activated microglia. Axonal damage was assessed by the accumulation of proteins, which are transported by fast axonal flow, amyloid protein precursor (APP), synaptophysin, and chromogranin A.
Results Although there was no difference in numerical density of GFAP-immunoreactive astroglia in each group, regressive astroglia were observed in 7 of 17 patients with Binswanger's disease. LCA-immunoreactive microglia were 1.7 times more numerous in Binswanger's disease than in group 1 (P<.05). HLA-DR–immunoreactive–activated microglia were 3.4 times and 2.1 times more numerous in Binswanger's disease as compared with group 1 (P<.01) and group 2 (P<.05), respectively. There was frequent perivascular lymphocyte cuffing, and clusters of macrophages with a decreased number of oligodendroglia were observed in the rarefied white matter. The grading scores for the number of axons immunoreactive for either APP, synaptophysin, or chromogranin A were significantly higher in Binswanger's disease than in group 1 or 2.
Conclusions The pathological alterations in Binswanger's diseased brains include regressive changes in the astroglia and activation of the microglia with a decrease in the oligodendroglia, which were associated with the degradation of both myelin and axonal components. These results indicate that an inflammatory reaction and compromised axonal transport, mediated by chronic ischemia, may play an important role in the pathophysiology of Binswanger's disease.
Key Words: white matter • Binswanger's disease • astrocytes • microglia
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