Alterations in glia and axons in the brains of Binswanger's disease patients

Ichiro Akiguchi, Hidekazu Tomimoto, Toshihiko Suenaga, Hideaki Wakita, Herbert Budka

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Abstract

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 extras 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 nonneurological 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.

Original languageEnglish
Pages (from-to)1423-1429
Number of pages7
JournalStroke
Volume28
Issue number7
DOIs
Publication statusPublished - 01-01-1997

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Vascular Dementia
Brain Diseases
Neuroglia
Axons
Microglia
Astrocytes
CD45 Antigens
Chromogranin A
Synaptophysin
Amyloid beta-Protein Precursor
Glial Fibrillary Acidic Protein
Oligodendroglia
HLA-DR Antigens
Brain
Axonal Transport
Myelin Sheath
Ischemia
Macrophages
Lymphocytes
Control Groups

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

Cite this

Akiguchi, Ichiro ; Tomimoto, Hidekazu ; Suenaga, Toshihiko ; Wakita, Hideaki ; Budka, Herbert. / Alterations in glia and axons in the brains of Binswanger's disease patients. In: Stroke. 1997 ; Vol. 28, No. 7. pp. 1423-1429.
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abstract = "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 extras 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 nonneurological 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.",
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Akiguchi, I, Tomimoto, H, Suenaga, T, Wakita, H & Budka, H 1997, 'Alterations in glia and axons in the brains of Binswanger's disease patients', Stroke, vol. 28, no. 7, pp. 1423-1429. https://doi.org/10.1161/01.STR.28.7.1423

Alterations in glia and axons in the brains of Binswanger's disease patients. / Akiguchi, Ichiro; Tomimoto, Hidekazu; Suenaga, Toshihiko; Wakita, Hideaki; Budka, Herbert.

In: Stroke, Vol. 28, No. 7, 01.01.1997, p. 1423-1429.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Alterations in glia and axons in the brains of Binswanger's disease patients

AU - Akiguchi, Ichiro

AU - Tomimoto, Hidekazu

AU - Suenaga, Toshihiko

AU - Wakita, Hideaki

AU - Budka, Herbert

PY - 1997/1/1

Y1 - 1997/1/1

N2 - 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 extras 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 nonneurological 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.

AB - 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 extras 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 nonneurological 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.

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