Cytopathological alterations and therapeutic approaches in Binswanger's disease

I. Akiguchi, H. Tomimoto, H. Wakita, Y. Yamamoto, T. Suenaga, M. Ueno, H. Budka

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Abstract

Binswanger's disease (BD) is a condition characterized by prominent brain atrophy with ventricular dilatation, diffuse white matter (WM) lesions and a scattering of lacunar infarcts. BD patients have dementia, and have vascular risk factors, focal cerebrovascular deficits and evidence of subcortical cerebral dysfunction. From our clinical studies, the most effective prophylaxis against the development of BD is to manage the hypertension, especially a high nocturnal blood pressure, in the early stage patients showing only a scattering of lacunes and/or mild WM lesions. The pathogenesis of BD is likely to be chronic cerebral ischemia due to hypertensive small artery disease with capillary collagenosis, which causes the multiple lacunes and the alterations in the glia and axons. In addition, arterial hypertension and a subsequent dysfunction of the blood-brain barrier (BBB) may cause the WM lesions. A compromised BBB will permit the entry of serum components, immunoglobulins, complements and fibrinogen into the perivascular neural parenchyma. These substances may subsequently activate both astro- and microglia and thus damage the myelin structures. Experimentally, immunosuppressants, cyclosporin A and FK 506 suppressed both the glial activation and WM changes after chronic cerebral hypoperfusion. The prothrombotic state of the microcirculation in BD patients may also contribute to local inflammation and the BBB dysfunction, because thrombin and prostanoids are involved in various tissue reactions including brain edema and glial activation. Therefore, novel therapeutic approaches using the administration of anti-thrombin and cyclo-oxygenase-2 inhibitors as well as immunosuppressants may be useful for preventing the progression of BD.

Original languageEnglish
Pages (from-to)119-128
Number of pages10
JournalNeuropathology
Volume19
Issue number1
DOIs
Publication statusPublished - 08-03-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Clinical Neurology

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    Akiguchi, I., Tomimoto, H., Wakita, H., Yamamoto, Y., Suenaga, T., Ueno, M., & Budka, H. (1999). Cytopathological alterations and therapeutic approaches in Binswanger's disease. Neuropathology, 19(1), 119-128. https://doi.org/10.1046/j.1440-1789.1999.00208.x