title: [The role of immunologic reactions in the pathogenesis in Binswanger's disease; a clue to therapeutic approach].
abstract: We examined the alterations of glial cells in the brains with Binswanger's disease. In comparison to the brains with lacunar cerebral infarction and those from non-neurological controls, oligodendroglia was decreased in number, and microglia was increased and activated in the white matter lesions in Binswanger's disease. Astroglia occasionally showed a regressive change, termed clasmatodendrosis. In rodents, similar white matter lesions could be induced after chronic cerebral hypoperfusion along with a numerical decrease of oligodendroglia, an increase of astroglia and activation of microglia in the corresponding white matter. These white matter lesions were suppressed by injection of immunosuppressant, cyclosporin A or FK506, with a suppression of microglial activation. These findings indicate that the lesion development in the white matter may be mediated by an immunologic reaction. Unfortunately, these drugs may be inappropriate for a practical use in terms of their side effects. Alternatively, we tried the use of anti-thrombin drug, argatroban. In acute neurological exacerbation of Binswanger's disease, markers for coagulation-fibrinolysis pathway were elevated significantly, and this activation was suppressed along with a recovery of neurological symptoms such as parkinsonism and pseudobulbar palsy. Thrombin contributes to a microcirculatory disturbance and may also enhance an inflammatory response through the action of thrombin receptor.
authors.affiliation: Department of Neurology, Faculty of Medicine, Kyoto University.
authors.forename: H
authors.initials: H
authors.lastname: Tomimoto
authors.forename: I
authors.initials: I
authors.lastname: Akiguchi
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives; D001779:Blood Coagulation Factors / Q000378:metabolism; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology; D015140:Dementia, Vascular / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D009457:Neuroglia / Q000473:pathology; D010875:Pipecolic Acids / Q000627:therapeutic use; D013449:Sulfonamides; D013917:Thrombin / Q000502:physiology
chemical_list: D000991:Antithrombins; D001779:Blood Coagulation Factors; D007166:Immunosuppressive Agents; D010875:Pipecolic Acids; D013449:Sulfonamides; D016572:Cyclosporine; D001120:Arginine; D013917:Thrombin; C031942:argatroban