title: Expression of S100 protein and protective effect of arundic acid on the rat brain in chronic cerebral hypoperfusion.
abstract: S100 protein is expressed primarily by astroglia in the brain, and accumulates in and around the ischemic lesions. Arundic acid, a novel astroglia-modulating agent, is neuroprotective in acute cerebral infarction, whereas the protective effects remain unknown during chronic cerebral hypoperfusion. Rats undergoing chronic cerebral hypoperfusion were subjected to a bilateral ligation of the common carotid arteries, and were allowed to survive for 3, 7 and 14 days. The animals received a daily intraperitoneal injection of 5.0, 10.0 or 20.0 mg/kg of arundic acid, or vehicle, for 14 days. Alternatively, other groups of rats received a delayed intraperitoneal injection of 20.0 mg/kg of arundic acid or vehicle, which started from 1, 3 or 7 days after ligation and continued to 14 days. The degree of white matter (WM) lesions and the numerical density of S100 protein-immunoreactive astroglia were estimated. In the WM of rats with vehicle injections, the number of S100 protein-immunoreactive astroglia increased significantly after chronic cerebral hypoperfusion as compared to the sham-operation. A dosage of 10.0 and 20.0 mg/kg of arundic acid suppressed the numerical increase in S100 protein-immunoreactive astroglia and the WM lesions. These pathological changes were suppressed with delayed treatment up to 7 days in terms of astroglial activation, and up to 3 days in terms of the WM lesions. The protective effects of arundic acid against WM lesions were demonstrated in a dose-dependent manner, and even after postischemic treatments. These results suggest the potential usefulness of arundic acid in the treatment of cerebrovascular WM lesions.
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Shogoin, Kyoto 606-8507, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Ohtani
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tomimoto
authors.forename: Hideaki
authors.initials: H
authors.lastname: Wakita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitaguchi
authors.forename: Kayoko
authors.initials: K
authors.lastname: Nakaji
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000401:mortality / Q000473:pathology* / Q000517:prevention & control; D002210:Caprylates / Q000008:administration & dosage*; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D009418:S100 Proteins / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002210:Caprylates; C459360:ONO2506; D009418:S100 Proteins