Expression of S100 protein and protective effect of arundic acid on the rat brain in chronic cerebral hypoperfusion.
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.
Ohtani
Ryo
R
Department of Neurology, Kyoto University Graduate School of Medicine, Shogoin, Kyoto 606-8507, Japan.
Tomimoto
Hidekazu
H
Wakita
Hideaki
H
Kitaguchi
Hiroshi
H
Nakaji
Kayoko
K
Takahashi
Ryosuke
R
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
D002210:Caprylates; C459360:ONO2506; D009418:S100 Proteins