Immunohistochemical analysis of brain lesions using S100B and glial fibrillary acidic protein antibodies in arundic acid- (ONO-2506) treated stroke-prone spontaneously hypertensive rats.
Stroke-prone spontaneously hypertensive rats (SHRSP) used as a model of essential hypertension cause a high incidence of brain stroke on the course of hypertension. Incidences and sizes of brain lesions are known to relate to the astrocyte activities. Therefore, relation between brain damage and the expression profile of the astrocytes was investigated with morphometric and immunohistochemical analyses using astrocyte marker antibodies of S100B and glial fibrillary acidic protein (GFAP) with or without arundic acid administration, a suppressor on the activation of astrocytes. Arundic acid extended the average life span of SHRSP. An increase in brain tissue weight was inhibited concomitant with a lower rate of gliosis/hemosiderin deposit/scarring in brain lesions. S100B- or GFAP-positive dot and filamentous structures were decreased in arundic acid-treated SHRSP, and this effect was most pronounced in the cerebral cortex, white matter, and pons, and less so in the hippocampus, diencephalon, midbrain, and cerebellum. Blood pressure decreased after administration of arundic acid in the high-dose group (100 mg/kg/day arundic acid), but not in the low-dose group (30 mg/kg/day). These data indicate that arundic acid can prevent hypertension-induced stroke, and may inhibit the enlargement of the stroke lesion by preventing the inflammatory changes caused by overproduction of the S100B protein in the astrocytes.
Higashino
Hideaki
H
Department of Pharmacology, Kinki University School of Medicine, Osaka-Sayama, Osaka, 589-8511, Japan. higasino@med.kindai.ac.jp
Niwa
Atsuko
A
Satou
Takao
T
Ohta
Yoshio
Y
Hashimoto
Shigeo
S
Tabuchi
Masaki
M
Ooshima
Kana
K
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D002210:Caprylates / Q000008:administration & dosage / Q000494:pharmacology*; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology / Q000378:metabolism*; D005911:Gliosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006485:Hemosiderin / Q000378:metabolism; D007150:Immunohistochemistry; D008136:Longevity / Q000187:drug effects; D008297:Male; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D009929:Organ Size; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D002210:Caprylates; D002491:Central Nervous System Agents; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; C459360:ONO2506; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat; D006485:Hemosiderin