Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats. Part I: enhanced astrocytic synthesis of s-100beta in the periinfarct area precedes delayed infarct expansion.
An astrocytic protein S-100beta enhances the expression of inducible nitric oxide synthase in cultured astrocytes at micromolar concentrations, leading to nitric oxide-mediated death of cocultured neurons. The present study examined whether S-100beta production by reactive astrocytes accumulating within the periinfarct area was related to delayed expansion of infarct volume after permanent middle cerebral artery occlusion in the rat. After rapid increases during the initial 24 hours, the increase of infarct volume then decelerated while maintaining the increasing tendency until 168 hours in this model, attaining a significant difference compared with that at 24 hours. In the periinfarct area, the number of reactive astrocytes expressing both S-100 and glial fibrillary acidic protein, the tissue level of S-100beta as measured by the sandwich enzyme-linked immunosolvent assay method using anti-S-100beta monoclonal antibody, and the number of terminal deoxynucleotidyl transferase-mediated 2;-deoxyuridine 5;-triphosphate-biotin nick end labeling-positive cells were significantly increased preceding the delayed expansion of infarct volume. The CSF concentration of S-100beta showed a biphasic increase, presumably reflecting the immediate release from astrocytes within the ischemic core and the subsequent production in reactive astrocytes within the periinfarct area. These results show for the first time that the enhanced synthesis of S-100beta by reactive astrocytes participates in the inflammatory responses within the periinfarct area, which may be related to the occurrence of delayed infarct expansion as a major component of the cytokine network.
Matsui
Toru
T
Department of Neurosurgery and Institute of Laboratory Animal Science, Saitama Medical Center/School, Kawagoe, Saitama, Japan.
Mori
Takashi
T
Tateishi
Narito
N
Kagamiishi
Yoshifumi
Y
Satoh
Souichi
S
Katsube
Nobuo
N
Morikawa
Eiharu
E
Morimoto
Tadashi
T
Ikuta
Fusahiro
F
Asano
Takao
T
D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009414:Nerve Growth Factors; D051381:Rats; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins