Overexpression of human S100B exacerbates brain damage and periinfarct gliosis after permanent focal ischemia.
OBJECTIVE
We have previously demonstrated that augmented and prolonged activation of astrocytes detrimentally influences both the subacute and chronic phases of cerebral ischemia. Furthermore, we have suggested that the astrocyte-derived protein S100B may be important in these pathogenic events. However, the causal relationship between S100B and exacerbation of brain damage in vivo remains to be elucidated.


METHODS
Using transgenic mice overexpressing human S100B (Tg huS100B mice), we examined whether S100B plays a cardinal role in aggravation of brain damage after permanent middle cerebral artery occlusion (pMCAO).


RESULTS
Tg huS100B mice had significantly larger infarct volumes and worse neurological deficits at any time point examined after pMCAO as compared with CD-1 background strain-matched control mice. Infarct volumes in Tg huS100B mice were significantly increased from 1 to 3 and 5 days after pMCAO (delayed infarct expansion), whereas those in control mice were not significantly altered. S100, glial fibrillary acidic protein, and Iba1 burdens in the periinfarct area were significantly increased through to 7 days after pMCAO in Tg huS100B mice, whereas those in control mice reached a plateau at 3 days after pMCAO.


CONCLUSIONS
These results provide genetic evidence that overexpression of human S100B acts to exacerbate brain damage and periinfarct reactive gliosis (astrocytosis and microgliosis) during the subacute phase of pMCAO.
Mori
Takashi
T
Institute of Medical Science, Saitama Medical Center/University, 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan. t_mori@saitama-med.ac.jp
Tan
Jun
J
Arendash
Gary W
GW
Koyama
Naoki
N
Nojima
Yoshiko
Y
Town
Terrence
T
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001930:Brain Injuries / Q000175:diagnosis / Q000378:metabolism; D002545:Brain Ischemia / Q000175:diagnosis* / Q000378:metabolism*; D005786:Gene Expression Regulation; D005911:Gliosis / Q000473:pathology*; D006720:Homozygote; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000096:biosynthesis*
D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C579159:S100b protein, mouse