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(Stroke. 2008;39:2114.)
© 2008 American Heart Association, Inc.

Original Contributions

Overexpression of Human S100B Exacerbates Brain Damage and Periinfarct Gliosis After Permanent Focal Ischemia

Takashi Mori, DVM, PhD; Jun Tan, MD, PhD; Gary W. Arendash, PhD; Naoki Koyama, PhD; Yoshiko Nojima, PhD Terrence Town, PhD

From the Institute of Medical Science (T.M., N.K., Y.N.), Saitama Medical Center/University, Saitama, Japan; the Department of Psychiatry and Behavioral Medicine (J.T.), University of South Florida College of Medicine, Tampa, Fla; The Byrd Alzheimer’s Center and Research Institute (G.W.A.), Tampa, Fla; the Department of Immunobiology (T.T.), Yale University School of Medicine, New Haven, Conn; and the Departments of Biomedical Sciences and Neurosurgery (T.T.), Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, Calif.

Correspondence to Takashi Mori, DVM, PhD, Institute of Medical Science, Saitama Medical Center/University, 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan. E-mail t_mori{at}saitama-med.ac.jp

Background and Purpose— 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.

Key Words: astrocyte • delayed infarct expansion • focal cerebral ischemia • microglia • S100B