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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on November 20, 2007; DOI: 10.1124/jpet.107.127746

0022-3565/08/3242-834-849$20.00
JPET 324:834-849, 2008
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CARDIOVASCULAR

Stromal Cell-Derived Factor-1{alpha} Promotes Neuroprotection, Angiogenesis, and Mobilization/Homing of Bone Marrow-Derived Cells in Stroke Rats

Woei-Cherng Shyu, Shinn-Zong Lin, Pao-Sheng Yen, Ching-Yuan Su, Der-Cherng Chen, Hsiao-Jung Wang, and Hung Li

Department of Neurology, Center for Neuropsychiatry, China Medical University and Hospital, Taichung, Taiwan (W.-C.S., S.-Z.L., D.-C.C., H.-J.W.); Department of Radiology, Tzu-Chi Buddhist General Hospital, Tzu-Chi University, Hualien, Taiwan (P.-S.Y.); and Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan (C.-Y.S., H.L.)

Stromal cell-derived factor (SDF)-1{alpha} is involved in the trafficking of hematopoietic stem cells from bone marrow to peripheral blood, and its expression is increased in the penumbra of the ischemic brain. In this study, SDF-1{alpha} was found to exert neuroprotective effects that rescued primary cortical cultures from H2O2 neurotoxicity, and to modulate neurotrophic factor expression. Rats receiving intracerebral administration of SDF-1{alpha} showed less cerebral infarction due to up-regulation of antiapoptotic proteins, and they had improved motor performance. SDF-1{alpha} injection enhanced the targeting of bone marrow (BM)-derived cells to the injured brain, as demonstrated in green fluorescent protein-chimeric mice with cerebral ischemia. In addition, increased vascular density in the ischemic cortex of SDF-1{alpha}-treated rats enhanced functional local cerebral blood flow. In summary, intracerebral administration of SDF-1{alpha} resulted in neuroprotection against neurotoxic insult, and it induced increased BM-derived cell targeting to the ischemic brain, thereby reducing the volume of cerebral infarction and improving neural plasticity.

Received June 25, 2007; accepted November 19, 2007.

Address correspondence to: Dr. Hung Li, Institute of Molecular Biology, Academia Sinica, 128 Sec. 2, Academia Rd., Nankang, Taipei 11529, Taiwan. E-mail: hungli{at}ccvax.sinica.edu.tw






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