Stromal cell-derived factor-1 alpha promotes neuroprotection, angiogenesis, and mobilization/homing of bone marrow-derived cells in stroke rats.
Stromal cell-derived factor (SDF)-1alpha 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-1alpha was found to exert neuroprotective effects that rescued primary cortical cultures from H(2)O(2) neurotoxicity, and to modulate neurotrophic factor expression. Rats receiving intracerebral administration of SDF-1alpha showed less cerebral infarction due to up-regulation of antiapoptotic proteins, and they had improved motor performance. SDF-1alpha 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-1alpha-treated rats enhanced functional local cerebral blood flow. In summary, intracerebral administration of SDF-1alpha 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.
Shyu
Woei-Cherng
WC
Institute of Molecular Biology, Academia Sinica, 128 Sec. 2, Academia Rd., Nankang, Taipei 11529, Taiwan.
Lin
Shinn-Zong
SZ
Yen
Pao-Sheng
PS
Su
Ching-Yuan
CY
Chen
Der-Cherng
DC
Wang
Hsiao-Jung
HJ
Li
Hung
H
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D054377:Chemokine CXCL12 / Q000494:pharmacology / Q000627:therapeutic use*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000473:pathology / Q000517:prevention & control*
D054377:Chemokine CXCL12; D018696:Neuroprotective Agents