SDF1-a facilitates Lin-/Sca1+ cell homing following murine experimental cerebral ischemia.
BACKGROUND
Hematopoietic stem cells mobilize to the peripheral circulation in response to stroke. However, the mechanism by which the brain initiates this mobilization is uncharacterized.


METHODS
Animals underwent a murine intraluminal filament model of focal cerebral ischemia and the SDF1-A pathway was evaluated in a blinded manner via serum and brain SDF1-A level assessment, Lin-/Sca1+ cell mobilization quantification, and exogenous cell migration confirmation; all with or without SDF1-A blockade.


RESULTS
Bone marrow demonstrated a significant increase in Lin-/Sca1+ cell counts at 24 hrs (272 ± 60%; P<0.05 vs sham). Mobilization of Lin-/Sca1+ cells to blood was significantly elevated at 24 hrs (607 ± 159%; P<0.05). Serum SDF1-A levels were significant at 24 hrs (Sham (103 ± 14), 4 hrs (94 ± 20%, p = NS) and 24 hrs (130 ± 17; p<0.05)). Brain SDF1-A levels were significantly elevated at both 4 hrs and 24 hrs (113 ± 7 pg/ml and 112 ± 10 pg/ml, respectively; p<0.05 versus sham 76 ± 11 pg/ml). Following administration of an SDF1-A antibody, Lin-/Sca1+ cells failed to mobilize to peripheral blood following stroke, despite continued up regulation in bone marrow (stroke bone marrow cell count: 536 ± 65, blood cell count: 127 ± 24; p<0.05 versus placebo). Exogenously administered Lin-/Sca1+ cells resulted in a significant reduction in infarct volume: 42 ± 5% (stroke alone), versus 21 ± 15% (Stroke+Lin-/Sca1+ cells), and administration of an SDF1-A antibody concomitant to exogenous administration of the Lin-/Sca1+ cells prevented this reduction. Following stroke, exogenously administered Lin-/Sca1+ FISH positive cells were significantly reduced when administered concomitant to an SDF1-A antibody as compared to without SDF1-A antibody (10 ± 4 vs 0.7 ± 1, p<0.05).


CONCLUSIONS
SDF1-A appears to play a critical role in modulating Lin-/Sca1+ cell migration to ischemic brain.
Department of Neurological Surgery, Vanderbilt University, Nashville, Tennessee, United States of America.
J
J
Mocco
Department of Neurological Surgery, Vanderbilt University, Nashville, Tennessee, United States of America.
Aqeela
A
Afzal
Department of Neurosurgery, University of Florida, Gainesville, Florida, United States of America.
Saeed
S
Ansari
Department of Neurosurgery, University of Florida, Gainesville, Florida, United States of America.
Annemarie
A
Wolfe
Department of Neurosurgery, University of Florida, Gainesville, Florida, United States of America.
Kenneth
K
Caldwell
Department of Neurological Surgery, Columbia University, New York, New York, United States of America.
E S
ES
Connolly
Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America.
Edward W
EW
Scott
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice
D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse