Persistent production of neurons from adult brain stem cells during recovery after stroke.
Neural stem cells in the subventricular zone of adult rodents produce new striatal neurons that may replace those that have died after stroke; however, the neurogenic response has been considered acute and transient, yielding only small numbers of neurons. In contrast, we show herein that striatal neuroblasts are generated without decline at least for 4 months after stroke in adult rats. Neuroblasts formed early or late after stroke either differentiate into mature neurons, which survive for several months, or die through caspase-mediated apoptosis. The directed migration of the new neurons toward the ischemic damage is regulated by stromal cell-derived factor-1alpha and its receptor CXCR4. These results show that endogenous neural stem cells continuously supply the injured adult brain with new neurons, which suggests novel self-repair strategies to improve recovery after stroke.
Thored
Pär
P
Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, SE-221 84 Lund, Sweden.
Arvidsson
Andreas
A
Cacci
Emanuele
E
Ahlenius
Henrik
H
Kallur
Therése
T
Darsalia
Vladimer
V
Ekdahl
Christine T
CT
Kokaia
Zaal
Z
Lindvall
Olle
O
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000378:metabolism; D020127:Recovery of Function; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D020521:Stroke / Q000378:metabolism* / Q000473:pathology
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C486264:Cxcr4 protein, rat; D019718:Receptors, CXCR4; D020169:Caspases