CCL11 promotes migration and proliferation of mouse neural progenitor cells.
Neonatal hypoxia-ischemia induces massive brain damage during the perinatal period, resulting in long-term consequences to central nervous system structural and functional maturation. Although neural progenitor cells (NPCs) migrate through the parenchyma and home in to injury sites in the rodent brain, the molecular mechanisms are unknown. We examined the role of chemokines in mediating NPC migration after neonatal hypoxic-ischemic brain injury.



Nine-day-old mice were exposed to a 120-minute hypoxia following unilateral carotid occlusion. Chemokine levels were quantified in mouse brain extract. Migration and proliferation assays were performed using embryonic and infant mouse NPCs.



The neonatal hypoxic-ischemic brain injury resulted in an ipsilateral lesion, which was extended to the cortical and striatal areas. NPCs migrated toward an injured area, where a marked increase of CC chemokines was detected. In vitro studies showed that incubation of NPCs with recombinant mouse CCL11 promoted migration and proliferation. These effects were partly inhibited by a CCR3 antagonist, SB297006.



Our data implicate an important effect of CCL11 for mouse NPCs. The effective activation of NPCs may offer a promising strategy for neuroregeneration in neonatal hypoxic-ischemic brain injury.
Center for Innovative and Translational Medicine, Kochi University Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan. f-wang@kochi-u.ac.jp.
Feifei
F
Wang
Center for Innovative and Translational Medicine, Kochi University Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
Nobuyasu
N
Baba
Center for Innovative and Translational Medicine, Kochi University Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
Yuan
Y
Shen
Center for Innovative and Translational Medicine, Kochi University Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
Tatsuyuki
T
Yamashita
Center for Innovative and Translational Medicine, Kochi University Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.|Institute for Laboratory Animal Research, Science Research Center, Kochi University Medical School, Kochi, Japan.
Emi
E
Tsuru
Center for Innovative and Translational Medicine, Kochi University Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.|Institute for Laboratory Animal Research, Science Research Center, Kochi University Medical School, Kochi, Japan.
Masayuki
M
Tsuda
Center for Innovative and Translational Medicine, Kochi University Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.|Department of Obstetrics and Gynecology, Kochi University Medical School, Kochi, Japan.
Nagamasa
N
Maeda
Center for Innovative and Translational Medicine, Kochi University Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
Yusuke
Y
Sagara
D000818:Animals; D000831:Animals, Newborn; D001549:Benzamides / Q000494:pharmacology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D002339:Carotid Arteries / Q000601:surgery; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000601:surgery; D054413:Chemokine CCL11 / Q000378:metabolism / Q000494:pharmacology*; D019742:Chemokines, CC / Q000378:metabolism; D004195:Disease Models, Animal; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D061251:Primary Cell Culture; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D001549:Benzamides; C515457:Ccl11 protein, mouse; C515351:Ccr3 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D054397:Receptors, CCR3; C417502:SB 297006; D010649:Phenylalanine
CC chemokine; Hypoxic-ischemic encephalopathy; Neural progenitor cell; Neurogenesis