Neural stem cells reduce brain injury after unilateral carotid ligation.
Neonatal stroke presents with seizures and results in neurologic morbidity, including epilepsy, hemiparesis, and cognitive deficits. Stem cell-based therapy offers a possible therapeutic strategy for neonatal stroke. We developed an immature mouse model of stroke with acute seizures and ischemic brain injury. Postnatal day 12 CD1 mice received right-sided carotid ligation. Two or 7 days after ligation, mice received an intrastriatal injection of B5 embryonic stem cell-derived neural stem cells. Four weeks after ligation, hemispheric brain atrophy was measured. Pups receiving stem cells 2 days after ligation had less severe hemispheric brain atrophy compared with either noninjected or vehicle-injected ligated controls. Transplanted cells survived, but 3 out of 10 pups injected with stem cells developed local tumors. No difference in hemispheric brain atrophy was seen in mice injected with stem cells 7 days after ligation. Neural stem cells have the potential to ameliorate ischemic injury in the immature brain, although tumor development is a serious concern.
Comi
Anne M
AM
Division of Neurology and Developmental Medicine, Kennedy Krieger Institute, and Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA. comi@kennedykrieger.org
Cho
Eunpi
E
Mulholland
Justin D
JD
Hooper
Andrew
A
Li
Qun
Q
Qu
Yun
Y
Gary
Devin S
DS
McDonald
John W
JW
Johnston
Michael V
MV
D000818:Animals; D001284:Atrophy; D002545:Brain Ischemia / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D001932:Brain Neoplasms / Q000473:pathology; D002339:Carotid Arteries / Q000502:physiology*; D002470:Cell Survival; D008026:Ligation; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000637:transplantation*; D012640:Seizures / Q000209:etiology; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013234:Stem Cells / Q000187:drug effects; D013238:Stereotaxic Techniques; D020521:Stroke / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D013724:Teratoma / Q000473:pathology; D014212:Tretinoin / Q000494:pharmacology
D014212:Tretinoin