Neural stem cells reduce brain injury after unilateral carotid ligation |
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Authors: | Comi Anne M Cho Eunpi Mulholland Justin D Hooper Andrew Li Qun Qu Yun Gary Devin S McDonald John W Johnston Michael V |
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Institution: | 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 |
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Abstract: | 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. |
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