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Studies found that neural stem cell (NSC<\/jats:styled-content>) therapy benefits HIE<\/jats:styled-content> rats; however, the mechanisms underlying are still unclear. The current study investigated the efficacy and molecular events of human embryonic neural stem cells (hNSC<\/jats:styled-content>s) in neonatal hypoxic\u2013ischemic (HI<\/jats:styled-content>) rats.<\/jats:p><\/jats:sec>Methods<\/jats:title>PKH<\/jats:styled-content>\u201026\u2010labeled hNSC<\/jats:styled-content>s were intranasally delivered to P7 Sprague Dawley rats 24\u00a0h after HI<\/jats:styled-content>. Neurobehavioral tests were performed at the indicated time after delivery: righting reflex and gait testing at D1, 3, 5, and 7; grid walking at D7 and 14; social choice test (SCT<\/jats:styled-content>) at D28; and Morris water maze from D35 to 40. Protein expression was determined by Western blot analysis. Brain damage was assessed by cresyl violet staining and MBP<\/jats:styled-content> staining. hNSC<\/jats:styled-content> distribution and differentiation were observed by in\u00a0vivo<\/jats:italic> bioluminescence imaging and immunofluorescence staining.<\/jats:p><\/jats:sec>Results<\/jats:title>(1) hNSC<\/jats:styled-content>s migrated extensively into brain areas within 24\u00a0h after the delivery, survived even at D42 with the majority in ipsi\u2010hemisphere, and could be co\u2010labeled with NeuN or GFAP<\/jats:styled-content>. (2) hNSC<\/jats:styled-content>s reduced the upregulation in cytosolic IL<\/jats:styled-content>\u20101\u03b2<\/jats:italic>, p\u2010I\u03ba<\/jats:italic>B\u03b1<\/jats:italic>, and NF<\/jats:styled-content>\u2010\u03ba<\/jats:italic>B p65 levels, whereas enhanced nuclear p65 expression in HI<\/jats:styled-content> rats at D3 after the delivery. (3) hNSC<\/jats:styled-content>s decreased HI<\/jats:styled-content>\u2010induced brain tissue loss and white matter injury at D42 after the delivery. (4) hNSC<\/jats:styled-content>s improved neurological outcomes in HI<\/jats:styled-content> rats in the tests of righting reflex (within 3\u00a0days), gait (D5), grid (D7), SCT<\/jats:styled-content> (D28), and water maze (D42).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Intranasal delivery of hNSC<\/jats:styled-content>s could prevent HI<\/jats:styled-content>\u2010induced brain injury and improve neurobehavioral outcomes in neonatal HI<\/jats:styled-content> rats, which is possibly related to the modulation of NF<\/jats:styled-content>\u2010\u03ba<\/jats:italic>B signaling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12441","type":"journal-article","created":{"date-parts":[[2015,8,8]],"date-time":"2015-08-08T06:59:54Z","timestamp":1439017194000},"page":"926-935","source":"Crossref","is-referenced-by-count":63,"title":["NF<\/scp>\u2010\u03ba<\/i>B Signaling is Involved in the Effects of Intranasally Engrafted Human Neural Stem Cells on Neurofunctional Improvements in Neonatal Rat Hypoxic\u2013Ischemic Encephalopathy"],"prefix":"10.1111","volume":"21","author":[{"given":"Gang","family":"Ji","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology School of Basic Medical Sciences Shanghai Medical College Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology School of Basic Medical Sciences Shanghai Medical College Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong\u2010Fei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shanghai Angecon Biotechnology Co., Ltd. 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