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Moreover, most studies have focused on mild CP models (unilateral carotid artery occlusion [UCAO] model). This study explored the effect and mechanism of hUC\u2010MSCs in a rat model of moderate\u2010to\u2010severe CP (bilateral carotid artery occlusion [BCAO] model). On postnatal Day 4 (P4), Wistar rat pups underwent BCAO induction. Subsequently, they received either a single intrathecal injection of hUC\u2010MSCs on P21 or repeated injections on P21, P28, P35, and P42. Motor performance was assessed using the rotarod and front\u2010limb suspension tests, while neuronal regeneration and inflammation were evaluated via biomarkers including neuronal nuclear antigen (NeuN), ionized calcium\u2010binding adapter molecule\u20101 (Iba\u20101), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and brain\u2010derived neurotrophic factor (BDNF). P18 model screening confirmed that the BCAO model resulted in more severe brain damage and motor impairment than the UCAO model. After injection of lentivirally transfected hUC\u2010MSCs, it was found that hUC\u2010MSCs could nest in the damaged area and survive for at least 3 days. Administration of hUC\u2010MSCs following BCAO modeling led to notable improvements in both behavioral performance and histological outcomes. Furthermore, repeated injections offered greater therapeutic benefits compared to single injection. It indicated that the efficacy of repeated injections of hUC\u2010MSCs in the treatment of moderate\u2010to\u2010severe CP was superior to that of single injection. Its mechanism was related to the improvement of damaged myelin structure, reduced immunoinflammatory responses, and increased neurotrophic support.<\/jats:p>","DOI":"10.1155\/sci\/4337435","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T02:20:21Z","timestamp":1766974821000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repeated Intrathecal Stem Cells Optimize Neuroplasticity and Motor Function in Moderate\u2010to\u2010Severe Cerebral Palsy of 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