β-Sitosterol Improves Synaptic Plasticity in High-risk Children with Cerebral Palsy by Regulating Inflammatory Homeostasis

ABSTRACT

Background: Cerebral palsy (CP) is a serious childhood disease characterized by changes in inflammatory responses and synaptic plasticity. Recent evidence highlighted the anti-inflammatory properties of β-sitosterol and that the nerve growth factor (NGF) regulates neuronal and synaptic plasticity. Objectives: This study aimed to explore the mechanism by which β-sitosterol regulates inflammatory homeostasis through NGF, thereby improving synaptic plasticity in high-risk children with CP. Materials and Methods: A rat model of CP was constructed, and the animals were divided into a model group, β-sitosterol group, β-sitosterol group + NGF group, and β-sitosterol + K252α group. Following treatment, the Morris water maze and Bederson score were used to evaluate the behavioral performance of rats, Western blot analysis was used to detect the expression of NGF and hippocampal protein, and enzyme-linked immunosorbent assay (ELISA) was used to measure inflammatory factor levels. Additionally, immunofluorescence examined the expression of synaptophysin in rat brains, and the brain tissue was observed by hematoxylin and eosin (HE) staining. Results: The CP rat model was successfully constructed. Of note, β-sitosterol treatment improved the synaptic plasticity of the CP rats with decreased Abnormal Involuntary Movement Scale (AIMS) and Bederson scores and a shorter latent period. Moreover, β-sitosterol inhibited the production of pro-inflammatory factors and increased the number of synapses in the hippocampus of rats while increasing the expression of brain-derived neurotrophic factor (BDNF), SYN, N-methyl d-aspartate receptor subtype 2B (NR2B), and NGF. Interestingly, administration of NGF inhibitor enhanced the inflammation response and decreased the protein expressions in synaptic receptors. Conclusion: β-Sitosterol improves synaptic plasticity in high-risk children with CP and alleviates inflammation and nerve cell apoptosis through up-regulation of NGF expression.

KEYWORDS

• β-Sitosterol
• nerve growth factor
• inflammatory homeostasis
• cerebral palsy
• synaptic plasticity

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• DOI10.1177/09731296251324723Copy

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