Xiao-Kun Wang1, Chao Gao2,3, He-Quan Zhong1, Xiang-Yu Kong1, Rui Qiao4, Hui-Chun Zhang2, Bai-Yun Chen2, Yang Gao2, Bing Li1. 1. Research Center for Clinical Medicine, JinShan Hospital, Fudan University, Shanghai, China. 2. Department of Rehabilitation, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China. 3. Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Zhengzhou, China. 4. College of Acupuncture-Massage and Rehabilitation, Yunnan University of Traditional Chinese Medicine, Yunnan, China.
Abstract
Objective: Several studies have shown the significance of neuroinflammation in the pathological progress of cerebral palsy (CP). However, the etiology of CP remains poorly understood. Spastic CP is the most common form of CP, comprising 80% of all cases. Therefore, identifying the specific factors may serve to understand the etiology of spastic CP. Our research aimed to find some relevant factors through protein profiling, screening, and validation to help understand the pathogenesis of cerebral palsy. Materials and methods: In the current study, related clinical parameters were assessed in 18 children with spastic CP along with 20 healthy individuals of the same age. Blood samples of the spastic CP children and controls were analyzed with proteomics profiling to detect differentially expressed proteins. On the other hand, after hypoxic-ischemic encephalopathy (HIE) was induced in the postnatal day 7 rat pups, behavioral tests were performed followed by detection of the differentially expressed markers and inflammatory cytokines in the peripheral blood and cerebral cortex of the CP model rats by Elisa and Western blot. Independent sample t-tests, one-way analysis of variance, and the Pearson correlation were used for statistical analysis. Results: Through proteomic analysis, differentially expressed proteins were identified. Among them, tissue-nonspecific alkaline phosphatase (TNAP), the gene expression product of alkaline phosphatase (ALPL), was downregulated in spastic CP. In addition, significantly lower TNAP levels were found in the children with CP and model rats. In contrast, compared with the sham rats, the model rats demonstrated a significant increase in osteopontin and proinflammatory biomarkers in both the plasma and cerebral cortex on the ischemic side whereas serum 25 hydroxyvitamin D and IL-10 were significantly decreased. Moreover, serum TNAP level was positively correlated with serum CRP and IL-10 in model rats. Conclusion: These results suggest that TNAP is the potential molecule playing a specific and critical role in the neuroinflammation in spastic CP, which may provide a promising target for the diagnosis and treatment of spastic CP.
Objective: Several studies have shown the significance of neuroinflammation in the pathological progress of cerebral palsy (CP). However, the etiology of CP remains poorly understood. Spastic CP is the most common form of CP, comprising 80% of all cases. Therefore, identifying the specific factors may serve to understand the etiology of spastic CP. Our research aimed to find some relevant factors through protein profiling, screening, and validation to help understand the pathogenesis of cerebral palsy. Materials and methods: In the current study, related clinical parameters were assessed in 18 children with spastic CP along with 20 healthy individuals of the same age. Blood samples of the spastic CP children and controls were analyzed with proteomics profiling to detect differentially expressed proteins. On the other hand, after hypoxic-ischemic encephalopathy (HIE) was induced in the postnatal day 7 rat pups, behavioral tests were performed followed by detection of the differentially expressed markers and inflammatory cytokines in the peripheral blood and cerebral cortex of the CP model rats by Elisa and Western blot. Independent sample t-tests, one-way analysis of variance, and the Pearson correlation were used for statistical analysis. Results: Through proteomic analysis, differentially expressed proteins were identified. Among them, tissue-nonspecific alkaline phosphatase (TNAP), the gene expression product of alkaline phosphatase (ALPL), was downregulated in spastic CP. In addition, significantly lower TNAP levels were found in the children with CP and model rats. In contrast, compared with the sham rats, the model rats demonstrated a significant increase in osteopontin and proinflammatory biomarkers in both the plasma and cerebral cortex on the ischemic side whereas serum 25 hydroxyvitamin D and IL-10 were significantly decreased. Moreover, serum TNAP level was positively correlated with serum CRP and IL-10 in model rats. Conclusion: These results suggest that TNAP is the potential molecule playing a specific and critical role in the neuroinflammation in spastic CP, which may provide a promising target for the diagnosis and treatment of spastic CP.
Authors: Divine C Nwafor; Sreeparna Chakraborty; Allison L Brichacek; Sujung Jun; Catheryne A Gambill; Wei Wang; Elizabeth B Engler-Chiurazzi; Duaa Dakhlallah; Anthony B Pinkerton; José Luis Millán; Stanley A Benkovic; Candice M Brown Journal: Brain Behav Immun Date: 2019-11-25 Impact factor: 7.217
Authors: T M Kesar; L Sawaki; J H Burdette; M N Cabrera; K Kolaski; B P Smith; T M O'Shea; L A Koman; G F Wittenberg Journal: Clin Neurophysiol Date: 2011-12-06 Impact factor: 3.708
Authors: Rafael C Magalhães; Letícia P Pimenta; Izabela G Barbosa; Janaina M Moreira; João L V M de Barros; Antônio L Teixeira; Ana C Simões E Silva Journal: Int J Dev Neurosci Date: 2017-10-16 Impact factor: 2.457
Authors: Courtney A McDonald; Tayla R Penny; Madison C B Paton; Amy E Sutherland; Lakshmi Nekkanti; Tamara Yawno; Margie Castillo-Melendez; Michael C Fahey; Nicole M Jones; Graham Jenkin; Suzanne L Miller Journal: J Neuroinflammation Date: 2018-02-17 Impact factor: 8.322