TNAP—a potential cytokine in the cerebral inflammation in spastic cerebral palsy
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 m...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.926791/full |
| _version_ | 1828405901919256576 |
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| author | Xiao-Kun Wang Chao Gao Chao Gao He-Quan Zhong Xiang-Yu Kong Rui Qiao Hui-Chun Zhang Bai-Yun Chen Yang Gao Bing Li |
| author_facet | Xiao-Kun Wang Chao Gao Chao Gao He-Quan Zhong Xiang-Yu Kong Rui Qiao Hui-Chun Zhang Bai-Yun Chen Yang Gao Bing Li |
| author_sort | Xiao-Kun Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T11:02:49Z |
| format | Article |
| id | doaj.art-cac14fc8d55043ee8008591001b26726 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-10T11:02:49Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-cac14fc8d55043ee8008591001b267262022-12-22T01:51:39ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-09-011510.3389/fnmol.2022.926791926791TNAP—a potential cytokine in the cerebral inflammation in spastic cerebral palsyXiao-Kun Wang0Chao Gao1Chao Gao2He-Quan Zhong3Xiang-Yu Kong4Rui Qiao5Hui-Chun Zhang6Bai-Yun Chen7Yang Gao8Bing Li9Research Center for Clinical Medicine, JinShan Hospital, Fudan University, Shanghai, ChinaDepartment of Rehabilitation, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, ChinaHenan Key Laboratory of Children’s Genetics and Metabolic Diseases, Zhengzhou, ChinaResearch Center for Clinical Medicine, JinShan Hospital, Fudan University, Shanghai, ChinaResearch Center for Clinical Medicine, JinShan Hospital, Fudan University, Shanghai, ChinaCollege of Acupuncture-Massage and Rehabilitation, Yunnan University of Traditional Chinese Medicine, Yunnan, ChinaDepartment of Rehabilitation, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, ChinaDepartment of Rehabilitation, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, ChinaDepartment of Rehabilitation, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, ChinaResearch Center for Clinical Medicine, JinShan Hospital, Fudan University, Shanghai, ChinaObjective: 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.https://www.frontiersin.org/articles/10.3389/fnmol.2022.926791/fullspastic cerebral palsyhypoxic ischemic encephalopathyTNAPALPLproteomics |
| spellingShingle | Xiao-Kun Wang Chao Gao Chao Gao He-Quan Zhong Xiang-Yu Kong Rui Qiao Hui-Chun Zhang Bai-Yun Chen Yang Gao Bing Li TNAP—a potential cytokine in the cerebral inflammation in spastic cerebral palsy Frontiers in Molecular Neuroscience spastic cerebral palsy hypoxic ischemic encephalopathy TNAP ALPL proteomics |
| title | TNAP—a potential cytokine in the cerebral inflammation in spastic cerebral palsy |
| title_full | TNAP—a potential cytokine in the cerebral inflammation in spastic cerebral palsy |
| title_fullStr | TNAP—a potential cytokine in the cerebral inflammation in spastic cerebral palsy |
| title_full_unstemmed | TNAP—a potential cytokine in the cerebral inflammation in spastic cerebral palsy |
| title_short | TNAP—a potential cytokine in the cerebral inflammation in spastic cerebral palsy |
| title_sort | tnap a potential cytokine in the cerebral inflammation in spastic cerebral palsy |
| topic | spastic cerebral palsy hypoxic ischemic encephalopathy TNAP ALPL proteomics |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.926791/full |
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