TNAP—a potential cytokine in the cerebral inflammation in spastic cerebral palsy

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.

Development and validation of a predictive model for poor prognosis of communication disorders in children with cerebral palsy after cervical perivascular sympathectomy

“…ALP comprises zinc (II) metalloenzymes that catalyze the hydrolysis of phosphate esters by forming phosphorylated serine intermediates [ 18 ]. Wang et al [ 19 ] conducted a proteomic analysis to compare the serums of children with spastic CP and healthy controls and identified differentially expressed proteins. The gene expression product of tissue-nonspecific ALP, known as the tissue-nonspecific isozyme of ALP (TNAP), was downregulated in children with spastic CP.…”

Bioinformatic analysis of underlying mechanisms of Kawasaki disease via Weighted Gene Correlation Network Analysis (WGCNA) and the Least Absolute Shrinkage and Selection Operator method (LASSO) regression model

“…Alkaline phosphatase (ALPL), which could regulate tissue mineralization and execute an integral function in cardiovascular remodeling [52], has been identified to be increased in acute KD patients and decreased after IVIG infusion [53], which are concordant with our analysis. In addition, ALPL could predict the morbidity and mortality of cardiovascular-related disease [54,55], and is associated with inflammation [56]. Hexokinase 3 (HK3) is involved in the glucose metabolic pathway and also correlated with immune cell infiltration [57].…”

Serum alkaline phosphatase was independently associated with depression in patients with cerebrovascular disease

“…Despite the heterogeneous characteristics of the serum origin of ALP, human and rodent brain tissues express higher levels of TNAP ( 37 , 53 , 54 ). In a mouse model of sepsis, TNAP mediated vascular endothelial cell damage that led to BBB destruction, resulting in decreased interest in spatial exploration and a reduction in spontaneous locomotion ( 55 ).…”