Integrated metabolomics and proteomics analysis in children with cerebral palsy exposed to botulinum toxin-A.

[BACKGROUND] We previously examined plasma metabolic changes before and after botulinum toxin-A injections of cerebral palsy (CP) children and showed that the glycine, serine and threonine metabolism may play a key role in neuritogenesis. This study analysed untargeted metabolomics combined with proteomics of plasma to discussed which substances are meaningfully changed, to what extent they affect the effects of action.

[METHODS] Blood samples were collected from 91 children with spastic CP at 4 time points: pre-injection (T1), 1 month post-injection (T2), 3 months post-injection (T3) and 6 months post-injection (T4). Differentially changed metabolites and proteins were selected, and co-expression pathways were constructed to explore the key molecular processes.

[RESULTS] A total of 674 proteins and 354 metabolites were identified. The differential metabolites were mainly involved in the linoleic acid metabolism, beta-Alanine metabolism, citrate cycle, pyruvate metabolism and glycolysis or gluconeogenesis. Differential proteins were primarily associated with glucose metabolism, lipid metabolism, immune and inflammation responses. Co-expression pathways showed that ECM-receptor interaction, complement and coagulation cascades, glycolysis or gluconeogenesis, pyruvate metabolism, and linoleic acid metabolism were the main pathways.

[CONSLUSIONS] Our results indicated the botulinum toxin-A predominantly activated the glucose metabolism, lipid metabolism, and immune and inflammation responses, and energy metabolism changed significantly in this process.

[TRIAL REGISTRATION DETAILS] ChiCTR2000033800, Research on the mechanism of botulinum toxin relieving spasticity in children with cerebral palsy. Approval No. 202023041. Registered 13 June 2020, http://www.chictr.org.cn/showproj.html?proj=52267 .

[IMPACT STATEMENT] This is the first study that combined dynamic metabolomics and proteomics analysis to investigate the molecular changes in children with spastic cerebral palsy after botulinum toxin-A injections, which might provide a theoretical reference for the further subsequent study for targets to increase the efficacy and prolong the duration of botulinum toxin-A, and would be a valuable resource for the metabolomics and proteomics field in this group.