## 5 Conclusions  
* Elevated serum concentrations of S100B, VEGF, CNTF, IL-6, APAs, and decreased END levels are predictive immunoenzymatic biomarkers in pediatric IS.
* The S100B protein is a marker for brain injury and neurorecovery prediction. Higher S100B levels indicate more severe recovery processes and increased neurological complications. It is recommended that S100B be assessed in all children with IS to determine the severity and progression of IS and the effectiveness of neurorecovery strategies.
* VEGF serves as a clinical biomarker for infarct volume assessment and as a prognostic marker for the long-term neurological outcomes post-IS.
* The identification of serum concentration imbalances in the studied markers allowed for the determination of common characteristics in the acute phase of IS in children: (1) the presence of inflammation and toxicity, mediated by significantly increased IL-6 and CNTF levels, contributing to early neurological depression and infarct expansion; (2) homeostasis disruption, confirmed by elevated serum VEGF and CNTF levels, indicating the disease severity; (3) the dysregulation of angiogenesis mechanisms, as evidenced by low CD105 (endoglin) levels, which influence the disease prognosis; (4) the disturbance of thrombotic mechanisms due to increased APA levels, reflecting coagulation cascade activation; and (5) the activation of ischemic remodeling processes, indicated by increased levels of VEGF and CNTF, which promote neuronal plasticity and stimulate blood vessel formation under inflammatory conditions.
* A six-month follow-up VEGF assessment in IS patients revealed that persistently elevated serum levels correlated with ongoing pro-inflammatory processes, delayed recovery, and a higher likelihood of epileptogenesis. VEGF serves as a peripheral prognostic marker for predicting long-term neurological complications and sequelae.  
Validation, N.W.; Investigation, M.S.; Data curation, S.H. and N.W.; Writing--original draft, M.S., L.S. and S.H.; Writing--review & editing, M.S., L.S., S.S., S.H. and N.W. All authors have read and agreed to the published version of the manuscript.  
This research was funded by the state program \"Systemogenesis of Risk Factors, Optimization of Healthcare Service, Sustainable Evaluation, and Mathematical Modeling of Stroke\". This project included a dedicated pediatric component: the \"Evaluation of Incidence, Prevalence, Risk Factors, and Research of Clinical, Neuroimaging, Neurophysiological, and Neurotrophic Management of Strokes in Children\".  
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of Nicolae Tsetemitanu State University of Medicine and Farmacy (protocol No. 69 dated 21 March 2017).  
**Informed Consent Statement:** Informed consent was obtained from all subjects involved in the study.  
**Data Availability Statement:** The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy reason.  
**Conflicts of Interest:** Author [PERSON] was employed by the company MSB Medical School Berlin GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.