## 4 Discussion
They are among the triggers of neuroinflammation and contribute to the disruption of cerebral circulation, ultimately leading to the deregulation of angiogenesis in the cerebral ischemic focus. IL-6, VEGF, CNTF, S100B, CD105, and APAs are important markers of pediatric ischemic stroke that can be detected in peripheral blood, reflecting the extent of brain tissue damage and the long-term neurological prognosis. These diagnostic parameters will aid specialists in pediatric monitoring and facilitate early stroke diagnosis in children. The findings of this study emphasize the significant role of VEGF and IL-6 as key biomarkers in pediatric ischemic stroke (PIS). The strong correlations observed between the serum IL-6 and VEGF levels and the disease severity, infarct size, and functional outcomes at six months post-stroke reinforce their prognostic value. Additionally, while CNTF, APAs, endoglin (CD105), and the S100B protein showed moderate to weak correlations, their statistical significance underscores their potential supplementary role in evaluating pediatric IS. This study underscores the complex interplay between angiogenesis and neuroinflammation in stroke recovery. VEGF emerges as a potent peripheral marker for acute pediatric IS, whereas IL-6 serves as a strong inflammatory marker in this context. Further research into supplementary markers, including CNTF, APAs, ENG/CD105, and S100B, is necessary to refine their clinical applications. A key aspect of this research was the role of ENG/CD105 in stroke recovery. The observed lower serum concentrations of ENG/CD105 in children with acute stroke suggest that its deficiency may impair angiogenesis, delay inflammatory resolution, and exacerbate ischemic damage. While the literature on ENG/CD105 remains inconclusive, previous studies have indicated its involvement in stroke recovery. [PERSON], A et al. demonstrated an increased expression of ENG in human stroke penumbra regions, correlating with enhanced angiogenesis [31; 32]. Similarly, research by [PERSON], [PERSON] supports the role of cytokines such as IL-6, IL-1\(\beta\), and VEGF in stroke pathology and recovery [33; 34]. Moreover, this study establishes VEGF as a predictor of the neurological prognosis in children with IS, with elevated VEGF levels in peripheral circulation strongly linked to childhood disabilities, including paresis, paralysis, and communication disorders. These findings are consistent with prior biomolecular studies highlighting the importance of inflammatory and angiogenic biomarkers in pediatric stroke [35]. The results suggest that targeted therapeutic approaches focusing on modulating the IL-6 and VEGF pathways could improve recovery outcomes. The incorporation of anti-inflammatory strategies alongside standard stroke management holds promise for enhancing functional recovery in pediatric IS [36]. Future research should aim to expand the data set to improve generalizability. A larger cohort obtained through multicenter collaboration and extended study periods would enhance the robustness of these findings. Additionally, longitudinal studies could further elucidate the dynamic roles of these biomarkers throughout stroke progression and recovery. VEGF-A is a key mediator of cerebral angiogenesis, with increased levels observed after IS in rodents and humans [37]. Brain angiogenesis is a well-regulated process controlled by neuroectoderm-derived growth factors that bind to tyrosine kinase receptors expressed on endothelial cells [2]. In the rat brain, angiogenesis is completed around postnatal day 20. However, in the adult brain, under pathological conditions such as hypoxia/ischemia and brain tumor growth, endothelial cells can proliferate. Current evidence suggests that physiological angiogenesis in the brain is regulated by mechanisms similar to those of pathological angiogenesis induced by tumors or hypoxia/ischemia [38]. Hypoxia-inducible endothelial mitogen, vascular permeability factor, and VEGF appear to play essential roles in most of these processes.