Changes in the neuro-glial-vascular interface in metabolic intoxications in children (based on acetonemic syndrome and hyperammonemia)
DOI:
https://doi.org/10.25305/unj.331349Keywords:
neuro-glial-vascular interface, acetonemic syndrome; hyperammonemia, blood-brain barrie, astrocytes, excitotoxicity, neuroinflammation, childrenAbstract
Objective: To investigate morphofunctional changes of the neuro-glial-vascular interface in children with metabolic intoxications, particularly in acetonemic syndrome and hyperammonemia.
Materials and methods: A systematic literature review with elements of narrative analysis was conducted following PRISMA guidelines. Literature search was performed in PubMed/MEDLINE, Web of Science Core Collection, Scopus, and Cochrane Library for the period 1990-2024. Included studies involved children from birth to 18 years and investigated neurotoxic effects of acetonemic syndrome and hyperammonemia. Study quality was assessed using Newcastle-Ottawa Scale, AMSTAR-2, and SYRCLE tools.
Results: Key morphofunctional disorders of the neuro-glial-vascular interface were identified: cytotoxic astrocytic swelling due to glutamine accumulation during ammonia detoxification; blood-brain barrier disruption with decreased expression of tight junction proteins (claudin-5, occludin, ZO-1); impaired energy metabolism due to glycolysis inhibition and mitochondrial dysfunction; excitotoxicity resulting from glutamate-glutamine cycle disruption; microglial activation with increased expression of CD68, Iba1, MHC II, and pro-inflammatory cytokine secretion.
Conclusions: Morphofunctional changes of the neuro-glial-vascular interface with acetonemic syndrome and hyperammonemia are characterized by complex disruptions of blood-brain barrier (BBB) structure and function, energy metabolism, neurotransmitter balance, and neuroinflammatory processes. A personalized approach to diagnosis and treatment using biomarkers of BBB damage and neuroinflammation is necessary.
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