Glutamic acid, glutamate receptors, and nitric oxide in hypoxic brain damage

Introduction. Multifunctional glutamic acid (glutamate, Glu) is the main excitatory neurotransmitter in the central nervous system (CNS). By providing excitatory neurotransmission, Glu activates glutamate receptors (GluRc) associated with the intake of calcium (Ca²⁺). Acute and chronic Glu excitotoxicity and nitric oxide (NO) play a leading role in the mechanisms of neuron death during brain hypoxia, which accompanies cerebral circulatory disorders (CCD), strokes, epilepsy, traumatic brain injury (TBI), and neurodegenerative diseases. The aim of the study was to determine changes in the content of glutamic acid in the blood and cerebrospinal fluid (CSF) and the functional activity of GluRc receptors in children with various forms of hypoxic brain damage.

Materials and methods. Seventy nine CCD newborns, 36 children with congenital hydrocephalus, 58 children with acute lymphoblastic leukemia complicated by neuroleukemia, 42 children with epilepsy and paroxysmal conditions, and 159 children with TBI were examined. The content of Glu, glutamine (Gln), ammonia and biochemical markers of hypoxia (glucose, lactate) were determined in CSF and blood in CCD newborns using enzyme methods. The content of autoantibodies to NMDA and AMP GluRc was determined by enzyme immunoassay methods. The content of NO and its transformation products was estimated by the total content of nitrites and nitrates using the Griss method.

Results. As the severity of hypoxic brain damage increased, glucose levels decreased in the CSF of newborns, the content of lactate, protein, ammonia, and Glu increased, and the permeability of the brain-blood barrier increased. At the same time, the more pronounced brain damage was observed in children with various hypoxic CNS injuries, the higher the levels of Glu, total protein, and CA were observed in CSF.

Conclusion. The established patterns allowed determining the importance of NO and its conversion products in the functional activity of GluRc and showing the involvement of NO in protective and damaging processes in brain tissue.

Contribution:
Sorokina E.G., Reutov V.P. — the concept and design of the study;
Sorokina E.G., Karaseva O.V., Semenova Zh.B., Globa O.V., Kuzenkova L.M., Pinelis V.G. — collection and processing of the material;
Sorokina E.G., Globa O.V., Reutov V.P. — statistical processing and writing the text;
Smirnov I.E. — editing the text.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgment. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: April 30, 2025
Accepted: May 20, 2025
Published: June 27, 2025

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