Morphological characteristics of neuroinflammation and gene expression of neurotrophic factors in the brain on the 30th day after traumatic brain injury and administration of the interleukin-1 receptor antagonist

Anastasiia S. Diatlova; Дятлова Анастасия Сергеевна; Nataliia S. Novikova; Новикова Наталия Сергеевна; Tatyana A. Filatenkova; Филатенкова Татьяна Александровна; Sergey N. Shanin; Шанин Сергей Николаевич; Elena E. Fomicheva; Фомичева Елена Евгеньевна; Evgeniia N. Petrunina; Петрунина Евгения Николаевна; Yulia S. Parshina; Паршина Юлия Сергеевна; Aleksandr M. Ishchenko; Ищенко Александр Митрофанович; Natalia B. Serebryanaya; Серебряная Наталья Борисовна

doi:10.17816/MAJ643401

Morphological characteristics of neuroinflammation and gene expression of neurotrophic factors in the brain on the 30th day after traumatic brain injury and administration of the interleukin-1 receptor antagonist

Authors: Diatlova A.S.¹, Novikova N.S.¹, Filatenkova T.A.¹, Shanin S.N.¹, Fomicheva E.E.¹, Petrunina E.N.¹^,2, Parshina Y.S.², Ishchenko A.M.³, Serebryanaya N.B.¹^,2
Affiliations:
1. Federal State Budgetary Scientific Institution «Institute of Experimental Medicine»
2. Federal State Budgetary Educational Institution of Higher Education "Saint-Petersburg State University"
3. Saint-Petersburg Pasteur Institute
Section: Original research
Published: 25.02.2025
URL: https://journals.eco-vector.com/MAJ/article/view/643401
DOI: https://doi.org/10.17816/MAJ643401
ID: 643401

Cite item

Abstract

Relevance. Traumatic brain injury (TBI) causes not only primary brain damage but also secondary inflammation, which contributes to further neuronal injury and dysfunction. Microglial cells are key participants in neuroinflammation, and they can remain activated for extended periods of time following TBI. This study is the first to describe the effects of recombinant IL-1 receptor antagonist (rIL-1RA) on microglial cells and the expression of neurotrophic factors in the hypothalamus 30 days after TBI in rats.

Aim. To investigate the effect of rIL-1RA on the morphological characteristics of microglia in brain areas susceptible to injury and to evaluate the expression of genes of neurotrophic factors Bdnf, Ngf, Vegf, and the inflammation marker S100a12 in the hypothalamus, as a potential structure with secondary inflammation, on the 30th day after TBI.

Materials and Methods. A weight-drop model was used to induce diffuse brain injury. rIL-1RA was administered subcutaneously at a dose of 50 mg/kg, 1 hour after TBI, and then twice more over the following two days. Microglial activation was assessed using immunohistochemistry and morphometry. The expression of neurotrophic factors Bdnf, Ngf, Vegf, and the inflammation marker S100a12 was measured by quantitative real-time PCR.

Results. Thirty days after the injury, no significant changes in the expression of neurotrophic factors (Bdnf, Ngf) or the inflammation marker S100a12 were observed in the hypothalamus. However, a significant increase in Vegf expression was recorded in animals treated with rIL-1RA. Immunohistochemical analysis revealed that activated microglial cells persisted in certain brain regions, but their numbers were significantly reduced compared to the untreated TBI group.

Conclusions. rIL-1RA modulates inflammatory responses after TBI by reducing microglial activation and improving neurotrophic processes, which opens prospects for its use in treating TBI-related sequelae.

Keywords

Traumatic brain injury, IL-1 receptor antagonist, neuroinflammation, microglia, VEGF

Full Text

About the authors