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Correction of Behavioral Disorders and State of Microglia with Recombinant IL-1 Receptor Antagonist in Experimental Traumatic Brain Injury

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Abstract

Traumatic brain injury (TBI) is a multifactorial disease that can lead to the development of neurological diseases. To correct violations of physiological functions, anti-inflammatory cytokines are used, in particular, the IL-1 receptor antagonist (IL-1RA). The aim of this work is to evaluate the effectiveness of the rIL-1RA preparation for the correction of post-traumatic neuroinflammation. TBI in rats was simulated by dropping a 115 g weight from a height of 120 cm into the center of the parietal region, and the drug was injected subcutaneously at a dose of 50 mg/kg 60 min after injury. We studied blood corticosterone levels and behavioral responses in the “Open field” test. To characterize the activation pattern of microglia in different parts of the brain, the expression of the Iba1 marker and morphological changes of cells were evaluated. Counting the total number and changing the shape and size of Iba1-positive microglial cells on 7th day after TBI showed that in animals treated with rIL-1RA the number of activated microglial cells was significantly higher than in intact animals, but the degree of their activation was significantly lower. Studies of CNS function disorders after TBI showed that motor and orientation-exploratory activities were significantly inhibited, which, together with the disturbance of the emotional status of the animals, indicates the development of a neurological deficit in intact rats. In animals treated with rIL-1RА, changes in behavioral characteristics were less pronounced. The decrease in neurological deficit in treated animals was directly related to the normalization of the state of microglia. The data obtained in the work indicate that the use of rIL-1RA 1 h after TBI allows correction of motor, orientation-exploratory activity and reduce microglia activation in different parts of the CNS.

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ACKNOWLEDGMENTS

The authors would like to express their heartfelt gratitude to Zharkova Maria Sergeevna Ph.D., Senior Researcher of the Department of Pathophysiology at the Institute of Experimental Medicine for her help in the discussion of the results and preparing of the article.

Funding

The work was performed in accordance with the planned research (State Assignment) on “Pathophysiological basis of disorders of the interaction between the nervous and immune systems and the search for innovative ways to correct various forms of pathology” 2019–2021.

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Authors and Affiliations

  1. Institute of Experimental Medicine, St. Petersburg, Russia

    E. E. Fomicheva, S. N. Shanin, T. A. Filatenkova, N. S. Novikova, A. S. Dyatlova & N. B. Serebryanaya

  2. Saint Petersburg Pasteur Institute, St. Petersburg, Russia

    A. M. Ishchenko

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  1. E. E. Fomicheva
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Contributions

S.N.B.—idea of the work, general management, discussion, writing and editing of the article; F.E.E.—data collection in the experiment, data processing, article writing and editing; Sh.S.N.—data collection in the experiment, data processing, article writing; F.T.A.—data collection and processing, article writing; N.N.S.—planning a morphological study of the animals’ brain, describing the results obtained; D.A.S.—collecting and processing morphological data; I.A.M.—idea of the work, justification of the order of experiments.

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Correspondence to N. B. Serebryanaya.

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The authors declare no apparent or potential conflicts of interest related to the publication of this article.

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Translated by A. Dyomina

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 10, pp. 1264–1278https://doi.org/10.31857/S0869813922100077.

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Fomicheva, E.E., Shanin, S.N., Filatenkova, T.A. et al. Correction of Behavioral Disorders and State of Microglia with Recombinant IL-1 Receptor Antagonist in Experimental Traumatic Brain Injury. J Evol Biochem Phys 58, 1571–1582 (2022). https://doi.org/10.1134/S0022093022050258

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