Influence of trace elements changes in the cerebellum on the rat’s behavior in elevated plus maze in the early period of mild blast-induced traumatic brain injury

Authors

DOI:

https://doi.org/10.14739/2310-1237.2024.1.296887

Keywords:

traumatic brain injury, trace elements, elevated plus maze, cerebellum

Abstract

The aim of the current study was to determine whether there are changes in brain trace elements of rats with blast-induced trauma and if these changes affect behavior in the elevated plus maze.

Materials and methods. The study was carried out on 126 sexually mature male Wistar and were divided into 3 groups: Experimental – exposed to a shock wave 26.4 ± 3.6 kPa (n = 42); Sham (n = 42), the animals of which were subjected to inhalation anesthesia with halothane and fixation in a horizontal position; and Intact (n = 42). Behavior was study in elevated plus maze. The duration of presence in the open and closed arms, the number of stands, the duration of grooming was recorded in all groups of rats for 3 minutes. After, the animals were euthanized with halothane, followed by removal of the brain. The cerebellum was completely separated for spectral analysis using energy dispersive X-ray fluorescence analysis (EDRFA) on the analyzer EXPERT 3 XL.

Results. Results showed significant changes of cognitive activity in experimental group which are indicate functional disorders of the cerebellum in the form of maladaptation in space with subsequent inhibition of motor centers. Cu/Fe ratio was decreased in the 14th and 21st days and increased in the 28th. Cu/Zn ratio was decreased on the 14th day. Zn/Fe ratio was higher on the 14th and 28th days. The existence of correlations between changes in trace elements and behavioral disorders in experimental rats was established.

Conclusions. In the early period of blast-induced traumatic brain injury, cerebellar dysfunction in the form of spatial maladaptation with subsequent depression of motor centers was observed in the experimental rats Correlation analysis showed the presence of different strengths and directions of relationships between the ratios of Cu/Fe, Cu/Zn and Zn/Fe in the cerebellum and behavioral indicators in the elevated plus maze (duration of stay in open and closed arms, grooming and vertical motor activity) of experimental rats.

Author Biography

Yu. V. Kozlova, Dnipro State Medical University, Ukraine

MD, PhD, Associate Professor of the Department of Pathological Anatomy, Forensic Medicine and Pathological Physiology

References

Tomura S, Seno S, Kawauchi S, Miyazaki H, Sato S, Kobayashi Y, et al. A novel mouse model of mild traumatic brain injury using laser-induced shock waves. Neuro-sci Lett. 2020;721:134827. doi: https://doi.org/10.1016/j.neulet.2020.134827

Nonaka M, Taylor WW, Bukalo O, Tucker LB, Fu AH, Kim Y, et al. Behavioral and myelin-related abnormalities after blast-induced mild traumatic brain injury in mice. J Neurotrauma. 2021;38(11):1551-71. doi: https://doi.org/10.1089/neu.2020.7254

Chen S, Siedhoff HR, Zhang H, Liu P, Balderrama A, Li R, et al. Low-intensity blast induces acute glutamatergic hyperexcitability in mouse hippocampus leading to long-term learning deficits and altered expression of proteins involved in synaptic plastici-ty and serine protease inhibitors. Neurobiol Dis. 2022;165:105634. doi: https://doi.org/10.1016/j.nbd.2022.105634

Dickerson MR, Murphy SF, Urban MJ, White Z, VandeVord PJ. Chronic anxiety- and depression-like behaviors are associated with glial-driven pathology following repeat-ed blast induced neurotrauma. Front Behav Neurosci. 2021;15:787475. doi: https://doi.org/10.3389/fnbeh.2021.787475

Raj K., Kaur P., Gupta G.D., Singh S. Metals associated neurodegeneration in Parkin-son's disease: Insight to physiological, pathological mechanisms and management. Neurosci Lett. 2021;753:135873. doi: https://doi.org/10.1016/j.neulet.2021.135873

Mezzaroba L, Alfieri DF, Colado Simão AN, Vissoci Reiche EM. The role of zinc, copper, manganese and iron in neurodegenerative diseases. Neurotoxicology. 2019;74:230-41. doi: https://doi.org/10.1016/j.neuro.2019.07.007

Kawahara M, Kato-Negishi M, Tanaka KI. Dietary trace elements and the pathogene-sis of neurodegenerative diseases. Nutrients. 2023;15(9):2067. doi: https://doi.org/10.3390/nu15092067

Kozlova YV, Abdul-Ogly LV, Kosharnyj AV, Kytova IV, Korzachenko MA, inven-tors. [Device for studying the effect of the shock wave of an explosion on the body]. Ukraine patent UA 146858. 2021 Mar 25.

Ari C, D'Agostino DP, Diamond DM, Kindy M, Park C, Kovács Z. Elevated Plus Maze Test Combined with Video Tracking Software to Investigate the Anxiolytic Ef-fect of Exogenous Ketogenic Supplements. J Vis Exp. 2019;(143). doi: https://doi.org/10.3791/58396

Mikhailov IF, Mikhailov AI, Borisova SS, Fomina LP. X-ray fluorescent method for the analysis of trace elements in bio-materials with correction of the matrix effect. Rev Sci Instrum. 2023;94(12):124101. doi: https://doi.org/10.1063/5.0168861

Leão LK, Bittencourt LO, Oliveira AC, Nascimento PC, Miranda GH, Ferreira RO, et al. Long-term lead exposure since adolescence causes proteomic and morphological alterations in the cerebellum associated with motor deficits in adult rats. Int J Mol Sci. 2020;21(10):3571. doi: https://doi.org/10.3390/ijms21103571

Zhang JK, Botterbush KS, Bagdady K, Lei CH, Mercier P, Mattei TA. Blast-related traumatic brain injuries secondary to thermobaric explosives: implications for the war in Ukraine. World Neurosurg. 2022;167:176-183.e4. doi: https://doi.org/10.1016/j.wneu.2022.08.073

Wei T, Zhou M, Gu L, Zhou Y, Li M. How shockwaves open tight junctions of blood-brain barrier: comparison of three biomechanical effects. J Phys Chem B. 2022;126(27):5094-102. doi: https://doi.org/10.1021/acs.jpcb.2c02903

Kuriakose M, Younger D, Ravula AR, Alay E, Rama Rao KV, Chandra N. Synergistic role of oxidative stress and blood-brain barrier permeability as injury mechanisms in the acute pathophysiology of blast-induced neurotrauma. Sci Rep. 2019;9(1):7717. doi: https://doi.org/10.1038/s41598-019-44147-w

Thirupathi A, Chang YZ. Brain Iron metabolism and CNS diseases. Adv Exp Med Biol. 2019;1173:1-19. doi: https://doi.org/10.1007/978-981-13-9589-5_1

Sullivan B, Robison G, Osborn J, Kay M, Thompson P, Davis K, et al. On the nature of the Cu-rich aggregates in brain astrocytes. Redox Biol. 2017;11:231-9. doi: https://doi.org/10.1016/j.redox.2016.12.007

Willekens J, Runnels LW. Impact of Zinc transport mechanisms on embryonic and brain development. Nutrients. 2022;14(12):2526. doi: https://doi.org/10.3390/nu14122526

Rojas-Carvajal M, Chinchilla-Alvarado J, Brenes JC. Muscarinic regulation of self-grooming behavior and ultrasonic vocalizations in the context of open-field habitua-tion in rats. Behav. Brain. Res. 2022;418:113641. doi: https://doi.org/10.1016/j.bbr.2021.113641

Takemoto Y. Topographic carotid vasoconstriction in the rostral ventrolateral medulla of rats. Auton Neurosci. 2020;229:102720. doi: https://doi.org/10.1016/j.autneu.2020.102720

Maung MT, Carlson A, Olea-Flores M, Elkhadragy L, Schachtschneider KM, Navar-ro-Tito N, et al. The molecular and cellular basis of copper dysregulation and its rela-tionship with human pathologies. FASEB J. 2021;35(9):e21810. doi: https://doi.org/10.1096/fj.202100273RR

Andrade VM, Aschner M, Marreilha Dos Santos AP. Neurotoxicity of metal mixtures. Adv Neurobiol. 2017;18:227-65. doi: https://doi.org/10.1007/978-3-319-60189-2_12

Li B, Xia M, Zorec R, Parpura V, Verkhratsky A. Astrocytes in heavy metal neurotox-icity and neurodegeneration. Brain Res. 2021;1752:147234. doi: https://doi.org/10.1016/j.brainres.2020.147234

Ghio AJ, Soukup JM, Ghio C, Gordon CJ, Richards JE, Schladweiler MC, et al. Iron and zinc homeostases in female rats with physically active and sedentary lifestyles. Biometals. 2021;34(1):97-105. doi: https://doi.org/10.1007/s10534-020-00266-w

Rand D, Ravid O, Atrakchi D, Israelov H, Bresler Y, Shemesh C, et al. Endothelial Iron Homeostasis Regulates Blood-Brain Barrier Integrity via the HIF2α-Ve-Cadherin Pathway. Pharmaceutics. 2021;13(3):311. doi: https://doi.org/10.3390/pharmaceutics13030311

Peng Y, Chang X, Lang M. Iron homeostasis disorder and Alzheimer's disease. Int J Mol Sci. 2021;22(22):12442. doi: https://doi.org/10.3390/ijms222212442

Cheng Y, Gao Y, Li J, Rui T, Li Q, Chen H, et al. TrkB agonist N-acetyl serotonin promotes functional recovery after traumatic brain injury by suppressing ferroptosis via the PI3K/Akt/Nrf2/Ferritin H pathway. Free Radic Biol Med. 2023;194:184-98. doi: http://doi.org/10.1016/j.freeradbiomed.2022.12.002

Zhao Y, Liu Y, Xu Y, Li K, Zhou L, Qiao H, et al. The role of ferroptosis in blood-brain barrier injury. Cell Mol Neurobiol. 2023;43(1):223-36. doi: https://doi.org/10.1007/s10571-022-01197-5

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Published

2024-04-22

How to Cite

1.
Kozlova YV. Influence of trace elements changes in the cerebellum on the rat’s behavior in elevated plus maze in the early period of mild blast-induced traumatic brain injury. Pathologia [Internet]. 2024Apr.22 [cited 2024Nov.2];21(1):28-33. Available from: http://pat.zsmu.edu.ua/article/view/296887

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Original research