Trace elements changes in the forebrain and their influence on the rats behavior in elevated plus maze in acute period of mild blast-induced traumatic brain injury

Yu.V. Kozlova

doi:10.26641/2307-0404.2023.2.283151

Authors

Yu.V. Kozlova Dnipro State Medical University, Volodymyra Vernadskoho str., 9, Dnipro, 49044, Ukraine https://orcid.org/0000-0002-1364-1910

DOI:

https://doi.org/10.26641/2307-0404.2023.2.283151

Keywords:

blast-induced trauma, iron, elevated plus maze, copper, zinc, forebrain, behavior

Abstract

The relevance of the study is related to the high frequency of blast-induced brain injury in both military and civilian populations, which is caused by the use of various types of explosives in military conflicts, including in Ukraine today. Changes of biometals in the acute period of a mild blast-induced traumatic brain injury, including forebrain that participates in the implementation of various behavioral and cognitive processes, remain unexplained. The study was carried out on 54 sexually mature male Wistar rats, which were divided into 3 groups: experimental (influenced by a baroacoustic wave with an excess pressure of 26-36 kPa, previously anesthetized with halothane and softly fixed), sham (under the influence of halothane and fixation), intact. Behavior was studied in an elevated plus maze. Biometals in the forebrain were determined using energy dispersive X-ray fluorescence analysis. Standard deviation, Mann-Whitney U test (р<0.01, р<0.05), Spearman's correlation coefficient (r, р<0.01) were statistically calculated. According to the results of the study, behavioral changes in the elevated plus maze were found in the rats of the experimental group, which indicate the absence of fear on day 1 and 3 and the increase of anxiety on day 7 of the post-traumatic period. Spectral analysis of the forebrain showed significant (р<0.01) changes in the Cu/Fe, Cu/Zn and Zn/Fe ratios, which are the result of iron accumulation due to disruption of the blood-brain barrier. The obtained changes in the ratio of biometals lead to the development of anxiety, which is confirmed by correlation analysis. This indicates that the imbalance of biometals is an important secondary factor in the pathogenesis of blast-induced brain traumatic injury, which is important to consider for diagnosis, treatment and prevention of complications.

References

Rusiecki J, Levin LI, Wang L, et al. Blast traumatic brain injury and serum inflammatory cytokines: a repeated measures case-control study among U.S. military service members. J Neuroinflammation. 2020;17(1):20. doi: https://doi.org/10.1186/s12974-019-1624-z

Murugan M, Ravula A, Gandhi A, et al. Chemokine signaling mediated monocyte infiltration affects anxiety-like behavior following blast injury. Brain Behav Immun. 2020Jan.1;88:340-52.

Rutter B, Song H, DePalma RG, et al. Shock wave physics as related to primary non-impact blast-induced traumatic brain injury. Mil Med. 2021;186(Suppl 1):601-9. doi: https://doi.org/10.1093/milmed/usaa290

Fievisohn E, Bailey Z, Guettler A, et al. Primary blast brain injury mechanisms: current knowledge, limitations, and future directions. J Biomech Eng. 2018;140(2). doi: https://doi.org/10.1115/1.4038710

Chen S, Siedhoff HR, Zhang H, 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 plasticity and serine protease inhibitors. Neurobiol Dis. 2022;165:105634. doi: https://doi.org/10.1016/j.nbd.2022.105634

Sajja VS, LaValle C, Salib JE, et al. The role of very low level blast overpressure in symptomatology. Front Neurol. 2019;10:891. doi: https://doi.org/10.3389/fneur.2019.00891

Acosta G, Race N, Herr S, et al. Acrolein-mediated alpha-synuclein pathology involvement in the early post-injury pathogenesis of mild blast-induced Parkinsonian neurodegeneration. Mol Cell Neurosci. 2019;98:140-54. doi: https://doi.org/10.1016/j.mcn.2019.06.004

Acevedo K, Masaldan S, Opazo CM, et al. Redox active metals in neurodegenerative diseases. J Biol Inorg Chem. 2019;24(8):1141-57. doi: https://doi.org/10.1007/s00775-019-01731-9

Lippi SL, Neely CL, Amaya AL. Trace concentrations, heavy implications: Influences of biometals on major brain pathologies of Alzheimer’s disease. Int J Biochem Cell Biol. 2022Jan.1;143:106136.

Kozlova YuV, Abdul-Ohly LV, Kosharnyi AV, Kytova IV, Korzachenko MA, inventor. [Device for studying the effect of the shock wave of an explosion on the body]. Patent Ukraine No. U202100358. 2021 Feb 01. Ukrainian. Available from: https://base.uipv.org/searchINV/search.php?action=viewdetails&IdClaim=275098

Ari C, D'Agostino DP, Diamond DM, et al. Elevated plus maze test combined with video tracking software to investigate the anxiolytic effect of exogenous ketogenic supplements. J of Visual Exper. 2019;(143):1-10. doi: https://doi.org/10.3791/58396

Rojekar S, Abadi LF, Pai R, et al. Mannose-An-chored nano-selenium loaded nanostructured lipid carriers of etravirine for delivery to HIV reservoirs. AAPS PharmSciTech. 2022;23(7):230. doi: https://doi.org/10.1208/s12249-022-02377-8

Antomonov МY, Korobeinikov HV, Khmelnytska ІV, et al. Mathematical methods of processing and modeling the results of experimental studies. Kyiv; 2021.

Ozsoy HZ. Carbonic anhydrase enzymes: Likely targets for inhalational anesthetics. Med Hypotheses. 2019;123:118-24. doi: https://doi.org/10.1016/j.mehy.2019.01.005

Gao FJ, Klinedinst D, Fernandez FX, et al. Forebrain Shh overexpression improves cognitive function and locomotor hyperactivity in an aneuploid mouse model of Down syndrome and its euploid littermates. Acta Neuropathol Commun. 2021;9(1):137. doi: https://doi.org/10.1186/s40478-021-01237-z

Swanson LW, Hahn JD, Sporns O. Structure-function subsystem model and computational lesions of the central nervous system's rostral sector (forebrain and midbrain). Proc Natl Acad Sci USA. 2022;119(45):e2210931119. doi: https://doi.org/10.1073/pnas.2210931119

Nonaka M, Taylor WW, Bukalo O. 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

Kozlova YuV, Maslak HS, Abraimova OE, et al. State of spatial memory and antioxidant system activity of rats in the dynamics of development of Blast-induced traumatic brain injury. Medicni perspektivi. 2022;27(3):27-32. doi: https://doi.org/10.26641/2307-0404.2022.3.265769

Kraeuter AK, Guest PC, Sarnyai Z. The elevated plus maze test for measuring anxiety-like behavior in rodents. Methods Mol Biol. 2019;1916:69-74. doi: https://doi.org/10.1007/978-1-4939-8994-2_4

Estanislau C, Veloso AW, Filgueiras GB, et al. Rat self-grooming and its relationships with anxiety, dearousal and perseveration: Evidence for a self-grooming trait. Physiol Behav. 2019;209:112585. doi: https://doi.org/10.1016/j.physbeh.2019.112585

Shultz SR, McDonald SJ, Corrigan F, et al. Clinical relevance of behavior testing in animal models of traumatic brain injury. J Neurotrauma. 2020Jan.1;37(22):2381-400.

Aravind A, Ravula AR, Chandra N, et al. Behavioral deficits in animal models of blast traumatic brain injury. Front Neurol. 2020;11:990. doi: https://doi.org/10.3389/fneur.2020.00990

Kuriakose M, Younger D, Ravula AR, et al. Synergistic role of oxidative stress and bloodbrain barrier permeability as injury mechanisms in the acute patho-physiology 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. Advances in experim medicine and biol. 2019;1173:1-19.

doi: https://doi.org/10.1007/978-981-13-9589-5_1

Gromadzka G, Tarnacka B, Flaga A, et al. Copper dyshomeostasis in neurodegenerative diseases-therapeutic implications. International journal of molecular sciences. 2020;21(23):9259. doi: https://doi.org/10.3390/ijms21239259

Ghio AJ, Soukup JM, Ghio C, et al. Iron and zinc homeostases in female rats with physically active and sedentary lifestyles. Biometals: an internat J on the role of metal ions in biol, biochem, and med. 2021;34(1):97-105. doi: https://doi.org/10.1007/s10534-020-00266-w

Shayganfard M. Are essential trace elements effective in modulation of mental disorders? Update and perspectives. Biol Trace Elem Res. 2022;200(3):1032-59. doi: https://doi.org/10.1007/s12011-021-02733-y

Sahin Z, Ozkurkculer A, Kalkan OF, et al. Investigation of effects of two chronic stress protocols on depression-like behaviors and brain mineral levels in female rats: an evaluation of 7-day immobilization stress. Biol Trace Elem Res. 2021;199(2):660-7. doi: https://doi.org/10.1007/s12011-020-02160-5

Juan SM, Daglas M, Adlard PA. Tau pathology, metal dyshomeostasis and repetitive mild traumatic brain injury: an unexplored link paving the way for neuro-degeneration. J Neurotrauma. 2022;39(13-14):902-22. doi: https://doi.org/10.1089/neu.2021.0241

Lopez-Caperuchipi S, Kürzinger L, Hopp-Krämer S, et al. Posttraumatic learning deficits correlate with initial trauma severity and chronic cellular reactions after closed head injury in male mice. Exp Neurol. 2021;341:113721. doi: https://doi.org/10.1016/j.expneurol.2021.113721

Zhaba WD, Deji QZ, Gao SQ, et al. Deferoxamine reduces amyloid-beta peptides genesis and alleviates neural apoptosis after traumatic brain injury. Neuroreport. 2021;32(6):472-8. doi: https://doi.org/10.1097/WNR.0000000000001619