Long-term consequences of wildfire smoke exposure on the central nervous system of rats in experimental modeling

Introduction. The annual increase in air temperature is one of the reasons for the occurrence of large-scale destructive fires throughout the world. The consequences of the negative impact of air pollution during forest fires on the respiratory and cardiovascular systems have been widely and well studied. At the same time, insufficient attention is paid to the influence of forest fire smoke on the functioning of the central nervous system.

The study aims to study the morphofunctional state of the central nervous system of white male rats under prolonged exposure to forest fire smoke.

Materials and methods. The study was conducted on 60 outbred white mature male rats weighing 200–220 grams. Animals in the experimental group (n=30) were exposed to daily smoke inhalation for 4 weeks, 4 hours a day, 5 days a week. Rats in the control group (n=30) were supplied with clean air into the chamber. The examination of animals exposed to smoke was carried out in two stages. At the first stage, the morphofunctional state of experimental animals was assessed 24 hours after the end of exposure. At the second stage — 60 days after exposure (long-term period). The examination included an analysis of indicators of the central nervous system: histology and morphometry of the brain.

Results. Analysis of the results of the studied indicators indicates a decrease in motor and exploratory activity in animals exposed to smoke, as well as impairment of the ability to navigate and spatial memory. In the tissue structure of the sensorimotor cerebral cortex, multiple foci of neuronophagia, an increase in the number of degeneratively changed neurons, the formation of glial nodules and expansion of perivascular spaces were found. At the same time, the results of the examination in the long-term period indicated the absence of complete restoration of the identified violations.

Conclusions. The results of experimental modeling revealed cause-and-effect relationships between exposure to forest fire smoke and disturbances in the morphofunctional state of the central nervous system.

Limitations. The study is limited to studying the effects of prolonged 4 weeks, 5 days a week, 4 hours a day, exposure to wildfire smoke on outbred male white rats.

Ethics. The study was conducted in compliance with the rules of humane treatment of animals in accordance with the Helsinki Association of the World Medical Association for the Humane Treatment of Animals (edition — October 2008) in accordance with the requirements of applicability to the protection of vertebrate animals or in another scientific research (ETS). No. 123), Directive 2010/63/EC of the European Parliament and of the Council of the European Union of September 22, 2010, on the protection of animals used for scientific purposes. Permission was obtained from the Local Ethics Committee of the Federal State Budgetary Scientific Institution VSIMEI to conduct experiments (protocol No. 32/19 dated May 10, 2019).

Contribution:
Andreeva E.S. — the concept and design of the study, data collection and processing, writing the text, editing;
Novikov M.A. — the concept and design of the study, data collection and processing;
Titov E.A. — the concept and design of the study, data collection and processing.

Acknowledgment. The author expresses his gratitude to the staff of the Laboratory of Biomodeling and Translational Medicine and the Laboratory of Analytical Ecotoxicology and Biomonitoring of the East-Siberian Institute of Medical and Ecological Research for their assistance in the study.

Funding. The work was carried out according to the research plan within the framework of the state task.

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

Received: 20.11.2023 / Accepted: 10.12.2023 / Published: 29.12.2023

1. Romanello M., McGushin A., Napoli C.D., Drummond P., Hughes N., Jamart L., et al. The 2021 report of the Lancet Countdown on health and climate change: code red for a healthy future. 2021; 398: 1619–1662. https://doi.org/10.1016/S0140-6736(21)01787-6

2. Johnston F.H., Henderson S.B., Chen Y., Randerson J.T., Marlier M., DeFries R.S., et. al. Estimated global mortality attributable to smoke from landscape fires. Environ. Health Perspect. 2012; 120: 695–701.

3. Banes C.J. Firefighters' cardiovascular risk behaviors. Workplace Health Safety. 2014; 62(1): 2734. https://doi.org/10.1177/216507991406200

4. Burgess J.L., Nanson C.J., Bolstad-Johnson D.M., Gerkin R., Hysong T.A., Lantz R.C., et al. Adverse respiratory effects following overhaul in firefighters. J. Occup. Environ. Med. 2001; 43(5): 467–473.

5. Lee D.J., Koru-Sengul T., Hernandez M.N., Caban-Martinez A.J., McClure L.A., Mackinnon J.A., et al. Cancer risk among career male and female Florida firefighters: evidence from the Florida firefighter Cancer registry (1981-2014). Am J Ind Med. 2020; 63(4): 285–299. https://doi.org/10.1002/ajim.23086

6. Swiston J.R., Davidson W., Attridge S., Li G.T., Brauer M., van Eeden S.F. Wood smoke exposure induces a pulmonary and systemic inflammatory response in firefighters. European Respiratory Journal. 2008; 32: 129–138. https://doi.org/10.1183/09031936.00097707

7. Neitzel R., Naeher L., Paulsen M., Dunn K., Stock A., Simpson C.D. Biological monitoring of smoke exposure among wildland firefighters: A pilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particular matter, and levoglucosan. J. Expo. Sci. Environ. Epidemiol. 2009; 19: 349–358. https://doi.org/10.1038/jes.2008.21

8. Reisen F., Hansen D., Meyer C.P. Exposure to bushfire smoke during prescribed burns and wildfires: firefighters’ exposure risks and options. Environ. Int. 2011; 37: 314–321.

9. Adetona O., Dunn K., Hall D.B. Achtemeier G., Stock A., Naeher L.P. Personal PM2,5 exposure among wildland firefighters working at prescribed forest burns in Southeastern United States. J. of Occup. and Environ. Hygiene. 2011; 8(8): 503–511. https://doi.org/10.1080/15459624.2011.595257

10. Reinhardt T.E., Broyles G. Factors affecting smoke and crystalline silica exposure among wildland firefighters. J. of Occup. and Environ. Hygiene. 2019; 16(2): 151–64. https://doi.org/10.1080/15459624.2018.1540873

11. Milton L.A., White A.R. The potential impact of bushfire smoke on brain health. Neurochemistry International. 2020; 139: 104796. https://doi.org/10.1016/j.neuint.2020.104796

12. Braithwaite I., Zhang S., Kirkbride J.B., Osborn D.P., Hayes J.F. Air pollution (particulate matter) exposure and associations with depression, anxiety, bipolar, psychosis and suicide risk: a systematic review and meta-analysis. Environ Health Perspect. 2019; 127(12): 126002. https://doi.org/10.1289/EHP4595

13. Saijo Y., Ueno T., Hashimoto Y. Job stress and depressive symptoms among Japanese fire fighters. J. Nerv. Ment. Dis. 2007; 195(1): 31–40.

14. Morley J., Beauchamp G., Suyama J., Guyette F.X., Reis S.E., Callaway & David Hostler C.W. Cognitive function following treadmill exercise in thermal protective clothing. Eur. J. Appl. Physiol. 2012; 112: 1733–1740. https://doi.org/10.1007/s00421-011-2144-4

15. Vokina V.A., Andreeva E.S., Novikov M.A., Sosedova L.M. Device for simulating intoxication in small laboratory animals with biomass combustion products. Patent No. 213283U1 Ros. Federacija: MPK G09B23/28; № 2022107278; 2022 (in Russian).

16. Domitrovich J.W., Broyles G.A., Ottmar R.D., Reinhardt T.E., Naeher L.P., Kleinman M.T., et al. Wildland fire smoke health effects on wildland firefighters and the public. Final report: Joint Fire Sciences Program. 2017.

17. Gaughan D.M., Siegel P.D., Hughes M.D., Chang C., Law B.F., Campbell C.R., et. al. Arterial stiffness, oxidative stress, and smoke exposure in wildland firefighters. Am J Ind Med. 2014; 57(7): 748–756. https://doi.org/10.1002/ajim.22331

18. Banes C.J. Firefighters' cardiovascular risk behaviors. Workplace Health Safety. 2014; 62(1): Р. 2734.

19. Timonen K.L., Vanninen E., de Hartog J., Ibald-Mulli A., Brunekreef B., Gold D.R., et al. Effects of ultrafine and fine particulate and gaseous air pollution on cardiac autonomic control in subjects with coronary artery disease: The ULTRA study. J of Exp Sci and Environ Epidemiol. 2006; 16(4): 332–341.

20. Chumaeva Ju.V., Psjadlo Je.M., Shafran L.M. Medical and psychological rehabilitation as a system for the prevention and correction of work-related psychosomatic disorders of firefighters and rescuers. Aktual'nye problemy transportnoj mediciny. 2010; 19(1): 70–80 (in Russian).

21. Chernjak Ju.I., Grassman D.A., Shelepchikov A.A. Markers of exposure and effect of dioxins in firefighters who participated in extinguishing the fire at JSC Irkutskkabel. Med. truda i prom.ekol. 2005; 12: 41–46 (in Russian).

22. Amendola L.U., Weary D.M. Understanding rat emotional responses to CO2. Transl. Psychiatry. 2020; 10: 253. https://doi.org/10.1038/s41398-020-00936-w

23. Lee S., Lee P., Liang H., Tang C., Chen T., Cheng T., et. al. Brain lipid profiles in the spontaneously hypertensive rat after subchronic real-world exposure to ambient fine particulate matter. Sci Total Environ. 2020; 707: 135603. https://doi.org/10.1016/j.scitotenv.2019.135603

24. Harris E. Wildfire exposure linked to changes in cognition and brain activity. JAMA. 2023; 329(6): 457. https://doi.org/10.1001/jama.2023.0388