Characterization of the cognitive and motor changes revealed by the elevated plus maze in an experimental rat model of radiation-induced brain injury

Njamnshi, Alfred K; Ahidjo, Nene; Ngarka, Leonard; Nfor, Leonard N; Mengnjo, Michel K; Njamnshi, Wepnyu Y; Basseguin Atchou, Jonas Guy; Tatah, Godwin Y; Dong À Zok, Faustin; Etet, Paul F Seke

Characterization of the cognitive and motor changes revealed by the elevated plus maze in an experimental rat model of radiation-induced brain injury

Document Type : Original Article

Authors

¹ Department of Neuroscience, Faculty of Medicine & Biomedical Sciences, Neuroscience Laboratory, The University of Yaoundé I, Yaoundé, Cameroon; Department of Translational Neuroscience, Brain Research Africa Initiative (BRAIN), Geneva, Switzerland; Department of Translational Neuroscience, Brain Research Africa Initiative (BRAIN); Department of Neurology, Yaoundé Central Hospital, Yaoundé, Cameroon

² Department of Neuroscience, Faculty of Medicine & Biomedical Sciences, Neuroscience Laboratory, The University of Yaoundé I, Yaoundé, Cameroon; Department of Translational Neuroscience, Brain Research Africa Initiative (BRAIN), Geneva, Switzerland; Department of Translational Neuroscience, Brain Research Africa Initiative (BRAIN), Yaoundé, Cameroon

³ Department of Radiotherapy, Yaoundé General Hospital, Yaoundé, Cameroon

⁴ Department of Translational Neuroscience, Brain Research Africa Initiative (BRAIN), Geneva, Switzerland; Department of Translational Neuroscience, Brain Research Africa Initiative (BRAIN); Center for Sustainable Health and Development; Department of Physiological Sciences and Biochemistry, University of Ngaoundéré, Garoua, Cameroon

Abstract

Background: Experimental models are needed to better understand the pathophysiology of neurodegenerative diseases to develop novel therapeutics. The neuropathology and clinical signs of acute radiation syndrome resemble those of neurodegenerative conditions. We characterized elevated plus maze (EPM) indicators of cognitive and motor impairment in rats exposed to brain-damaging doses of gamma radiation to develop a model for neurological component of the acute radiation syndrome. Materials and Methods: Technetium 99 m was administered once through tail vein to male Wistar rats to reach an absorbed dose of Gamma radiation of 667 mGy (66.7Rad). Animal performance in the EPM was assessed every 14 days. Rats were observed for 9 weeks for the occurrence of systemic and neurological signs. Comparisons were done between irradiated and nonirradiated rats, and in each group with baseline performance. Results: EPM indicators of cognitive and motor impairment, anxiety, and depression were observed concomitantly and increased with the severity of acute radiation syndrome-like systemic and neurological signs. Alterations in EPM indicators appeared 3 weeks postirradiation and their severity increased with time. Notably, arm transitions and the distance covered in the maze were decreased (−56.71% and −73.62%, P < 0.001), as well as open arm entries and time spent in open arms (−77.78% and −76.19%, P < 0.05) and the indicator of thigmotaxis rearing (−92.45, P < 0.001). Conclusions: Our results suggest that irradiated rat performance in the EPM paradigm reflects disease severity and could be used to perform both acute and subchronic pharmacological studies in acute radiation syndrome-like diseases in rats.

Keywords

References

1.	Hachinski V, Einhaupl K, Ganten D, Alladi S, Brayne C, Stephan BC, et al. Preventing dementia by preventing stroke: The Berlin Manifesto, Alzheimer's & dementia. J Alzheimer's Assoc 2019;15:961-84.
2.	Erkkinen MG, Kim MO, Geschwind MD. Clinical neurology and epidemiology of the major neurodegenerative diseases. Cold Spring Harbor Perspect Biol 2018;10:a033118.
3.	Kalaria RN, Akinyemi R, Ihara M, Stroke injury, cognitive impairment and vascular dementia. Biochim et Biophys Acta 2016;1862:915-25.
4.	Song X, Liu B, Cui L, Zhou B, Liu W, Xu F, et al. Silibinin ameliorates anxiety/depression-like behaviors in amyloid beta-treated rats by upregulating BDNF/TrkB pathway and attenuating autophagy in hippocampus. Physiol Behav 2017;179:487-93.
5.	Pinz MP, Dos Reis AS, Vogt AG, Kruger R, Alves D, Jesse CR, et al. Current advances of pharmacological properties of 7-chloro-4-(phenylselanyl) quinoline: Prevention of cognitive deficit and anxiety in Alzheimer's disease model. Biomed pharm 2018;105:1006-14.
6.	Khan A, Shal B, Naveed M, Shah FA, Atiq A, Khan NU, et al. Matrine ameliorates anxiety and depression-like behaviour by targeting hyperammonemia-induced neuroinflammation and oxidative stress in CCl4 model of liver injury. Neurotoxicology 2019;72:38-50.
7.	Guignet M, Dhakal K, Flannery BM, Hobson BA, Zolkowska D, Dhir A, et al. Persistent behavior deficits, neuroinflammation, and oxidative stress in a rat model of acute organophosphate intoxication. Neurobiol Dis 2020;133:104431.
8.	>Happold C, Ernemann U, Roth P, Wick W, Weller M, Schmidt F. Anticoagulation for radiation-induced neurotoxicity revisited. J Neuro Oncol 2008;90:357-62.
9.	Behin A, Delattre JY. Complications of radiation therapy on the brain and spinal cord. Seminars Neurol 2004;24:405-17.
10.	Duran A, Duran E, Castro J. Diagnosis of brain death scintigraphy with HMPAO-TC99m. Neurologia (Barcelona, Spain) 2003;18:389.
11.	Zolotov VA, Lomanov MF, Luk'iashin VE, Shimchuk GG, Minakova EI. Experimental study of the mechanism of local radiation damage to the brain by means of penetration of 99mTc through the hematoencephalic barrier. Med Radiol (Mosk) 1982;7:53-8.
12.	Norton S, Mullenix P, Culver B. Comparison of the structure of hyperactive behavior in rats after brain damage from x-irradiation, carbon monoxide and pallidal lesions. Brain Res 1976;116:49-67.
13.	Peng Y, Lu K, Li Z, Zhao Y, Wang Y, Hu B, et al. Blockade of Kv1.3 channels ameliorates radiation-induced brain injury. Neuro Oncol 2014;16:528-39.
14.	Thabet NM, Moustafa EM. Protective effect of rutin against brain injury induced by acrylamide or gamma radiation: Role of PI3K/AKT/GSK-3β/NRF-2 signalling pathway. Arch Physiol Biochem 2018;124:185-93.
15.	Vuralli D, Wattiez AS, Russo AF, Bolay H. Behavioral and cognitive animal models in headache research. J Headache Pain 2019;20:11.
16.	Castanheira L, Ferreira MF, Sebastiao AM, Telles-Correia D. Anxiety assessment in pre-clinical tests and in clinical trials: A critical review. Curr Topics Med Chem 2018;18:1656-76.
17.	Seke Etet PF, Farahna M, Khayr MA, Omar KM, Deniz OG, Mustafa HN, et al. Evaluation of the safety of conventional lighting replacement by artificial daylight. J Microscopy Ultrastructure 2017;5:206-15.
18.	Padurariu M, Antioch I, Balmus I, Ciobica A, El-Lethey HS, Kamel MM. Describing some behavioural animal models of anxiety and their mechanistics with special reference to oxidative stress and oxytocin relevance. Int J Veterinary Sci Med 2017;5:98-104.
19.	Djiogue S, Djiyou Djeuda AB, Seke Etet PF, Ketcha Wanda GJ, Djikem Tadah RN, Njamen D. Memory and exploratory behavior impairment in ovariectomized Wistar rats. Behav Brain Funct 2018;14:14.
20.	Pasquier D, Hoelscher T, Schmutz J, Dische S, Mathieu D, Baumann M, et al. Hyperbaric oxygen therapy in the treatment of radio-induced lesions in normal tissues: A literature review, Radiotherapy and oncology. J Europ Soc Therapeutic Radiol Oncol 2004;72:1-13.
21.	Kelsey CR, Mukundan S, Wang Z Jr., Hahn CA, Soher BJ, Kirkpatrick JP. Assessing neurotoxicity from the low-dose radiation component of radiosurgery using magnetic resonance spectroscopy. Neuro Oncol 2010;12:145-52.
22.	Wilkinson GS, Tietjen GL, Wiggs LD, Galke WA, Acquavella JF, Reyes M, et al. Mortality among plutonium and other radiation workers at a plutonium weapons facility. Am J Epidemiol 1987;125:231-50.
23.	Beral V, Fraser P, Carpenter L, Booth M, Brown A, Rose G. Mortality of employees of the atomic weapons establishment, 1951-82. BMJ 1988;297:757-70.

Advanced Biomedical Research