Ameliorative effect of hydrogen water on mice with anxiety and depression-like behavior after repetitive mild brain injury

doi:10.3877/cma.j.issn.2095-9141.2021.02.002

Abstract

Abstract:

Objective

To establish and verify the animal model of repetitive mild traumatic brain injury (rmTBI), and to verify the protective effect of hydrogen water on rmTBI model animals and the behavioral improvement caused by hydrogen water.

Methods

Twenty C57BL/6 mice were randomly divided into control group (n=4), impact group (n=8) and intervention group (n=8). The impact group and intervention group were treated with closed craniocerebral percussion device once a day for 5 consecutive days. The control group and the impact group were fed with pure water, and the intervention group were fed with hydrogen water (H₂ content 0.003‰). The open-field test, elevated plus-maze and tail suspension test were used to evaluate the anxiety and depression-like behavior of mice on the 1^st, 3^rd, 5^th, 7^th, 15^th, 30^th day-post impact (DPI).

Results

On DPI 3, the resting latency of the suspended tail test in the control was significantly longer than that in the impact group (P<0.05), whereas it was not significantly different from that in the intervention group; on DPI 3, the open-arm exploring time of elevated plus-mazae by the control group was significantly longer than that of the impact group (P<0.05), whereas it was not significantly different from that of the intervention group; on DPI 15, the resting time of the control group in the open-field test was significantly shorter than that of the intervention group (P<0.05), and the number of wall climbing was significantly greater than that of the intervention group (P<0.05), whereas there was no significant difference between the impact group and the intervention group. On DPI 30, the open arm time of the elevated plus-maze exploration in the control mice was significantly longer than that in the impact and intervention groups (P<0.05), whereas there was no statistical difference between the impact and intervention groups.

Conclusion

Hydrogen water showed some ameliorative effects on symptoms such as irritability and reduced activity in the early stage after injury in rmTBI mice, but it was not effective in preventing and treating depression-like behaviors and exploratory memory impairment in long term observation after injury.

Key words: Repetitive mild traumatic brain injury, Brain concussion, Post-concussion syndrome, Chronic traumatic encephalopathy, Equipment design, Animal behavior test

Shenghua Lu, Xiaojian Xu, Xuejiao Wang, Fei Gao, Bin Zhang, Qianqian Ge, Mengshi Yang, Fei Niu, Jinqian Dong, Yuan Zhuang, Baiyun Liu, Runfa Tian. Ameliorative effect of hydrogen water on mice with anxiety and depression-like behavior after repetitive mild brain injury[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2021, 07(02): 68-74.

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References 26

[1]	Nguyen R, Fiest KM, Mcchesney J, et al. The International incidence of traumatic brain injury: a systematic review and meta-analysis[J]. Can J Neurol Sci, 2016, 43(6): 774-785.
[2]	Halstead ME, Walter KD. American academy of pediatrics. Clinical report--sport-related concussion in children and adolescents[J]. Pediatrics, 2010, 126(3): 597-615.
[3]	Cheng WH, Martens KM, Bashir A, et al. CHIMERA repetitive mild traumatic brain injury induces chronic behavioural and neuropathological phenotypes in wild-type and APP/PS1 mice[J]. Alzheimers Res Ther, 2019, 11(1): 6.
[4]	Mckee AC, Cantu RC, Nowinski CJ, et al. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury[J]. J Neuropathol Exp Neurol, 2009, 68(7): 709-735.
[5]	Mannix R, Berglass J, Berkner J, et al. Chronic gliosis and behavioral deficits in mice following repetitive mild traumatic brain injury[J]. J Neurosurg, 2014, 121(6): 1342-1350.
[6]	Shin N, Kim HG, Shin HJ, et al. Uncoupled endothelial nitric oxide synthase enhances p-Tau in chronic traumatic encephalopathy mouse model[J]. Antioxid Redox Signal, 2019, 30(13): 1601-1620.
[7]	Broussard JI, Acion L, De Jesús-Cortés H, et al. Repeated mild traumatic brain injury produces neuroinflammation, anxiety-like behaviour and impaired spatial memory in mice[J]. Brain Inj, 2018, 32(1): 113-122.
[8]	Chen H, Desai A, Kim HY. Repetitive closed-head impact model of engineered rotational acceleration induces long-term cognitive impairments with persistent astrogliosis and microgliosis in mice[J]. J Neurotrauma, 2017, 34(14): 2291-2302.
[9]	Lindqvist D, Dhabhar FS, James SJ, et al. Oxidative stress, inflammation and treatment response in major depression[J]. Psychoneuroendocrinology, 2017, 76: 197-205.
[10]	Goshen I, Kreisel T, Ben-Menachem-Zidon O, et al. Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression[J]. Mol Psychiatry, 2008, 13(7): 717-728.
[11]	Adler UC, Marques AH, Calil HM. Inflammatory aspects of depression[J]. Inflamm Allergy Drug Targets, 2008, 7(1): 19-23.
[12]	Rehman SU, Ikram M, Ullah N, et al. Neurological enhancement effects of melatonin against brain injury-induced oxidative stress, neuroinflammation, and neurodegeneration via AMPK/CREB signaling[J]. Cells, 2019, 8(7): 760.
[13]	Han L, Tian R, Yan H, et al. Hydrogen-rich water protects against ischemic brain injury in rats by regulating calcium buffering proteins[J]. Brain Res, 2015, 1615: 129-138.
[14]	Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals[J]. Nat Med, 2007, 13(6): 688-694.
[15]	Yoneda T, Tomofuji T, Kunitomo M, et al. Preventive effects of drinking hydrogen-rich water on gingival oxidative stress and alveolar bone resorption in rats fed a high-fat diet[J]. Nutrients, 2017, 9(1): 64.
[16]	Jackson K, Dressler N, Ben-Shushan RS, et al. Effects of alkaline-electrolyzed and hydrogen-rich water, in a high-fat-diet nonalcoholic fatty liver disease mouse model[J]. World J Gastroenterol, 2018, 24(45): 5095-5108.
[17]	Acosta SA, Tajiri N, Shinozuka K, et al. Long-term upregulation of inflammation and suppression of cell proliferation in the brain of adult rats exposed to traumatic brain injury using the controlled cortical impact model[J]. PLoS One, 2013, 8(1): e53376.
[18]	Cao T, Thomas TC, Ziebell JM, et al. Morphological and genetic activation of microglia after diffuse traumatic brain injury in the rat[J]. Neuroscience, 2012, 225: 65-75.
[19]	Schmidt RH, Scholten KJ, Maughan PH. Cognitive impairment and synaptosomal choline uptake in rats following impact acceleration injury[J]. J Neurotrauma, 2000, 17(12): 1129-1139.
[20]	Spain A, Daumas S, Lifshitz J, et al. Mild fluid percussion injury in mice produces evolving selective axonal pathology and cognitive deficits relevant to human brain injury[J]. J Neurotrauma, 2010, 27(8):1429-1438.
[21]	Mckee AC, Stern RA, Nowinski CJ, et al. The spectrum of disease in chronic traumatic encephalopathy[J]. Brain, 2013, 136(Pt 1): 43-64.
[22]	白若靖，高华斌，韩召利，等.小胶质细胞表型在反复轻度脑创伤模型大鼠中的变化研究[J].中华神经医学杂志, 2017, 16(3): 246-250.
[23]	Marmarou A, Foda MA, van den Brink W, et al. A new model of diffuse brain injury in rats. Part I: pathophysiology and biomechanics[J]. J Neurosurg, 1994, 80(2): 291-300.
[24]	Kane MJ, Angoa-Pérez M, Briggs DI, et al. A mouse model of human repetitive mild traumatic brain injury[J]. J Neurosci Methods, 2012, 203(1): 41-49.
[25]	Morin A, Mouzon B, Ferguson S, et al. Nilvadipine suppresses inflammation via inhibition of P-SYK and restores spatial memory deficits in a mouse model of repetitive mild TBI[J]. Acta Neuropathol Commun, 2020, 8(1): 166.
[26]	Xu X, Cowan M, Beraldo F, et al. Repetitive mild traumatic brain injury in mice triggers a slowly developing cascade of long-term and persistent behavioral deficits and pathological changes[J]. Acta Neuropathol Commun, 2021, 9(1): 60.

评价项目		得分
一过性呼吸暂停时间（s）
	<2	0
	2~15	1
	>15	2
一过性反射消失时间（s）
	<5	0
	5~20	1
	>20	0
意识恢复后无运动障碍和反射异常
	无	1
	有	2
肉眼可见外观畸形
	无	0
	有	4

评价项目		得分
一过性呼吸暂停时间（s）
	<2	0
	2~15	1
	>15	2
一过性反射消失时间（s）
	<5	0
	5~20	1
	>20	0
意识恢复后无运动障碍和反射异常
	无	1
	有	2
肉眼可见外观畸形
	无	0
	有	4

组别	只数	死亡数量	打击较轻（次）	效果理想（次）	打击过重（次）	总次数
打击组	8	0	5	33	2	40
干预组	8	1	7	26	4	37

组别	只数	死亡数量	打击较轻（次）	效果理想（次）	打击过重（次）	总次数
打击组	8	0	5	33	2	40
干预组	8	1	7	26	4	37

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