Sex differences in learning and memory ability in hypoxic-ischemic brain injury in newborn mice_West China Medical Journal

Authors：

LIN Aijin , WANG Jieqiong , YI Shasha ,  AO Lijuan ,  CHEN Moxian

College of Rehabilitation, Kunming Medical University, Kunming, Yunnan 650500, P. R. China;

Corresponding author：

AO Lijuan, Email: 13508710081@qq.com; CHEN Moxian, Email: 37774290@qq.com

Keywords：

Gender; Hypoxic ischemia; Brain injury; Y maze; Morris water maze

DOI：

10.7507/1002-0179.201907161

Video：

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Objective To investigate the effect of sex on learning and memory ability of newborn mice with hypoxic-ischemic brain injury.Methods Fifty C57BL/6 mice aged 10 days were divided into hypoxia-ischemia group and sham group according to the random number table method, and there were 28 in the hypoxic-ischemic group and 22 in the sham group with half female and half male respectively. In the ischemia-hypoxia group, the left common carotid artery was ligated and then the mice were placed in 34℃ hypoxia chambers with 8% oxygen and 92% nitrogen mixture for 45 minutes. In the sham group, only the skin of the left neck was cut and sutured. After 2 months, Y maze test and Morris water maze test were used to evaluate the learning and memory ability of mice.Results The success rate of the hypoxic-ischemic group was 71.4% (20/28), and that of the sham group was 100.0% (22/22), a total of 42 mice were enrolled in the experiment. In Y maze test, there were differences in entries and total distance of new arms between the two groups (entries: F=16.068, P<0.001; total distance: F=8.532, P=0.007); compared between different groups in the same gender, the entries and total distance of new arms in the hypoxic-ischemic group were lower than those in the sham group with statistically significant differences (entries in males: P=0.001, entries in females: P=0.012; total distance in males: P=0.010, total distance in females: P=0.046). Compared between males and females in the same group, the entries and total distance of new arms of females were higher than those of males in the hypoxic-ischemic group, with statistically significant differences (P=0.039, 0.043). In Morris water maze test, the escape latency of positioning navigation in the hypoxic-ischemic group was higher than that in the sham group, and males showed more obviously poor performance (P<0.001); in the experiment of space exploration, differences were found in the duration of stay and the target quadrant entries between the two groups (duration of stay: F=8.297, P<0.001; entries: F=4.042, P=0.014), and there were statistically significant differences in the same gender males and females in the hypoxic-ischemic group and the sham group (duration of stay in males: P=0.003, duration of stay in females: P=0.038; entries in males: P=0.006, entries in females: P=0.041). Compared between males and females in the same group, the duration of stay and the target quadrant entries of females were higher than those of males in the hypoxic-ischemic group, with statistically significant differences (duration of stay: P=0.018; entries: P=0.032).Conclusions The learning and memory ability of newborn mice may be slightly impaired after hypoxic ischemic brain injury. There is significant difference in the effect on learning and memory ability between different genders, and the effect on males is higher than that on females.

Citation： LIN Aijin, WANG Jieqiong, YI Shasha, AO Lijuan, CHEN Moxian. Sex differences in learning and memory ability in hypoxic-ischemic brain injury in newborn mice. West China Medical Journal, 2019, 34(12): 1412-1416. doi: 10.7507/1002-0179.201907161 Copy

1.	Schneider J, Miller SP. Chapter 7- preterm brain injury: white matter injury. Handb Clin Neurol, 2019, 162: 155-172.
2.	Novak CM, Ozen M, Burd I. Perinatal brain injury: mechanisms, prevention, and outcomes. Clin Perinatol, 2018, 45(2): 357-375.
3.	Salmaso N, Tomasi S, Vaccarino FM. Neurogenesis and maturation in neonatal brain injury. Clin Perinatol, 2014, 41(1): 229-239.
4.	Frey HA, Klebanoff MA. The epidemiology, etiology, and costs of preterm birth. Semin Fetal Neonatal Med, 2016, 21(2): 68-73.
5.	Barfield WD. Public health implications of very preterm birth. Clin Perinatol, 2018, 45(3): 565-577.
6.	张丹, 周玉陶, 徐玉庭, 等. 新生小鼠缺氧缺血性脑损伤模型的建立. 中国实验动物学报, 2017, 25(5): 486-493.
7.	Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation, 2016, 133(4): e38-e360.
8.	Millar LJ, Shi L, Hoerder-Suabedissen A, et al. Neonatal hypoxia ischaemia: mechanisms, models, and therapeutic challenges. Front Cell Neurosci, 2017, 11: 78.
9.	Takada SH, Motta-Teixeira LC, Machado-Nils AV, et al. Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior. Behav Brain Res, 2016, 296: 331-338.
10.	Kim M, Yu JH, Seo JH, et al. Neurobehavioral assessments in a mouse model of neonatal hypoxic-ischemic brain injury. J Vis Exp, 2017: 129.
11.	Smith AL, Alexander M, Rosenkrantz TS, et al. Sex differences in behavioral outcome following neonatal hypoxia ischemia: insights from a clinical meta-analysis and a rodent model of induced hypoxic ischemic brain injury. Exp Neurol, 2014, 254: 54-67.
12.	Bolisetty S, Dhawan A, Abdel-Latif M, et al. Intraventricular hemorrhage and neurodevelopmental outcomes in extreme preterm infants. Pediatrics, 2014, 133(1): 55-62.
13.	Mallard C, Vexler ZS. Modeling ischemia in the immature brain: how translational are animal models?. Stroke, 2015, 46(10): 3006-3011.
14.	张志强, 张莉, 张跃奇. 重复经颅磁刺激对卒中后大鼠的学习记忆功能和海马区胰岛素样生长因子-1表达的影响. 中国康复医学杂志, 2018, 33(9): 1024-1028, 1049.
15.	Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc, 2006, 1(2): 848-858.
16.	Pimentel-Coelho PM, Michaud JP, Rivest S. C-C chemokine receptor type 2 (CCR2) signaling protects neonatal male mice with hypoxic-ischemic hippocampal damage from developing spatial learning deficits. Behav Brain Res, 2015, 286: 146-151.
17.	黄忠兴, 何宏星, 王亚新, 等. 成年小鼠大脑神经细胞特异性ADAM10基因敲除的认知功能研究. 实验动物科学, 2018, 35(4): 61-66.
18.	Sukhanova IA, Sebentsova EA, Khukhareva DD, et al. Gender-dependent changes in physical development, BDNF content and GSH redox system in a model of acute neonatal hypoxia in rats. Behav Brain Res, 2018, 350: 87-98.
19.	Hill CA, Threlkeld SW, Fitch RH. Early testosterone modulated sex differences in behavioral outcome following neonatal hypoxia ischemia in rats. Int J Dev Neurosci, 2011, 29(4): 381-388.

1. Schneider J, Miller SP. Chapter 7- preterm brain injury: white matter injury. Handb Clin Neurol, 2019, 162: 155-172.
2. Novak CM, Ozen M, Burd I. Perinatal brain injury: mechanisms, prevention, and outcomes. Clin Perinatol, 2018, 45(2): 357-375.
3. Salmaso N, Tomasi S, Vaccarino FM. Neurogenesis and maturation in neonatal brain injury. Clin Perinatol, 2014, 41(1): 229-239.
4. Frey HA, Klebanoff MA. The epidemiology, etiology, and costs of preterm birth. Semin Fetal Neonatal Med, 2016, 21(2): 68-73.
5. Barfield WD. Public health implications of very preterm birth. Clin Perinatol, 2018, 45(3): 565-577.
6. 张丹, 周玉陶, 徐玉庭, 等. 新生小鼠缺氧缺血性脑损伤模型的建立. 中国实验动物学报, 2017, 25(5): 486-493.
7. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation, 2016, 133(4): e38-e360.
8. Millar LJ, Shi L, Hoerder-Suabedissen A, et al. Neonatal hypoxia ischaemia: mechanisms, models, and therapeutic challenges. Front Cell Neurosci, 2017, 11: 78.
9. Takada SH, Motta-Teixeira LC, Machado-Nils AV, et al. Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior. Behav Brain Res, 2016, 296: 331-338.
10. Kim M, Yu JH, Seo JH, et al. Neurobehavioral assessments in a mouse model of neonatal hypoxic-ischemic brain injury. J Vis Exp, 2017: 129.
11. Smith AL, Alexander M, Rosenkrantz TS, et al. Sex differences in behavioral outcome following neonatal hypoxia ischemia: insights from a clinical meta-analysis and a rodent model of induced hypoxic ischemic brain injury. Exp Neurol, 2014, 254: 54-67.
12. Bolisetty S, Dhawan A, Abdel-Latif M, et al. Intraventricular hemorrhage and neurodevelopmental outcomes in extreme preterm infants. Pediatrics, 2014, 133(1): 55-62.
13. Mallard C, Vexler ZS. Modeling ischemia in the immature brain: how translational are animal models?. Stroke, 2015, 46(10): 3006-3011.
14. 张志强, 张莉, 张跃奇. 重复经颅磁刺激对卒中后大鼠的学习记忆功能和海马区胰岛素样生长因子-1表达的影响. 中国康复医学杂志, 2018, 33(9): 1024-1028, 1049.
15. Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc, 2006, 1(2): 848-858.
16. Pimentel-Coelho PM, Michaud JP, Rivest S. C-C chemokine receptor type 2 (CCR2) signaling protects neonatal male mice with hypoxic-ischemic hippocampal damage from developing spatial learning deficits. Behav Brain Res, 2015, 286: 146-151.
17. 黄忠兴, 何宏星, 王亚新, 等. 成年小鼠大脑神经细胞特异性ADAM10基因敲除的认知功能研究. 实验动物科学, 2018, 35(4): 61-66.
18. Sukhanova IA, Sebentsova EA, Khukhareva DD, et al. Gender-dependent changes in physical development, BDNF content and GSH redox system in a model of acute neonatal hypoxia in rats. Behav Brain Res, 2018, 350: 87-98.
19. Hill CA, Threlkeld SW, Fitch RH. Early testosterone modulated sex differences in behavioral outcome following neonatal hypoxia ischemia in rats. Int J Dev Neurosci, 2011, 29(4): 381-388.

West China Medical Journal

Sex differences in learning and memory ability in hypoxic-ischemic brain injury in newborn mice

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