Analysis of nerve excitability in the dentate gyrus of the hippocampus in cerebral ischaemia-reperfusion mice_Journal of Biomedical Engineering

Authors：

ZHU Yucan ^1,2,3 ,  YU Hongli ^1,2,3 , ZHAO Xiuzhi ^1,2,3 ,  WANG Chunfang ⁴

1. School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin 300130, P. R. China;
2. Tianjin Key Laboratory of Bioelectromagnetic Technology and Intelligent Health, Hebei University of Technology, Tianjin 300130, P. R. China;
3. State Key Laboratory of Reliability and Intelligence of Electrical Equipment, Hebei University of Technology, Tianjin 300130, P. R. China;
4. Rehabilitation Medical Department, Tianjin Union Medical Center, Tianjin 300121, P. R. China;

Corresponding author：

YU Hongli, Email: yhlzyn@hebut.edu.cn; WANG Chunfang, Email: chfwang@tju.edu.cn

Keywords：

Cerebral ischaemia reperfusion; Neural excitability; Local field potentials; Time-frequency analysis; Multiscale sample entropy

DOI：

10.7507/1001-5515.202311055

Video：

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Abstract Full text Figures/Tables Video References Cited by

Ischemic stroke often leads to cognitive dysfunction, which delays the recovery process of patients. However, its pathogenesis is not yet clear. In this study, the cerebral ischemia-reperfusion model was built as the experimental object, and the hippocampal dentate gyrus (DG) was the target brain area. TTC staining was used to evaluate the degree of cerebral infarction, and nerve cell membrane potentials and local field potentials (LFPs) signals were collected to explore the mechanism of cognitive impairment in ischemia-reperfusion mice. The results showed that the infarcted area on the right side of the brain of the mice in the model group was white. The resting membrane potential, the number of action potential discharges, the post-hyperpolarization potential and the maximum ascending slope of the hippocampal DG nerve cells in the model mice were significantly lower than those in the control group (P < 0.01); the peak time, half-wave width, threshold and maximum descending slope of the action potential were significantly higher than those in the control group (P < 0.01). The time-frequency energy values of LFPs signals in the θ and γ bands of mice in the ischemia and reperfusion groups were significantly reduced (P < 0.01), and the time-frequency energy values in the reperfusion group were increased compared with the ischemia group (P < 0.01). The signal complexity of LFPs in the ischemia and reperfusion group was significantly reduced (P < 0.05), and the signal complexity in the reperfusion group was increased compared with the ischemia group (P < 0.05). In summary, cerebral ischemia-reperfusion reduced the excitability of nerve cells in the DG area of the mouse hippocampus; cerebral ischemia reduced the discharge activity and signal complexity of nerve cells, and the electrophysiological indicators recovered after reperfusion, but it failed to reach the healthy state during the experiment period.

Citation： ZHU Yucan, YU Hongli, ZHAO Xiuzhi, WANG Chunfang. Analysis of nerve excitability in the dentate gyrus of the hippocampus in cerebral ischaemia-reperfusion mice. Journal of Biomedical Engineering, 2024, 41(5): 926-934. doi: 10.7507/1001-5515.202311055 Copy

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1. Feigin V L, Brainin M, Norrving B, et al. World Stroke Organization (WSO): global stroke fact sheet 2022. Int J Stroke, 2022, 17(1): 18-29.
2. Rost N S, Brodtmann A, Pase M P, et al. Post-stroke cognitive impairment and dementia. Circ Res, 2022, 130(8): 1252-1271.
3. Weaver N A, Kuijf H J, Aben H P, et al. Strategic infarct locations for post-stroke cognitive impairment: a pooled analysis of individual patient data from 12 acute ischaemic stroke cohorts. Lancet Neurol, 2021, 20(6): 448-459.
4. Rost N S, Meschia J F, Gottesman R, et al. Cognitive impairment and dementia after stroke: design and rationale for the DISCOVERY study. Stroke, 2021, 52(8): e499-e516.
5. Zhang X, Yuan M, Yang S, et al. Enriched environment improves post-stroke cognitive impairment and inhibits neuroinflammation and oxidative stress by activating Nrf2-ARE pathway. Int J Neurosci, 2021, 131(7): 641-649.
6. Yang L, Song J, Nan D, et al. Cognitive impairments and blood-brain barrier damage in a mouse model of chronic cerebral hypoperfusion. Neurochem, 2022, 47(12): 3817-3828.
7. Treder M S, Charest I, Michelmann S, et al. The hippocampus as the switchboard between perception and memory. PNAS, 2021, 118(50): e2114171118.
8. Zhang X, Gl A S, Jonas P. Selective routing of spatial information flow from input to output in hippocampal granule cells. Neuron, 2020, 107(6): 1-14.
9. Zhu H, Xu G, Fu L, et al. The effects of repetitive transcranial magnetic stimulation on the cognition and neuronal excitability of mice. Electromagn Biol Med, 2020, 39(1): 9-19.
10. Zhao Z, Gu H. Transitions between classes of neuronal excitability and bifurcations induced by autapse. Sci Rep, 2017, 7(1): 6760.
11. Unakafova V A, Gail A. Comparing open-source toolboxes for processing and analysis of spike and local field potentials data. Front Neuroinform, 2019, 13: 57.
12. Herweg N A, Solomon E A, Kahana M J. Theta oscillations in human memory. Trends Cogn Sci, 2020, 24(3): 208-227.
13. Mably A J, Colgin L L. Gamma oscillations in cognitive disorders. Curr Opin Neurobiol, 2018, 52: 182-187.
14. Elsayed S, El-Habeby M, El-Sherif N, et al. Influence of global cerebral ischemia/reperfusion injury on rat dentate gyrus and the possible protective effect of beetroot extract. Eur J Anat, 2021, 25(4): 493-503.
15. Kathner-Schaffert C, Karapetow L, Günther M, et al. Early stroke induces long-term impairment of adult neurogenesis accompanied by hippocampal-mediated cognitive decline. Cells, 2019, 8(12): 1654.
16. Go A S, Mozaffarian D, Roger V L, et al. Heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation, 2014, 129(3): e28-e292.
17. 甄毅岚, 王亚男, 李晟, 等. 线栓法制备不同体重KM小鼠局灶性脑缺血/再灌注模型的建立及评价. 中国实验动物学报, 2013, 21(2): 39-44, 93.
18. Paxinos G, Franklin K B J. Paxinos and Franklin’s the mouse brain in stereotaxic coordinates. 5th ed. New York: Academic Press, 2019: 1-162.
19. 徐桂芝, 王宁, 郭苗苗, 等. 高频重复经颅磁刺激后大鼠工作记忆局部场电位时频特征与相干性差异分析. 生物医学工程学杂志, 2020, 37(5): 756-764.
20. Azami H, Abásolo D, Simons S, et al. Univariate and multivariate generalized multiscale entropy to characterise EEG signals in Alzheimer’s disease. Entropy, 2017, 19(1): 31.
21. He A, Wang Z, Wu X, et al. Incidence of post-stroke cognitive impairment in patients with first-ever ischemic stroke: a multicenter cross-sectional study in China. The Lancet Regional Health–Western Pacific, 2023, 33: 100687.
22. Zhang W, Mi Y, Jiao K, et al. Kellerin alleviates cognitive impairment in mice after ischemic stroke by multiple mechanisms. Phytother Res, 2020, 34(9): 2258-2274.
23. Sun D, Daniels T E, Rolfe A, et al. Inhibition of injury-induced cell proliferation in the dentate gyrus of the hippocampus impairs spontaneous cognitive recovery after traumatic brain injury. J Neurotraum, 2015, 32(7): 495-505.
24. Dunn A R, Kaczorowski C C. Regulation of intrinsic excitability: Roles for learning and memory, aging and Alzheimer’s disease, and genetic diversity. Neurobiol Learn Mem, 2019, 164: 107069.
25. Burghardt N S, Park E H, Hen R, et al. Adult‐born hippocampal neurons promote cognitive flexibility in mice. Hippocampus, 2012, 22(9): 1795-1808.
26. Caglayan A B, Beker M C, Caglayan B, et al. Acute and post-acute neuromodulation induces stroke recovery by promoting survival signaling, neurogenesis, and pyramidal tract plasticity. Front Cell Neurosci, 2019, 13: 144.
27. Ip Z, Rabiller G, He J W, et al. Local field potentials identify features of cortico-hippocampal communication impacted by stroke and environmental enrichment therapy. J Neural Eng, 2021, 18(4): 0460a1.
28. He J W, Rabiller G, Nishijima Y, et al. Experimental cortical stroke induces aberrant increase of sharp-wave-associated ripples in the hippocampus and disrupts cortico-hippocampal communication. J Cerebr Blood F Met, 2020, 40(9): 1778-1796.
29. Sutherland B A, Fordsmann J C, Martin C, et al. Multi-modal assessment of neurovascular coupling during cerebral ischaemia and reperfusion using remote middle cerebral artery occlusion. J Cerebr Blood F Met, 2017, 37(7): 2494-2508.
30. Sato Y, Schmitt O, Ip Z, et al. Pathological changes of brain oscillations following ischemic stroke. J Cerebr Blood F Met, 2022, 42(10): 1753-1776.

Journal of Biomedical Engineering

Analysis of nerve excitability in the dentate gyrus of the hippocampus in cerebral ischaemia-reperfusion mice

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