Short-term voluntary exercise enhances the activation of endogenous neural stem cells inintracerebral hemorrhage mice with hyperlipidemia

Xiaoxuan HU; Qian Liu; Tongzhuo Wang; Meiqi Sun; Zixuan Zhang; Pengyu Huang; Yujia Luo; Si Wang; Haixia LÜ

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Short-term voluntary exercise enhances the activation of endogenous neural stem cells inintracerebral hemorrhage mice with hyperlipidemia

VernacularTitle:短期自愿运动对高脂血症小鼠脑出血后内源性神经干细胞的影响
Author: Xiaoxuan HU ^{1
,

2
,

3} ; Qian LIU ^{1
,

2} ; Tongzhuo WANG ^{1
,

2} ; Meiqi SUN ^{1
,

2} ; Zixuan ZHANG ^{1
,

2
,

3} ; Pengyu HUANG ^{1
,

2} ; Yujia LUO ^{1
,

2} ; Si WANG ⁴ ; Haixia LÜ ^{1
,

2}
Author Information

1. Department & Institute of Neurobiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center
2. of Xi’an Jiaotong University, Xi’an 710061, China
3. Department of Human Anatomy & Histoembryology, School of Basic Medical Sciences of Xi’an Jiaotong University, Xi’an 710061, China
4. The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
Publication Type:Journal Article
Keywords: intracerebral hemorrhage; hyperlipidemia; short-term voluntary exercise; endogenous neural stem cell
From: Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(3):396-402
CountryChina
Language:Chinese
Abstract: 【Objective】 To investigate the improvement of motor function recovery and the activation of endogenous neural stem cells (eNSCs) via voluntary exercise in mice with hyperlipidemia after intracerebral hemorrhage (ICH). 【Methods】 Four-month-old male Nestin-CreERT2: tdTomato transgenic mice were fed with high-fat diet (HFD) for eight weeks. Type Ⅳ collagenase was micro-injected into the corpus striatum to construct mouse ICH model with the help of stereotaxic apparatus. Voluntary exercise (wheel running) was initiated on the second day after ICH and monitored daily for seven days. Neurological severity score (NSS) and beam walking test were applied to evaluate motor function and coordination. Liver and brain tissues were collected at day 9 after ICH and sliced for staining. Then the Nestin-labeled cells, Ki67⁺, and doublecortin (DCX)⁺ in subventricular zone (SVZ) were counted to evaluate eNSCs activation. 【Results】 ① Compared with those of mice fed by chow diet (CD), the body weight, blood glucose level, concentration of lipid metabolism factors and the number of Nile Red positive cells in liver tissue were significantly higher in HFD-fed mice, confirming hyperlipidemia. ② Compared with the sham group, NSS score increased and the distance of cross-beam walking of ICH mice significantly decreased, showing the deficiency of motor function. It could be rescued by 7-day wheel running, as shown by a lower NSS score and a longer cross-beam walking distance. ③ Compared with the sham group, the number of Nestin⁺/Ki67⁺ cells decreased and Nestin⁺/DCX⁺ cells increased after ICH. After 7-day voluntary exercise, the number of Nestin⁺/Ki67⁺ cells decreased but that of Nestin⁺/DCX⁺ cells further increased significantly. However, compared with ICH, the increase of Nestin⁺/DCX⁺ cells in ICH+Ex was not significant. 【Conclusion】 Short-term voluntary exercise during the acute stage of ICH improved the recovery of motor function and enhance the proliferation of eNSCs in mice with hyperlipidemia. This provides a new idea for further developing ICH accelerated rehabilitation strategy based on eNSCs.