Protective effect of Huatuo Zaizao pills on white matter injury and cognitive impairment in mice with chronic cerebral hypoperfusion
10.3760/cma.j.issn.1673-4165.2024.07.006
- VernacularTitle:华佗再造丸在慢性脑低灌注小鼠脑白质损伤和认知损害中的保护作用
- Author:
Hua LI
1
;
Zhentong LI
;
Jiancong CHEN
;
Kaibin HUANG
;
Suyue PAN
Author Information
1. 南方医科大学南方医院神经内科，广州 510515
- Keywords:
Brain ischemia;
Carotid stenosis;
Cognitive dysfunction;
Cognition;
Hua Tuo Zaizao pills;
White matter;
Janus kinase 2;
STAT3 transcription factor;
Disea
- From:
International Journal of Cerebrovascular Diseases
2024;32(7):512-520
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protective effect and related mechanisms of Huatuo Zaizao pills (HT) on white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion in mice. Methods:Forty adult male C57BL/6J mice were randomly divided into sham-operation group, bilateral carotid artery stenosis (BCAS) model group, and HT group. An animal model of BCAS was constructed using the spring loop into the bilateral common carotid arteries. After continuous treatment with 5 g/kg HT (or an equal amount of purified water) for 4 weeks, cognitive function was evaluated using the novel object recognition test. Morphological and structural changes in myelin sheath were evaluated by LFB myelin staining. White matter damage and glial cell expression were detected by myelin associated glycoprotein (MAG) in the corpus callosum, ionized calcium-binding adapter molecule 1 (IBA-1), and glial fibrillar acidic protein (GFAP) in corpus callosum and hippocampus through immunofluorescence staining. Real time quantitative polymerase chain reaction (qPCR) was used to detect mRNA expressions of myelin-associated proteins, Janus kinase 2 (JAK2), signal transducer and activator of the transcription 3 (STAT3) in corpus callosum, as well as brain-derived neurotrophic factor (BDNF), glutathione peroxidase 1 (GPx-1), and various inflammatory factors in hippocampus.Results:The novel object recognition test showed that mice had significant working memory impairment at 4 weeks after BCAS ( P<0.01), while the HT group showed significant improvement in working memory impairment compared to the BCAS group ( P<0.01). LFB myelin staining showed significant myelin damage in the BCAS group ( P<0.001), while the degree of myelin damage in the HT group was significantly improved compared to the BCAS group. Immunofluorescence staining showed that both the BCAS and HT groups had proliferation of microglia in the corpus callosum and hippocampus, and there was no significant difference between the two groups. In contrast, the activation of astrocytes in the corpus callosum was significantly improved in the HT group compared to the BCAS group ( P<0.05). qPCR showed upregulation of myelin-associated proteins as well as JAK2 and STAT3 mRNA expression in the BCAS group. Compared with the BCAS group, the expressions of JAK2 and STAT3 mRNA were decreased in the HT group (all P<0.05), while the expression of myelin-associated proteins were upregulated (all P<0.05). There were no significant difference in the expressions of inflammatory factors, BDNF, and GPX1 mRNA in the hippocampal tissue between the BCAS group and the HT group. Conclusion:HT may improve cognitive impairment and white matter damage in mice with chronic cerebral hypoperfusion, and the JAK2-STAT3 pathway may be one of its effect pathways.
