Low-intensity focused ultrasound stimulation promotes stroke recovery via astrocytic HMGB1 and CAMK2N1 in mice.

Autor:	Qi L; Shanghai Jiao Tong Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, Shanghai, China., Wang C; Shanghai Jiao Tong Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, Shanghai, China., Deng L; Shanghai Jiao Tong Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, Shanghai, China., Pan JJ; Department of Neurosurgery, Huashan Hospital, Shanghai Medical Collage, Fudan University, Shanghai, China., Suo Q; Shanghai Jiao Tong Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, Shanghai, China., Wu S; Shanghai Jiao Tong Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, Shanghai, China., Cai L; Department of Neurosurgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China., Shi X; Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Beijing, China., Sun J; Shanghai Jiao Tong Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, Shanghai, China., Wang Y; Shanghai Jiao Tong Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, Shanghai, China., Tang Y; Shanghai Jiao Tong Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, Shanghai, China., Qiu W; Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Beijing, China., Yang GY; Neuroscience and Neuroengineering Center, Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai, China.; Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China., Wang J; Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China zhangzj@sjtu.edu.cn wangjixian6@163.com., Zhang Z; Shanghai Jiao Tong Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, Shanghai, China zhangzj@sjtu.edu.cn wangjixian6@163.com.
Jazyk:	angličtina
Zdroj:	Stroke and vascular neurology [Stroke Vasc Neurol] 2024 Nov 05; Vol. 9 (5), pp. 505-518. Date of Electronic Publication: 2024 Nov 05.
DOI:	10.1136/svn-2023-002614
Abstrakt:	Background: Low-intensity focused ultrasound stimulation (LIFUS) has been developed to enhance neurological repair and remodelling during the late acute stage of ischaemic stroke in rodents. However, the cellular and molecular mechanisms of neurological repair and remodelling after LIFUS in ischaemic stroke are unclear. Methods: Ultrasound stimulation was treated in adult male mice 7 days after transient middle cerebral artery occlusion. Angiogenesis was measured by laser speckle imaging and histological analyses. Electromyography and fibre photometry records were used for synaptogenesis. Brain atrophy volume and neurobehaviour were assessed 0-14 days after ischaemia. iTRAQ proteomic analysis was performed to explore the differentially expressed protein. scRNA-seq was used for subcluster analysis of astrocytes. Fluorescence in situ hybridisation and Western blot detected the expression of HMGB1 and CAMK2N1. Results: Optimal ultrasound stimulation increased cerebral blood flow, and improved neurobehavioural outcomes in ischaemic mice (p<0.05). iTRAQ proteomic analysis revealed that the expression of HMGB1 increased and CAMK2N1 decreased in the ipsilateral hemisphere of the brain at 14 days after focal cerebral ischaemia with ultrasound treatment (p<0.05). scRNA-seq revealed that this expression pattern belonged to a subcluster of astrocytes after LIFUS in the ischaemic brain. LIFUS upregulated HMGB1 expression, accompanied by VEGFA elevation compared with the control group (p<0.05). Inhibition of HMGB1 expression in astrocytes decreased microvessels counts and cerebral blood flow (p<0.05). LIFUS reduced CAMK2N1 expression level, accompanied by increased extracellular calcium ions and glutamatergic synapses (p<0.05). CAMK2N1 overexpression in astrocytes decreased dendritic spines, and aggravated neurobehavioural outcomes (p<0.05). Conclusion: Our results demonstrated that LIFUS promoted angiogenesis and synaptogenesis after focal cerebral ischaemia by upregulating HMGB1 and downregulating CAMK2N1 in a subcluster of astrocytes, suggesting that LIFUS activated specific astrocyte subcluster could be a key target for ischaemic brain therapy. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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