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脑出血后经鼻给予的重组白细胞介素-10在嗅神经和血管周围间隙的分布

Distribution of Intranasally Administered rIL-10 Along the Olfactory Nerve and Perivascular Space After Intracerebral Hemorrhage.

作者信息

Wang Shaoshuai, Wang Junmin, Zhang Xinru, Xu Shijun, Peng Qinfeng, Li Yifei, Ding Ruoqi, Jiang Bing, Wang Shuyu, Zhang Shuaibing, Hu Siyuan, Rastegar-Kashkooli Yousef, Xing Na, Li Nan, Wang Menglu, Wang Junyang, Chen Xuemei, Jiang Chao, Fan Xiaochong, Wang Jian

机构信息

Department of Pain Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.

出版信息

CNS Neurosci Ther. 2025 Apr;31(4):e70372. doi: 10.1111/cns.70372.

DOI:10.1111/cns.70372
PMID:40237247
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12000929/
Abstract

RATIONALE

The utilization of anti-inflammatory therapy for treating brain diseases holds promise; however, research on intranasal administration of drug compounds remains limited. Quantitative data, particularly pharmacokinetics, are scant, and direct evidence of the distribution of intranasally administered recombinant interleukin 10 (rIL-10) within the brain is lacking.

METHODS

Employing fluorescent labeling, in vivo imaging, and confocal microscopy, we meticulously monitored the distribution and delivery pathways of intranasally administered rIL-10 in the brain.

RESULTS AND CONCLUSIONS

Our findings demonstrate that rIL-10 can permeate the blood-brain barrier and reach the perihematomal area in the striatum of mice with intracerebral hemorrhage. Intranasally administered rIL-10 primarily targets the cerebral cortex, striatum, and thalamus, traversing the olfactory nerve pathway and perivascular space to access these brain regions. This mode of delivery effectively mitigated secondary brain injury after intracerebral hemorrhage. This study contributes to intranasal drug delivery research, offering compelling evidence to support the intranasal delivery of anti-inflammatory cytokines or alternative drug candidates for treating brain diseases.

摘要

理论依据

利用抗炎疗法治疗脑部疾病具有前景;然而,关于药物化合物鼻内给药的研究仍然有限。定量数据,尤其是药代动力学数据匮乏,且缺乏鼻内给药的重组白细胞介素10(rIL-10)在脑内分布的直接证据。

方法

采用荧光标记、体内成像和共聚焦显微镜技术,我们精心监测了鼻内给药的rIL-10在脑内的分布和递送途径。

结果与结论

我们的研究结果表明,rIL-10能够穿透血脑屏障并到达脑出血小鼠纹状体的血肿周围区域。鼻内给药的rIL-10主要靶向大脑皮层、纹状体和丘脑,通过嗅觉神经途径和血管周围间隙进入这些脑区。这种递送方式有效减轻了脑出血后的继发性脑损伤。本研究为鼻内给药研究做出了贡献,提供了有力证据支持鼻内递送抗炎细胞因子或其他治疗脑部疾病的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea10/12000929/555e83fbfd6d/CNS-31-e70372-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea10/12000929/0903822f2a66/CNS-31-e70372-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea10/12000929/a9604825eaa2/CNS-31-e70372-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea10/12000929/d40f0e3ee61d/CNS-31-e70372-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea10/12000929/bd48af6dc15f/CNS-31-e70372-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea10/12000929/555e83fbfd6d/CNS-31-e70372-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea10/12000929/0903822f2a66/CNS-31-e70372-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea10/12000929/a9604825eaa2/CNS-31-e70372-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea10/12000929/d40f0e3ee61d/CNS-31-e70372-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea10/12000929/bd48af6dc15f/CNS-31-e70372-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea10/12000929/555e83fbfd6d/CNS-31-e70372-g002.jpg

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本文引用的文献

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Proc Natl Acad Sci U S A. 2023 Sep 12;120(37):e2309221120. doi: 10.1073/pnas.2309221120. Epub 2023 Sep 5.
2
Improving outcomes in intracerebral hemorrhage through microglia/macrophage-targeted IL-10 delivery with phosphatidylserine liposomes.通过磷脂酰丝氨酸脂质体靶向小胶质细胞/巨噬细胞递送白细胞介素-10改善脑出血的预后
Biomaterials. 2023 Oct;301:122277. doi: 10.1016/j.biomaterials.2023.122277. Epub 2023 Aug 15.
3
Role of neuroinflammation in neurodegeneration development.
神经炎症在神经退行性变发展中的作用。
Signal Transduct Target Ther. 2023 Jul 12;8(1):267. doi: 10.1038/s41392-023-01486-5.
4
Intranasal delivery of mitochondrial protein humanin rescues cell death and promotes mitochondrial function in Parkinson's disease.鼻内递送线粒体蛋白神经保护因子可挽救帕金森病中的细胞死亡并促进线粒体功能。
Theranostics. 2023 May 29;13(10):3330-3345. doi: 10.7150/thno.84165. eCollection 2023.
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Blocking autofluorescence in brain tissues affected by ischemic stroke, hemorrhagic stroke, or traumatic brain injury.阻断脑缺血性脑卒中、出血性脑卒中或脑创伤影响的脑组织的自发荧光。
Front Immunol. 2023 May 29;14:1168292. doi: 10.3389/fimmu.2023.1168292. eCollection 2023.
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