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

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-04-16 DOI:10.1111/cns.70372

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

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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.

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脑出血后鼻内给药il -10沿嗅觉神经和血管周围间隙的分布

利用抗炎疗法治疗脑部疾病是有希望的；然而，药物化合物经鼻给药的研究仍然有限。定量数据，特别是药代动力学，缺乏，并且缺乏鼻内给药重组白细胞介素10 （il -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，仔细监测经鼻给药rIL-10在脑内的分布和传递途径。结果与结论il -10可穿透血脑屏障到达脑出血小鼠纹状体的血肿周围区。经鼻给药的rIL-10主要作用于大脑皮层、纹状体和丘脑，通过嗅觉神经通路和血管周围空间到达这些大脑区域。这种分娩方式有效地减轻了脑出血后的继发性脑损伤。本研究有助于鼻内给药研究，为支持抗炎细胞因子或替代候选药物的鼻内给药治疗脑部疾病提供了令人信服的证据。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.