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紫杉醇和雷帕霉素在短暂性血脑屏障开放大鼠模型中的神经毒性

Neurotoxicity of Paclitaxel and Rapamycin in a Rat Model with Transient Blood-Brain Barrier Opening.

作者信息

Cho Won-Sang, Choi Jung Hoon, Kwon O-Ki

机构信息

Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.

Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chuncheon, Korea.

出版信息

J Korean Neurosurg Soc. 2022 Mar;65(2):180-185. doi: 10.3340/jkns.2021.0077. Epub 2022 Feb 17.

DOI:10.3340/jkns.2021.0077
PMID:35172471
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8918238/
Abstract

OBJECTIVE

Drug-eluting stents and balloons are occasionally used to reduce restenosis in medically intractable intracranial atherosclerotic stenosis. The authors aimed to determine whether such drugs can cause neurotoxicity due to local effects in a rat model.

METHODS

Intra-arterial catheters were placed in the right common carotid artery of rats. Mannitol was injected to transiently open the brain-blood barrier (BBB), followed by high-dose drug (paclitaxel and rapamycin) injection. The optimal time interval of transient BBB opening for maximal drug penetration was determined to be 10 minutes. Paclitaxel and rapamycin were intraarterially administered in various doses. All the rats were neurologically evaluated, and their brain tissues were histologically examined.

RESULTS

Neither neurological deficits nor histological abnormalities were observed in all the rats.

CONCLUSION

Paclitaxel and rapamycin did not cause neurotoxicity in a rat model with transient BBB opening.

摘要

目的

药物洗脱支架和球囊偶尔用于降低药物治疗无效的颅内动脉粥样硬化狭窄的再狭窄率。作者旨在确定此类药物在大鼠模型中是否会因局部作用而导致神经毒性。

方法

将动脉内导管置于大鼠右侧颈总动脉。注射甘露醇以短暂打开血脑屏障（BBB），随后注射高剂量药物（紫杉醇和雷帕霉素）。确定短暂打开血脑屏障以实现最大药物渗透的最佳时间间隔为10分钟。以不同剂量动脉内给予紫杉醇和雷帕霉素。对所有大鼠进行神经学评估，并对其脑组织进行组织学检查。

结果

所有大鼠均未观察到神经功能缺损或组织学异常。

结论

在短暂打开血脑屏障的大鼠模型中，紫杉醇和雷帕霉素未引起神经毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df62/8918238/853678b7db62/jkns-2021-0077f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df62/8918238/eacffd927e01/jkns-2021-0077f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df62/8918238/9b296abacc3f/jkns-2021-0077f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df62/8918238/24f03d11161f/jkns-2021-0077f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df62/8918238/853678b7db62/jkns-2021-0077f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df62/8918238/eacffd927e01/jkns-2021-0077f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df62/8918238/9b296abacc3f/jkns-2021-0077f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df62/8918238/24f03d11161f/jkns-2021-0077f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df62/8918238/853678b7db62/jkns-2021-0077f4.jpg

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Taxane-Induced Peripheral Neurotoxicity.紫杉烷引起的周围神经毒性。
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