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Subarachnoid Hemorrhage pp 69–75Cite as

17-Allylamino-Demethoxygeldanamycin Ameliorate Microthrombosis Via HSP90/RIP3/NLRP3 Pathway After Subarachnoid Hemorrhage in Rats

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Part of the book series: Acta Neurochirurgica Supplement ((NEUROCHIRURGICA,volume 127))

Abstract

Background: Subarachnoid hemorrhage (SAH) is a severe and emergent cerebrovascular disease, the prognosis of which usually very poor. Microthrombi formation highlighted with inflammation occurs early after SAH. As the main cause of DCI, microthrombosis associated with the prognosis of SAH. The aim of this study was to show HSP90 inhibitor 17-AAG effect on microthrombosis after SAH in rats.

Methods: Ninety-five SD rats were used for the experiment. For time course study, the rats were randomly divided into five groups: sham group and SAH group with different time point (1d, 2d, 3d, 5d). Endovascular perforation method was conducted for SAH model. Neurological score, SAH grade, and mortality were measured after SAH. The samples of the left hemisphere brain were collected. The expression of HSP90 was detected by Western blot. The microthrombosis after SAH in rats’ brain was detected by immunohistochemistry. For mechanism study, rats were randomly divided into three groups: sham, SAH + vehicle, and SAH +17-AAG (n = 6/group). 17-AAG was given by intraperitoneal injection (80 mg/kg) 1 h after SAH. Neurological function were measured at 24 h after SAH. The expression of RIP3, NLRP3, ASC, and IL-1β was measured by Western blot. Microthrombosis was detected by immunohistochemistry.

Results: Our results showed that the HSP90 protein level increased and peaked at 2 days after SAH. Microthrombosis caused by SAH was increased in 1 day and peaked at 2 days after SAH. Administration HSP90 specific inhibitor 17-AAG reduced expression of RIP3, NLRP3, ASC, and IL-1β, reduced microthrombosis after SAH, and improved neurobehavior when compared to vehicle group.

Conclusions: 17-AAG can ameliorate microthrombosis via HSP90/RIP3/NLRP3 pathway and improve neurobehavior after SAH.

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Acknowledgments

This project was funded by Grant 81571150 from National Natural Science Foundation of China.

Conflict of Interest: The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, China

    Yuchun Zuo, Tibiao He, Peiqiang Liao, Kai Zhuang & Fei Liu

  2. Department of Anatomy, The XiangYa Medical School, Central South University, Changsha, China

    Xiaoxin Yan

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  1. Yuchun Zuo
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  2. Tibiao He
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  4. Kai Zhuang
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  5. Xiaoxin Yan
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Editors and Affiliations

  1. Department of Anethesiology, Loma Linda University Medical Center, Loma Linda, CA, USA

    Robert D. Martin

  2. Department of Neurosurgery, Loma Linda University Medical Center, Loma Linda, CA, USA

    Warren Boling

  3. Department of Neurosurgery, First Affiliated Hospital of Soochow University, Suzhou, China

    Gang Chen

  4. Department of Anesthesiology and Physiology, Loma Linda University Medical Center, Loma Linda, CA, USA

    John H. Zhang

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Zuo, Y., He, T., Liao, P., Zhuang, K., Yan, X., Liu, F. (2020). 17-Allylamino-Demethoxygeldanamycin Ameliorate Microthrombosis Via HSP90/RIP3/NLRP3 Pathway After Subarachnoid Hemorrhage in Rats. In: Martin, R., Boling, W., Chen, G., Zhang, J. (eds) Subarachnoid Hemorrhage. Acta Neurochirurgica Supplement, vol 127. Springer, Cham. https://doi.org/10.1007/978-3-030-04615-6_12

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  • DOI: https://doi.org/10.1007/978-3-030-04615-6_12

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-04614-9

  • Online ISBN: 978-3-030-04615-6

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