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Higher Plasma Osteopontin Concentrations Associated with Subsequent Development of Chronic Shunt-Dependent Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage

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Abstract

A matricellular protein osteopontin (OPN) is considered to exert neuroprotective and healing effects on neurovascular injuries in an acute phase of aneurysmal subarachnoid hemorrhage (SAH). However, the relationships between OPN expression and chronic shunt-dependent hydrocephalus (SDHC) have never been investigated. In 166 SAH patients (derivation and validation cohorts, 110 and 56, respectively), plasma OPN levels were serially measured at days1−3, 4−6, 7−9, and 10−12 after aneurysmal obliteration. The OPN levels and clinical factors were compared between patients with and without subsequent development of chronic SDHC. Plasma OPN levels in the SDHC patients increased from days 1−3 to days 4−6 and remained high thereafter, while those in the non-SDHC patients peaked at days 4−6 and then decreased over time. Plasma OPN levels had no correlation with serum levels of C-reactive protein (CRP), a systemic inflammatory marker. Univariate analyses showed that age, modified Fisher grade, acute hydrocephalus, cerebrospinal fluid drainage, and OPN and CRP levels at days 10−12 were significantly different between patients with and without SDHC. Multivariate analyses revealed that higher plasma OPN levels at days 10−12 were an independent factor associated with the development of SDHC, in addition to a more frequent use of cerebrospinal fluid drainage and higher modified Fisher grade at admission. Plasma OPN levels at days 10−12 maintained similar discrimination power in the validation cohort and had good calibration on the Hosmer-Lemeshow goodness-of-fit test. Prolonged higher expression of OPN may contribute to the development of post-SAH SDHC, possibly by excessive repairing effects promoting fibrosis in the subarachnoid space.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

We thank Ms. Chiduru Nakamura (Department of Neurosurgery, Mie University Graduate School of Medicine) for her technical assistance.

Funding

This work was supported by JSPS KAKENHI Grant Number JP17K10825 and JP20K09346 to Dr. Hidenori Suzuki.

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Authors and Affiliations

  1. Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan

    Reona Asada, Yoshinari Nakatsuka, Hideki Kanamaru, Fumihiro Kawakita, Masashi Fujimoto, Yoichi Miura, Masato Shiba, Ryuta Yasuda, Naoki Toma & Hidenori Suzuki

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Correspondence to Hidenori Suzuki.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the ethical committee of Mie University Hospital (Ethics approval number: 2544 and H2018-031).

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Asada, R., Nakatsuka, Y., Kanamaru, H. et al. Higher Plasma Osteopontin Concentrations Associated with Subsequent Development of Chronic Shunt-Dependent Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage. Transl. Stroke Res. 12, 808–816 (2021). https://doi.org/10.1007/s12975-020-00886-x

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