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Subarachnoid Hemorrhage pp 77–81Cite as

TAK-242, Toll-Like Receptor 4 Antagonist, Attenuates Brain Edema in Subarachnoid Hemorrhage Mice

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

Abstract

Background: Brain edema is a common and critical pathology following subarachnoid hemorrhage (SAH). Toll-like receptor 4 (TLR4) activation may exacerbate brain edema. The purpose of this study was to clarify if TAK-242, a TLR4 antagonist, suppresses brain edema formation and neurological impairments after SAH in mice.

Methods: A total of 46 mice underwent endovascular perforation to induce SAH or sham operation and were classified as Sham+TAK-242, SAH+ phosphate-buffered saline (PBS), and SAH + TAK-242 groups. The PBS or TAK-242 was administered intracerebroventricularly to mice at 30 min from the operation. Neurobehavioral tests, SAH severity, and brain water content were evaluated at 24 h from the operation.

Results: The SAH + PBS group was significantly worse in neurological tests (P < 0.001) and brain water content of the cerebral hemisphere in the bleeding side (p = 0.005) compared with the Sham+PBS group, while there were no differences between the SAH + TAK-242 and Sham+PBS groups. SAH severity in the SAH + PBS group was similar to that in the SAH + TAK-242 group.

Conclusions: Intracerebroventricular administration of TAK-242 possibly prevents neurological impairments at least via suppression of brain edema.

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Acknowledgments

This work was funded by a Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science to Drs. Fujimoto and Suzuki.

Conflict of Interest: The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

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Authors and Affiliations

  1. Department of Neurosurgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan

    Takeshi Okada, Liu Lei, Hirofumi Nishikawa, Fumi Nakano, Yoshinari Nakatsuka & Hidenori Suzuki

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  1. Takeshi Okada
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  2. Liu Lei
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  3. Hirofumi Nishikawa
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  4. Fumi Nakano
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  5. Yoshinari Nakatsuka
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  6. Hidenori Suzuki
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Corresponding author

Correspondence to Takeshi Okada .

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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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Okada, T., Lei, L., Nishikawa, H., Nakano, F., Nakatsuka, Y., Suzuki, H. (2020). TAK-242, Toll-Like Receptor 4 Antagonist, Attenuates Brain Edema in Subarachnoid Hemorrhage Mice. 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_13

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  • DOI: https://doi.org/10.1007/978-3-030-04615-6_13

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-04614-9

  • Online ISBN: 978-3-030-04615-6

  • eBook Packages: MedicineMedicine (R0)

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