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Toll-Like Receptor 4 and Tenascin-C Signaling in Cerebral Vasospasm and Brain Injuries After Subarachnoid Hemorrhage

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Subarachnoid Hemorrhage

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

Abstract

Toll-like receptor 4 (TLR4) is expressed in various cell types in the central nervous system and exerts maximal inflammatory responses among the TLR family members. TLR4 can be activated by many endogenous ligands having damage-associated molecular patterns including heme and fibrinogen at the rupture of a cerebral aneurysm, and therefore its activation is reasonable as an initial step of cascades to brain injuries after aneurysmal subarachnoid hemorrhage (SAH). TLR4 activation induces tenascin-C (TNC), a representative of matricellular proteins that are a class of inducible, nonstructural, secreted, and multifunctional extracellular matrix glycoproteins. TNC is also an endogenous activator and inducer of TLR4, forming positive feedback mechanisms leading to more activation of the signaling transduction. Our studies have demonstrated that TLR4 as well as TNC are involved in inflammatory reactions, blood-brain barrier disruption, neuronal apoptosis, and cerebral vasospasm after experimental SAH. This article reviews recent understanding of TLR4 and TNC in SAH to suggest that the TLR4-TNC signaling may be an important therapeutic target for post-SAH brain injuries.

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References

  1. Chiquet M, Sarasa-Renedo A, Tunc-Civelek V. Induction of tenascin-C by cyclic tensile strain versus growth factors: distinct contributions by Rho/ROCK and MAPK signaling pathways. Biochim Biophys Acta. 2004;1693:193–204.

    Article  CAS  Google Scholar 

  2. De S, Zhou H, DeSantis D, Croniger CM, Li X, Stark GR. Erlotinib protects against LPS-induced endotoxicity because TLR4 needs EGFR to signal. PNAS. 2015;112:9680–5.

    Article  CAS  Google Scholar 

  3. Eberwein P, Laird D, Schulz S, Reinhard T, Steinberg T, Tomakidi P. Modulation of focal adhesion constituents and their down-stream events by EGF: on the cross-talk of integrins and growth factor receptors. Biochim Biophys Acta. 2015;1853:2183–98.

    Article  CAS  Google Scholar 

  4. Fujimoto M, Shiba M, Kawakita F, Liu L, Nakasaki A, Shimojo N, Imanaka-Yoshida K, Yoshida T, Suzuki H. Epidermal growth factor-like repeats of tenascin-C-induced constriction of cerebral arteries via activation of epidermal growth factor receptors in rats. Brain Res. 2016;1642:436–44.

    Article  CAS  Google Scholar 

  5. Fujimoto M, Shiba M, Kawakita F, Liu L, Shimojo N, Imanaka-Yoshida K, Yoshida T, Kanamaru K, Suzuki H. Early brain injury and mitogen-activated protein kinase after subarachnoid hemorrhage: evaluation using tenascin-C knockout mice. In: Sasaki T, Ohkuma H, Kanamaru K, Suzuki M, editors. Neurovascular events after subarachnoid hemorrhage. Tokyo: Narunia; 2017. p. 131–6.

    Google Scholar 

  6. Fujimoto M, Shiba M, Kawakita F, Liu L, Shimojo N, Imanaka-Yoshida K, Yoshida T, Suzuki H. Deficiency of tenascin-C and attenuation of blood-brain barrier disruption following experimental subarachnoid hemorrhage in mice. J Neurosurg. 2016;124:1693–702.

    Article  CAS  Google Scholar 

  7. Fujimoto M, Shiba M, Kawakita F, Liu L, Shimojo N, Imanaka-Yoshida K, Yoshida T, Suzuki H. Effects of tenascin-C knockout on cerebral vasospasm after experimental subarachnoid hemorrhage in mice. Mol Neurobiol. 2017; https://doi.org/10.1007/s12035-017-0466-x.

    Article  Google Scholar 

  8. Hanafy KA. The role of microglia and the TLR4 pathway in neuronal apoptosis and vasospasm after subarachnoid hemorrhage. J Neuroinflammation. 2013; https://doi.org/10.1186/1742-2094-10-83.

  9. Ishigaki T, Imanaka-Yoshida K, Shimojo N, Matsushima S, Taki W, Yoshida T. Tenascin-C enhances crosstalk signaling of integrin αvβ3/PDGFR-β complex by SRC recruitment promoting PDGF-induced proliferation and migration in smooth muscle cells. J Cell Physiol. 2011;226:2617–24.

    Article  CAS  Google Scholar 

  10. Kawakita F, Fujimoto M, Liu L, Nakano F, Nakatsuka Y, Suzuki H. Effects of Toll-like receptor 4 antagonists against cerebral vasospasm after experimental subarachnoid hemorrhage in mice. Mol Neurobiol. 2017;54:6624–33.

    Article  CAS  Google Scholar 

  11. Liu L, Fujimoto M, Kawakita F, Nakano F, Imanaka-Yoshida K, Yoshida T, Suzuki H. Anti-vascular endothelial growth factor treatment suppresses early brain injury after subarachnoid hemorrhage in mice. Mol Neurobiol. 2016;53:4529–38.

    Article  CAS  Google Scholar 

  12. Liu L, Kawakita F, Fujimoto M, Nakano F, Imanaka-Yoshida K, Yoshida T, Suzuki H. Role of periostin in early brain injury after subarachnoid hemorrhage in mice. Stroke. 2017;48:1108–11.

    Article  Google Scholar 

  13. Midwood KS, Chiquet M, Tucker RP, Orend G. Tenascin-C at a glance. J Cell Sci. 2016;129:4321–7.

    Article  CAS  Google Scholar 

  14. Midwood KS, Orend G. The role of tenascin-C in tissue injury and tumorigenesis. J Cell Commun Signal. 2009;3:287–310.

    Article  Google Scholar 

  15. Nakano F, Fujimoto M, Kawakita F, Nakazaki A, Liu L, Nakatsuka Y, Imanaka-Yoshida K, Yoshida T, Suzuki H. Receptors that mediate tenascin-C-induced constriction of cerebral arteries in rats. In: Sasaki T, Ohkuma H, Kanamaru K, Suzuki M, editors. Neurovascular events after subarachnoid hemorrhage. Tokyo: Narunia; 2017. p. 151–6.

    Google Scholar 

  16. Nakatsuka Y, Kawakita F, Yasuda R, Umeda Y, Toma N, Sakaida H, Suzuki H, pSEED group. Preventive effects of cilostazol against the development of shunt-dependent hydrocephalus after subarachnoid hemorrhage. J Neurosurg. 2017;127:319–26.

    Article  CAS  Google Scholar 

  17. Nishikawa H, Nakatsuka Y, Shiba M, Kawakita F, Fujimoto M, Suzuki H, pSEED group. Increased plasma galectin-3 preceding the development of delayed cerebral infarction and eventual poor outcome in non-severe aneurysmal subarachnoid hemorrhage. Transl Stroke Res. 2017; https://doi.org/10.1007/s12975-017-0564-0.

    Article  Google Scholar 

  18. Nong Y, Wu D, Lin Y, Zhang Y, Bai L, Tang H. Tenascin-C expression is associated with poor prognosis in hepatocellular carcinoma (HCC) patients and the inflammatory cytokine TNF-α-induced TNC expression promotes migration in HCC cells. Am J Cancer Res. 2015;5:782–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Okada T, Suzuki H. Toll-like receptor 4 as a possible therapeutic target for delayed brain injuries after aneurysmal subarachnoid hemorrhage. Neural Regen Res. 2017;12:193–6.

    Article  Google Scholar 

  20. Shiba M, Fujimoto M, Imanaka-Yoshida K, Yoshida T, Taki W, Suzuki H. Tenascin-C causes neuronal apoptosis after subarachnoid hemorrhage in rats. Transl Stroke Res. 2014;5:238–47.

    Article  Google Scholar 

  21. Suzuki H. What is early brain injury? Transl Stroke Res. 2015;6:1–3.

    Article  Google Scholar 

  22. Suzuki H, Ayer R, Sugawara T, Chen W, Sozen T, Hasegawa Y, Kanamaru K, Zhang JH. Protective effects of recombinant osteopontin on early brain injury after subarachnoid hemorrhage in rats. Crit Care Med. 2010;38:612–8.

    Article  CAS  Google Scholar 

  23. Suzuki H, Hasegawa Y, Chen W, Kanamaru K, Zhang JH. Recombinant osteopontin in cerebral vasospasm after subarachnoid hemorrhage. Ann Neurol. 2010;68:650–60.

    Article  CAS  Google Scholar 

  24. Suzuki H, Hasegawa Y, Kanamaru K, Zhang JH. Mechanisms of osteopontin-induced stabilization of blood-brain barrier disruption after subarachnoid hemorrhage in rats. Stroke. 2010;41:1783–90.

    Article  CAS  Google Scholar 

  25. Suzuki H, Kanamaru K, Suzuki Y, Aimi Y, Matsubara N, Araki T, Takayasu M, Kinoshita N, Imanaka-Yoshida K, Yoshida T, Taki W. Tenascin-C is induced in cerebral vasospasm after subarachnoid hemorrhage in rats and humans: a pilot study. Neurol Res. 2010;32:179–84.

    Article  CAS  Google Scholar 

  26. Suzuki H, Kawakita F. Tenascin-C in aneurysmal subarachnoid hemorrhage: deleterious or protective? Neural Regen Res. 2016;11:230–1.

    Article  Google Scholar 

  27. Suzuki H, Kinoshita N, Imanaka-Yoshida K, Yoshida T, Taki W. Cerebrospinal fluid tenascin-C increases preceding the development of chronic shunt-dependent hydrocephalus after subarachnoid hemorrhage. Stroke. 2008;39:1610–2.

    Article  CAS  Google Scholar 

  28. Suzuki H, Nakano F. To improve translational research in subarachnoid hemorrhage. Transl Stroke Res. 2017; https://doi.org/10.1007/s12975-017-0546-2.

    Article  Google Scholar 

  29. Suzuki H, Shiba M, Nakatsuka Y, Nakano F, Nishikawa H. Higher cerebrospinal fluid pH may contribute to the development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Transl Stroke Res. 2017;8:165–73.

    Article  CAS  Google Scholar 

  30. Wan J, Shan Y, Fan Y, Fan C, Chen S, Sun J, Zhu L, Qin L, Yu M, Lin Z. NF-κB inhibition attenuates LPS-induced TLR4 activation in monocyte cells. Mol Med Rep. 2016;14:4505–10.

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported in part by a grant-in-aid for Scientific Research from Japan Society for the Promotion of Science to Drs. Suzuki and Shiba.

Conflict of Interest Statement

The authors declare that they have no conflict of interest.

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Authors and Affiliations

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

    Hidenori Suzuki, Masashi Fujimoto, Fumihiro Kawakita, Lei Liu, Fumi Nakano, Hirofumi Nishikawa, Takeshi Okada & Masato Shiba

  2. Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, Mie, Japan

    Kyoko Imanaka-Yoshida & Toshimichi Yoshida

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  1. Hidenori Suzuki
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  2. Masashi Fujimoto
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  3. Fumihiro Kawakita
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  6. Hirofumi Nishikawa
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  8. Kyoko Imanaka-Yoshida
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  9. Toshimichi Yoshida
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  10. Masato Shiba
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Correspondence to Hidenori Suzuki .

Editor information

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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Suzuki, H. et al. (2020). Toll-Like Receptor 4 and Tenascin-C Signaling in Cerebral Vasospasm and Brain Injuries After Subarachnoid Hemorrhage. 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_15

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  • DOI: https://doi.org/10.1007/978-3-030-04615-6_15

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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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