Skip to main content

Advertisement

SpringerLink
Log in

Tenascin-C Causes Neuronal Apoptosis After Subarachnoid Hemorrhage in Rats

  • Original Article
  • Published:
Translational Stroke Research Aims and scope Submit manuscript

Abstract

The role of tenascin-C (TNC), a matricellular protein, in brain injury is unknown. The aim of this study was to examine if TNC causes neuronal apoptosis after subarachnoid hemorrhage (SAH), a deadly cerebrovascular disorder, using imatinib mesylate (a selective inhibitor of platelet-derived growth factor receptor [PDGFR] that is reported to suppress TNC induction) and recombinant TNC. SAH by endovascular perforation caused caspase-dependent neuronal apoptosis in the cerebral cortex irrespective of cerebral vasospasm development at 24 and 72 h post-SAH, associated with PDGFR activation, mitogen-activated protein kinases (MAPKs) activation, and TNC induction in rats. PDGFR inactivation by an intraperitoneal injection of imatinib mesylate prevented neuronal apoptosis, as well as MAPKs activation and TNC induction in the cerebral cortex at 24 h. A cisternal injection of recombinant TNC reactivated MAPKs and abolished anti-apoptotic effects of imatinib mesylate. The TNC injection also induced TNC itself in SAH brain, which may internally augment neuronal apoptosis after SAH. These findings suggest that TNC upregulation by PDGFR activation causes neuronal apoptosis via MAPK activation, and that the positive feedback mechanisms may exist to augment neuronal apoptosis after SAH. TNC-induced neuronal apoptosis would be a new target to improve outcome after SAH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Matsui Y, Morimoto J, Uede T. Role of matricellular proteins in cardiac tissue remodeling after myocardial infarction. World J Biol Chem. 2010;1:69–80.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Chiquet-Ehrismann R, Chiquet M. Tenascins: regulation and putative functions during pathological stress. J Pathol. 2003;200:488–99.

    Article  CAS  PubMed  Google Scholar 

  3. Jones PL, Jones FS. Tenascin-C in development and disease: gene regulation and cell function. Matrix Biol. 2000;19:581–96.

    Article  CAS  PubMed  Google Scholar 

  4. Suzuki H, Kanamaru K, Shiba M, Fujimoto M, Imanaka-Yoshida K, Yoshida T, et al. Cerebrospinal fluid tenascin-C in cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Neurosurg Anesthesiol. 2011;23:310–7.

    Article  PubMed  Google Scholar 

  5. Suzuki H, Kanamaru K, Suzuki Y, Aimi Y, Matsubara N, Araki T, et al. 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  PubMed  Google Scholar 

  6. Shiba M, Suzuki H, Fujimoto M, Shimojo N, Imanaka-Yoshida K, Yoshida T, et al. Imatinib mesylate prevents cerebral vasospasm after subarachnoid hemorrhage via inhibiting tenascin-C expression in rats. Neurobiol Dis. 2012;46:172–9.

    Article  CAS  PubMed  Google Scholar 

  7. Sehba FA, Pluta RM, Zhang JH. Metamorphosis of subarachnoid hemorrhage research: from delayed vasospasm to early brain injury. Mol Neurobiol. 2011;43:27–40.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Fujii M, Yan J, Rolland WB, Soejima Y, Caner B, Zhang JH. Early brain injury, an evolving frontier in subarachnoid hemorrhage research. Transl Stroke Res. 2013;4:432–46.

    Article  PubMed  Google Scholar 

  9. Hasegawa Y, Suzuki H, Altay O, Zhang JH. Preservation of tropomyosin-related kinase B (TrkB) signaling by sodium orthovanadate attenuates early brain injury after subarachnoid hemorrhage in rats. Stroke. 2011;42:477–83.

    Article  CAS  PubMed  Google Scholar 

  10. Wallner K, Li C, Shah PK, Wu KJ, Schwartz SM, Sharifi BG. EGF-Like domain of tenascin-C is proapoptotic for cultured smooth muscle cells. Arterioscler Thromb Vasc Biol. 2004;24:1416–21.

    Article  CAS  PubMed  Google Scholar 

  11. Titova E, Ostrowski RP, Zhang JH, Tang J. Experimental models of subarachnoid hemorrhage for studies of cerebral vasospasm. Neurol Res. 2009;31:568–81.

    Article  PubMed  Google Scholar 

  12. Sugawara T, Ayer R, Jadhav V, Zhang JH. A new grading system evaluating bleeding scale in filament perforation subarachnoid hemorrhage rat model. J Neurosci Methods. 2008;167:327–34.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Suzuki H, Kanamaru K, Tsunoda H, Inada H, Kuroki M, Sun H, et al. Heme oxygenase-1 gene induction as an intrinsic regulation against delayed cerebral vasospasm in rats. J Clin Invest. 1999;104:59–66.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. 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  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Chiquet-Ehrismann R, Matsuoka Y, Hofer U, Spring J, Bernasconi C, Chiquet M. Tenascin variants: differential binding to fibronectin and distinct distribution in cell cultures and tissues. Cell Regul. 1991;2:927–38.

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Bennett SA, Tenniswood M, Chen JH, Davidson CM, Keyes MT, Fortin T, et al. Chronic cerebral hypoperfusion elicits neuronal apoptosis and behavioral impairment. Neuroreport. 1998;9:161–6.

    Article  CAS  PubMed  Google Scholar 

  18. Li Y, Lei Z, Xu ZC. Enhancement of inhibitory synaptic transmission in large aspiny neurons after transient cerebral ischemia. Neuroscience. 2009;159:670–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Yatsushige H, Ostrowski RP, Tsubokawa T, Colohan A, Zhang JH. Role of c-Jun N-terminal kinase in early brain injury after subarachnoid hemorrhage. J Neurosci Res. 2007;85:1436–48.

    Article  CAS  PubMed  Google Scholar 

  20. Macdonald RL, Kassell NF, Mayer S, Ruefenacht D, Schmiedek P, Weidauer S, et al. Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial. Stroke. 2008;39:3015–21.

    Article  CAS  PubMed  Google Scholar 

  21. Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, et al. Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurol. 2011;10:618–25.

    Article  CAS  PubMed  Google Scholar 

  22. Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, et al. Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling. Stroke. 2012;43:1463–9.

    Article  CAS  PubMed  Google Scholar 

  23. 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  PubMed  Google Scholar 

  24. Hindermann W, Berndt A, Borsi L, Luo X, Hyckel P, Katenkamp D, et al. Synthesis and protein distribution of the unspliced large tenascin-C isoform in oral squamous cell carcinoma. J Pathol. 1999;189:475–80.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  PubMed  Google Scholar 

  26. Tredici G, Miloso M, Scuteri A, Foudah D. MAPKs as mediators of cell fate determination: an approach to neurodegenerative diseases. Curr Med Chem. 2008;15:538–48.

    Article  PubMed  Google Scholar 

  27. Lin CL, Dumont AS, Tsai YJ, Huang JH, Chang KP, Kwan AL, et al. 17β-estradiol activates adenosine A(2a) receptor after subarachnoid hemorrhage. J Surg Res. 2009;157:208–15.

    Article  CAS  PubMed  Google Scholar 

  28. Kusaka G, Ishikawa M, Nanda A, Granger DN, Zhang JH. Signaling pathways for early brain injury after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2004;24:916–25.

    Article  CAS  PubMed  Google Scholar 

  29. 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. 2010;226:2617–24.

    Article  Google Scholar 

  30. Wang HH, Hsieh HL, Yang CM. Calmodulin kinase II-dependent transactivation of PDGF receptors mediates astrocytic MMP-9 expression and cell motility induced by lipoteichoic acid. J Neuroinflammation. 2010;7:84.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Smits A, Kato M, Westermark B, Nister M, Heldin CH, Funa K. Neurotrophic activity of platelet-derived growth factor (PDGF): rat neuronal cells possess functional PDGF β-type receptors and respond to PDGF. Proc Natl Acad Sci U S A. 1991;88:8159–63.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Nishio T, Kawaguchi S, Iseda T, Kawasaki T, Hase T. Secretion of tenascin-C by cultured astrocytes: regulation of cell proliferation and process elongation. Brain Res. 2003;990:129–40.

    Article  CAS  PubMed  Google Scholar 

  33. Peng B, Dutreix C, Mehring G, Hayes MJ, Ben-Am M, Seiberling M, et al. Absolute bioavailability of imatinib (Glivec®) orally versus intravenous infusion. J Clin Pharmacol. 2004;44:158–62.

    Article  PubMed  Google Scholar 

  34. Breedveld P, Pluim D, Cipriani G, Wielinga P, van Tellingen O, Schinkel AH, et al. The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in patients. Cancer Res. 2005;65:2577–82.

    Article  CAS  PubMed  Google Scholar 

  35. El-Karef A, Yoshida T, Gabazza EC, Nishioka T, Inada H, Sakakura T, et al. Deficiency of tenascin-C attenuates liver fibrosis in immune-mediated chronic hepatitis in mice. J Pathol. 2007;211:86–94.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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

This work was supported in part by a grant-in-aid for Scientific Research from Japan Society for the Promotion of Science and the NOVARTIS Foundation (Japan) for the Promotion of Science to Dr. Suzuki.

Compliance with Ethics Requirements

ᅟ

Conflict of Interest

The authors report no conflicts of interest.

All institutional and national guidelines for the care and use of laboratory animals were followed.

Author information

Authors and Affiliations

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

    Masato Shiba, Masashi Fujimoto, Waro Taki & Hidenori Suzuki

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

    Kyoko Imanaka-Yoshida & Toshimichi Yoshida

  3. Research Center for Matrix Biology, Mie University Graduate School of Medicine, Tsu, Japan

    Kyoko Imanaka-Yoshida, Toshimichi Yoshida & Hidenori Suzuki

Authors
  1. Masato Shiba
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masashi Fujimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kyoko Imanaka-Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Toshimichi Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Waro Taki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hidenori Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hidenori Suzuki.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 400 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shiba, M., Fujimoto, M., Imanaka-Yoshida, K. et al. Tenascin-C Causes Neuronal Apoptosis After Subarachnoid Hemorrhage in Rats. Transl. Stroke Res. 5, 238–247 (2014). https://doi.org/10.1007/s12975-014-0333-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12975-014-0333-2

Keywords

Search

Navigation