Skip to main content

The Effects of Tetrahydrobiopterin on Intracerebral Hemorrhage-Induced Brain Injury in Mice

  • Conference paper
  • First Online:
Brain Edema XIV

Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 106))

Abstract

Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase (NOS) and is presently used clinically to treat forms of phenylketonuria. BH4 has been reported to restrain superoxide generation of NOS and chemically reduce superoxide. However, there has been no report concerning the effects of BH4 in intracerebral hemorrhage (ICH). In the present study, we investigated the neuroprotective effect of BH4 against ICH-induced brain injury in a mouse model.

A total of 26 male CD1 mice (31–39 g) were divided into sham, ICH-vehicle, and ICH-treated with BH4 groups (n = 8 in each group). ICH was induced by collagenase injection into the right basal ganglia. BH4 (20 mg/kg) was administrated intraperitoneally at 1 h after ICH. The effect of BH4 was measured by neurological score and brain water content at 24 h after ICH.

Our data demonstrates that ICH caused significant neurological deficit that is associated with brain edema. Treatment with BH4 did not reduce brain edema and neurological deficits at 24 h after ICH in mice. Further study is required to investigate the long-term effect of BH4 in ICH-induced brain injury.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Chen M, Regan RF (2007) Time course of increased heme oxygenase activity and expression after experimental intracerebral hemorrhage: correlation with oxidative injury. J Neurochem 103:2015–2021

    Article  PubMed  CAS  Google Scholar 

  2. Garcia JH, Wagner S, Liu KF, Hu XJ (1995) Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke 26:627–634

    Article  PubMed  CAS  Google Scholar 

  3. Ishii M, Shimizu S, Nawata S, Kiuchi Y, Yamamoto T (2000) Involvement of reactive oxygen species and nitric oxide in gastric ischemia-reperfusion injury in rats: protective effect of tetrahydrobiopterin. Dig Dis Sci 45:93–98

    Article  PubMed  CAS  Google Scholar 

  4. Kakoki M, Hirata Y, Hayakawa H, Suzuki E, Nagata D, Tojo A, Nishimatsu H, Nakanishi N, Hattori Y, Kiuchi K, Nagano T, Omata M (2000) Effects of tetrahydrobiopterin on endothelial dysfunction in rats with ischemic acute renal failure. J Am Soc Nephrol 11:301–309

    PubMed  CAS  Google Scholar 

  5. Kaufman S (1993) New tetrahydrobiopterin-dependent systems. Annu Rev Nutr 13:261–286

    Article  PubMed  CAS  Google Scholar 

  6. Kidd GA, Hong H, Majid A, Kaufman DI, Chen AF (2005) Inhibition of brain GTP cyclohydrolase I and tetrahydrobiopterin attenuates cerebral infarction via reducing inducible NO synthase and peroxynitrite in ischemic stroke. Stroke 36: 2705–2711

    Article  PubMed  CAS  Google Scholar 

  7. Ortiz de Montellano PR, Nishida C, Rodriguez-Crespo I, Gerber N (1998) Nitric oxide synthase structure and electron transfer. Drug Metab Dispos 26:1185–1189

    PubMed  CAS  Google Scholar 

  8. Rosenberg GA, Mun-Bryce S, Wesley M, Kornfeld M (1990) Collagenase-induced intracerebral hemorrhage in rats. Stroke 21:801–807

    Article  PubMed  CAS  Google Scholar 

  9. Schmid RA, Hillinger S, Walter R, Zollinger A, Stammberger U, Speich R, Schaffner A, Weder W, Schoedon G (1999) The nitric oxide synthase cofactor tetrahydrobiopterin reduces allograft ischemia–reperfusion injury after lung transplantation. J Thorac Cardiovasc Surg 118:726–732

    Article  PubMed  CAS  Google Scholar 

  10. Shinozaki K, Nishio Y, Okamura T, Yoshida Y, Maegawa H, Kojima H, Masada M, Toda N, Kikkawa R, Kashiwagi A (2000) Oral administration of tetrahydrobiopterin prevents endothelial dysfunction and vascular oxidative stress in the aortas of insulin-resistant rats. Circ Res 87:566–573

    Article  PubMed  CAS  Google Scholar 

  11. Teruaki Wajima, Shunichi Shimizu, Toshihito Hiroi, Masakazu Ishii, Yuji Kiuchi (2006) Reduction of myocardial infarct size by tetrahydrobiopterin: possible involvement of mitochondrial KATP channels activation through nitric oxide production. J Cardiovasc Pharmacol 47:243–249

    Article  Google Scholar 

  12. Titova E, Ostrowski RP, Sowers LC, Zhang JH, Tang J (2007) Effects of apocynin and ethanol on intracerebral haemorrhage-induced brain injury in rats. Clin Exp Pharmacol Physiol 34:845–850

    Article  PubMed  CAS  Google Scholar 

  13. Vásquez-Vivar J, Kalyanaraman B, Martásek P (2003) The role of tetrahydrobiopterin in superoxide generation from eNOS: enzymology and physiological implications. Free Radic Res 37: 121–127

    Article  PubMed  Google Scholar 

  14. Vásquez-Vivar J, Kalyanaraman B, Martásek P, Hogg N, Masters BSS, Karoui H, Tordo P, Pritchard KA Jr (1998) Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci USA 35:9220–9225

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jiping Tang .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag/Wien

About this paper

Cite this paper

Tsuchiyama, R., Sozen, T., Titova, E., Zhang, J.H., Tang, J. (2010). The Effects of Tetrahydrobiopterin on Intracerebral Hemorrhage-Induced Brain Injury in Mice. In: Czernicki, Z., Baethmann, A., Ito, U., Katayama, Y., Kuroiwa, T., Mendelow, D. (eds) Brain Edema XIV. Acta Neurochirurgica Supplementum, vol 106. Springer, Vienna. https://doi.org/10.1007/978-3-211-98811-4_28

Download citation

  • DOI: https://doi.org/10.1007/978-3-211-98811-4_28

  • Published:

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-98758-2

  • Online ISBN: 978-3-211-98811-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics