Skip to main content
SpringerLink
Log in

Low-Dose Lipopolysaccharide Injection Prior to Subarachnoid Hemorrhage Modulates Delayed Deterioration Associated with Vasospasm in Subarachnoid Hemorrhage

  • Chapter
  • First Online:
Cerebral Vasospasm: Neurovascular Events After Subarachnoid Hemorrhage

Part of the book series: Acta Neurochirurgica Supplement ((NEUROCHIRURGICA,volume 115))

Abstract

There is increasing evidence that inflammation plays a role in the development of Delayed Deterioration associated with vasospasm (DDAV) after subarachnoid hemorrhage (SAH). Lipopolysaccharide (LPS) is an activator of the innate inflammatory system that causes DDAV in animal models. The effect of low-dose LPS has been shown to be protective in stroke models but has not been investigated in SAH. Two treatments were studied: (1) a single intraperitoneal dose of 0.6 mg/kg injected 24 h prior to SAH and (2) four daily doses administered prior to SAH. DDAV was determined by India ink angiography at day 6; behavioral testing was done in a different cohort of animals, and analysis of brain chemokine levels was accomplished by dot blot. Vessel caliber was improved compared to the SAH group in the single-injection group (ldLPS ×1) (p < 0.05). In the multiple-injection group (ldLPS ×4), the vessel caliber was similar to SAH (p < 0.05). ldLPS ×1 improved performance on the Barnes maze test, whereas the ldLPS ×4 was worse (p < 0.001). Brain levels of the inflammatory chemokine KC (keratinocyte-derived chemokine) were decreased in the ldLPS ×1 and increased in the ldLPS ×4 group. Single-injection low-dose LPS preconditioning was protective for delayed deterioration associated with vasospasm (DDAV), whereas the multiple-injection course exacerbated DDAV. This further supports that inflammation plays an important role in the development of DDAV, and that modulating the inflammatory system may be a potential target for future therapies in SAH.

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

Access this chapter

Log in via an institution
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. van Gijn J, Rinkel GJ (2001) Subarachnoid haemorrhage: diagnosis, causes and management. Brain 124:249–278

    Article  PubMed  Google Scholar 

  2. Etminan N, Vergouwen MD, Ilodigwe D, Macdonald RL (2011) Effect of pharmaceutical treatment on vasospasm, delayed cerebral ischemia, and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. J Cereb Blood Flow Metab. doi:10.1038/jcbfm.2011.7

  3. Stein SC, Levine JM, Nagpal S, LeRoux PD (2006) Vasospasm as the sole cause of cerebral ischemia: how strong is the evidence? Neurosurg Focus 21:E2

    Article  PubMed  Google Scholar 

  4. Vergouwen MD, Ilodigwe D, Macdonald RL (2011) Cerebral infarction after subarachnoid hemorrhage contributes to poor outcome by vasospasm-dependent and -independent effects. Stroke 42:924–929. doi:10.1161/STROKEAHA.110.597914

    Article  PubMed  Google Scholar 

  5. Provencio JJ, Fu X, Siu A, Rasmussen PA, Hazen SL, Ransohoff RM (2010) CSF neutrophils are implicated in the development of vasospasm in subarachnoid hemorrhage. Neurocrit Care 12:244–251. doi:10.1007/s12028-009-9308-7

    Article  PubMed  CAS  Google Scholar 

  6. Provencio JJ, Altay T, Smithason S, Moore SK, Ransohoff RM (2010) Depletion of Ly6G/C(+) cells ameliorates delayed cerebral vasospasm in subarachnoid hemorrhage. J Neuroimmunol. doi:10.1016/j.jneuroim.2010.10.016

  7. Pradilla G, Wang PP, Legnani FG, Ogata L, Dietsch GN, Tamargo RJ (2004) Prevention of vasospasm by anti-CD11/CD18 monoclonal antibody therapy following subarachnoid hemorrhage in rabbits. J Neurosurg 101:88–92

    Article  PubMed  CAS  Google Scholar 

  8. Zubkov AY, Tibbs RE, Aoki K, Zhang JH (2000) Prevention of vasospasm in penetrating arteries with MAPK inhibitors in dog double-hemorrhage model. Surg Neurol 54:221–227, discussion 227–228

    Article  PubMed  CAS  Google Scholar 

  9. Recinos PF, Pradilla G, Thai Q-A, Perez M, Hdeib AM, Tamargo RJ (2006) Controlled release of lipopolysaccharide in the subarachnoid space of rabbits induces chronic vasospasm in the absence of blood. Surg Neurol 66:463–469, discussion 469

    Article  PubMed  Google Scholar 

  10. Zhou C, Yamaguchi M, Kusaka G, Schonholz C, Nanda A, Zhang JH (2004) Caspase inhibitors prevent endothelial apoptosis and cerebral vasospasm in dog model of experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab 24:419–431

    Article  PubMed  CAS  Google Scholar 

  11. Smithason S, Moore SK, Provencio JJ (2011) Systemic administration of LPS worsens delayed deterioration associated with vasospasm after subarchnoid hemorrhage through a myeloid cell dependent mechanism. Neurocrit Care 16(2):327–334, Epub ahead of print

    Article  Google Scholar 

  12. Rosenzweig HL, Lessov NS, Henshall DC, Minami M, Simon RP, Stenzel-Poore MP (2004) Endotoxin preconditioning prevents cellular inflammatory response during ischemic neuroprotection in mice. Stroke 35:2576–2581. doi:10.1161/01.STR.0000143450.04438.ae01.STR.0000143450.04438.ae[pii]

    Article  PubMed  CAS  Google Scholar 

  13. Rosenzweig HL, Minami M, Lessov NS, Coste SC, Stevens SL, Henshall DC, Meller R, Simon RP, Stenzel-Poore MP (2007) Endotoxin preconditioning protects against the cytotoxic effects of TNFalpha after stroke: a novel role for TNFalpha in LPS-ischemic tolerance. J Cereb Blood Flow Metab 27:1663–1674. doi:10.1038/sj.jcbfm.9600464

    Article  PubMed  CAS  Google Scholar 

  14. Tasaki K, Ruetzler CA, Ohtsuki T, Martin D, Nawashiro H, Hallenbeck JM (1997) Lipopolysaccharide pre-treatment induces resistance against subsequent focal cerebral ischemic damage in spontaneously hypertensive rats. Brain Res 748:267–270

    Article  PubMed  CAS  Google Scholar 

  15. Stevens SL, Leung PY, Vartanian KB, Gopalan B, Yang T, Simon RP, Stenzel-Poore MP (2011) Multiple preconditioning paradigms converge on interferon regulatory factor-dependent signaling to promote tolerance to ischemic brain injury. J Neurosci 31:8456–8463. doi:10.1523/JNEUROSCI.0821-11.2011

    Article  PubMed  CAS  Google Scholar 

  16. Altay T, Smithason S, Volokh N, Rasmussen PA, Ransohoff RM, Provencio JJ (2009) A novel method for subarachnoid hemorrhage to induce vasospasm in mice. J Neurosci Methods 183:136–140. doi:10.1016/j.jneumeth.2009.06.027

    Article  PubMed  Google Scholar 

  17. Marsh B, Stevens SL, Packard AE, Gopalan B, Hunter B, Leung PY, Harrington CA, Stenzel-Poore MP (2009) Systemic lipopolysaccharide protects the brain from ischemic injury by reprogramming the response of the brain to stroke: a critical role for IRF3. J Neurosci 29:9839–9849. doi:10.1523/JNEUROSCI.2496-09.2009

    Article  PubMed  CAS  Google Scholar 

  18. Broad A, Kirby JA, Jones DE (2007) Toll-like receptor interactions: tolerance of MyD88-dependent cytokines but enhancement of MyD88-independent interferon-beta production. Immunology 120:103–111. doi:10.1111/j.1365-2567.2006.02485.x

    Article  PubMed  CAS  Google Scholar 

  19. Broad A, Jones DE, Kirby JA (2006) Toll-like receptor (TLR) response tolerance: a key physiological “damage limitation” effect and an important potential opportunity for therapy. Curr Med Chem 13:2487–2502

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Shu-mei Man for help with confocal imaging.

Financial Disclosure

This work was supported by a grant from the National Institutes of Health (K08-NS051350 J.J.P.) and the Cleveland Clinic Cerebrovascular Center (Institutional Support J.J.P.).

Conflicts of Interest Statement

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Cleveland Clinic, Cleveland, OH, USA

    Saksith Smithason M.D.

  2. Neuroinflammation Research Center, Cleveland Clinic, Cleveland, OH, USA

    Shari K. Moore BA.

  3. Neuroinflammation Research Center and Cerebrovascular Center, NC30 Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    J. Javier Provencio M.D.

Authors
  1. Saksith Smithason M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shari K. Moore BA.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Javier Provencio M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Javier Provencio M.D. .

Editor information

Editors and Affiliations

  1. , Department of Neurosurgery, University of Cincinnati, Stetson, Suite 2200 260, Cincinnati, 45267-0515, Ohio, USA

    Mario Zuccarello

  2. College of Medicine, Department of Neurology, University of Cincinnati, Albert Sabin Way 231MSB room 1, Cincinnati, 46267-0536, Ohio, USA

    Joseph F. Clark

  3. College of Medicine, Dept. of Neurology and Neurosurgery, University of Cincinnati, Albert Sabin Way 231ML0517, Cincinnati, 45267-0517, Ohio, USA

    Gail Pyne-Geithman

  4. College of Medicine, Dept. of Neurosurgery, University of Cincinnati, Stetson St. Suite 260ML0515, Cincinnati, 45219, Ohio, USA

    Norberto Andaluz

  5. College of Medicine, Dept. of Neurosurgery, University of Cincinnati, Stetson, Suite 2200 260, Cincinnati, 45219, Ohio, USA

    Jed A. Hartings

  6. , Dept. of Emergency Medicine, University of Cincinnati, Albert Sabin Way 231ML0769, Cincinnati, 45267-0769, Ohio, USA

    Opeolu M. Adeoye

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Wien

About this chapter

Cite this chapter

Smithason, S., Moore, S.K., Provencio, J.J. (2013). Low-Dose Lipopolysaccharide Injection Prior to Subarachnoid Hemorrhage Modulates Delayed Deterioration Associated with Vasospasm in Subarachnoid Hemorrhage. In: Zuccarello, M., Clark, J., Pyne-Geithman, G., Andaluz, N., Hartings, J., Adeoye, O. (eds) Cerebral Vasospasm: Neurovascular Events After Subarachnoid Hemorrhage. Acta Neurochirurgica Supplement, vol 115. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1192-5_45

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-1192-5_45

  • Published:

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-1191-8

  • Online ISBN: 978-3-7091-1192-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation