Skip to main content
SpringerLink
Log in

Human Data Supporting Glyburide in Ischemic Stroke

  • Chapter
Brain Edema XVI

Part of the book series: Acta Neurochirurgica Supplement ((NEUROCHIRURGICA,volume 121))

Abstract

The SUR1-TRPM4 channel is a critical determinant of edema and hemorrhagic transformation after focal ischemia. Blockade of this channel by the small molecule glyburide results in improved survival and neurological outcome in multiple preclinical models of ischemic stroke. A robust, compelling body of evidence suggests that an intravenous formulation of glyburide, RP-1127, can prevent swelling and improve outcome in patients with stroke. Retrospective studies of diabetic stroke patients show improved outcomes in patients who are continued on sulfonylureas after stroke onset. An early phase II study using magnetic resonance imaging and plasma biomarkers supports the conclusion that RP-1127 may decrease swelling and hemorrhagic transformation. Finally, the ongoing phase II RP-1127 development program has demonstrated continued safety as well as feasibility of enrollment and tolerability of the intervention. Continued efforts to complete the ongoing phase II study and definitive efficacy studies are needed to bring a candidate pharmacotherapy to a population of severe stroke patients that currently have no alternative.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

Similar content being viewed by others

References

  1. Jauch EC, Saver JL, Adams HP Jr et al (2013) Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 44(3):870–947. doi:10.1161/STR.0b013e318284056a

    Article  PubMed  Google Scholar 

  2. Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, von Kummer R (1996) ‘Malignant’ middle cerebral artery territory infarction: clinical course and prognostic signs. Arch Neurol 53(4):309–315

    Article  CAS  PubMed  Google Scholar 

  3. Wijdicks EF, Sheth KN, Carter BS et al (2014) Recommendations for the management of cerebral and cerebellar infarction with swelling: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 45(4):1222–1238. doi:10.1161/01.str.0000441965.15164.d6

    Article  PubMed  Google Scholar 

  4. Broderick JP, Palesch YY, Demchuk AM et al (2013) Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 368(10):893–903. doi:10.1056/NEJMoa1214300

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Mlynash M, Lansberg MG, Straka M et al (2011) Refining the definition of the malignant profile: insights from the DEFUSE-EPITHET pooled data set. DEFUSE-EPITHET Investigators. Stroke 42(5):1270–1275. doi:10.1161/STROKEAHA.110.601609. [Epub 2011 Apr 7]

    Google Scholar 

  6. Molina CA, Selim MH (2011) Decompressive hemicraniectomy in elderly patients with malignant hemispheric infarction: open questions remain beyond DESTINY. Stroke 42(3):847–848. doi:10.1161/STROKEAHA.110.603613

    Article  PubMed  Google Scholar 

  7. Juttler E, Bosel J, Amiri H et al (2011) DESTINY II: DEcompressive surgery for the treatment of malignant INfarction of the middle cerebral arterY II. Int J Stroke 6(1):79–86. doi:10.1111/j.1747-4949.2010.00544.x

    Article  PubMed  Google Scholar 

  8. Sheth KN (2013) Novel approaches to the primary prevention of edema after ischemia. Stroke 44(6 Suppl 1):S136. doi:10.1161/STROKEAHA.113.001821

    Article  PubMed  Google Scholar 

  9. Simard JM, Chen M, Tarasov KV et al (2006) Newly expressed SUR1-regulated NC(ca-ATP) channel mediates cerebral edema after ischemic stroke. Nat Med 12(4):433–440. doi:10.1038/nm1390

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Simard JM, Tsymbalyuk N, Tsymbalyuk O, Ivanova S, Yurovsky V, Gerzanich V (2010) Glibenclamide is superior to decompressive craniectomy in a rat model of malignant stroke. Stroke 41(3):531–537. doi:10.1161/STROKEAHA.109.572644

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Simard JM, Sheth KN, Kimberly WT et al (2013) Glibenclamide in cerebral ischemia and stroke. Neurocrit Care. doi:10.1007/s12028-013-9923-1

    Google Scholar 

  12. Fisher M, Feuerstein G, Howells DW et al (2009) Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke 40(6):2244–2250. doi:10.1161/STROKEAHA.108.541128

    Article  PubMed Central  PubMed  Google Scholar 

  13. Simard JM, Kent TA, Kunte H (2011) Letter by Simard et al regarding article, “Sulfonylurea use before stroke does not influence outcome”. Stroke. doi:10.1161/STROKEAHA.111.620666

    PubMed  Google Scholar 

  14. Favilla CG, Mullen MT, Ali M, Higgins P, Kasner SE, Virtual International Stroke Trials Archive (VISTA) Collaboration (2011) Sulfonylurea use before stroke does not influence outcome. Stroke 42(3):710–715. doi:10.1161/STROKEAHA.110.599274

    Google Scholar 

  15. Horsdal HT, Mehnert F, Rungby J, Johnsen SP (2012) Type of preadmission antidiabetic treatment and outcome among patients with ischemic stroke: a nationwide follow-up study. J Stroke Cerebrovasc Dis 21(8):717–725. doi:10.1016/j.jstrokecerebrovasdis.2011.03.007

    Article  PubMed  Google Scholar 

  16. Kunte H, Schmidt S, Eliasziw M et al (2007) Sulfonylureas improve outcome in patients with type 2 diabetes and acute ischemic stroke. Stroke 38(9):2526–2530. doi:10.1161/STROKEAHA.107.482216

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Kunte H, Busch M, Trostdorf K et al (2012) Hemorrhagic transformation of ischemic stroke in diabetics on sulfonylureas. Ann Neurol 72:799–806

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Mehta RI, Ivanova S, Tosun C, Castellani RJ, Gerzanich V, Simard JM (2013) Sulfonylurea receptor 1 expression in human cerebral infarcts. J Neuropathol Exp Neurol 72(9):871–883. doi:10.1097/NEN.0b013e3182a32e40

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Sheth KN, Taylor Kimberly W, Elm JJ et al (2014) Exploratory analysis of glyburide as a novel therapy for preventing brain swelling. Neurocrit Care 21(1):43–51. doi:10.1007/s12028-014-9970-2

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Sheth KN, Kimberly WT, Elm JJ et al (2013) Pilot study of intravenous glyburide in patients with a large ischemic stroke. Stroke. doi:10.1161/STROKEAHA.113.003352

    PubMed Central  Google Scholar 

  21. Thomalla G, Hartmann F, Juettler E et al (2010) Prediction of malignant middle cerebral artery infarction by magnetic resonance imaging within 6 hours of symptom onset: a prospective multicenter observational study. Ann Neurol 68(4):435–445. doi:10.1002/ana.22125

    Article  PubMed  Google Scholar 

  22. Yoo AJ, Sheth KN, Kimberly WT et al (2012) Validating imaging biomarkers of cerebral edema in patients with severe ischemic stroke. J Stroke Cerebrovasc Dis. doi:10.1016/j.jstrokecerebrovasdis.2012.01.002

    PubMed Central  Google Scholar 

  23. Davis SM, Donnan GA, Parsons MW et al (2008) Effects of alteplase beyond 3 h after stroke in the echoplanar imaging thrombolytic evaluation trial (EPITHET): a placebo-controlled randomised trial. Lancet Neurol 7(4):299–309. doi:10.1016/S1474-4422(08)70044-9

    Article  PubMed  Google Scholar 

  24. Todd NV, Picozzi P, Crockard A, Russell RW (1986) Duration of ischemia influences the development and resolution of ischemic brain edema. Stroke 17(3):466–471

    Article  CAS  PubMed  Google Scholar 

  25. Schaefer PW (2000) Diffusion-weighted imaging as a problem-solving tool in the evaluation of patients with acute strokelike syndromes. Top Magn Reson Imaging 11(5):300–309

    Article  CAS  PubMed  Google Scholar 

  26. Jha R, Battey TW, Pham L et al (2014) Fluid-attenuated inversion recovery hyperintensity correlates with matrix metalloproteinase-9 level and hemorrhagic transformation in acute ischemic stroke. Stroke 45(4):1040–1045. doi:10.1161/STROKEAHA.113.004627

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Castellanos M, Leira R, Serena J et al (2003) Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke 34(1):40–46

    Article  CAS  PubMed  Google Scholar 

  28. Kimberly WT, Battey TW, Pham L et al (2013) Glyburide is associated with attenuated vasogenic edema in stroke patients. Neurocrit Care. doi:10.1007/s12028-013-9917-z

    Google Scholar 

  29. Kimberly WT, Sheth KN (2011) Approach to severe hemispheric stroke. Neurology 76(7 Suppl 2):S50–S56. doi:10.1212/WNL.0b013e31820c35f4

    Article  PubMed  Google Scholar 

  30. Simard JM, Sahuquillo J, Sheth KN, Kahle KT, Walcott BP (2011) Managing malignant cerebral infarction. Curr Treat Options Neurol 13(2):217–229. doi:10.1007/s11940-010-0110-9

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Neurocritical Care and Emergency Neurology, Yale University School of Medicine, 15 York Street, LCI 10th Floor, New Haven, CT, 06520, USA

    Kevin N. Sheth MD

  2. Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA

    J. Marc Simard MD, PhD

  3. Department of Public Health Sciences, Medical School of South Carolina, Charleston, SC, USA

    Jordan Elm PhD

  4. Department of Neurology, Charité Hospital, Berlin, Germany

    Golo Kronenberg MD & Hagen Kunte MD

  5. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

    W. Taylor Kimberly MD, PhD

Authors
  1. Kevin N. Sheth MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Marc Simard MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jordan Elm PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Golo Kronenberg MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hagen Kunte MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. W. Taylor Kimberly MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kevin N. Sheth MD .

Editor information

Editors and Affiliations

  1. Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, California, USA

    Richard L. Applegate

  2. Department of Neurosurgery, Soochow University The First Affiliated Hospital, Suzhou, Jiangsu, China

    Gang Chen

  3. Department of Neurosurgery, Third Military Medical University Southwest Hospital, Chongqing, China

    Hua Feng

  4. Dept.of Anesthesiology, Physiology and Neurosurgery, Loma Linda University School of Medicine, Loma Linda, California, USA

    John H. Zhang

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Sheth, K.N., Simard, J.M., Elm, J., Kronenberg, G., Kunte, H., Kimberly, W.T. (2016). Human Data Supporting Glyburide in Ischemic Stroke. In: Applegate, R., Chen, G., Feng, H., Zhang, J. (eds) Brain Edema XVI. Acta Neurochirurgica Supplement, vol 121. Springer, Cham. https://doi.org/10.1007/978-3-319-18497-5_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-18497-5_3

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-18496-8

  • Online ISBN: 978-3-319-18497-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation