Skip to main content
SpringerLink
Log in

Focal Cerebral Ischemia by Permanent Middle Cerebral Artery Occlusion in Sheep: Surgical Technique, Clinical Imaging, and Histopathological Results

  • Protocol
  • First Online:
Experimental Neurosurgery in Animal Models

Part of the book series: Neuromethods ((NM,volume 116))

Abstract

According to the recommendation of international expert committees, large animal stroke models are demanded for preclinical research. Based on a brief introduction to the ovine cranial anatomy, a sheep model of permanent middle cerebral artery occlusion (MCAO) will be described in this chapter. The model was particularly designed to verify several therapeutic strategies during both, acute and long-term studies, but is also feasible for development of diagnostic procedures. Further, exemplary application of imaging procedures and imaging data analyses using magnetic resonance imaging (MRI) and positron emission tomography (PET) are described. The chapter also includes recommendations for appropriate animal housing and medication.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 59.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 79.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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. O’Donnell MJ, Xavier D, Liu L et al (2010) Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet 376:112–123

    Article  PubMed  Google Scholar 

  2. Hacke W, Kaste M, Bluhmki E et al (2008) Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 359:1317–1329

    Article  CAS  PubMed  Google Scholar 

  3. Wahlgren N, Ahmed N, Davalos A et al (2008) Thrombolysis with alteplase 3–4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet 372:1303–1309

    Article  CAS  PubMed  Google Scholar 

  4. Hachinski V, Donnan GA, Gorelick PB et al (2010) Stroke: working toward a prioritized world agenda. Cerebrovasc Dis 30:127–147

    Article  PubMed  PubMed Central  Google Scholar 

  5. Traystman RJ (2003) Animal models of focal and global cerebral ischemia. ILAR J 44:85–95

    Article  CAS  PubMed  Google Scholar 

  6. STAIR-group (1999) Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke 30:2752–2758

    Article  Google Scholar 

  7. Savitz SI, Chopp M, Deans R et al (2011) Stem cell therapy as an emerging paradigm for stroke (STEPS) II. Stroke 42:825–829

    Article  PubMed  Google Scholar 

  8. Amiridze N, Gullapalli R, Hoffman G et al (2009) Experimental model of brainstem stroke in rabbits via endovascular occlusion of the basilar artery. J Stroke Cerebrovasc Dis 18:281–287

    Article  PubMed  Google Scholar 

  9. Kang BT, Lee JH, Jung DI et al (2007) Canine model of ischemic stroke with permanent middle cerebral artery occlusion: clinical and histopathological findings. J Vet Sci 8:369–376

    Article  PubMed  PubMed Central  Google Scholar 

  10. Garcia JH, Kalimo H, Kamijyo Y et al (1977) Cellular events during partial cerebral ischemia. I. Electron microscopy of feline cerebral cortex after middle-cerebral-artery occlusion. Virchows Arch B Cell Pathol 25:191–206

    CAS  PubMed  Google Scholar 

  11. Imai H, Konno K, Nakamura M et al (2006) A new model of focal cerebral ischemia in the miniature pig. J Neurosurg 104:123–132

    PubMed  Google Scholar 

  12. Marshall JW, Ridley RM (2003) Assessment of cognitive and motor deficits in a marmoset model of stroke. ILAR J 44:153–160

    Article  CAS  PubMed  Google Scholar 

  13. Shuaib A, Lees KR, Lyden P et al (2007) NXY-059 for the treatment of acute ischemic stroke. N Engl J Med 357:562–571

    Article  CAS  PubMed  Google Scholar 

  14. Boltze J, Forschler A, Nitzsche B et al (2008) Permanent middle cerebral artery occlusion in sheep: a novel large animal model of focal cerebral ischemia. J Cereb Blood Flow Metab 28:1951–1964

    Article  PubMed  Google Scholar 

  15. Behrens H, Ganter M, Hiepe T (2009) [Textbook of ovine diseases]. Parey, Stuttgart, Germany, Chapter in German

    Google Scholar 

  16. Nitzsche B, Frey S, Collins L et al (2015) A stereotaxic, population-averaged T1w ovine brain atlas including cerebral morphology and tissue volumes. Front Neuroanat 9:69. doi:10.3389/fnana.2015.00069

    Article  PubMed  PubMed Central  Google Scholar 

  17. Salomon FV, Geyer H, Gille U (2008) [Textbook of anatomy for veterinary medicine]. Enke Verlag, Leipzig, Germany, Chapter in German

    Google Scholar 

  18. Forschler A, Boltze J, Waldmin D et al (2007) [MRI of experimental focal cerebral ischemia in sheep]. Rofo 179:516–524, Article in German

    Article  CAS  PubMed  Google Scholar 

  19. Ashwini CA, Shubha A, Jayanthi KS (2008) Comparative anatomy of the circle of Willis in man, cow, sheep, goat, and pig. Neuroanatomy 2008:54–65

    Google Scholar 

  20. Muir KW, Santosh C (2005) Imaging of acute stroke and transient ischaemic attack. J Neurol Neurosurg Psychiatry 76:19–28

    Article  Google Scholar 

  21. Wechsler LR (2011) Imaging evaluation of acute ischemic stroke. Stroke 42:12–15

    Article  Google Scholar 

  22. Nucifora PG, Verma R, Lee SK et al (2007) Diffusion-tensor MR imaging and tractography: exploring brain microstructure and connectivity. Radiology 245:367–384

    Article  PubMed  Google Scholar 

  23. Swanson RA, Morton MT, Tsao-Wu G et al (1990) A semiautomated method for measuring brain infarct volume. J Cereb Blood Flow Metab 10:290–293

    Article  CAS  PubMed  Google Scholar 

  24. Alpert NM, Eriksson L, Chang JY et al (1984) Strategy for the measurement of regional cerebral blood flow using short-lived tracers and emission tomography. J Cereb Blood Flow Metab 4:28–34

    Article  CAS  PubMed  Google Scholar 

  25. Baron JC (2001) Perfusion thresholds in human cerebral ischemia: historical perspective and therapeutic implications. Cerebrovasc Dis 1:2–8

    Google Scholar 

  26. Dreyer A, Stroh A, Nitzsche B et al (2012) Frameless stereotaxy in sheep—neurosurgical and imaging techniques for translational stroke research. INTECH Open Access Publisher, London

    Book  Google Scholar 

  27. Wells AJ, Vink R, Blumbergs PC, Brophy BP, Helps SC, Knox SJ, Turner RJ (2012) A surgical model of permanent and transient middle cerebral artery stroke in the sheep. PLoS One 7(7):e42157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cooley KR, Vanderwolf CH (2004) The sheep brain—a photographic series. A.J. Kirby Co, London, ON

    Google Scholar 

  29. Mitchell JF (1958) The characteristics of some points of cardiovascular and respiratory representation in the cerebral cortex of sheep. J Physiol 144:17–8P

    CAS  PubMed  Google Scholar 

  30. Gierthmuehlen M, Wang X, Gkogkidis A et al (2014) Mapping of sheep sensory cortex with a novel micro-electrocorticography grid. J Comp Neurol 522(16):3590–3608

    Article  PubMed  Google Scholar 

  31. Hoffmann A, Stoffel MH, Nitzsche B et al (2014) The ovine cerebral venous system: comparative anatomy, visualization, and implications for translational research. PLoS One 9(4):e92990

    Article  PubMed  PubMed Central  Google Scholar 

  32. Latchaw RE (2004) Cerebral perfusion imaging in acute stroke. J Vasc Interv Radiol 15:29–46

    Article  Google Scholar 

  33. Rosset A, Spadola L, Ratib O (2004) OsiriX: an open-source software for navigating in multidimensional DICOM images. J Digit Imaging 17:205–216

    Article  PubMed  PubMed Central  Google Scholar 

  34. Schmidt KF, Ziu M, Schmidt NO et al (2004) Volume reconstruction techniques improve the correlation between histological and in vivo tumor volume measurements in mouse models of human gliomas. J Neurooncol 68:207–215

    Article  PubMed  Google Scholar 

  35. Watabe H, Itoh M, Cunningham V et al (1996) Noninvasive quantification of rCBF using positron emission tomography. J Cereb Blood Flow Metab 16:311–319

    Article  CAS  PubMed  Google Scholar 

  36. Mena H, Cadavid D, Rushing EJ (2004) Human cerebral infarct: a proposed histopathologic classification based on 137 cases. Acta Neuropathol 108:524–530

    Article  PubMed  Google Scholar 

  37. Garcia JH, Kamijyo Y (1974) Cerebral infarction. Evolution of histopathological changes after occlusion of a middle cerebral artery in primates. J Neuropathol Exp Neurol 33:408–421

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors want to thank Dr. Karl-Titus Hoffmann, professor of neuroradiology, and Dr. Osama Sabri, professor of nuclear medicine, for the allowance to use the scanners in their departments at Leipzig University. The authors are further grateful to Dr. Uwe Gille, Dr. Johannes Seeger, and Dr. Heinz-Adolf Schoon, professors at the Faculty for Veterinary Medicine at Leipzig University.

Author information

Author notes

    Authors and Affiliations

    1. Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Perlickstraße 1, Leipzig, 04103, Germany

      Björn Nitzsche & Antje Y. Dreyer

    2. Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany

      Björn Nitzsche, Henryk Barthel & Vilia Zeisig

    3. Department of Neuroradiology, University of Leipzig, Leipzig, Germany

      Donald Lobsien

    4. Department of Medical Cell Technology, Fraunhofer Research Institution for Marine Biotechnology, Lübeck, Germany

      Johannes Boltze

    5. Neuroscience Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA

      Johannes Boltze

    Authors
    1. Björn Nitzsche
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Henryk Barthel
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Donald Lobsien
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Johannes Boltze
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Vilia Zeisig
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Antje Y. Dreyer
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Björn Nitzsche .

    Editor information

    Editors and Affiliations

    1. Mossakowski Medical Research Centre, Department of Neurosurgery, Warsaw, Poland

      Miroslaw Janowski

    Rights and permissions

    Reprints and permissions

    Copyright information

    © 2016 Springer Science+Business Media New York

    About this protocol

    Cite this protocol

    Nitzsche, B., Barthel, H., Lobsien, D., Boltze, J., Zeisig, V., Dreyer, A.Y. (2016). Focal Cerebral Ischemia by Permanent Middle Cerebral Artery Occlusion in Sheep: Surgical Technique, Clinical Imaging, and Histopathological Results. In: Janowski, M. (eds) Experimental Neurosurgery in Animal Models. Neuromethods, vol 116. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3730-1_15

    Download citation

    • DOI: https://doi.org/10.1007/978-1-4939-3730-1_15

    • Published:

    • Publisher Name: Humana Press, New York, NY

    • Print ISBN: 978-1-4939-3728-8

    • Online ISBN: 978-1-4939-3730-1

    • eBook Packages: Springer Protocols

    Publish with us

    Policies and ethics

    Search

    Navigation