Skip to main content
SpringerLink
Log in

Transfemoral Approach to Induce Transient Middle Cerebral Artery Occlusion in Rats: The Use of Commercially Available Endovascular Wires

  • Original Work
  • Published:
Neurocritical Care Aims and scope Submit manuscript

Abstract

Background

Animal models of stroke play a crucial role in determining the pathophysiology of stroke progression and assessment of any new therapeutic approaches. Transient middle cerebral artery occlusion (tMCAo) in rodent models are the most common site-specific type of ischemia because of their relevance to the clinical setting. Compared with the intraluminal filament technique for inducing tMCAo, the transfemoral approach using endovascular wires is relatively a new technique

Methods

Here we present the use of commercially available wires used for neuro-endovascular surgical procedures to induce tMCAo in rats via a transfemoral approach. We used male Wistar rats in four groups to assess the effect of occlusion time (1 vs. 2 hours) and the wire type (PT2 TM 0.014″ vs. TransendTM EX, 0.014″, Boston Scientific, MA, USA). Infarct volume, edema, neurological deficits, and pro-inflammatory/anti-inflammatory blood biomarkers were used as outcome measures.

Results

We observed a significant effect of the wire type on the infarct volume (p value = 0.0096) where infarcts were slightly larger in the PT2 wiregroups. However, the occlusion time had no significant effect on infarct volume, even though the interaction between wire-type * occlusion-time was significant (p value = 0.024). Also, the amount of edema and blood pro-inflammatory/anti-inflammatory biomarkers were not statistically different among the wire-type and occlusion-time groups.

Conclusions

The choice of appropriate endovascular wire should probably be the focus of the study design instead of the occlusion time when planning an experiment. The transfemoral approach using endovascular wires for inducing tMCAo in rats provides a more consistent outcome with fewer complications compared with suture filament models.

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

Similar content being viewed by others

References

  1. Bagherpour R, Dykstra DD, Barrett AM, Luft AR, Divani AA. A comprehensive neurorehabilitation program should be an integral part of a comprehensive stroke center. Front Neurol. 2014;5:57.

    Article  Google Scholar 

  2. Sicard KM, Fisher M. Emerging drugs for acute ischemic stroke. Expert opinion on emerging drugs. 2009;14:33–42.

    Article  CAS  Google Scholar 

  3. Divani AA, Chow R, Sadeghi-Bazargani H, Murphy AJ, Nordberg JA, Tokarev JV, et al. Focal middle cerebral artery ischemia in rats via a transfemoral approach using a custom designed microwire. J Neurointerv Surg. 2015;8:608–14.

    Article  Google Scholar 

  4. Sicard KM, Fisher M. Animal models of focal brain ischemia. Exp Transl Stroke Med. 2009;1:7.

    Article  Google Scholar 

  5. Wang CX, Yang Y, Yang T, Shuaib A. A focal embolic model of cerebral ischemia in rats: introduction and evaluation. Brain Research Protoc. 2001;7:115–20.

    Article  CAS  Google Scholar 

  6. Koizumi J, Yoshida Y, Nakazawa T, Ooneda G. Experimental studies of ischemic brain edema. I. A new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area. Jpn J Stroke. 1986;8:1–8.

    Article  Google Scholar 

  7. Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke J Cereb Circul. 1989;20:84–91.

    Article  CAS  Google Scholar 

  8. Dittmar M, Spruss T, Schuierer G, Horn M. External carotid artery territory ischemia impairs outcome in the endovascular filament model of middle cerebral artery occlusion in rats. Stroke J Cereb Circul. 2003;34:2252–7.

    Article  Google Scholar 

  9. Dittmar MS, Vatankhah B, Fehm NP, Retzl G, Schuierer G, Bogdahn U, et al. The role of ECA transection in the development of masticatory lesions in the MCAO filament model. Exp Neurol. 2005;195:372–8.

    Article  Google Scholar 

  10. Trueman RC, Harrison DJ, Dwyer DM, Dunnett SB, Hoehn M, Farr TD. A critical re-examination of the intraluminal filament MCAO model: impact of external carotid artery transection. Transl Stroke Res. 2011;2:651–61.

    Article  Google Scholar 

  11. Trotman-Lucas M, Kelly ME, Janus J, Fern R, Gibson CL. An alternative surgical approach reduces variability following filament induction of experimental stroke in mice. Dis Model Mech. 2017;10:931–8.

    Article  Google Scholar 

  12. Shimamura N, Matsuda N, Katayama K, Ohkuma H. Novel rat middle cerebral artery occlusion model: trans-femoral artery approach combined with preservation of the external carotid artery. J Neurosci Methods. 2009;184:195–8.

    Article  Google Scholar 

  13. Sun F, Lopez-Sanchez C, Martin-Romero FJ, Luis L, Gutierrez-Merino C, Garcia-Martinez V. Transfemoral selective “intraluminal wiring” technique for transient middle cerebral artery occlusion in rats. J Neurosci Methods. 2005;149:82–9.

    Article  Google Scholar 

  14. Buhalog A, Yasuda R, Consigny D, Maurer K, Strother CM. A method for serial selective arterial catheterization and digital subtraction angiography in rodents. AJNR Am J Neuroradiol. 2010;31:1508–11.

    Article  CAS  Google Scholar 

  15. Arnberg F, Lundberg J, Soderman M, Damberg P, Holmin S. Image-guided method in the rat for inducing cortical or striatal infarction and for controlling cerebral blood flow under MRI. Stroke A J Cereb Circul. 2012;43:2437–43.

    Article  Google Scholar 

  16. Divani AA, Patel A, Fredrickson VL, Siljander B, Vazquez G. Association between changes in weight and cerebral arteries in rats. Transl Stroke Res. 2010;1:122–6.

    Article  Google Scholar 

  17. Garcia JH, Wagner S, Liu KF, Hu XJ. Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke A J Cereb Circul. 1995;26:627–34 discussion 35.

    Article  CAS  Google Scholar 

  18. Bachour SP, Hevesi M, Bachour O, Sweis BM, Mahmoudi J, Brekke JA, et al. Comparisons between Garcia, Modo, and Longa rodent stroke scales: optimizing resource allocation in rat models of focal middle cerebral artery occlusion. J Neurol Sci. 2016;364:136–40.

    Article  Google Scholar 

  19. Bhatia PM, Chamberlain R, Luo X, Hartley EW, Divani AA. Elevated blood pressure causes larger hematoma in a rat model of intracerebral hemorrhage. Transl Stroke Res. 2012;3:428–34.

    Article  CAS  Google Scholar 

  20. Divani AA, Murphy AJ, Meints J, Sadeghi-Bzargani H, Nordberg J, Monga M, et al. A novel preclinical model of moderate primary blast-induced traumatic brain injury. J Neurotrauma. 2015;32:1109–16.

    Article  Google Scholar 

  21. Divani AA, Berezina TL, Vazquez G, Zaets SB, Tummala R, Qureshi AI. Augmenting regional cerebral blood flow using external-to-internal carotid artery flow diversion method. Ann Biomed Eng. 2009;37:2428–35.

    Article  Google Scholar 

  22. Keep RF, Hua Y, Xi G. Brain water content. A misunderstood measurement? Transl Stroke Res. 2012;3:263–5.

    Article  Google Scholar 

  23. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. Osteoarthr Cartil. 2012;20:256–60.

    Article  CAS  Google Scholar 

  24. Ingberg E, Dock H, Theodorsson E, Theodorsson A, Strom JO. Effect of laser Doppler flowmetry and occlusion time on outcome variability and mortality in rat middle cerebral artery occlusion: inconclusive results. BMC Neurosci. 2018;19:24.

    Article  Google Scholar 

  25. Du C, Hu R, Csernansky CA, Hsu CY, Choi DW. Very delayed infarction after mild focal cerebral ischemia: a role for apoptosis? J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 1996;16:195–201.

    Article  CAS  Google Scholar 

  26. Hattori K, Lee H, Hurn PD, Crain BJ, Traystman RJ, DeVries AC. Cognitive deficits after focal cerebral ischemia in mice. Stroke A J Cere Circul. 2000;31:1939–44.

    Article  CAS  Google Scholar 

  27. Yeh SJ, Tang SC, Tsai LK, Jeng JS, Chen CL, Hsieh ST. Neuroanatomy- and pathology-based functional examinations of experimental stroke in rats: development and validation of a new behavioral scoring system. Front Behav Neurosci. 2018;12:316.

    Article  CAS  Google Scholar 

  28. Coyle P, Heistad DD. Development of collaterals in the cerebral circulation. Blood vessels. 1991;28:183–9.

    CAS  PubMed  Google Scholar 

  29. Liebeskind DS. Collateral circulation. Stroke J Cereb Circul. 2003;34:2279–84.

    Article  Google Scholar 

  30. Belayev L, Alonso OF, Busto R, Zhao W, Ginsberg MD. Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. Stroke J Cereb Circul. 1996;27:1616–22 discussion 23.

    Article  CAS  Google Scholar 

  31. Spratt NJ, Fernandez J, Chen M, Rewell S, Cox S, van Raay L, et al. Modification of the method of thread manufacture improves stroke induction rate and reduces mortality after thread-occlusion of the middle cerebral artery in young or aged rats. J Neurosci Methods. 2006;155:285–90.

    Article  Google Scholar 

  32. Zhao H, Mayhan WG, Sun H. A modified suture technique produces consistent cerebral infarction in rats. Brain Res. 2008;1246:158–66.

    Article  CAS  Google Scholar 

  33. Trueman RC, Diaz C, Farr TD, Harrison DJ, Fuller A, Tokarczuk PF, et al. Systematic and detailed analysis of behavioural tests in the rat middle cerebral artery occlusion model of stroke: tests for long-term assessment. J Cerebral Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 2017;37:1349–61.

    Article  Google Scholar 

  34. Gerriets T, Stolz E, Walberer M, Muller C, Rottger C, Kluge A, et al. Complications and pitfalls in rat stroke models for middle cerebral artery occlusion: a comparison between the suture and the macrosphere model using magnetic resonance angiography. Stroke J Cereb Circul. 2004;35:2372–7.

    Article  Google Scholar 

  35. Hill JW, Nemoto EM. Transient middle cerebral artery occlusion with complete reperfusion in spontaneously hypertensive rats. MethodsX. 2014;1:283–91.

    Article  Google Scholar 

Download references

Acknowledgements

The authors express their gratitude toward Charles River Laboratories for providing gratis rats used in this study. Further, we thank Apameh Salari, MD, for her help with performing some of the experiments.

Author information

Authors and Affiliations

  1. Department of Neurology, University of Minnesota, MMC 295, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA

    Afshin A. Divani, Alibay Jafarli & Mostafa Jafari

  2. Department of Neurological Surgery, University of Minnesota, Minneapolis, MN, USA

    Afshin A. Divani

  3. Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA

    Afshin A. Divani

  4. Faculty of Medicine and Health Sciences, School of Life Sciences, University of Nottingham, Nottingham, UK

    Tracy D. Farr

  5. Department of Neurology, San Camillo de’ Lellis District General Hospital, Rieti, Italy

    Mario Di Napoli

  6. Vital Images, Minnetonka, MN, USA

    Pascal Salazar

  7. Department of Pathology, University of New Mexico, Albuquerque, NM, USA

    Karen S. SantaCruz

  8. Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Marc Fisher

Authors
  1. Afshin A. Divani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tracy D. Farr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mario Di Napoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pascal Salazar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karen S. SantaCruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alibay Jafarli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mostafa Jafari
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marc Fisher
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AAD designed the study, performed the experiments, interpreted the results, prepared the manuscript the subsequent revisions, and supervise the project. TDF, MDN, KSS and MF contributed to the study design, manuscript preparation, and subsequent revisions. PS designed and performed statistical analysis, contributed to manuscript preparation, and subsequent revisions. AJ and MJ performed the experiments and contributed to data collection.

Corresponding author

Correspondence to Afshin A. Divani.

Ethics declarations

Conflict of interest

Dr. Salazar is an employee of Vital Images (Minnetonka, MN, USA).

Ethical Approval

The study was approved by and conducted according to the guidelines set by the IACUC at the University of Minnesota. The data are reported based on the recommendations from “Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research”.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 18 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Divani, A.A., Farr, T.D., Di Napoli, M. et al. Transfemoral Approach to Induce Transient Middle Cerebral Artery Occlusion in Rats: The Use of Commercially Available Endovascular Wires. Neurocrit Care 32, 575–585 (2020). https://doi.org/10.1007/s12028-019-00791-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12028-019-00791-8

Keywords

Search

Navigation