Skip to main content

Advertisement

Log in

Gradual common carotid artery occlusion as a novel model for cerebrovascular Hypoperfusion

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Chronic cerebrovascular hypoperfusion results in vascular dementia and increases predisposition to lacunar infarcts. However, there are no suitable animal models. In this study, we developed a novel model for chronic irreversible cerebral hypoperfusion in mice. Briefly, an ameroid constrictor was placed on the right carotid artery to gradually occlude the vessel, while a microcoil was placed on the left carotid artery to prevent compensation of the blood flow. This procedure resulted in a gradual hypoperfusion developing over a period of 34 days with no cerebral blood flow recovery. Histological analysis of the brain revealed neuronal and axonal degeneration as well as necrotic lesions. The most severely affected regions were located in the hippocampus and the corpus callosum. Overall, our paradigm is a viable model to study brain pathology resulting from gradual cerebrovascular hypoperfusion.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Black S, Gao F, Bilbao J (2009) Understanding white matter disease: imaging-pathological correlations in vascular cognitive impairment. Stroke 40:S48–S52

    Article  Google Scholar 

  • Bottiger BW, Schmitz B, Wiessner C, Vogel P, Hossmann KA (1998) Neuronal stress response and neuronal cell damage after cardiocirculatory arrest in rats. Brain Res Mol Brain Res 18:1077–1087

    CAS  Google Scholar 

  • Bottiger BW, Teschendorf P, Krumnikl JJ, Vogel P, Galmbacher R, Schmitz B, Motsch J, Martin E, Gass P (1999) Global cerebral ischemia due to cardiocirculatory arrest in mice causes neuronal degeneration and early induction of transcription factor genes in the hippocampus. Brain Res Mol Brain Res 65:135–142

    Article  CAS  Google Scholar 

  • Carmichael ST (2005) Rodent models of focal stroke: size, mechanism, and purpose. NeuroRx 2:396–409

    Article  Google Scholar 

  • Cechetti F, Worm PV, Pereira LO, Siqueira IR, AN C (2010) The modified 2VO ischemia protocol causes cognitive impairment similar to that induced by the standard method, but with a better survival rate. Braz J Med Biol Res 43:1178–1183

    Article  CAS  Google Scholar 

  • Clark WM, Lessov NS, Dixon MP, Eckenstein F (1997) Monofilament intraluminal middle cerebral artery occlusion in the mouse. Neurol Res 19:641–648

    Article  CAS  Google Scholar 

  • Connolly ES Jr, Winfree CJ, Stern DM, Solomon RA, Pinsky DJ (1996) Procedural and strain-related variables significantly affect outcome in a murine model of focal cerebral ischemia. Neurosurgery 38:523–531 discussion 532

    PubMed  Google Scholar 

  • Hattori Y, Enmi J, Kitamura A, Yamamoto Y, Saito S, Takahashi Y, Iguchi S, Tsuji M, Yamahara K, Nagatsuka K, Iida H, Ihara M (2015) A novel mouse model of subcortical infarcts with dementia. J Neurosci 35:3915–3928

    Article  CAS  Google Scholar 

  • Hattori Y, Enmi J, Iguchi S, Saito S, Yamamoto Y, Nagatsuka K, Iida H, Ihara M (2016) Substantial reduction of parenchymal cerebral blood flow in mice with bilateral common carotid artery stenosis. Sci Rep 6:32179

    Article  CAS  Google Scholar 

  • Kitagawa K, Matsumoto M, Yang G, Mabuchi T, Yagita Y, Hori M, Yanagihara T (1998) Cerebral ischemia after bilateral carotid artery occlusion and intraluminal suture occlusion in mice: evaluation of the patency of the posterior communicating artery. J Cereb Blood Flow Metab 18:570–579

    Article  CAS  Google Scholar 

  • Kitamura A, Saito S, Maki T, Oishi N, Ayaki T, Hattori Y, Yamamoto Y, Urushitani M, Kalaria RN, Fukuyama H, Horsburgh K, Takahashi R, Ihara M (2016) Gradual cerebral hypoperfusion in spontaneously hypertensive rats induces slowly evolving white matter abnormalities and impairs working memory. J Cereb Blood Flow Metab 36:1592–1602

    Article  CAS  Google Scholar 

  • Kynast J, Lampe L, Luck T, Frisch S, Arelin K, Hoffmann KT, Loeffler M, Riedel-Heller SG, Villringer A, Schroeter ML (2017) White matter hyperintensities associated with small vessel disease impair social cognition beside attention and memory. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism:271678X17719380

  • Longa EZ, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91

    Article  CAS  Google Scholar 

  • Matin N, Fisher C, Jackson WF, Dorrance AM (2016) Bilateral common carotid artery stenosis in normotensive rats impairs endothelium-dependent dilation of parenchymal arterioles. Am J Phys Heart Circ Phys 310:H1321–H1329

    Google Scholar 

  • Ohta H, Nishikawa H, Kimura H, Anayama H, Miyamoto M (1997) Chronic cerebral hypoperfusion by permanent internal carotid ligation produces learning impairment without brain damage in rats. Neuroscience 79:1039–1050

    Article  CAS  Google Scholar 

  • Onken M, Berger S, Kristian T (2012) Simple model of forebrain ischemia in mouse. J Neurosci Methods 204:254–261

    Article  Google Scholar 

  • Patel A, Moalem A, Cheng H, Babadjouni RM, Patel K, Hodis DM, Chandegara D, Cen S, He S, Liu Q, Mack WJ (2017) Chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis causes selective recognition impairment in adult mice. Neurol Res 39:910–917

    Article  Google Scholar 

  • Pulsinelli WA, Buchan AM (1988) The four-vessel occlusion rat model: method for complete occlusion of vertebral arteries and control of collateral circulation. Stroke 19:913–914

    Article  CAS  Google Scholar 

  • Shibata M, Ohtani R, Ihara M, Tomimoto H (2004) White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion. Stroke 35:2598–2603

    Article  Google Scholar 

  • Shibata M, Yamasaki N, Miyakawa T, Kalaria RN, Fujita Y, Ohtani R, Ihara M, Takahashi R, Tomimoto H (2007) Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion. Stroke 38:2826–2832

    Article  Google Scholar 

  • Srinivasan VJ, Yu E, Radhakrishnan H, Can A, Climov M, Leahy C, Ayata C, Eikermann-Haerter K (2015) Micro-heterogeneity of flow in a mouse model of chronic cerebral hypoperfusion revealed by longitudinal Doppler optical coherence tomography and angiography. J Cereb Blood Flow Metab 35:1552–1560

    Article  Google Scholar 

  • Takano K, Tatlisumak T, Bergmann AG, Gibson DG 3rd, Fisher M (1997) Reproducibility and reliability of middle cerebral artery occlusion using a silicone-coated suture (Koizumi) in rats. J Neurol Sci 153:8–11

    Article  CAS  Google Scholar 

  • Thal SC, Thal SE, Plesnila N (2010) Characterization of a 3-vessel occlusion model for the induction of complete global cerebral ischemia in mice. J Neurosci Methods 192:219–227

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Uchihara T (2007) Silver diagnosis in neuropathology: principles, practice and revised interpretation. Acta Neuropathol 113:483–499

    Article  Google Scholar 

  • Vasquez BP, Zakzanis KK (2015) The neuropsychological profile of vascular cognitive impairment not demented: a meta-analysis. J Neuropsychol 9:109–136

    Article  Google Scholar 

  • Wells GA, Wells M (1989) Neuropil vacuolation in brain: a reproducible histological processing artefact. J Comp Pathol 101:355–362

    Article  CAS  Google Scholar 

  • Xiong Y, Mahmood A, Lu D, Qu C, Kazmi H, Goussev A, Zhang ZG, Noguchi CT, Schallert T, Chopp M (2008) Histological and functional outcomes after traumatic brain injury in mice null for the erythropoietin receptor in the central nervous system. Brain Res 1230:247–257

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Dr. Gregory Konat for revising and editing the manuscript. This study was supported by the Helen Marie Lewis Medical Research Foundation (to JWS, XR, and AM), NIH CoBRE (P20 GM109098 to JWS), AHA SDG (16SDG31170008 to XR), NIH T32 (AG052375 to JWS), and funding from the Department of Neurology at WVU (to AM).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Xuefang Ren or Mohammad Alvi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Quintana, D.D., Ren, X., Hu, H. et al. Gradual common carotid artery occlusion as a novel model for cerebrovascular Hypoperfusion. Metab Brain Dis 33, 2039–2044 (2018). https://doi.org/10.1007/s11011-018-0312-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-018-0312-5

Keywords

Navigation