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Cerebrovascular Imaging in a Rodent Stroke Model

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Models and Techniques in Stroke Biology

Abstract

Cerebrovascular imaging and its anatomy are an important determining component of blood flow dynamics, the pathophysiology and severity of brain injuries after stroke. Currently, various tools and techniques are available for vascular network imaging in rodent stroke models like intravascular perfusion of carbon black ink (CB) and others. This technique is widely used for imaging and studying the blood vessels after stroke. These methods are simple, feasible, cost-effective, and often used with the combination of CB to provide effective validation of the anterior cerebral artery (ACA) and middle cerebral artery (MCA). During the intravascular perfusion, combined ink is injected into the thoracic aorta allowing it to disperse throughout all parts of the body along with the brain providing high-contrast cerebrovascular images. Furthermore, this mixed infusion allows capturing images with a smaller vessel diameter in a larger area of the vessel compared to perfusion with latex infusion. Intravascular perfusion of CB provides a high repeatability and measurement accuracy to visualize the cerebrovascular structure of the vessels. Given the above, this chapter offers a concise summary and brief historical reference of different imaging techniques. Moreover, it offers an overview of the available protocols for CB, to identify cerebral vascular architecture and the connection between ACA and MCA as well as anastomotic line study. It also describes the analysis of the macroscopic anatomy of the cerebral vessels.

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Abbreviations

MCA:

Middle cerebral artery

ACA:

Anterior cerebral artery

CBF:

Cerebral blood flow

CB:

Carbon black

PFA:

Paraformaldehyde

References

  • Aswendt M, Schwarz M, Abdelmoula WM, Dijkstra J, Dedeurwaerdere S (2017) Whole-brain microscopy meets in vivo neuroimaging: techniques, benefits, and limitations. Mol Imaging Biol 19(1):1–9

    Article  PubMed  Google Scholar 

  • Aum DJ, Vellimana AK, Singh I, Milner E, Nelson JW, Han BH, Zipfel GJ (2017) A novel fluorescent imaging technique for assessment of cerebral vasospasm after experimental subarachnoid hemorrhage. Sci Rep 7(1):1–2

    Article  CAS  Google Scholar 

  • Benedek A, Móricz K, Jurányi Z, Gigler G, Lévay G, Hársing LG Jr, Mátyus P, Szénási G, Albert M (2006) Use of TTC staining for the evaluation of tissue injury in the early phases of reperfusion after focal cerebral ischemia in rats. Brain Res 1116(1):159–165

    Article  CAS  PubMed  Google Scholar 

  • Busch HJ, Buschmann IR, Mies G, Bode C, Hossmann KA (2003) Arteriogenesis in hypoperfused rat brain. J Cereb Blood Flow Metab 23(5):621–628

    Article  PubMed  Google Scholar 

  • Campbell BC, De Silva DA, Macleod MR, Coutts SB, Schwamm LH, Davis SM, Donnan GA (2019) Ischaemic stroke. Nat Rev Dis Primers 5(1):1–22

    Article  Google Scholar 

  • Cao Y, Wu T, Li D, Ni S, Hu J, Lu H (2015) Three-dimensional imaging of microvasculature in the rat spinal cord following injury. Sci Rep 5:12643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coyle P (1984) Diameter and length changes in cerebral collaterals after middle cerebral artery occlusion in the young rat. Anat Rec 210(2):357–364

    Article  CAS  PubMed  Google Scholar 

  • Coyle P (1987) Dorsal cerebral collaterals of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY). Anat Rec 218(1):40–44

    Article  CAS  PubMed  Google Scholar 

  • Coyle P, Jokelainen PT (1982) Dorsal cerebral arterial collaterals of the rat. Anat Rec 203(3):397–404

    Article  CAS  PubMed  Google Scholar 

  • Dhanesha N, Jain M, Tripathi A, Doddapattar P, Chorawala M, Bathla G, Nayak MK, Ghatge M, Lentz SR, Kon S, Chauhan AK (2020) Targeting myeloid-specific integrin α9β1 improves short and long-term stroke outcomes in murine models with preexisting comorbidities by limiting thrombosis and inflammation. Circ Res 126(12):1779–1794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doeppner TR, Nagel F, Dietz GP, Weise J, Tönges L, Schwarting S, Bähr M (2009) TAT-Hsp70-mediated neuroprotection and increased survival of neuronal precursor cells after focal cerebral ischemia in mice. J Cereb Blood Flow Metab 29(6):1187–1196

    Article  CAS  PubMed  Google Scholar 

  • Doomernik DE, Kruse RR, Reijnen MM, Kozicz TL, Kooloos JG (2016) A comparative study of vascular injection fluids in fresh-frozen and embalmed human cadaver forearms. J Anat 229(4):582–590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • ElAli A, Doeppner TR, Zechariah A, Hermann DM (2011) Increased blood–brain barrier permeability and brain edema after focal cerebral ischemia induced by hyperlipidemia: role of lipid peroxidation and calpain-1/2, matrix metalloproteinase-2/9, and RhoA overactivation. Stroke 42(11):3238–3244

    Article  CAS  PubMed  Google Scholar 

  • Gage GJ, Kipke DR, Shain W (2012) Whole animal perfusion fixation for rodents. JoVE e3564:65

    Google Scholar 

  • Garland P, Morton MJ, Haskins W, Zolnourian A, Durnford A, Gaastra B, Toombs J, Heslegrave AJ, More J, Okemefuna AI, Teeling JL (2020) Haemoglobin causes neuronal damage in vivo which is preventable by haptoglobin. Brain Commun 2(1):fcz053

    Article  PubMed  PubMed Central  Google Scholar 

  • Hasan MR, Herz J, Hermann DM, Doeppner TR (2012) Visualization of macroscopic cerebral vessel anatomy—a new and reliable technique in mice. J Neurosci Methods 204(2):249–253

    Article  PubMed  Google Scholar 

  • Hasan MR, Herz J, Hermann DM, Doeppner TR (2013) Intravascular perfusion of carbon black ink allows reliable visualization of cerebral vessels. JoVE 71:e4374

    Google Scholar 

  • Hu X, De Silva TM, Chen J, Faraci FM (2017) Cerebral vascular disease and neurovascular injury in ischemic stroke. Circ Res 120(3):449–471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalaria RN (2010) Vascular basis for brain degeneration: faltering controls and risk factors for dementia. Nutr Rev 68(suppl_2):S74–S87

    Article  PubMed  Google Scholar 

  • Kim CB, Park SJ, Jeong JC, Choi SM, Krause HJ, Song DY, Hong H (2019) Construction of 3D-rendering imaging of an ischemic rat brain model using the planar FMMD technique. Sci Rep 9(1):1–9

    Google Scholar 

  • Kisler K, Lazic D, Sweeney MD, Plunkett S, El Khatib M, Vinogradov SA, Boas DA, Sakadži S, Zlokovic BV (2018) In vivo imaging and analysis of cerebrovascular hemodynamic responses and tissue oxygenation in the mouse brain. Nat Protoc 13(6):1377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lefevre S, Stecyk JA, Torp MK, Løvold LY, Sørensen C, Johansen IB, Stensløkken KO, Couturier CS, Sloman KA, Nilsson GE (2017) Re-oxygenation after anoxia induces brain cell death and memory loss in the anoxia-tolerant crucian carp. J Exp Biol 220(21):3883–3895

    Article  PubMed  Google Scholar 

  • Li Z, Bishop N, Chan SL, Cipolla MJ (2018) Effect of TTC treatment on immunohistochemical quantification of collagen IV in rat brains after stroke. Transl Stroke Res 9(5):499–505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luo Y, Yin X, Shi S, Ren X, Zhang H, Wang Z, Cao Y, Tang M, Xiao B, Zhang M (2019) Non-destructive 3D microtomography of cerebral angioarchitecture changes following ischemic stroke in rats using synchrotron radiation. Front Neuroanat 13:5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maeda K, Hata R, Hossmann KA (1998) Differences in the cerebrovascular anatomy of C57black/6 and SV129 mice. Neuroreport 9(7):1317–1319

    Article  CAS  PubMed  Google Scholar 

  • Maeda K, Hata R, Hossmann KA (1999) Regional metabolic disturbances and cerebrovascular anatomy after permanent middle cerebral artery occlusion in C57black/6 and SV129 mice. Neurobiol Dis 6(2):101–108

    Article  CAS  PubMed  Google Scholar 

  • Mahmoudi S, Xu L, Brunet A (2019) Turning back time with emerging rejuvenation strategies. Nat Cell Biol 21(1):32–43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meng H, Peng Y, Hasan R, Yu G, Wang MM (2009) Nuclear contrast angiography: a simple method for morphological characterization of cerebral arteries. Brain Res 1261:75–81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mikhail P, Le MG, Mair G (2020) Computational image analysis of nonenhanced computed tomography for acute ischaemic stroke: a systematic review. J Stroke Cerebrovasc Dis 2020:104715

    Article  Google Scholar 

  • Milner E, Johnson AW, Nelson JW, Harries MD, Gidday JM, Han BH, Zipfel GJ (2015) HIF-1α mediates isoflurane-induced vascular protection in subarachnoid hemorrhage. Ann Clin Transl Neurol 2(4):325–337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moskowitz MA, Lo EH, Iadecola C (2010) The science of stroke: mechanisms in search of treatments. Neuron 67(2):181–198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nahirney PC, Reeson P, Brown CE (2016) Ultrastructural analysis of blood–brain barrier breakdown in the peri-infarct zone in young adult and aged mice. J Cereb Blood Flow Metab 36(2):413–425

    Article  PubMed  Google Scholar 

  • Pál É, Hricisák L, Lékai Á, Nagy D, Fülöp Á, Erben RG, Várbíró S, Sándor P, Benyó Z (2020) Ablation of vitamin D signaling compromises cerebrovascular adaptation to carotid artery occlusion in mice. Cell 9(6):1457

    Article  CAS  Google Scholar 

  • Rekik I, Allassonnière S, Carpenter TK, Wardlaw JM (2012) Medical image analysis methods in MR/CT-imaged acute-subacute ischemic stroke lesion: segmentation, prediction and insights into dynamic evolution simulation models. A critical appraisal. NeuroImage 1(1):164–178

    Article  PubMed  PubMed Central  Google Scholar 

  • Renard Y, Hossu G, Chen B, Krebs M, Labrousse M, Perez M (2018) A guide for effective anatomical vascularization studies: useful ex vivo methods for both CT and MRI imaging before dissection. J Anat 232(1):15–25

    Article  PubMed  Google Scholar 

  • Rink C, Khanna S (2011) Significance of brain tissue oxygenation and the arachidonic acid cascade in stroke. Antioxid Redox Signal 14(10):1889–1903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rousselet E, Kriz J, Seidah NG (2012) Mouse model of intraluminal MCAO: cerebral infarct evaluation by cresyl violet staining. JoVE 6(69):e4038

    Google Scholar 

  • Sanchez Bezanilla S, Nilsson M, Walker FR, Ong LK (2019) Can we use 2,3,5-triphenyltetrazolium chloride stained brain slices for other purposes? The application of western blotting. Front Mol Neurosci 12:181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shih AY, Hyacinth HI, Hartmann DA, van Veluw SJ (2018) Rodent models of cerebral microinfarct and microhemorrhage. Stroke 49(3):803–810

    Article  PubMed  PubMed Central  Google Scholar 

  • Sugiyama Y, Yagita Y, Oyama N, Terasaki Y, Omura-Matsuoka E, Sasaki T, Kitagawa K (2011) Granulocyte colony-stimulating factor enhances arteriogenesis and ameliorates cerebral damage in a mouse model of ischemic stroke. Stroke 42(3):770–775

    Article  CAS  PubMed  Google Scholar 

  • Sweeney MD, Kisler K, Montagne A, Toga AW, Zlokovic BV (2018) The role of brain vasculature in neurodegenerative disorders. Nat Neurosci 21(10):1318–1331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Todo K, Kitagawa K, Sasaki T, Omura-Matsuoka E, Terasaki Y, Oyama N, Yagita Y, Hori M (2008) Granulocyte-macrophage colony-stimulating factor enhances leptomeningeal collateral growth induced by common carotid artery occlusion. Stroke 39(6):1875–1882

    Article  CAS  PubMed  Google Scholar 

  • Vellimana AK, Milner E, Azad TD, Harries MD, Zhou ML, Gidday JM, Han BH, Zipfel GJ (2011) Endothelial nitric oxide synthase mediates endogenous protection against subarachnoid hemorrhage-induced cerebral vasospasm. Stroke 42(3):776–782

    Article  CAS  PubMed  Google Scholar 

  • Vital SA, Gavins FN (2016) Surgical approach for middle cerebral artery occlusion and reperfusion induced stroke in mice. JoVE 116:e54302

    Google Scholar 

  • Wang Y, Kilic E, Kilic Ü, Weber B, Bassetti CL, Marti HH, Hermann DM (2005) VEGF overexpression induces post-ischaemic neuroprotection, but facilitates haemodynamic steal phenomena. Brain 128(1):52–63

    Article  PubMed  Google Scholar 

  • Yemisci M, Gursoy-Ozdemir Y, Vural A, Can A, Topalkara K, Dalkara T (2009) Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med 15(9):1031–1037

    Article  CAS  PubMed  Google Scholar 

  • Zhang MQ, Zhou L, Deng QF, Xie YY, Xiao TQ, Cao YZ, Zhang JW, Chen XM, Yin XZ, Xiao B (2015) Ultra-high-resolution 3D digitalized imaging of the cerebral angioarchitecture in rats using synchrotron radiation. Sci Rep 5:14982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Author notes

  1. Saroj Kumar Amar and Uttpal Anand contributed equally with all other contributors.

Authors and Affiliations

  1. School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India

    Saroj Kumar Amar

  2. Oak Rindge Institute for Science and Education, Oak Ridge, TN, USA

    Saroj Kumar Amar

  3. Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel

    Uttpal Anand & Ankit Verma

Authors
  1. Saroj Kumar Amar
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  2. Uttpal Anand
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  3. Ankit Verma
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Corresponding author

Correspondence to Ankit Verma .

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Editors and Affiliations

  1. School of Biomedical Engineering, Indian Institute of Technology BHU, Varanasi, Uttar Pradesh, India

    Amit Kumar Tripathi

  2. Amity Institute of Neuropsychology and Neurosciences, Amity University, Noida, Uttar Pradesh, India

    Abhishek Kumar Singh

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Amar, S.K., Anand, U., Verma, A. (2021). Cerebrovascular Imaging in a Rodent Stroke Model. In: Tripathi, A.K., Singh, A.K. (eds) Models and Techniques in Stroke Biology . Springer, Singapore. https://doi.org/10.1007/978-981-33-6679-4_7

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