This site uses cookies, tags, and tracking settings to store information that help give you the very best browsing experience. Dismiss this warning

Endothelial molecular changes in a rodent model of arteriovenous malformation

Laboratory investigation

Athula Karunanyaka Prince of Wales Medical Research Institute, University of New South Wales, Sydney; and

Search for other papers by Athula Karunanyaka in
Current site
Google Scholar
PubMed Close
 M.B.B.S.
,
Jian Tu Prince of Wales Medical Research Institute, University of New South Wales, Sydney; and

Search for other papers by Jian Tu in
Current site
Google Scholar
PubMed Close
 M.B.B.S., Ph.D.
,
Amy Watling Prince of Wales Medical Research Institute, University of New South Wales, Sydney; and

Search for other papers by Amy Watling in
Current site
Google Scholar
PubMed Close
 B.Sc.
,
Kingsley P. Storer Prince of Wales Medical Research Institute, University of New South Wales, Sydney; and

Search for other papers by Kingsley P. Storer in
Current site
Google Scholar
PubMed Close
 M.B.B.S., Ph.D.
,
Apsara Windsor Prince of Wales Medical Research Institute, University of New South Wales, Sydney; and

Search for other papers by Apsara Windsor in
Current site
Google Scholar
PubMed Close
 M.B.B.S.
, and
Marcus A. Stoodley Prince of Wales Medical Research Institute, University of New South Wales, Sydney; and
Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia

Search for other papers by Marcus A. Stoodley in
Current site
Google Scholar
PubMed Close
 Ph.D., F.R.A.C.S.
Page Range:
1165–1172
Volume/Issue:
Volume 109: Issue 6
DOI link:
https://doi.org/10.3171/JNS.2008.109.12.1165
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $536.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $636.00
Click here for subscription options

  • Purchase Now

    USD  $45.00

  • JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

    USD  $536.00

  • JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

    USD  $636.00
USD  $45.00
USD  $536.00
USD  $636.00
Print or Print + Online Sign in

Object

The cellular and molecular processes underlying arteriovenous malformation (AVM) development and response to radiosurgery are largely unknown. An animal model mimicking the molecular properties of AVMs is required to examine these processses. This study was performed to determine whether the endothelial molecular changes in an animal model of arteriovenous fistula (AVF) are similar to those in human AVMs.

Methods

Arteriovenous fistulas were created in 18 Sprague–Dawley rats by end-to-side anastomosis of the left jugular vein to the common carotid artery creating a model “nidus” of arterialized branching veins that coalesce into a “draining vein” (sigmoid sinus). Six control animals underwent sham operations.

Results

After 1 or 3 days, or 1, 3, 6, or 12 weeks, fresh-frozen sections of the fistula, nidus vessels, and contralateral vessels were studied immunohistochemically for thrombomodulin, von Willebrand factor, E-selectin, P-selectin, and vascular endothelial growth factor.

Conclusions

The AVF model has a “nidus” with endothelial molecular changes similar to those observed in human AVMs, supporting its use as a model for studying the effects of radiosurgery on AVMs.

Abbreviations used in this paper:

AVF = arteriovenous fistula; AVM = arteriovenous malformation; bFGF = basic fibroblast growth factor; CA = carotid artery; CCA = common CA; TGF-α= transforming growth factor–α; VEGF = vascular endothelial growth factor; vWF = von Willebrand factor.
  • Collapse
  • Expand
Volume 109: Issue 6

Contributor Notes

Address correspondence to: Marcus Stoodley, Ph.D., F.R.A.C.S., Institute of Neurological Sciences, Prince of Wales Hospital, Barker Street, Randwick, New South Wales 2031, Australia. email: m.stoodley@unsw.edu.au.
  • 1

    Cicciarello R, , d'Avella D, , Gagliardi ME, , Albiero F, , Vega J, & Angileri FF, et al.: Time-related ultrastructural changes in an model of whole brain irradiation. Neurosurgery 38:772–779, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    De Salles AA, , Solberg TD, , Mischel P, , Massoud TF, , Plasencia A, & Goetsch S, et al.: Arteriovenous malformation animal model for radiosurgery: the rete mirabile. AJNR Am J Neuroradiol 17:1451–1458, 1996

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Dimitrievich GS, , Fischer-Dzoga K, & Griem ML: Radiosensitivity of vascular tissue. I. Differential radiosensitivity of capillaries: a quantitative in vivo study. Radiat Res 99:511–535, 1984

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Elisevich K, , Redekop G, , Munoz D, , Fisher B, , Wiese K, & Drake C: Neuropathology of intracranial arteriovenous malformations following conventional radiation therapy. Stereotact Funct Neurosurg 63:250–254, 1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Fijardo LF, & Berthrong M: Vascular lesions following radiation. Pathol Annu 23:297–330, 1988

  • 6

    Hallahan D, , Clark ET, , Kuchibhotla J, , Gewertz BL, & Collins T: E-selectin gene induction by ionizing radiation is independent of cytokine induction. Biochem Biophys Res Commun 217:784–795, 1995

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Hartmann A, , Mast H, , Mohr JP, , Koennecke HC, , Osipov A, & Pile-Spellman J, et al.: Morbidity of intracranial hemorrhage in patients with cerebral arteriovenous malformation. Stroke 29:931–934, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Hashimoto T, , Lam T, , Boudreau NJ, , Bollen AW, , Lawton MT, & Young WL: Abnormal balance in the angiopoietin-tie2 system in human brain arteriovenous malformations. Circ Res 89:111–113, 2001

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Hopewell JW: Letter: the late vascular effects of radiation. Br J Radiol 47:157–158, 1974

  • 10

    Hopewell JW, , Campling D, , Calvo W, , Reinhold HS, , Wilkinson JH, & Yeung TK: Vascular irradiation damage: its cellular basis and likely consequences. Br J Cancer Suppl 7:181–191, 1986

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Huang J, , Choudhri TF, , Winfree CJ, , McTaggart RA, , Kiss S, & Mocco J, et al.: Postischemic cerebrovascular e-selectin expression mediates tissue injury in murine stroke. Stroke 31:3047–3053, 2000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Kamiryo T, , Lopes MB, , Berr SS, , Lee KS, , Kassell NF, & Steiner L: Occlusion of the anterior cerebral artery after Gamma Knife irradiation in a rat. Acta Neurochir (Wien) 138:983– 990, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Kamiryo T, , Lopes MB, , Kassell NF, , Steiner L, & Lee KS: Radiosurgery-induced microvascular alterations precede necrosis of the brain neuropil. Neurosurgery 49:409–414, 2001

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Kilic T, , Pamir MN, , Kullu S, , Eren F, , Ozek MM, & Black PM: Expression of structural proteins and angiogenic factors in cerebrovascular anomalies. Neurosurgery 46:1179–1191, 2000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Koch AE, , Halloran MM, , Haskell CJ, , Shah MR, & Polverini PJ: Angiogenesis mediated by soluble forms of e-selectin and vascular cell adhesion molecule-1. Nature 376:517–519, 1995

  • 16

    Louis EL, , McLoughlin MJ, & Wortzman G: Chronic damage to medium and large arteries following irradiation. J Can Assoc Radiol 25:94–104, 1974

  • 17

    Mast H, , Young WL, , Koennecke HC, , Sciacca RR, , Osipov A, & Pile-Spellman J, et al.: Risk of spontaneous haemorrhage after diagnosis of cerebral arteriovenous malformation. Lancet 350:1065–1068, 1997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Masuda H, , Zhuang YJ, , Singh TM, , Kawamura K, , Murakami M, & Zarins CK, et al.: Adaptive remodeling of internal elastic lamina and endothelial lining during flow-induced arterial enlargement. Arterioscler Thromb Vasc Biol 19:2298–2307, 1999

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Morgan MK, , Johnston I, , Besser M, & Baines D: Cerebral arteriovenous malformations, steal, and the hypertensive breakthrough threshold. An experimental study in rats. J Neurosurg 66:563–567, 1987

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Morgan MK, , Anderson RE, & Sundt TM Jr: A model of the pathophysiology of cerebral arteriovenous malformations by a carotid-jugular fistula in the rat. Brain Res 496:241–250, 1989

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Murayama Y, , Massoud TF, & Vinuela F: Transvenous hemodynamic assessment of experimental arteriovenous malformations: doppler guidewire monitoring of embolotherapy in a swine model. Stroke 27:1365–1372, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Paris F, , Fuks Z, , Kang A, , Capodieci P, , Juan G, & Ehleiter D, et al.: Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice. Science 293:293–297, 2001

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Pinsky DJ, , Naka Y, , Liao H, , Oz MC, , Wagner DD, & Mayadas TN, et al.: Hypoxia-induced exocytosis of endothelial cell weibelpalade bodies. A mechanism for rapid neutrophil recruitment after cardiac preservation. J Clin Invest 97:493–500, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Rhoten RL, , Comair YG, , Shedid D, , Chyatte D, & Simonson MS: Specific repression of the preproendothelin-1 gene in intracranial arteriovenous malformations. J Neurosurg 86:101–108, 1997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Rothbart D, , Awad IA, , Lee J, , Kim J, , Harbaugh R, & Criscuolo GR: Expression of angiogenic factors and structural proteins in central nervous system vascular malformations. Neurosurgery 38:915–924, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Shen WY, , Yu MJ, , Barry CJ, , Constable IJ, & Rakoczy PE: Expression of cell adhesion molecules and vascular endothelial growth factor in experimental choroidal neovascularisation in the rat. Br J Ophthalmol 82:1063–1071, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Sonstein WJ, , Kader A, , Michelsen WJ, , Llena JF, , Hirano A, & Casper D: Expression of vascular endothelial growth factor in pediatric and adult cerebral arteriovenous malformations: an immunocytochemical study. J Neurosurg 85:838–845, 1996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Storer KP, , Tu J, , Karunanayaka A, , Morgan MK, & Stoodley MA: Thrombotic molecule expression in cerebral vascular malformations. J Clin Neurosci 14:975–980, 2007

  • 29

    Szeifert GT: Radiosurgery and AVM histopathology. J Neurosurg 88:356–357, 1998

  • 30

    Szeifert GT, , Major O, , Fazekas I, & Nagy Z: Effects of radiation on cerebral vasculature: a review. Neurosurgery 48:452–453, 2001

  • 31

    The Arteriovenous Malformation Study Group: Arteriovenous malformations of the brain in adults. N Engl J Med 340:1812–1818, 1999

  • 32

    Tu J, , Stoodley MA, , Morgan MK, & Storer KP: Responses of arteriovenous malformations to radiosurgery: ultrastructural changes. Neurosurgery 58:749–758, 2006

  • 33

    Tu J, , Stoodley MA, , Morgan MK, & Storer KP: Ultrastructure of perinidal capillaries in cerebral arteriovenous malformations. Neurosurgery 58:961–969, 2006

  • 34

    Uranishi R, , Awadallah NA, , Ogunshola OO, & Awad IA: Further study of cd31 protein and messenger ribonucleic acid expression in human cerebral vascular malformations. Neurosurgery 50:110–115, 2002

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Vestweber D, & Blanks JE: Mechanisms that regulate the function of the selectins and their ligands. Physiol Rev 79:181–213, 1999

  • 36

    Wong JH, , Awad IA, & Kim JH: Ultrastructural pathological features of cerebrovascular malformations: a preliminary report. Neurosurgery 46:1454–1459, 2000

  • 37

    Yamaguchi N, , Yamashima T, & Yamashita J: A histological and flow cytometric study of dog brain endothelial cell injuries in delayed radiation necrosis. J Neurosurg 74:625–632, 1991

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Yassari R, , Sayama T, , Jahromi BS, , Aihara Y, , Stoodley M, & Macdonald RL: Angiographic, hemodynamic and histological characterization of an arteriovenous fistula in rats. Acta Neurochir (Wien) 146:495–504, 2004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Young WL, Intracranial arteriovenous malformations: pathophysiology and hemodynamics. Jafar JJ, , Awad IA, & Rosenwasser RH: Vascular Malformations of the Central Nervous System New York, Lippincott Williams & Wilkins, 1999. 95–126

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Zhou Q, , Zhao Y, , Li P, , Bai X, & Ruan C: Thrombomodulin as a marker of radiation-induced endothelial cell injury. Radiat Res 131:285–289, 1992

  • 41

    Zhou W, , Bush RL, , Lin PH, & Lumsden AB: Radiation-associated venous stenosis: endovascular treatment options. J Vasc Surg 40:179–182, 2004

Metrics

All Time Past Year Past 30 Days
Abstract Views 622 49 6
Full Text Views 189 23 3
PDF Downloads 161 16 1
EPUB Downloads 0 0 0