Vascular corrosion casts mirroring early morphological changes that lead to the formation of saccular cerebral aneurysm: an experimental study in rats

Mohammad A. Jamous M.D. 1 , Shinji Nagahiro M.D., Ph.D. 1 , Keiko T. Kitazato B.S. 1 , Koichi Satoh M.D., Ph.D. 1 and Junichiro Satomi M.D., Ph.D. 1
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  • 1 Department of Neurosurgery, School of Medicine, The Institute of Health Bioscience, The University of Tokushima, Tokushima, Japan
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Object. The formation of cerebral aneurysms involves complex processes and little is known about the mechanisms by which they originate, grow, and rupture. The purpose of this study was to identify early ultrastructural morphological changes that lead to the formation of experimental cerebral aneurysms.

Methods. Twenty male Sprague—Dawley rats were subjected to cerebral aneurysm induction (renal hypertension and right common carotid artery ligation); 10 intact rats served as the control group. The animals were killed after 2 months, and a vascular corrosion cast of their cerebral arteries was prepared and screened for aneurysm development by using a scanning electron microscope.

Sequential morphological changes observed at the cerebral artery bifurcation in response to hemodynamic shear stress included endothelial changes, intimal pad elevation, and saccular dilation. Endothelial cell changes were the first observed morphological changes; they were followed by various degrees of artery wall dilation. No aneurysmal changes developed in any of the control rats. Of the 20 surgically treated rats, 11 displayed aneurysmal changes. In five of these animals only changes in the endothelial cell imprints could be identified. In the other six rats morphological changes in endothelial cells were associated with different stages of aneurysmal dilation.

Conclusions. This is the first study to demonstrate in vivo early morphological changes that lead to the formation of cerebral aneurysms. The morphological findings indicate the principal role of endothelial cells in the pathogenesis of cerebral aneurysms and suggest that hemodynamic shear stress and blood flow patterns may precipitate these early changes.

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Contributor Notes

Address reprint requests to: Mohammad A. Jamous, M.D., Department of Neurosurgery, School of Medicine, The University of Tokushima, 3–18–15 Kuramoto-cho, Tokushima City, Tokushima 770–8503, Japan. email: neuros@clin.med.tokushima-u.ac.jp.
  • 1

    Burleson AC, & Turitto VT: Identification of quantifiable hemodynamic factors in the assessment of cerebral aneurysm behavior. On behalf of the Subcommittee on Biorheology of the Scientific and Standardization Committee of the ISTH. Thromb Haemost 76:118123, 1996 Burleson AC, Turitto VT: Identification of quantifiable hemodynamic factors in the assessment of cerebral aneurysm behavior. On behalf of the Subcommittee on Biorheology of the Scientific and Standardization Committee of the ISTH. Thromb Haemost 76:118–123, 1996

    • Search Google Scholar
    • Export Citation
  • 2

    Cucina A, , Sterpetti AV, , Pupelis G, , Fragale A, , Lepidi S, & Cavallaro A, et al: Shear stress induces changes in the morphology and cytoskeleton organisation of arterial endothelial cells. Eur J Vasc Endovasc Surg 9:8692, 1995 Cucina A, Sterpetti AV, Pupelis G, Fragale A, Lepidi S, Cavallaro A, et al: Shear stress induces changes in the morphology and cytoskeleton organisation of arterial endothelial cells. Eur J Vasc Endovasc Surg 9:86–92, 1995

    • Search Google Scholar
    • Export Citation
  • 3

    Davies PF, , Remuzzi A, , Gordon EJ, , Dewey CF Jr, & Gimbrone MA Jr: Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro. Proc Natl Acad Sci USA 83:21142117, 1986 Davies PF, Remuzzi A, Gordon EJ, Dewey CF Jr, Gimbrone MA Jr: Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro. Proc Natl Acad Sci USA 83:2114–2117, 1986

    • Search Google Scholar
    • Export Citation
  • 4

    Hashimoto N, , Handa H, & Hazama F: Experimentally induced cerebral aneurysms in rats: Part II. Surg Neurol 11:243246, 1979 Hashimoto N, Handa H, Hazama F: Experimentally induced cerebral aneurysms in rats: Part II. Surg Neurol 11:243–246, 1979

    • Search Google Scholar
    • Export Citation
  • 5

    Hashimoto N, , Handa H, & Hazama F: Experimentally induced cerebral aneurysms in rats: Part III. Pathology. Surg Neurol 11:299304, 1979 Hashimoto N, Handa H, Hazama F: Experimentally induced cerebral aneurysms in rats: Part III. Pathology. Surg Neurol 11:299–304, 1979

    • Search Google Scholar
    • Export Citation
  • 6

    Hashimoto N, , Handa H, , Nagata I, & Hazama F: Animal model of cerebral aneurysms: pathology and pathogenesis of induced cerebral aneurysms in rats. Neurol Res 6:3340, 1984 Hashimoto N, Handa H, Nagata I, Hazama F: Animal model of cerebral aneurysms: pathology and pathogenesis of induced cerebral aneurysms in rats. Neurol Res 6:33–40, 1984

    • Search Google Scholar
    • Export Citation
  • 7

    Hashimoto N, , Handa H, , Nagata I, & Hazama F: Experimentally induced cerebral aneurysms in rats: Part V. Relation of hemodynamics in the circle of Willis to formation of aneurysms. Surg Neurol 13:4145, 1980 Hashimoto N, Handa H, Nagata I, Hazama F: Experimentally induced cerebral aneurysms in rats: Part V. Relation of hemodynamics in the circle of Willis to formation of aneurysms. Surg Neurol 13:41–45, 1980

    • Search Google Scholar
    • Export Citation
  • 8

    Hodde KC, & Nowell JA: SEM of micro-corrosion casts. Scan Electron Microsc (Pt 2):89106, 1980 Hodde KC, Nowell JA: SEM of micro-corrosion casts. Scan Electron Microsc (Pt 2):89–106, 1980

    • Search Google Scholar
    • Export Citation
  • 9

    Hoshina K, , Sho E, , Sho M, , Nakahashi TK, & Dalman RL: Wall shear stress and strain modulate experimental aneurysm cellularity. J Vasc Surg 37:10671074, 2003 Hoshina K, Sho E, Sho M, Nakahashi TK, Dalman RL: Wall shear stress and strain modulate experimental aneurysm cellularity. J Vasc Surg 37:1067–1074, 2003

    • Search Google Scholar
    • Export Citation
  • 10

    Ikeda K, , Hayase H, , Hayashi M, & Yamamoto S: [Aneurysm growth and enlargement of pre-aneurysmal lesions.] No Shinkei Geka 12:11511158, 1984 Ikeda K, Hayase H, Hayashi M, Yamamoto S: [Aneurysm growth and enlargement of pre-aneurysmal lesions.] No Shinkei Geka 12:1151–1158, 1984

    • Search Google Scholar
    • Export Citation
  • 11

    Itakura T, , Ozaki F, , Nakai E, , Fujii T, , Hayashi S, & Komai N: Bilateral aneurysm formation developing from junctional dilatation (infundibulum) of the posterior communicating arteries. Case report. J Neurosurg 58:117119, 1983 Itakura T, Ozaki F, Nakai E, Fujii T, Hayashi S, Komai N: Bilateral aneurysm formation developing from junctional dilatation (infundibulum) of the posterior communicating arteries. Case report. J Neurosurg 58:117–119, 1983

    • Search Google Scholar
    • Export Citation
  • 12

    Lametschwandtner A, , Lametschwandtner U, & Weiger T: Scanning electron microscopy of vascular corrosion casts—technique and applications: updated review. Scanning Microsc 4:889941, 1990 Lametschwandtner A, Lametschwandtner U, Weiger T: Scanning electron microscopy of vascular corrosion casts—technique and applications: updated review. Scanning Microsc 4:889–941, 1990

    • Search Google Scholar
    • Export Citation
  • 13

    Levesque MJ, , Cornhill JF, & Nerem RM: Vascular casting. A new method for the study of the arterial endothelium. Atherosclerosis 34:457467, 1979 Levesque MJ, Cornhill JF, Nerem RM: Vascular casting. A new method for the study of the arterial endothelium. Atherosclerosis 34:457–467, 1979

    • Search Google Scholar
    • Export Citation
  • 14

    Levesque MJ, , Nerem RM, & Sprague EA: Vascular endothelial cell proliferation in culture and the influence of flow. Biomaterials 11:702707, 1990 Levesque MJ, Nerem RM, Sprague EA: Vascular endothelial cell proliferation in culture and the influence of flow. Biomaterials 11:702–707, 1990

    • Search Google Scholar
    • Export Citation
  • 15

    Nerem RM, , Alexander RW, , Chappell DC, , Medford RM, , Varner SE, & Taylor WR: The study of the influence of flow on vascular endothelial biology. Am J Med Sci 316:169175, 1998 Nerem RM, Alexander RW, Chappell DC, Medford RM, Varner SE, Taylor WR: The study of the influence of flow on vascular endothelial biology. Am J Med Sci 316:169–175, 1998

    • Search Google Scholar
    • Export Citation
  • 16

    Nerem RM, , Harrison DG, , Taylor WR, & Alexander RW: Hemodynamics and vascular endothelial biology. J Cardiovasc Pharmacol 21 (Suppl 1):S6S10, 1993 Nerem RM, Harrison DG, Taylor WR, Alexander RW: Hemodynamics and vascular endothelial biology. J Cardiovasc Pharmacol 21 (Suppl 1):S6–S10, 1993

    • Search Google Scholar
    • Export Citation
  • 17

    Reidy MA, & Levesque MJ: A scanning electron microscopic study of arterial endothelial cells using vascular casts. Atherosclerosis 28:463470, 1977 Reidy MA, Levesque MJ: A scanning electron microscopic study of arterial endothelial cells using vascular casts. Atherosclerosis 28:463–470, 1977

    • Search Google Scholar
    • Export Citation
  • 18

    Roda JM, , Alvarez F, , Garcia-Villalon AL, , Ruiz MR, , Gutierrez M, & Garcia Blazquez M: An increment in unilateral carotid blood flow produces cerebral aneurysms in rats. Acta Neurochir Suppl 43:189192, 1988 Roda JM, Alvarez F, Garcia-Villalon AL, Ruiz MR, Gutierrez M, Garcia Blazquez M: An increment in unilateral carotid blood flow produces cerebral aneurysms in rats. Acta Neurochir Suppl 43:189–192, 1988

    • Search Google Scholar
    • Export Citation
  • 19

    Sato M, & Ohshima N: Flow-induced changes in shape and cytoskeletal structure of vascular endothelial cells. Biorheology 31:143153, 1994 Sato M, Ohshima N: Flow-induced changes in shape and cytoskeletal structure of vascular endothelial cells. Biorheology 31:143–153, 1994

    • Search Google Scholar
    • Export Citation
  • 20

    Ziegler T, , Silacci P, , Harrison VJ, & Hayoz D: Nitric oxide synthase expression in endothelial cells exposed to mechanical forces. Hypertension 32:351355, 1998 Ziegler T, Silacci P, Harrison VJ, Hayoz D: Nitric oxide synthase expression in endothelial cells exposed to mechanical forces. Hypertension 32:351–355, 1998

    • Search Google Scholar
    • Export Citation

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