Top

Published in:

01-06-2014 | Original Article

Smooth Muscle Cells and the Formation, Degeneration, and Rupture of Saccular Intracranial Aneurysm Wall—a Review of Current Pathophysiological Knowledge

Author: Juhana Frösen

Published in: Translational Stroke Research | Issue 3/2014

Abstract

Subarachnoid hemorrhage or intracerebral hemorrhage caused by rupture of a saccular intracranial aneurysm (sIA) is often fatal and causes significant loss of productive live years in addition to significant mortality. Around 3.5 % of the middle aged otherwise healthy population carries unruptured sIAs. Many sIAs never rupture, and since their prophylactic treatment is associated with risks of morbidity and even mortality, it is paramount to elucidate the biology that leads to sIA rupture in order be able to identify rupture-prone sIAs and to improve current therapies. Smooth muscle cells (SMCs) play a critical role both in the formation of sIAs, as well as in the repair and adaptation of the sIA wall to hemodynamic and proteolytic stress to which it is subjected. Loss of mural SMCs is characteristic to ruptured sIA walls, and experiments in animal models suggest that this loss of mural SMCs is causative to sIA growth and eventual rupture. Genetic factors that impair the function or survival of SMCs may predispose to sIA formation. Local or systemic therapy that increases the number of functioning SMCs in the sIA wall may have a potential to reduce the risk of sIA rupture. This review discusses the mechanisms and cellular interactions that SMCs have in the pathobiology of the sIA wall.

Rinkel GJ, Djibuti M, Algra A, van Gijn J. Prevalence and risk of rupture of intracranial aneurysms: a systematic review. Stroke. 1998;29:251–6.PubMedCrossRef

Vlak MH, Algra A, Brandenburg R, Rinkel GJ. Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis. Lancet Neurol. 2011;10:626–36.PubMedCrossRef

Juvela S, Poussa K, Lehto H, Porras M. Natural history of unruptured intracranial aneurysms: a long-term follow-up study. Stroke. 2013;44:2414–21.PubMedCrossRef

UCAS Japan Investigators, Morita A, Kirino T, Hashi K, Aoki N, Fukuhara S, et al. The natural course of unruptured cerebral aneurysms in a Japanese cohort. N Engl J Med. 2012;366:2474–82.PubMedCrossRef

Wermer MJ, van der Schaaf IC, Algra A, Rinkel GJ. Risk of rupture of unruptured intracranial aneurysms in relation to patient and aneurysm characteristics: an updated meta-analysis. Stroke. 2007;38:1404–10.PubMedCrossRef

Wiebers DO, Whisnant JP, Huston 3rd J, Meissner I, Brown Jr RD, Piepgras DG, et al. International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 2003;362:103–10.PubMedCrossRef

Bijlenga P, Ebeling C, Jaegersberg M, Summers P, Rogers A, Waterworth A, et al. Risk of rupture of small anterior communicating artery aneurysms is similar to posterior circulation aneurysms. Stroke. 2013;44:3018–26.PubMedCrossRef

Vlak MH, Rinkel GJ, Greebe P, Algra A. Risk of rupture of an intracranial aneurysm based on patient characteristics: a case-control study. Stroke. 2013;44:1256–9.PubMedCrossRef

Nieuwkamp DJ, Setz LE, Algra A, Linn FH, de Rooij NK, Rinkel GJ. Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: a meta-analysis. Lancet Neurol. 2009;8:635–42.PubMedCrossRef

10.

Karamanakos PN, von Und Zu Fraunberg M, Bendel S, Huttunen T, Kurki M, Hernesniemi J, et al. Risk factors for three phases of 12-month mortality in 1657 patients from a defined population after acute aneurysmal subarachnoid hemorrhage. World Neurosurg. 2012;78:631–9.PubMedCrossRef

11.

Malmivaara K, Juvela S, Hernesniemi J, Lappalainen J, Siironen J. Health-related quality of life and cost-effectiveness of treatment in subarachnoid haemorrhage. Eur J Neurol. 2012;19:1455–61.PubMedCrossRef

12.

Huttunen T, von und zu Fraunberg M, Frösen J, Lehecka M, Tromp G, Helin K, et al. Saccular intracranial aneurysm disease: distribution of site, size, and age suggests different etiologies for aneurysm formation and rupture in 316 familial and 1454 sporadic eastern Finnish patients. Neurosurgery. 2010;66:631–8.PubMedCrossRef

13.

Molyneux AJ, Kerr RS, Yu LM, Clarke M, Sneade M, Yarnold JA, et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet. 2005;366:809–17.PubMedCrossRef

14.

Naggara ON, Lecler A, Oppenheim C, Meder JF, Raymond J. Endovascular treatment of intracranial unruptured aneurysms: a systematic review of the literature on safety with emphasis on subgroup analyses. Radiology. 2012;263:828–35.PubMedCrossRef

15.

Kotowski M, Naggara O, Darsaut TE, Nolet S, Gevry G, Kouznetsov E, et al. Safety and occlusion rates of surgical treatment of unruptured intracranial aneurysms: a systematic review and meta-analysis of the literature from 1990 to 2011. J Neurol Neurosurg Psychiatry. 2013;84:42–8. Review.PubMedCrossRef

16.

Koroknay-Pál P, Lehto H, Niemelä M, Kivisaari R, Hernesniemi J. Long-term outcome of 114 children with cerebral aneurysms. J Neurosurg Pediatr. 2012;9:636–45.PubMedCrossRef

17.

Hashimoto N, Handa H, Hazama F. Experimentally induced cerebral aneurysms in rats. Surg Neurol. 1978;10:3–8.PubMed

18.

Nagata I, Handa H, Hashimoto N, Hazama F. Experimentally induced cerebral aneurysms in rats: Part VI. Hypertension. Surg Neurol. 1980;14:477–9.PubMed

19.

Hashimoto N, Kim C, Kikuchi H, Kojima M, Kang Y, Hazama F. Experimental induction of cerebral aneurysms in monkeys. J Neurosurg. 1987;67:903–5.PubMedCrossRef

20.

Hazama F, Kataoka H, Yamada E, Kayembe K, Hashimoto N, Kojima M, et al. Early changes of experimentally induced cerebral aneurysms in rats. Light-microscopic study. Am J Pathol. 1986;124:399–404.PubMedCentralPubMed

21.

Kim C, Kikuchi H, Hashimoto N, Kojima M, Kang Y, Hazama F. Involvement of internal elastic lamina in development of induced cerebral aneurysms in rats. Stroke. 1988;19:507–11.PubMedCrossRef

22.

Kondo S, Hashimoto N, Kikuchi H, Hazama F, Nagata I, Kataoka H. Apoptosis of medial smooth muscle cells in the development of saccular cerebral aneurysms in rats. Stroke. 1998;29:181–8.PubMedCrossRef

23.

Moriwaki T, Takagi Y, Sadamasa N, Aoki T, Nozaki K, Hashimoto N. Impaired progression of cerebral aneurysms in interleukin-1beta-deficient mice. Stroke. 2006;37:900–5.PubMedCrossRef

24.

Aoki T, Kataoka H, Ishibashi R, Nozaki K, Morishita R, Hashimoto N. Reduced collagen biosynthesis is the hallmark of cerebral aneurysm: contribution of interleukin-1beta and nuclear factor-kappaB. Arterioscler Thromb Vasc Biol. 2009;29:1080–6.PubMedCrossRef

25.

Aoki T, Kataoka H, Morimoto M, Nozaki K, Hashimoto N. Macrophage-derived matrix metalloproteinase-2 and -9 promote the progression of cerebral aneurysms in rats. Stroke. 2007;38:162–9.PubMedCrossRef

26.

Aoki T, Nishimura M, Kataoka H, Ishibashi R, Nozaki K, Miyamoto S. Complementary inhibition of cerebral aneurysm formation by eNOS and nNOS. Lab Invest. 2011;91:619–26.PubMedCrossRef

27.

Aoki T, Kataoka H, Ishibashi R, Nozaki K, Egashira K, Hashimoto N. Impact of monocyte chemoattractant protein-1 deficiency on cerebral aneurysm formation. Stroke. 2009;40:942–51.PubMedCrossRef

28.

Aoki T, Kataoka H, Nishimura M, Ishibashi R, Morishita R, Miyamoto S. Ets-1 promotes the progression of cerebral aneurysm by inducing the expression of MCP-1 in vascular smooth muscle cells. Gene Ther. 2010;17:1117–23.PubMedCrossRef

29.

Chen S, Feng H, Sherchan P, Klebe D, Zhao G, Sun X, Zhang J, Tang J, Zhang JH. Controversies and evolving new mechanisms in subarachnoid hemorrhage. Prog Neurobiol. 2013.

30.

Frösen J, Piippo A, Paetau A, Kangasniemi M, Niemelä M, Hernesniemi J, et al. Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases. Stroke. 2004;35:2287–93.PubMedCrossRef

31.

Meng H, Wang Z, Hoi Y, Gao L, Metaxa E, Swartz DD, et al. Complex hemodynamics at the apex of an arterial bifurcation induces vascular remodeling resembling cerebral aneurysm initiation. Stroke. 2007;38:1924–31.PubMedCentralPubMedCrossRef

32.

Juvela S, Poussa K, Porras M. Factors affecting formation and growth of intracranial aneurysms: a long-term follow-up study. Stroke. 2001;32:485–91.PubMedCrossRef

33.

Tulamo R, Frösen J, Junnikkala S, Paetau A, Pitkäniemi J, Kangasniemi M, et al. Complement activation associates with saccular cerebral artery aneurysm wall degeneration and rupture. Neurosurgery. 2006;59:1069–76.PubMed

34.

Coen M, Burkhardt K, Bijlenga P, Gabbiani G, Schaller K, Kövari E, et al. Smooth muscle cells of human intracranial aneurysms assume phenotypic features similar to those of the atherosclerotic plaque. Cardiovasc Pathol. 2013;22:339–44.PubMedCrossRef

35.

Thyberg J. Phenotypic modulation of smooth muscle cells during formation of neointimal thickenings following vascular injury. Histol Histopathol. 1998;13:871–91. Review.PubMed

36.

Newby AC, Zaltsman AB. Molecular mechanisms in intimal hyperplasia. J Pathol. 2000;190:300–9. Review.PubMedCrossRef

37.

Abruzzo T, Shengelaia GG, Dawson 3rd RC, Owens DS, Cawley CM, Gravanis MB. Histologic and morphologic comparison of experimental aneurysms with human intracranial aneurysms. AJNR Am J Neuroradiol. 1998;19:1309–14.PubMed

38.

Dai D, Ding YH, Danielson MA, Kadirvel R, Lewis DA, Cloft HJ, et al. Histopathologic and immunohistochemical comparison of human, rabbit, and swine aneurysms embolized with platinum coils. AJNR Am J Neuroradiol. 2005;26:2560–8.PubMed

39.

Bouzeghrane F, Naggara O, Kallmes DF, Berenstein A, Raymond J. International Consortium of Neuroendovascular Centres. In vivo experimental intracranial aneurysm models: a systematic review. AJNR Am J Neuroradiol. 2010;31:418–23. Review.PubMedCrossRef

40.

Frösen J, Marjamaa J, Myllärniemi M, Abo-Ramadan U, Tulamo R, Niemelä M, et al. Contribution of mural and bone marrow-derived neointimal cells to thrombus organization and wall remodeling in a microsurgical murine saccular aneurysm model. Neurosurgery. 2006;58:936–44.PubMedCrossRef

41.

Marbacher S, MD, Marjamaa J, MD, Bradacova K, von Gunten M, Honkanen P, Abo-Ramadan U, Hernesniemi J, Niemelä M, Frösen J. Loss of mural cells leads to wall degeneration, aneurysm growth, and eventual rupture in a rat aneurysm model. Stroke. In press.

42.

Kataoka K, Taneda M, Asai T, Kinoshita A, Ito M, Kuroda R. Structural fragility and inflammatory response of ruptured cerebral aneurysms. A comparative study between ruptured and unruptured cerebral aneurysms. Stroke. 1999;30:1396–401.PubMedCrossRef

43.

Frösen J, Tulamo R, Heikura T, Sammalkorpi S, Niemelä M, Hernesniemi J, et al. Lipid accumulation, lipid oxidation, and low plasma levels of acquired antibodies against oxidized lipids associate with degeneration and rupture of the intracranial aneurysm wall. Acta Neuropathol Commun. 2013;1:71.PubMedCentralPubMedCrossRef

44.

Hara A, Yoshimi N, Mori H. Evidence for apoptosis in human intracranial aneurysms. Neurol Res. 1998;20:127–30.PubMed

45.

Sakaki T, Kohmura E, Kishiguchi T, Yuguchi T, Yamashita T, Hayakawa T. Loss and apoptosis of smooth muscle cells in intracranial aneurysms. Studies with in situ DNA end labeling and antibody against single-stranded DNA. Acta Neurochir (Wien). 1997;139:469–74.CrossRef

46.

Pentimalli L, Modesti A, Vignati A, Marchese E, Albanese A, Di Rocco F, et al. Role of apoptosis in intracranial aneurysm rupture. J Neurosurg. 2004;101:1018–25.PubMedCrossRef

47.

Laaksamo E, Tulamo R, Liiman A, Baumann M, Friedlander RM, Hernesniemi J, et al. Oxidative stress is associated with cell death, wall degradation, and increased risk of rupture of the intracranial aneurysm wall. Neurosurgery. 2013;72:109–17.PubMedCrossRef

48.

Guo F, Li Z, Song L, Han T, Feng Q, Guo Y, et al. Increased apoptosis and cysteinyl aspartate specific protease-3 gene expression in human intracranial aneurysm. J Clin Neurosci. 2007;14:550–5.PubMedCrossRef

49.

Frösen J, Tulamo R, Paetau A, Laaksamo E, Korja M, Laakso A, et al. Saccular intracranial aneurysm: pathology and mechanisms. Acta Neuropathol. 2012;123:773–86.PubMedCrossRef

50.

Tulamo R, Frösen J, Junnikkala S, Paetau A, Kangasniemi M, Peláez J, et al. Complement system becomes activated by the classical pathway in intracranial aneurysm walls. Lab Invest. 2010;90:168–79.PubMedCrossRef

51.

Bygglin H, Laaksamo E, Myllärniemi M, Tulamo R, Hernesniemi J, Niemelä M, et al. Isolation, culture, and characterization of smooth muscle cells from human intracranial aneurysms. Acta Neurochir (Wien). 2011;153:311–8.CrossRef

52.

Krischek B, Inoue I. The genetics of intracranial aneurysms. J Hum Genet. 2006;51:587–94.PubMedCrossRef

53.

Ruigrok YM, Rinkel GJ. Genetics of intracranial aneurysms. Stroke. 2008;39:1049–55. Review.PubMedCrossRef

54.

Alg VS, Sofat R, Houlden H, Werring DJ. Genetic risk factors for intracranial aneurysms: a meta-analysis in more than 116,000 individuals. Neurology. 2013;80:2154–65.PubMedCentralPubMedCrossRef

55.

Helgadottir A, Thorleifsson G, Magnusson KP, Grétarsdottir S, Steinthorsdottir V, Manolescu A, et al. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet. 2008;40:217–24.PubMedCrossRef

56.

Yasuno K, Bilguvar K, Bijlenga P, Low SK, Krischek B, Auburger G, et al. Genome-wide association study of intracranial aneurysm identifies three new risk loci. Nat Genet. 2010;42:420–5.PubMedCentralPubMedCrossRef

57.

Leeper NJ, Raiesdana A, Kojima Y, Kundu RK, Cheng H, Maegdefessel L, et al. Loss of CDKN2B promotes p53-dependent smooth muscle cell apoptosis and aneurysm formation. Arterioscler Thromb Vasc Biol. 2013;33:e1–10. Epub 2012 Nov 15.PubMedCentralPubMedCrossRef

58.

Roder C, Kasuya H, Harati A, Tatagiba M, Inoue I, Krischek B. Meta-analysis of microarray gene expression studies on intracranial aneurysms. Neuroscience. 2012;201:105–13.PubMedCrossRef

59.

Aoki T, Kataoka H, Ishibashi R, Nozaki K, Hashimoto N. Gene expression profile of the intima and media of experimentally induced cerebral aneurysms in rats by laser-microdissection and microarray techniques. Int J Mol Med. 2008;22:595–603.PubMed

60.

Kurki MI, Häkkinen SK, Frösen J, Tulamo R, von und zu Fraunberg M, Wong G, et al. Upregulated signaling pathways in ruptured human saccular intracranial aneurysm wall: an emerging regulative role of Toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factors. Neurosurgery. 2011;68:1667–75.PubMedCrossRef

61.

Chen L, Wan JQ, Zhou JP, Fan YL, Jiang JY. Gene expression analysis of ruptured and un-ruptured saccular intracranial aneurysm. Eur Rev Med Pharmacol Sci. 2013;17:1374–81.PubMed

62.

Isaksen JG, Bazilevs Y, Kvamsdal T, Zhang Y, Kaspersen JH, Waterloo K, et al. Determination of wall tension in cerebral artery aneurysms by numerical simulation. Stroke. 2008;39:3172–8.PubMedCrossRef

63.

Cebral JR, Mut F, Weir J, Putman C. Quantitative characterization of the hemodynamic environment in ruptured and unruptured brain aneurysms. AJNR Am J Neuroradiol. 2011;32:145–51.PubMedCentralPubMedCrossRef

64.

Etminan N, Dreier R, Buchholz BA, Bruckner P, Steiger HJ, Hänggi D, et al. Exploring the age of intracranial aneurysms using carbon birth dating: preliminary results. Stroke. 2013;44:799–802.PubMedCentralPubMedCrossRef

65.

Koffijberg H, Buskens E, Algra A, Wermer MJ, Rinkel GJ. Growth rates of intracranial aneurysms: exploring constancy. J Neurosurg. 2008;109:176–85.PubMedCrossRef

66.

Villablanca JP, Duckwiler GR, Jahan R, Tateshima S, Martin NA, Frazee J, et al. Natural history of asymptomatic unruptured cerebral aneurysms evaluated at CT angiography: growth and rupture incidence and correlation with epidemiologic risk factors. Radiology. 2013;269:258–65.PubMedCrossRef

67.

Hasan D, Chalouhi N, Jabbour P, Dumont AS, Kung DK, Magnotta VA, et al. Early change in ferumoxytol-enhanced magnetic resonance imaging signal suggests unstable human cerebral aneurysm: a pilot study. Stroke. 2012;43:3258–65.PubMedCentralPubMedCrossRef

68.

Bruno G, Todor R, Lewis I, Chyatte D. Vascular extracellular matrix remodeling in cerebral aneurysms. J Neurosurg. 1998;89:431–40.PubMedCrossRef

69.

Bavinzski G, Talazoglu V, Killer M, Richling B, Gruber A, Gross CE, et al. Gross and microscopic histopathological findings in aneurysms of the human brain treated with Guglielmi detachable coils. J Neurosurg. 1999;91:284–93.PubMedCrossRef

70.

Szikora I, Seifert P, Hanzely Z, Kulcsar Z, Berentei Z, Marosfoi M, et al. Histopathologic evaluation of aneurysms treated with Guglielmi detachable coils or matrix detachable microcoils. AJNR Am J Neuroradiol. 2006;27:283–8.PubMed

71.

Ferns SP, Sprengers ME, van Rooij WJ, van Zwam WH, de Kort GA, Velthuis BK, et al. Late reopening of adequately coiled intracranial aneurysms: frequency and risk factors in 400 patients with 440 aneurysms. Stroke. 2011;42:1331–7.PubMedCrossRef

72.

Hayakawa M, Murayama Y, Duckwiler GR, Gobin YP, Guglielmi G, Viñuela F. Natural history of the neck remnant of a cerebral aneurysm treated with the Guglielmi detachable coil system. J Neurosurg. 2000;93:561–8.PubMedCrossRef

73.

Hasan DM, Mahaney KB, Brown RD Jr, Meissner I, Piepgras DG, Huston J, Capuano AW, Torner JC. International study of unruptured intracranial aneurysms investigators. Aspirin as a promising agent for decreasing incidence of cerebral aneurysm rupture. Stroke. 2011;42:3156–62.

74.

Yoshimura Y, Murakami Y, Saitoh M, Yokoi T, Aoki T, Miura K, et al. Statin use and risk of cerebral aneurysm rupture: a hospital-based case-control study in Japan. J Stroke Cerebrovasc Dis. 2014;23:343–8.PubMedCrossRef

75.

Allaire E, Muscatelli-Groux B, Guinault AM, Pages C, Goussard A, Mandet C, et al. Vascular smooth muscle cell endovascular therapy stabilizes already developed aneurysms in a model of aortic injury elicited by inflammation and proteolysis. Ann Surg. 2004;239:417–27.PubMedCentralPubMedCrossRef

76.

Raymond J, Desfaits AC, Roy D. Fibrinogen and vascular smooth muscle cell grafts promote healing of experimental aneurysms treated by embolization. Stroke. 1999;30:1657–64.PubMedCrossRef

77.

Ribourtout E, Desfaits AC, Salazkin I, Raymond J. Ex vivo gene therapy with adenovirus-mediated transforming growth factor beta1 expression for endovascular treatment of aneurysm: results in a canine bilateral aneurysm model. J Vasc Surg. 2003;38:576–83.PubMedCrossRef

78.

Kumar AH, Caplice NM. Clinical potential of adult vascular progenitor cells. Arterioscler Thromb Vasc Biol. 2010;30:1080–7. Review.PubMedCrossRef

79.

Schneider F, Saucy F, de Blic R, Dai J, Mohand F, Rouard H, et al. Bone marrow mesenchymal stem cells stabilize already-formed aortic aneurysms more efficiently than vascular smooth muscle cells in a rat model. Eur J Vasc Endovasc Surg. 2013;45:666–72.PubMedCrossRef

80.

Rouchaud A, Journé C, Louedec L, Ollivier V, Derkaoui M, Michel JB, et al. Autologous mesenchymal stem cell endografting in experimental cerebrovascular aneurysms. Neuroradiology. 2013;55:741–9.PubMedCrossRef

81.

Shimizu K, Sugiyama S, Aikawa M, Fukumoto Y, Rabkin E, Libby P, et al. Host bone-marrow cells are a source of donor intimal smooth- muscle-like cells in murine aortic transplant arteriopathy. Nat Med. 2001;7:738–41.PubMedCrossRef

82.

Religa P, Bojakowski K, Maksymowicz M, Bojakowska M, Sirsjö A, Gaciong Z, et al. Smooth-muscle progenitor cells of bone marrow origin contribute to the development of neointimal thickenings in rat aortic allografts and injured rat carotid arteries. Transplantation. 2002;74:1310–5.PubMedCrossRef

83.

Caplice NM, Bunch TJ, Stalboerger PG, Wang S, Simper D, Miller DV, et al. Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation. Proc Natl Acad Sci U S A. 2003;100:4754–9.PubMedCentralPubMedCrossRef

84.

Iwata H, Manabe I, Fujiu K, Yamamoto T, Takeda N, Eguchi K, et al. Bone marrow-derived cells contribute to vascular inflammation but do not differentiate into smooth muscle cell lineages. Circulation. 2010;122:2048–57.PubMedCrossRef

85.

Daniel JM, Sedding DG. Circulating smooth muscle progenitor cells in arterial remodeling. J Mol Cell Cardiol. 2011;50:273–9.PubMedCrossRef

86.

Hoh BL, Velat GJ, Wilmer EN, Hosaka K, Fisher RC, Scott EW. A novel murine elastase saccular aneurysm model for studying bone marrow progenitor-derived cell-mediated processes in aneurysm formation. Neurosurgery. 2010;66:544–50.PubMedCentralPubMedCrossRef

Title: Smooth Muscle Cells and the Formation, Degeneration, and Rupture of Saccular Intracranial Aneurysm Wall—a Review of Current Pathophysiological Knowledge
Author: Juhana Frösen
Publication date: 01-06-2014
Publisher: Springer US
Published in: Translational Stroke Research / Issue 3/2014
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-014-0340-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Smooth Muscle Cells and the Formation, Degeneration, and Rupture of Saccular Intracranial Aneurysm Wall—a Review of Current Pathophysiological Knowledge

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2014

Clinically Relevant Reperfusion in Acute Ischemic Stroke: MTT Performs Better than Tmax and TTP

Alzheimer’s Silent Partner: Cerebral Amyloid Angiopathy

Plasticity of Cerebrovascular Smooth Muscle Cells After Subarachnoid Hemorrhage

Phenotypic Transformation of Smooth Muscle in Vasospasm after Aneurysmal Subarachnoid Hemorrhage

Vascular Smooth Muscle Cells in Cerebral Aneurysm Pathogenesis

Smooth Muscle Cell Phenotypic Switching in Stroke