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Table of Contents    
Year : 2017  |  Volume : 65  |  Issue : 4  |  Page : 706-707

Inflammation and aneurysms

Department of Neurological Surgery, Jaslok Hospital and Research Centre, Mumbai, Maharashtra, India

Date of Web Publication5-Jul-2017

Correspondence Address:
Sudheer Ambekar
Department of Neurological Surgery, Jaslok Hospital and Research Centre, 15, Dr. Deshmukh Marg, Mumbai - 400 026, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/neuroindia.NI_289_16

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How to cite this article:
Ambekar S. Inflammation and aneurysms. Neurol India 2017;65:706-7

How to cite this URL:
Ambekar S. Inflammation and aneurysms. Neurol India [serial online] 2017 [cited 2020 Jan 21];65:706-7. Available from:

Subarachnoid hemorrhage due to an intracranial aneurysm (IA) rupture is a devastating condition. Approximately 40–50% of the patients with intracranial aneurysmal rupture die, and one-third are left with permanent neurological deficits.[1] Recent research has focused on the interplay between blood flow hemodynamics, inflammation, and morphology of IAs and their effects on the formation, growth, and rupture of IAs. The role of inflammation in IA formation, growth, and rupture is being increasingly recognized in the recent years. The fact that the inflammatory cascade is likely interrelated with mechanical flow-induced vascular dysfunction leading to aneurysm destabilization and rupture has also been shown in recent studies.[2]

In the article “Molecular mechanism of the association between the long non-coding RNA ANRIL and intracranial aneurysms,” the authors review the various inflammatory molecules that have been implicated in the pathogenesis of IA. ANRIL or Antisense Noncoding RNA in the INK Locus is a long intergenic noncoding ribonucleic acid (RNA) located on chromosome 9p, whose deletion leads to greater suppression of RNA encoded by Cdkn2a and Cdkn2b. Smooth muscle cells from mice containing mutant ANRIL have increased proliferative activity.[3]

Excessive shear stress leading to endothelial dysfunction seems to be the initial mechanism in IA formation. Flow-mediated endothelial dysfunction leads to the activation of inflammatory mediators such as nuclear factor-kappa B, proinflammatory cytokines, and cell adhesion molecules. Monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and vascular cell adhesion molecule-1 (VCAM-1) are also expressed on the endothelial surface.[4],[5] These inflammatory molecules attract mononuclear cells, monocytes, and T cells from peripheral blood that adhere and transmigrate into the endothelium and form macrophages leading to the cycle of arterial wall destruction and remodeling, thus, initiating aneurysm formation.[6] During remodeling, the intima, media and the internal elastic lamina are destroyed leading to aneurysm growth. High wall shear stress (WSS) and positive WSS gradient have been demonstrated to lead to matrix metalloproteinase protein production by the mural cells, endothelial cell degradation, medial thinning, and mural cell apoptosis; whereas low WSS and high oscillatory shear index (OSI) leads to endothelial cell dysfunction, increased reactive oxygen species, increased inflammatory cell infiltration, smooth muscle cell proliferation, and migration and thrombus formation.[7] The presence of estrogen receptor beta (ER-β) in human IAs and cerebral arteries possibly explains the protective effect of estrogen in premenopausal women. The protective effect of ER-β is dependent on the production of nitric oxide. It upregulates the production of inducible nitric oxide synthase (iNOS). This leads to s-nitrosylation of various proteins that prevent the oxidative modification of cysteine residues, thereby reducing the excessive tissue remodeling that leads to IA formation.[8]

In recent years, focus has also been on the noninvasive imaging of inflammation within the IA wall that may help to differentiate the stable IAs from the unstable IAs at a greater risk of rupture. Hasan et al., reported on the use of ferumoxytol-enhanced magnetic resonance imaging (MRI) to image inflammation within the aneurysmal wall.[9] Ferumoxytol is an iron-oxide, macrophage-selective nanoparticle and is cleared by the reticuloendothelial system macrophages. It has been used in MRI studies for cardiovascular imaging, endoleak detection in patients with aortic stent grafts, depiction of deep vein thrombosis, tumor progression, and cancer staging. The findings of these studies suggest that the early uptake of ferumoxytol on MRI indicates an active inflammatory process. These aneurysms are prone to rupture and warrant an early intervention to secure them.[10]

These exciting new findings have also led to the identification of new potential targets for the pharmacological management of IAs. The role of aspirin as a candidate for pharmacotherapy of IAs is being investigated. Depending on the dose, aspirin can inhibit several inflammatory mediators via its irreversible inhibition of cyclooxygenase-2. In the International Study of Unruptured Intracranial Aneurysms (ISUIA), patients with a history of aspirin usage 3 times weekly or greater, had a lower risk of IA rupture and subarachnoid hemorrhage than those who never used aspirin.[11] A clinical trial assessing the role of aspirin in human IAs has recently completed recruitment of subjects, the results of which are yet to be published. (

To conclude, inflammation plays a pivotal role in the pathogenesis of IA. Further studies are needed to understand the inflammatory cascade and develop potential targets for pharmacological therapy.

  References Top

Connolly ES, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage. A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2012;43:1711-37.  Back to cited text no. 1
Tamura T, Jamous MA, Kitazato KT, Yagi K, Tada Y, Uno M, et al. Endothelial damage due to impaired nitric oxide bioavailability triggers cerebral aneurysm formation in female rats. J Hypertens 2009;27:1284-92.  Back to cited text no. 2
Che J. Molecular mechanisms of the intracranial aneurysms and their association with the long noncoding ribonucleic acid ANRIL — A review of literature. Neurol India 2017;65:718-28.  Back to cited text no. 3
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Gimbrone MA, Topper JN, Nagel T, Anderson KR, Garcia-Cardeña G. Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann N Y Acad Sci 2000;902:230-9.  Back to cited text no. 4
Wang Z, Kolega J, Hoi Y, Gao L, Swartz DD, Levy EI, et al. Molecular alterations associated with aneurysmal remodeling are localized in the high hemodynamic stress region of a created carotid bifurcation. Neurosurgery 2009;65:169-77.  Back to cited text no. 5
Jamous MA, Nagahiro S, Kitazato KT, Tamura T, Aziz HA, Shono M, et al. Endothelial injury and inflammatory response induced by hemodynamic changes preceding intracranial aneurysm formation: Experimental study in rats. J Neurosurg 2007;107:405-11.  Back to cited text no. 6
Meng H, Tutino VM, Xiang J, Siddiqui A. High WSS or low WSS? Complex interactions of hemodynamics with intracranial aneurysm initiation, growth, and rupture: Toward a unifying hypothesis. AJNR Am J Neuroradiol 2014 Jul; 35:1254-62.  Back to cited text no. 7
Tabuchi S. Relationship between postmenopausal estrogen deficiency and aneurysmal subarachnoid hemorrhage. Behav Neurol 2015;2015:720141.  Back to cited text no. 8
Hasan DM, Mahaney KB, Magnotta VA, Kung DK, Lawton MT, Hashimoto T, et al. Macrophage imaging within human cerebral aneurysms wall using ferumoxytol-enhanced MRI: A pilot study. Arterioscler Thromb Vasc Biol 2012;32:1032-8.  Back to cited text no. 9
Chalouhi N, Jabbour P, Magnotta V, Hasan D. The emerging role of ferumoxytol-enhanced MRI in the management of cerebrovascular lesions. Mol Basel Switz 2013;18:9670-83.  Back to cited text no. 10
Hasan DM, Mahaney KB, Brown RD, Meissner I, Piepgras DG, Huston J, et al. Aspirin as a promising agent for decreasing incidence of cerebral aneurysm rupture. Stroke J Cereb Circ 2011;42:3156-62.  Back to cited text no. 11


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