Rupture of a saccular intracranial artery aneurysm (IA) causes subarachnoid hemorrhage, a significant cause of stroke and death. The current treatment options, endovascular coiling and clipping, are invasive and somewhat risky. Since only some IAs rupture, those IAs at risk for rupture should be identified. However, to improve the imaging of rupture-prone IAs and improve IA treatment, IA wall pathobiology requires more thorough knowledge. Chronic inflammation has become understood as an important phenomenon in IA wall pathobiology, featuring inflammatory cell infiltration as well as proliferative and fibrotic remodulatory responses. We review the literature on what is known about inflammation in the IA wall and also review the probable mechanisms of how inflammation would result in the degenerative changes that ultimately lead to IA wall rupture. We also discuss current options in imaging inflammation and how knowledge of inflammation in IA walls may improve IA treatment.
"However, there is a growing body of evidence that inflammation is contributing significantly to the pathogenesis of intracranial aneurysms. Starting with an endothelial dysfunction, an increasing inflammatory response results in a modulation of vascular smooth muscle cells and, finally, in an apoptotic degradation of the vascular wall giving rise to aneurysmal dilation and progression   . "
[Show abstract][Hide abstract] ABSTRACT: Recent studies demonstrated pigmented cells both in the murine heart, in pulmonary veins, and in brain arteries. Moreover, a role for melanocytes in the downregulation of inflammatory processes was suggested. As there is increasing evidence that inflammation is contributing significantly to the pathogenesis of intracranial aneurysms, melanocyte-like cells may be relevant in preventing age-related impairment of vessels. As pigmentation of the heart reflects that of coat color, aspects of body pigmentation might be associated with the incidence of intracranial aneurysms. We performed a case-control study to evaluate associations between the pigmentation of hair and eyes and the formation of aneurysms. In addition to hair and eye color, constitutive and facultative skin pigmentation were assessed in a replication study as well as individual handedness which can be seen as a neurophysiological correlate of developmental pigmentation processes. Hair pigmentation was highly associated with intracranial aneurysms in both samples, whereas eye pigmentation was not. In the replication cohort, facultative but not constitutive skin pigmentation proved significant. The strongest association was observed for individual handedness. Results indicate a significant association of intracranial aneurysms with particular aspects of body pigmentation as well as handedness, and imply clinical usefulness for screening of aneurysms and possible interventions.
BioMed Research International 05/2014; 2014:301631. DOI:10.1155/2014/301631 · 3.17 Impact Factor
"Several experimental and human studies have clarified the pathophysiology of aneurysm formation and rupture. Low shear stress elicits an inflammatory response in arterial walls.5,17–18 Endothelial dysfunction with activation of proinflammatory and proliferative pathways is an integral part of the inflammatory response and involves activation of nuclear factor kappa B (NF‐kB),2 monocyte chemoattractant protein 1,1,19 and vascular cell adhesion molecule 1,10,20 among other inflammatory mediators. "
[Show abstract][Hide abstract] ABSTRACT: Inflammatory cells and molecules may play a critical role in formation and rupture of cerebral aneurysms. Recently, an epidemiologic study reported that acetylsalicylic acid (ASA) decreases the risk of aneurysm rupture. The goal of this study was to determine the effects of ASA on inflammatory cells and molecules in the walls of human cerebral aneurysms, using radiographic and histological techniques.
Eleven prospectively enrolled patients harboring unruptured intracranial aneurysms were randomized into an ASA-treated (81 mg daily) group (n=6) and an untreated (control) group (n=5). Aneurysms were imaged at baseline using ferumoxytol-enhanced MRI to estimate uptake by macrophages. After 3 months, patients were reimaged before undergoing microsurgical clipping. Aneurysm tissues were collected for immunostaining with monoclonal antibodies for cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), microsomal prostaglandin E2 synthase-1 (mPGES-1), and macrophages. A decrease in signal intensity on ferumoxytol-enhanced MRI was observed after 3 months of ASA treatment. Expression of COX-2 (but not COX-1), mPGES-1, and macrophages was lower in the ASA group than in the control group.
This study provides preliminary radiographical and histological evidence that ASA may attenuate the inflammatory process in the walls of human cerebral aneurysms.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01710072.
Journal of the American Heart Association 12/2013; 2(1):e000019. DOI:10.1161/JAHA.112.000019 · 4.31 Impact Factor
"Another more intriguing hypothesis is that berry aneurysms, or a proportion of them, are autoimmune and due to an inflammatory disease of blood vessels. This is partially supported by finding inflammatory infiltrates in the walls of cerebral aneurysms . Only a few studies have investigated the possibility of some immunosuppressive medications commonly used in the treatment of immune-mediated diseases potentially contributing to an increased SAH risk. "
[Show abstract][Hide abstract] ABSTRACT: Subarachnoid hemorrhage (SAH) is a devastating cause of stroke, occurring in relatively young people. It has been suggested that some immune-mediated diseases may be associated with an increased ris k of SAH.
We analysed a database of linked statistical records of hospital admissions and death certificates for the whole of England (1999--2011). Rate ratios for SAH were determined, comparing immune-mediated disease cohorts with comparison cohorts.
There were significantly elevated risks of SAH after hospital admission for the following individual immune-mediated diseases: Addison's disease, ankylosing spondylitis, autoimmune haemolytic anaemia, Crohn's disease, diabetes mellitus, idiopathic thrombocytopenia purpura, myxoedema, pernicious anaemia, primary biliary cirrhosis, psoriasis, rheumatoid arthritis, scleroderma, Sjogren's syndrome, SLE and thyrotoxicosis. Elevated risks that were greater than 2-fold were found for Addison's disease (rate ratio (RR) = 2.01, 95% confidence interval 1.3-2.97), idiopathic thrombocytopenia purpura (RR = 2.42, 1.86-3.11), primary biliary cirrhosis (RR = 2.21, 1.43-3.16) and SLE (RR = 3.76, 3.08-4.55).
Our findings strongly support the suggestion that patients with some immune-mediated diseases have an increased risk of SAH. Further studies of the mechanisms behind this association are warranted.
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