{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:41:16Z","timestamp":1792806076428,"version":"4.5.0"},"reference-count":43,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1]]},"abstract":"\n OBJECTIVE<\/jats:title>\n There are no effective therapeutic drugs for cerebral aneurysms, partly because the pathogenesis remains unresolved. Chronic inflammation of the cerebral arterial wall plays an important role in aneurysm formation, but it is not clear what triggers the inflammation. The authors have observed that vascular endothelial P2X4 purinoceptor is involved in flow-sensitive mechanisms that regulate vascular remodeling. They have thus hypothesized that shear stress\u2013associated hemodynamic stress on the endothelium causes the inflammatory process in the cerebral aneurysm development.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n To test their hypothesis, the authors examined the role of P2X4 in cerebral aneurysm development by using\n P2X4<\/jats:italic>\n \n \u2212\n \/<\/jats:italic>\n \u2212\n <\/jats:sup>\n mice and rats that were treated with a P2X4 inhibitor, paroxetine, and subjected to aneurysm-inducing surgery. Cerebral aneurysms were induced by unilateral carotid artery ligation and renovascular hypertension.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n The frequency of aneurysm induction evaluated by light microscopy was significantly lower in the\n P2X4<\/jats:italic>\n \n \u2212\n \/<\/jats:italic>\n \u2212\n <\/jats:sup>\n mice (p = 0.0488) and in the paroxetine-treated male (p = 0.0253) and female (p = 0.0204) rats compared to control mice and rats, respectively. In addition, application of paroxetine from 2 weeks after surgery led to a significant reduction in aneurysm size in the rats euthanized 3 weeks after aneurysm-inducing surgery (p = 0.0145), indicating that paroxetine suppressed enlargement of formed aneurysms. The mRNA and protein expression levels of known inflammatory contributors to aneurysm formation (monocyte chemoattractant protein\u20131 [MCP-1], interleukin-1\u03b2 [IL-1\u03b2], tumor necrosis factor\u2013\u03b1 [TNF\u03b1], inducible nitric oxide synthase [iNOS], and cyclooxygenase-2 [COX-2]) were all significantly elevated in the rats that underwent the aneurysm-inducing surgery compared to the nonsurgical group, and the values in the surgical group were all significantly decreased by paroxetine administration according to quantitative polymerase chain reaction techniques and Western blotting. Although immunolabeling densities for COX-2, iNOS, and MCP-1 were not readily observed in the nonsurgical mouse groups, such densities were clearly seen in the arterial wall of\n P2X4<\/jats:italic>\n \n +\/+<\/jats:italic>\n <\/jats:sup>\n mice after aneurysm-inducing surgery. In contrast, in the\n P2X4<\/jats:italic>\n \n \u2212\n \/<\/jats:italic>\n \u2212\n <\/jats:sup>\n mice after the surgery, immunolabeling of COX-2 and iNOS was not observed in the arterial wall, whereas that of MCP-1 was readily observed in the adventitia, but not the intima.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n These data suggest that P2X4 is required for the inflammation that contributes to both cerebral aneurysm formation and growth. Enhanced shear stress\u2013associated hemodynamic stress on the vascular endothelium may trigger cerebral aneurysm development. Paroxetine may have potential for the clinical treatment of cerebral aneurysms, given that this agent exhibits efficacy as a clinical antidepressant.<\/jats:p>\n <\/jats:sec>","DOI":"10.3171\/2019.9.jns19270","type":"journal-article","created":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T20:46:21Z","timestamp":1577479581000},"page":"102-114","source":"Crossref","is-referenced-by-count":10,"title":["Disruption of P2X4 purinoceptor and suppression of the inflammation associated with cerebral aneurysm formation"],"prefix":"10.3171","volume":"134","author":[{"given":"Miyuki","family":"Fukuda","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, National Hospital Organization Kyoto Medical Center, Kyoto;"},{"name":"Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunichi","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, National Hospital Organization Kyoto Medical Center, Kyoto;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joji","family":"Ando","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Engineering, School of Medicine, Dokkyo Medical University, Mibu City, Tochigi;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimiko","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohiro","family":"Yonemoto","sequence":"additional","affiliation":[{"name":"Departments of Biostatistics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, National Hospital Organization Kyoto Medical Center, Kyoto;"},{"name":"Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youko","family":"Niwa","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, National Hospital Organization Kyoto Medical Center, Kyoto;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolism, and Hypertension Research, Clinical Research Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Satoh-Asahara","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolism, and Hypertension Research, Clinical Research Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Division of Translational Research, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Shimatsu","sequence":"additional","affiliation":[{"name":"Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Tsukahara","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, National Hospital Organization Kyoto Medical Center, Kyoto;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1227\/NEU.0000000000000016","article-title":"Intracranial aneurysms occur more frequently at bifurcation sites that typically experience higher hemodynamic stresses","volume":"73","author":"Alfano JM","year":"2013","unstructured":"Alfano JM, Kolega J, Natarajan SK, Xiang J, Paluch RA, Levy EI, : Intracranial aneurysms occur more frequently at bifurcation sites that typically experience higher hemodynamic stresses. Neurosurgery 73:497\u2013505, 201310.1227\/NEU.000000000000001623756745"},{"key":"b2","series-title":"Sci Signal","doi-asserted-by":"publisher","first-page":"eaah6037","DOI":"10.1126\/scisignal.aah6037","article-title":"Prostaglandin E2-EP2-NF-\u03baB signaling in macrophages as a potential therapeutic target for intracranial aneurysms","volume":"10","author":"Aoki T","year":"2017","unstructured":"Aoki T, Fr\u020dsen J, Fukuda M, Bando K, Shioi G, Tsuji K, : Prostaglandin E2-EP2-NF-\u03baB signaling in macrophages as a potential therapeutic target for intracranial aneurysms. Sci Signal 10:eaah6037, 20172817428010.1126\/scisignal.aah6037"},{"key":"b3","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1161\/STROKEAHA.107.503086","article-title":"Simvastatin suppresses the progression of experimentally induced cerebral aneurysms in rats","volume":"39","author":"Aoki T","year":"2008","unstructured":"Aoki T, Kataoka H, Ishibashi R, Nozaki K, Hashimoto N: Simvastatin suppresses the progression of experimentally induced cerebral aneurysms in rats. Stroke 39:1276\u20131285, 200810.1161\/STROKEAHA.107.50308618309148"},{"key":"b4","series-title":"Br J Pharmacol","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1111\/j.1476-5381.2011.01358.x","article-title":"PGE2 EP2 signalling in endothelium is activated by haemodynamic stress and induces cerebral aneurysm through an amplifying loop via NF-\u03baB","volume":"163","author":"Aoki T","year":"2011","unstructured":"Aoki T, Nishimura M, Matsuoka T, Yamamoto K, Furuyashiki T, Kataoka H, : PGE2 EP2 signalling in endothelium is activated by haemodynamic stress and induces cerebral aneurysm through an amplifying loop via NF-\u03baB. Br J Pharmacol 163:1237\u20131249, 20112142631910.1111\/j.1476-5381.2011.01358.x"},{"key":"b5","series-title":"Cell Tissue Res","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s00441-003-0758-5","article-title":"Tissue distribution of P2X4 receptors studied with an ectodomain antibody","volume":"313","author":"Bo X","year":"2003","unstructured":"Bo X, Kim M, Nori SL, Schoepfer R, Burnstock G, North RA: Tissue distribution of P2X4 receptors studied with an ectodomain antibody. Cell Tissue Res 313:159\u2013165, 200310.1007\/s00441-003-0758-512845522"},{"key":"b6","series-title":"Pharmacopsychiatria","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1055\/s-2007-1019535","article-title":"An early clinical phase II evaluation of paroxetine, a new potent and selective 5HT-uptake inhibitor in patients with depressive illness","volume":"15","author":"B\u00f8rup C","year":"1982","unstructured":"B\u00f8rup C, Meidahl B, Petersen IM, Vangtorp A, le F\u00e8vre Honor\u00e9 P: An early clinical phase II evaluation of paroxetine, a new potent and selective 5HT-uptake inhibitor in patients with depressive illness. Pharmacopsychiatria 15:183\u2013186, 198210.1055\/s-2007-10195356218507"},{"key":"b7","series-title":"Arterioscler Thromb Vasc Biol","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.1161\/ATVBAHA.114.303424","article-title":"Mechanoresponsive networks controlling vascular inflammation","volume":"34","author":"Bryan MT","year":"2014","unstructured":"Bryan MT, Duckles H, Feng S, Hsiao ST, Kim HR, Serbanovic-Canic J, : Mechanoresponsive networks controlling vascular inflammation. Arterioscler Thromb Vasc Biol 34:2199\u20132205, 20142494752310.1161\/ATVBAHA.114.303424"},{"key":"b8","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1161\/STROKEAHA.117.019972","article-title":"Lipid-lowering agents and high HDL (high-density lipoprotein) are inversely associated with intracranial aneurysm rupture","volume":"49","author":"Can A","year":"2018","unstructured":"Can A, Castro VM, Dligach D, Finan S, Yu S, Gainer V, : Lipid-lowering agents and high HDL (high-density lipoprotein) are inversely associated with intracranial aneurysm rupture. Stroke 49:1148\u20131154, 20182962262510.1161\/STROKEAHA.117.019972"},{"key":"b9","series-title":"Ann Biomed Eng","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1007\/s10439-007-9426-3","article-title":"Effects of disturbed flow on endothelial cells","volume":"36","author":"Chien S","year":"2008","unstructured":"Chien S: Effects of disturbed flow on endothelial cells. Ann Biomed Eng 36:554\u2013562, 20081817276710.1007\/s10439-007-9426-3"},{"key":"b10","series-title":"Pflugers Arch","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1007\/s00424-017-2025-8","article-title":"Stressed podocytes-mechanical forces, sensors, signaling and response","volume":"469","author":"Endlich K","year":"2017","unstructured":"Endlich K, Kliewe F, Endlich N: Stressed podocytes-mechanical forces, sensors, signaling and response. Pflugers Arch 469:937\u2013949, 20172868786410.1007\/s00424-017-2025-8"},{"key":"b11","series-title":"Int J Cardiovasc Imaging","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1007\/s10554-016-1055-1","article-title":"High wall shear stress and high-risk plaque: an emerging concept","volume":"33","author":"Eshtehardi P","year":"2017","unstructured":"Eshtehardi P, Brown AJ, Bhargava A, Costopoulos C, Hung OY, Corban MT, : High wall shear stress and high-risk plaque: an emerging concept. Int J Cardiovasc Imaging 33:1089\u20131099, 201710.1007\/s10554-016-1055-128074425"},{"key":"b12","series-title":"Nat Rev Neurol","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/nrneurol.2016.150","article-title":"Unruptured intracranial aneurysms: development, rupture and preventive management","volume":"12","author":"Etminan N","year":"2016","unstructured":"Etminan N, Rinkel GJ: Unruptured intracranial aneurysms: development, rupture and preventive management. Nat Rev Neurol 12:699\u2013713, 201610.1038\/nrneurol.2016.15027808265"},{"key":"b13","series-title":"Acta Neurochir Suppl","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/978-3-319-04981-6_2","article-title":"Molecular basis for intracranial aneurysm formation","volume":"120","author":"Fukuda M","year":"2015","unstructured":"Fukuda M, Aoki T: Molecular basis for intracranial aneurysm formation. Acta Neurochir Suppl 120:13\u201315, 201525366592"},{"key":"b14","series-title":"J Pharmacol Sci","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1254\/jphs.14148FP","article-title":"Exacerbation of intracranial aneurysm and aortic dissection in hypertensive rat treated with the prostaglandin F-receptor antagonist AS604872","volume":"126","author":"Fukuda M","year":"2014","unstructured":"Fukuda M, Aoki T, Manabe T, Maekawa A, Shirakawa T, Kataoka H, : Exacerbation of intracranial aneurysm and aortic dissection in hypertensive rat treated with the prostaglandin F-receptor antagonist AS604872. J Pharmacol Sci 126:230\u2013242, 20142534184510.1254\/jphs.14148FP"},{"key":"b15","series-title":"Circulation","doi-asserted-by":"publisher","first-page":"2532","DOI":"10.1161\/01.CIR.101.21.2532","article-title":"Prevention of rat cerebral aneurysm formation by inhibition of nitric oxide synthase","volume":"101","author":"Fukuda S","year":"2000","unstructured":"Fukuda S, Hashimoto N, Naritomi H, Nagata I, Nozaki K, Kondo S, : Prevention of rat cerebral aneurysm formation by inhibition of nitric oxide synthase. Circulation 101:2532\u20132538, 20001083152910.1161\/01.CIR.101.21.2532"},{"key":"b16","series-title":"Asian Biomed","first-page":"229","article-title":"Pathogenesis of cerebral aneurysms: evidences using experimentally induced cerebral aneurysm models","volume":"3","author":"Fukuda S","year":"2009","unstructured":"Fukuda S, Hashimoto N, Nozaki K, Nishimura M: Pathogenesis of cerebral aneurysms: evidences using experimentally induced cerebral aneurysm models. Asian Biomed 3:229\u2013236, 2009"},{"key":"b17","series-title":"AJNR Am J Neuroradiol","doi-asserted-by":"publisher","first-page":"834","DOI":"10.3174\/ajnr.A6030","article-title":"Differences in cerebral aneurysm rupture rate according to arterial anatomies depend on the hemodynamic environment","volume":"40","author":"Fukuda S","year":"2019","unstructured":"Fukuda S, Shimogonya Y, Yonemoto N: Differences in cerebral aneurysm rupture rate according to arterial anatomies depend on the hemodynamic environment. AJNR Am J Neuroradiol 40:834\u2013839, 20193097565010.3174\/ajnr.A6030"},{"key":"b18","series-title":"Cardiovasc Res","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1093\/cvr\/cvx213","article-title":"Atheroprone flow activates inflammation via endothelial ATP-dependent P2X7-p38 signalling","volume":"114","author":"Green JP","year":"2018","unstructured":"Green JP, Souilhol C, Xanthis I, Martinez-Campesino L, Bowden NP, Evans PC, : Atheroprone flow activates inflammation via endothelial ATP-dependent P2X7-p38 signalling. Cardiovasc Res 114:324\u2013335, 20182912622310.1093\/cvr\/cvx213"},{"key":"b19","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"3156","DOI":"10.1161\/STROKEAHA.111.619411","article-title":"Aspirin as a promising agent for decreasing incidence of cerebral aneurysm rupture","volume":"42","author":"Hasan DM","year":"2011","unstructured":"Hasan DM, Mahaney KB, Brown RD Jr, Meissner I, Piepgras DG, Huston J, : Aspirin as a promising agent for decreasing incidence of cerebral aneurysm rupture. Stroke 42:3156\u20133162, 201110.1161\/STROKEAHA.111.61941121980208"},{"key":"b20","series-title":"Surg Neurol","first-page":"3","article-title":"Experimentally induced cerebral aneurysms in rats","volume":"10","author":"Hashimoto N","year":"1978","unstructured":"Hashimoto N, Handa H, Hazama F: Experimentally induced cerebral aneurysms in rats. Surg Neurol 10:3\u20138, 1978684603"},{"key":"b21","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"903","DOI":"10.3171\/jns.1987.67.6.0903","article-title":"Experimental induction of cerebral aneurysms in monkeys","volume":"67","author":"Hashimoto N","year":"1987","unstructured":"Hashimoto N, Kim C, Kikuchi H, Kojima M, Kang Y, Hazama F: Experimental induction of cerebral aneurysms in monkeys. J Neurosurg 67:903\u2013905, 198710.3171\/jns.1987.67.6.09033681429"},{"key":"b22","series-title":"Am J Pathol","first-page":"399","article-title":"Early changes of experimentally induced cerebral aneurysms in rats. Light-microscopic study","volume":"124","author":"Hazama F","year":"1986","unstructured":"Hazama F, Kataoka H, Yamada E, Kayembe K, Hashimoto N, Kojima M, : Early changes of experimentally induced cerebral aneurysms in rats. Light-microscopic study. Am J Pathol 124:399\u2013404, 19863766700"},{"key":"b23","series-title":"Intern Med","doi-asserted-by":"publisher","first-page":"367","DOI":"10.2169\/internalmedicine.53.0603","article-title":"Low-dose aspirin and comorbidities are significantly related to bleeding peptic ulcers in elderly patients compared with nonelderly patients in Japan","volume":"53","author":"Higuchi T","year":"2014","unstructured":"Higuchi T, Iwakiri R, Hara M, Shimoda R, Sakata Y, Nakayama A, : Low-dose aspirin and comorbidities are significantly related to bleeding peptic ulcers in elderly patients compared with nonelderly patients in Japan. Intern Med 53:367\u2013373, 20142458342210.2169\/internalmedicine.53.0603"},{"key":"b24","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"2906","DOI":"10.1161\/STROKEAHA.114.006055","article-title":"Morphological, hemodynamic, and clinical independent risk factors for anterior communicating artery aneurysms","volume":"45","author":"Kaspera W","year":"2014","unstructured":"Kaspera W, \u0141adzi\u0144ski P, Larysz P, Hebda A, Ptaszkiewicz K, Kopera M, : Morphological, hemodynamic, and clinical independent risk factors for anterior communicating artery aneurysms. Stroke 45:2906\u20132911, 20142516994910.1161\/STROKEAHA.114.006055"},{"key":"b25","series-title":"Acta Psychiatr Scand Suppl","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1111\/j.1600-0447.1989.tb07176.x","article-title":"A review of the metabolism and pharmacokinetics of paroxetine in man","volume":"350","author":"Kaye CM","year":"1989","unstructured":"Kaye CM, Haddock RE, Langley PF, Mellows G, Tasker TC, Zussman BD, : A review of the metabolism and pharmacokinetics of paroxetine in man. Acta Psychiatr Scand Suppl 350:60\u201375, 198910.1111\/j.1600-0447.1989.tb07176.x"},{"key":"b26","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1161\/01.STR.15.5.846","article-title":"Cerebral aneurysms and variations in the circle of Willis","volume":"15","author":"Kayembe KNT","year":"1984","unstructured":"Kayembe KNT, Sasahara M, Hazama F: Cerebral aneurysms and variations in the circle of Willis. Stroke 15:846\u2013850, 1984647453610.1161\/01.STR.15.5.846"},{"key":"b27","series-title":"Transl Stroke Res","article-title":"Two diverse hemodynamic forces, a mechanical stretch and a high wall shear stress, determine intracranial aneurysm formation","author":"Koseki H","unstructured":"Koseki H, Miyata H, Shimo S, Ohno N, Mifune K, Shimano K, : Two diverse hemodynamic forces, a mechanical stretch and a high wall shear stress, determine intracranial aneurysm formation. Transl Stroke Res [epub ahead of print], 2019"},{"key":"b28","series-title":"AJNR Am J Neuroradiol","doi-asserted-by":"publisher","first-page":"587","DOI":"10.3174\/ajnr.A2339","article-title":"Hemodynamics of cerebral aneurysm initiation: the role of wall shear stress and spatial wall shear stress gradient","volume":"32","author":"Kulcs\u00e1r Z","year":"2011","unstructured":"Kulcs\u00e1r Z, Ugron A, Marosfoi M, Berentei Z, Pa\u00e1l G, Szikora I: Hemodynamics of cerebral aneurysm initiation: the role of wall shear stress and spatial wall shear stress gradient. AJNR Am J Neuroradiol 32:587\u2013594, 201110.3174\/ajnr.A233921310860"},{"issue":"5","key":"b29","series-title":"J Inflamm (Lond)","doi-asserted-by":"publisher","DOI":"10.1186\/1476-9255-4-5","article-title":"The role of the purinergic P2X7 receptor in inflammation","volume":"4","author":"Lister MF","year":"2007","unstructured":"Lister MF, Sharkey J, Sawatzky DA, Hodgkiss JP, Davidson DJ, Rossi AG, : The role of the purinergic P2X7 receptor in inflammation. J Inflamm (Lond) 4:5, 200710.1186\/1476-9255-4-517367517"},{"key":"b30","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1161\/STROKEAHA.110.593517","article-title":"High shear stress and flow velocity in partially occluded aneurysms prone to recanalization","volume":"42","author":"Luo B","year":"2011","unstructured":"Luo B, Yang X, Wang S, Li H, Chen J, Yu H, : High shear stress and flow velocity in partially occluded aneurysms prone to recanalization. Stroke 42:745\u2013753, 201110.1161\/STROKEAHA.110.59351721233477"},{"key":"b31","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"2450","DOI":"10.1161\/STROKEAHA.112.659821","article-title":"Pharmacological stabilization of intracranial aneurysms in mice: a feasibility study","volume":"43","author":"Makino H","year":"2012","unstructured":"Makino H, Tada Y, Wada K, Liang EI, Chang M, Mobashery S, : Pharmacological stabilization of intracranial aneurysms in mice: a feasibility study. Stroke 43:2450\u20132456, 20122279832810.1161\/STROKEAHA.112.659821"},{"key":"b32","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1161\/STROKEAHA.110.585992","article-title":"Characterization of critical hemodynamics contributing to aneurysmal remodeling at the basilar terminus in a rabbit model","volume":"41","author":"Metaxa E","year":"2010","unstructured":"Metaxa E, Tremmel M, Natarajan SK, Xiang J, Paluch RA, Mandelbaum M, : Characterization of critical hemodynamics contributing to aneurysmal remodeling at the basilar terminus in a rabbit model. Stroke 41:1774\u20131782, 201010.1161\/STROKEAHA.110.585992"},{"key":"b33","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1161\/01.STR.0000021000.19637.3D","article-title":"Mouse model of cerebral aneurysm: experimental induction by renal hypertension and local hemodynamic changes","volume":"33","author":"Morimoto M","year":"2002","unstructured":"Morimoto M, Miyamoto S, Mizoguchi A, Kume N, Kita T, Hashimoto N: Mouse model of cerebral aneurysm: experimental induction by renal hypertension and local hemodynamic changes. Stroke 33:1911\u20131915, 200210.1161\/01.STR.0000021000.19637.3D12105374"},{"key":"b34","series-title":"Mol Pain","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/1744-8069-5-20","article-title":"Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief","volume":"5","author":"Nagata K","year":"2009","unstructured":"Nagata K, Imai T, Yamashita T, Tsuda M, Tozaki-Saitoh H, Inoue K: Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief. Mol Pain 5:20, 200910.1186\/1744-8069-5-2019389225"},{"key":"b35","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"258","DOI":"10.3171\/jns.1991.74.2.0258","article-title":"Cerebral blood flow patterns at major vessel bifurcations and aneurysms in rats","volume":"74","author":"Nakatani H","year":"1991","unstructured":"Nakatani H, Hashimoto N, Kang Y, Yamazoe N, Kikuchi H, Yamaguchi S, : Cerebral blood flow patterns at major vessel bifurcations and aneurysms in rats. J Neurosurg 74:258\u2013262, 1991198859610.3171\/jns.1991.74.2.0258"},{"key":"b36","series-title":"J Biomech Sci Eng","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1299\/jbse.15-00488","article-title":"Computational and experimental studies into the hemodynamics of cerebral aneurysms","volume":"11","author":"Shimogonya Y","year":"2016","unstructured":"Shimogonya Y, Fukuda S: Computational and experimental studies into the hemodynamics of cerebral aneurysms. J Biomech Sci Eng 11:15-00488, 201610.1299\/jbse.15-00488"},{"key":"b37","series-title":"World Neurosurg","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.wneu.2018.04.143","article-title":"Hemodynamic stress, inflammation, and intracranial aneurysm development and rupture: a systemic review","volume":"115","author":"Signorelli F","year":"2018","unstructured":"Signorelli F, Sela S, Gesualdo L, Chevrel S, Tollet F, Pailler-Mattei C, : Hemodynamic stress, inflammation, and intracranial aneurysm development and rupture: a systemic review. World Neurosurg 115:234\u2013244, 201810.1016\/j.wneu.2018.04.143"},{"key":"b38","series-title":"Cerebrovasc Dis","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1159\/000381137","article-title":"Potential role of aspirin in the prevention of aneurysmal subarachnoid hemorrhage","volume":"39","author":"Starke RM","year":"2015","unstructured":"Starke RM, Chalouhi N, Ding D, Hasan DM: Potential role of aspirin in the prevention of aneurysmal subarachnoid hemorrhage. Cerebrovasc Dis 39:332\u2013342, 201510.1159\/00038113725967073"},{"key":"b39","series-title":"Front Pharmacol","doi-asserted-by":"publisher","first-page":"291","DOI":"10.3389\/fphar.2017.00291","article-title":"P2X4 receptor function in the nervous system and current breakthroughs in pharmacology","volume":"8","author":"Stokes L","year":"2017","unstructured":"Stokes L, Layhadi JA, Bibic L, Dhuna K, Fountain SJ: P2X4 receptor function in the nervous system and current breakthroughs in pharmacology. Front Pharmacol 8:291, 201710.3389\/fphar.2017.0029128588493"},{"key":"b40","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1227\/00006123-197809000-00013","article-title":"Saccular aneurysm associated with absence of the left cervical carotid arteries","volume":"3","author":"Waga S","year":"1978","unstructured":"Waga S, Okada M, Kojima T: Saccular aneurysm associated with absence of the left cervical carotid arteries. Neurosurgery 3:208\u2013212, 197810.1227\/00006123-197809000-00013703939"},{"key":"b41","series-title":"J Pharmacol Sci","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1254\/jphs.10R29FM","article-title":"New molecular mechanisms for cardiovascular disease: blood flow sensing mechanism in vascular endothelial cells","volume":"116","author":"Yamamoto K","year":"2011","unstructured":"Yamamoto K, Ando J: New molecular mechanisms for cardiovascular disease: blood flow sensing mechanism in vascular endothelial cells. J Pharmacol Sci 116:323\u2013331, 201110.1254\/jphs.10R29FM21757846"},{"key":"b42","series-title":"Nat Med","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nm1338","article-title":"Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice","volume":"12","author":"Yamamoto K","year":"2006","unstructured":"Yamamoto K, Sokabe T, Matsumoto T, Yoshimura K, Shibata M, Ohura N, : Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice. Nat Med 12:133\u2013137, 20061632780010.1038\/nm1338"},{"key":"b43","series-title":"Iran Biomed J","first-page":"94","article-title":"Paroxetine attenuates the development and existing pain in a rat model of neurophatic pain","volume":"18","author":"Zarei M","year":"2014","unstructured":"Zarei M, Sabetkasaei M, Moini Zanjani T: Paroxetine attenuates the development and existing pain in a rat model of neurophatic pain. Iran Biomed J 18:94\u2013100, 2014"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/134\/1\/article-p102.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/134\/1\/article-p102.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/134\/1\/article-p102.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:54:19Z","timestamp":1792803259000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/134\/1\/article-p102.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":43,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.3171\/2019.9.jns19270","relation":{},"ISSN":["0022-3085","1933-0693"],"issn-type":[{"value":"0022-3085","type":"print"},{"value":"1933-0693","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]}}}