Tomoki Hashimoto, MD


My research program focuses on basic and translational research of vascular diseases including, intracranial aneurysms, aortic aneurysms, and brain arteriovenous malformations. These vascular lesions usually remain asymptomatic until they rupture. In case of intracranial aneurysms, rupture results in subarachnoid hemorrhage that can potentially cause severe mortality and morbidity.

Prevention of rupture of these vascular lesions is critical. We are working to identify new therapeutic targets that induce stabilization and regression of vascular lesions so that they remain unruptured and asymptomatic. We utilize novel animal models and human specimens to achieve these goals.

Maekawa H, Tada Y, Yagi K, Miyamoto T, Kitazato KT, Korai M, Satomi J, Hashimoto T, Nagahiro S. Bazedoxifene, a selective estrogen receptor modulator, reduces cerebral aneurysm rupture in Ovariectomized rats. J Neuroinflammation. 2017 Oct 02; 14(1):197.
Kawai T, Takayanagi T, Forrester SJ, Preston KJ, Obama T, Tsuji T, Kobayashi T, Boyer MJ, Cooper HA, Kwok HF, Hashimoto T, Scalia R, Rizzo V, Eguchi S. Vascular ADAM17 (a Disintegrin and Metalloproteinase Domain 17) Is Required for Angiotensin II/ß-Aminopropionitrile-Induced Abdominal Aortic Aneurysm. Hypertension. 2017 Sep 25.
Cooke DL, McCoy DB, Halbach VV, Hetts SW, Amans MR, Dowd CF, Higashida RT, Lawson D, Nelson J, Wang CY, Kim H, Werb Z, McCulloch C, Hashimoto T, Su H, Sun Z. Endovascular Biopsy: In Vivo Cerebral Aneurysm Endothelial Cell Sampling and Gene Expression Analysis. Transl Stroke Res. 2017 Sep 13.
Kuwabara A, Liu J, Kamio Y, Liu A, Lawton MT, Lee JW, Hashimoto T. Protective Effect of Mesenchymal Stem Cells Against the Development of Intracranial Aneurysm Rupture in Mice. Neurosurgery. 2017 Apr 19.
Hashimoto T, Rizzo V. HIF1a in aortic aneurysms and beyond. Clin Sci (Lond). 2017 04 01; 131(7):621-623.
Liu J, Kuwabara A, Kamio Y, Hu S, Park J, Hashimoto T, Lee JW. Human Mesenchymal Stem Cell-Derived Microvesicles Prevent the Rupture of Intracranial Aneurysm in Part by Suppression of Mast Cell Activation via a PGE2-Dependent Mechanism. Stem Cells. 2016 Dec; 34(12):2943-2955.
Korai M, Kitazato KT, Tada Y, Miyamoto T, Shimada K, Matsushita N, Kanematsu Y, Satomi J, Hashimoto T, Nagahiro S. Hyperhomocysteinemia induced by excessive methionine intake promotes rupture of cerebral aneurysms in ovariectomized rats. J Neuroinflammation. 2016 Jun 27; 13(1):165.
Miyamoto T, Kung DK, Kitazato KT, Yagi K, Shimada K, Tada Y, Korai M, Kurashiki Y, Kinouchi T, Kanematsu Y, Satomi J, Hashimoto T, Nagahiro S. Site-specific elevation of interleukin-1ß and matrix metalloproteinase-9 in the Willis circle by hemodynamic changes is associated with rupture in a novel rat cerebral aneurysm model. J Cereb Blood Flow Metab. 2017 Aug; 37(8):2795-2805.
Shimada K, Furukawa H, Wada K, Korai M, Wei Y, Tada Y, Kuwabara A, Shikata F, Kitazato KT, Nagahiro S, Lawton MT, Hashimoto T. Protective Role of Peroxisome Proliferator-Activated Receptor-? in the Development of Intracranial Aneurysm Rupture. Stroke. 2015 Jun; 46(6):1664-72.
Makino H, Hokamura K, Natsume T, Kimura T, Kamio Y, Magata Y, Namba H, Katoh T, Sato S, Hashimoto T, Umemura K. Successful serial imaging of the mouse cerebral arteries using conventional 3-T magnetic resonance imaging. J Cereb Blood Flow Metab. 2015 Sep; 35(9):1523-7.
Shimada K, Furukawa H, Wada K, Wei Y, Tada Y, Kuwabara A, Shikata F, Kanematsu Y, Lawton MT, Kitazato KT, Nagahiro S, Hashimoto T. Angiotensin-(1-7) protects against the development of aneurysmal subarachnoid hemorrhage in mice. J Cereb Blood Flow Metab. 2015 Jul; 35(7):1163-8.
Tada Y, Makino H, Furukawa H, Shimada K, Wada K, Liang EI, Murakami S, Kudo M, Kung DK, Hasan DM, Kitazato KT, Nagahiro S, Lawton MT, Hashimoto T. Roles of estrogen in the formation of intracranial aneurysms in ovariectomized female mice. Neurosurgery. 2014 Dec; 75(6):690-5; discussion 695.
Takayanagi T, Crawford KJ, Kobayashi T, Obama T, Tsuji T, Elliott KJ, Hashimoto T, Rizzo V, Eguchi S. Caveolin 1 is critical for abdominal aortic aneurysm formation induced by angiotensin II and inhibition of lysyl oxidase. Clin Sci (Lond). 2014 Jun; 126(11):785-94.
Tada Y, Wada K, Shimada K, Makino H, Liang EI, Murakami S, Kudo M, Shikata F, Pena Silva RA, Kitazato KT, Hasan DM, Kanematsu Y, Nagahiro S, Hashimoto T. Estrogen protects against intracranial aneurysm rupture in ovariectomized mice. Hypertension. 2014 Jun; 63(6):1339-44.
Tada Y, Wada K, Shimada K, Makino H, Liang EI, Murakami S, Kudo M, Kitazato KT, Nagahiro S, Hashimoto T. Roles of hypertension in the rupture of intracranial aneurysms. Stroke. 2014 Feb; 45(2):579-86.
Wada K, Makino H, Shimada K, Shikata F, Kuwabara A, Hashimoto T. Translational research using a mouse model of intracranial aneurysm. Transl Stroke Res. 2014 Apr; 5(2):248-51.
Akamatsu S, Kojima A, Tanaka A, Hayashi K, Hashimoto T. Symmetric peripheral gangrene. Anesthesiology. 2013 Jun; 118(6):1455.
Hasan DM, Chalouhi N, Jabbour P, Dumont AS, Kung DK, Magnotta VA, Young WL, Hashimoto T, Richard Winn H, Heistad D. Evidence that acetylsalicylic acid attenuates inflammation in the walls of human cerebral aneurysms: preliminary results. J Am Heart Assoc. 2013 Feb 22; 2(1):e000019.
Hasan D, Chalouhi N, Jabbour P, Dumont AS, Kung DK, Magnotta VA, Young WL, Hashimoto T, Winn HR, Heistad D. Early change in ferumoxytol-enhanced magnetic resonance imaging signal suggests unstable human cerebral aneurysm: a pilot study. Stroke. 2012 Dec; 43(12):3258-65.
Hasan D, Chalouhi N, Jabbour P, Hashimoto T. Macrophage imbalance (M1 vs. M2) and upregulation of mast cells in wall of ruptured human cerebral aneurysms: preliminary results. J Neuroinflammation. 2012 Sep 21; 9:222.
Makino H, Tada Y, Wada K, Liang EI, Chang M, Mobashery S, Kanematsu Y, Kurihara C, Palova E, Kanematsu M, Kitazato K, Hashimoto T. Pharmacological stabilization of intracranial aneurysms in mice: a feasibility study. Stroke. 2012 Sep; 43(9):2450-6.
Hasan D, Hashimoto T, Kung D, Macdonald RL, Winn HR, Heistad D. Upregulation of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) in wall of ruptured human cerebral aneurysms: preliminary results. Stroke. 2012 Jul; 43(7):1964-7.
Hasan DM, Mahaney KB, Magnotta VA, Kung DK, Lawton MT, Hashimoto T, Winn HR, Saloner D, Martin A, Gahramanov S, Dósa E, Neuwelt E, Young WL. Macrophage imaging within human cerebral aneurysms wall using ferumoxytol-enhanced MRI: a pilot study. Arterioscler Thromb Vasc Biol. 2012 Apr; 32(4):1032-8.
Akamatsu S, Kondo Y, Ueda N, Kojima A, Fukuoka N, Takada M, Dohi S, Hashimoto T. Continuous cardiac output measurement with a Doppler-equipped pulmonary artery catheter. Anesth Analg. 2011 Apr; 112(4):851-7.
Tada Y, Kanematsu Y, Kanematsu M, Nuki Y, Liang EI, Wada K, Makino H, Hashimoto T. A mouse model of intracranial aneurysm: technical considerations. Acta Neurochir Suppl. 2011; 111:31-5.
Kanematsu Y, Kanematsu M, Kurihara C, Tada Y, Tsou TL, van Rooijen N, Lawton MT, Young WL, Liang EI, Nuki Y, Hashimoto T. Critical roles of macrophages in the formation of intracranial aneurysm. Stroke. 2011 Jan; 42(1):173-8.
Monson KL, Matsumoto MM, Young WL, Manley GT, Hashimoto T. Abrupt increase in rat carotid blood flow induces rapid alteration of artery mechanical properties. J Mech Behav Biomed Mater. 2011 Jan; 4(1):9-15.
Kanematsu Y, Kanematsu M, Kurihara C, Tsou TL, Nuki Y, Liang EI, Makino H, Hashimoto T. Pharmacologically induced thoracic and abdominal aortic aneurysms in mice. Hypertension. 2010 May; 55(5):1267-74.
Nuki Y, Tsou TL, Kurihara C, Kanematsu M, Kanematsu Y, Hashimoto T. Elastase-induced intracranial aneurysms in hypertensive mice. Hypertension. 2009 Dec; 54(6):1337-44.
Hashimoto T, Morita M, Hamaguchi S, Kitajima T. [Anesthetic management for pancreaticoduodenectomy in a patient with Charcot-Marie-Tooth disease and liver cirrhosis]. Masui. 2009 Oct; 58(10):1313-5.
Zhu W, Fan Y, Hao Q, Shen F, Hashimoto T, Yang GY, Gasmi M, Bartus RT, Young WL, Chen Y. Postischemic IGF-1 gene transfer promotes neurovascular regeneration after experimental stroke. J Cereb Blood Flow Metab. 2009 Sep; 29(9):1528-37.
Ota R, Kurihara C, Tsou TL, Young WL, Yeghiazarians Y, Chang M, Mobashery S, Sakamoto A, Hashimoto T. Roles of matrix metalloproteinases in flow-induced outward vascular remodeling. J Cereb Blood Flow Metab. 2009 Sep; 29(9):1547-58.
Nuki Y, Matsumoto MM, Tsang E, Young WL, van Rooijen N, Kurihara C, Hashimoto T. Roles of macrophages in flow-induced outward vascular remodeling. J Cereb Blood Flow Metab. 2009 Mar; 29(3):495-503.
Chen Y, Zhu W, Bollen AW, Lawton MT, Barbaro NM, Dowd CF, Hashimoto T, Yang GY, Young WL. Evidence of inflammatory cell involvement in brain arteriovenous malformations. Neurosurgery. 2008 Jun; 62(6):1340-9; discussion 1349-50.
Seo Y, Hashimoto T, Nuki Y, Hasegawa BH. In vivo microCT imaging of rodent cerebral vasculature. Phys Med Biol. 2008 Apr 07; 53(7):N99-107.
Frenzel T, Lee CZ, Kim H, Quinnine NJ, Hashimoto T, Lawton MT, Guglielmo BJ, McCulloch CE, Young WL. Feasibility of minocycline and doxycycline use as potential vasculostatic therapy for brain vascular malformations: pilot study of adverse events and tolerance. Cerebrovasc Dis. 2008; 25(1-2):157-63.
Du R, Hashimoto T, Tihan T, Young WL, Perry V, Lawton MT. Growth and regression of arteriovenous malformations in a patient with hereditary hemorrhagic telangiectasia. Case report. J Neurosurg. 2007 Mar; 106(3):470-7.
Chen Y, Fan Y, Poon KY, Achrol AS, Lawton MT, Zhu Y, McCulloch CE, Hashimoto T, Lee C, Barbaro NM, Bollen AW, Yang GY, Young WL. MMP-9 expression is associated with leukocytic but not endothelial markers in brain arteriovenous malformations. Front Biosci. 2006 Sep 01; 11:3121-8.
Hashimoto T, Meng H, Young WL. Intracranial aneurysms: links among inflammation, hemodynamics and vascular remodeling. Neurol Res. 2006 Jun; 28(4):372-80.
Hashimoto T, Pittet JF. Angiopoietin-2: modulator of vascular permeability in acute lung injury? PLoS Med. 2006 Mar; 3(3):e113.
Vates GE, Hashimoto T, Young WL, Lawton MT. Angiogenesis in the brain during development: the effects of vascular endothelial growth factor and angiopoietin-2 in an animal model. J Neurosurg. 2005 Jul; 103(1):136-45.
Hashimoto T, Wu Y, Lawton MT, Yang GY, Barbaro NM, Young WL. Coexpression of angiogenic factors in brain arteriovenous malformations. Neurosurgery. 2005 May; 56(5):1058-65; discussion 1058-65.
Hashimoto T, Matsumoto MM, Li JF, Lawton MT, Young WL. Suppression of MMP-9 by doxycycline in brain arteriovenous malformations. BMC Neurol. 2005 Jan 24; 5(1):1.
Chen Y, Xu B, Arderiu G, Hashimoto T, Young WL, Boudreau N, Yang GY. Retroviral delivery of homeobox D3 gene induces cerebral angiogenesis in mice. J Cereb Blood Flow Metab. 2004 Nov; 24(11):1280-7.
Pawlikowska L, Tran MN, Achrol AS, McCulloch CE, Ha C, Lind DL, Hashimoto T, Zaroff J, Lawton MT, Marchuk DA, Kwok PY, Young WL. Polymorphisms in genes involved in inflammatory and angiogenic pathways and the risk of hemorrhagic presentation of brain arteriovenous malformations. Stroke. 2004 Oct; 35(10):2294-300.
Lawton MT, Stewart CL, Wulfstat AA, Derugin N, Hashimoto T, Young WL. The transgenic arteriovenous fistula in the rat: an experimental model of gene therapy for brain arteriovenous malformations. Neurosurgery. 2004 Jun; 54(6):1463-71; discussion 1471.
Lee CZ, Xu B, Hashimoto T, McCulloch CE, Yang GY, Young WL. Doxycycline suppresses cerebral matrix metalloproteinase-9 and angiogenesis induced by focal hyperstimulation of vascular endothelial growth factor in a mouse model. Stroke. 2004 Jul; 35(7):1715-9.
Yang GY, Yao JS, Huey M, Hashimoto T, Young WL. Participation of PI3K and ERK1/2 pathways are required for human brain vascular smooth muscle cell migration. Neurochem Int. 2004 May; 44(6):441-6.
Hashimoto T, Wu Y, Boudreau N, Li J, Matsumoto M, Young W. Regulation of tie2 expression by angiopoietin--potential feedback system. Endothelium. 2004 May-Aug; 11(3-4):207-10.
Hashimoto T, Lawton MT, Wen G, Yang GY, Chaly T, Stewart CL, Dressman HK, Barbaro NM, Marchuk DA, Young WL. Gene microarray analysis of human brain arteriovenous malformations. Neurosurgery. 2004 Feb; 54(2):410-23; discussion 423-5.
Xu B, Wu YQ, Huey M, Arthur HM, Marchuk DA, Hashimoto T, Young WL, Yang GY. Vascular endothelial growth factor induces abnormal microvasculature in the endoglin heterozygous mouse brain. J Cereb Blood Flow Metab. 2004 Feb; 24(2):237-44.
Lee CZ, Litt L, Hashimoto T, Young WL. Physiologic monitoring and anesthesia considerations in acute ischemic stroke. J Vasc Interv Radiol. 2004 Jan; 15(1 Pt 2):S13-9.
Hashimoto T, Wen G, Lawton MT, Boudreau NJ, Bollen AW, Yang GY, Barbaro NM, Higashida RT, Dowd CF, Halbach VV, Young WL. Abnormal expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in brain arteriovenous malformations. Stroke. 2003 Apr; 34(4):925-31.
Yang GY, Xu B, Hashimoto T, Huey M, Chaly T, Wen R, Young WL. Induction of focal angiogenesis through adenoviral vector mediated vascular endothelial cell growth factor gene transfer in the mature mouse brain. Angiogenesis. 2003; 6(2):151-8.
Quick CM, James DJ, Ning K, Joshi S, Halim AX, Hashimoto T, Young WL. Relationship of nidal vessel radius and wall thickness to brain arteriovenous malformation hemorrhage. Neurol Res. 2002 Jul; 24(5):495-500.
Hashimoto T, Young WL, Prohovnik I, Gupta DK, Ostapkovich ND, Ornstein E, Halim AX, Quick CM. Increased cerebral blood flow after brain arteriovenous malformation resection is substantially independent of changes in cardiac output. J Neurosurg Anesthesiol. 2002 Jul; 14(3):204-8.
Hashimoto T, Gupta DK, Young WL. Interventional neuroradiology--anesthetic considerations. Anesthesiol Clin North America. 2002 Jun; 20(2):347-59, vi.
Gupta DK, Young WL, Hashimoto T, Halim AX, Marshall RS, Lazar RM, Joshi S, Pile-Spellman J, Ostapkovich N. Characterization of the cerebral blood flow response to balloon deflation after temporary internal carotid artery test occlusion. J Neurosurg Anesthesiol. 2002 Apr; 14(2):123-9.
Young WL, Lawton MT, Gupta DK, Hashimoto T. Anesthetic management of deep hypothermic circulatory arrest for cerebral aneurysm clipping. Anesthesiology. 2002 Feb; 96(2):497-503.
Hashimoto T, Young WL. Anesthesia-related considerations for cerebral arteriovenous malformations. Neurosurg Focus. 2001 Nov 15; 11(5):e5.
Quick CM, Hashimoto T, Young WL. Lack of flow regulation may explain the development of arteriovenous malformations. Neurol Res. 2001 Sep; 23(6):641-4.
Hashimoto T, Lam T, Boudreau NJ, Bollen AW, Lawton MT, Young WL. Abnormal balance in the angiopoietin-tie2 system in human brain arteriovenous malformations. Circ Res. 2001 Jul 20; 89(2):111-3.
Hashimoto T, Mesa-Tejada R, Quick CM, Bollen AW, Joshi S, Pile-Spellman J, Lawton MT, Young WL. Evidence of increased endothelial cell turnover in brain arteriovenous malformations. Neurosurgery. 2001 Jul; 49(1):124-31; discussion 131-2.
Joshi S, Hashimoto T, Ostapkovich N, Pile-Spellman J, Duong DH, Hacein-Bey L, Hacien-Bey L, Marshall RS, James DJ, Young WL. Effect of intracarotid papaverine on human cerebral blood flow and vascular resistance during acute hemispheric arterial hypotension. J Neurosurg Anesthesiol. 2001 Apr; 13(2):146-51.
Martinez D, Hwang D, Mawlawi O, Slifstein M, Kent J, Simpson N, Parsey RV, Hashimoto T, Huang Y, Shinn A, Van Heertum R, Abi-Dargham A, Caltabiano S, Malizia A, Cowley H, Mann JJ, Laruelle M. Differential occupancy of somatodendritic and postsynaptic 5HT(1A) receptors by pindolol: a dose-occupancy study with [11C]WAY 100635 and positron emission tomography in humans. Neuropsychopharmacology. 2001 Mar; 24(3):209-29.
Hashimoto T, Young WL, Aagaard BD, Joshi S, Ostapkovich ND, Pile-Spellman J. Adenosine-induced ventricular asystole to induce transient profound systemic hypotension in patients undergoing endovascular therapy. Dose-response characteristics. Anesthesiology. 2000 Oct; 93(4):998-1001.
Hashimoto T, Emala CW, Joshi S, Mesa-Tejada R, Quick CM, Feng L, Libow A, Marchuk DA, Young WL. Abnormal pattern of Tie-2 and vascular endothelial growth factor receptor expression in human cerebral arteriovenous malformations. Neurosurgery. 2000 Oct; 47(4):910-8; discussion 918-9.
Quick CM, Young WL, Leonard EF, Joshi S, Gao E, Hashimoto T. Model of structural and functional adaptation of small conductance vessels to arterial hypotension. Am J Physiol Heart Circ Physiol. 2000 Oct; 279(4):H1645-53.
Joshi S, Young WL, Duong DH, Ostapkovich ND, Aagaard BD, Hashimoto T, Pile-Spellman J. Intracarotid infusion of the nitric oxide synthase inhibitor, L-NMMA, modestly decreases cerebral blood flow in human subjects. Anesthesiology. 2000 Sep; 93(3):699-707.
Martinez D, Mawlawi O, Hwang DR, Kent J, Simpson N, Parsey RV, Hashimoto T, Slifstein M, Huang Y, Van Heertum R, Abi-Dargham A, Caltabiano S, Malizia A, Cowley H, Mann JJ, Laruelle M. Positron emission tomography study of pindolol occupancy of 5-HT(1A) receptors in humans: preliminary analyses. Nucl Med Biol. 2000 Jul; 27(5):523-7.
Hashimoto T, Iida H, Dohi S. Marked increases of aminotransferase levels after cresol ingestion. Am J Emerg Med. 1998 Nov; 16(7):667-8.
Hashimoto T, Armstead VE. Occlusion of the pilot tube in a Laser-Shield II endotracheal tube caused by methylene blue crystals: a case report. J Clin Anesth. 1998 Sep; 10(6):522-3.