{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T16:28:31Z","timestamp":1793809711164,"version":"4.6.1"},"reference-count":44,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec><jats:title>OBJECTIVE<\/jats:title><jats:p>A high level of vascular endothelial growth factor (VEGF) has been implicated in brain arteriovenous malformation (bAVM) bleeding and rupture. However, direct evidence is missing. In this study the authors used a mouse bAVM model to test the hypothesis that elevation of focal VEGF levels in bAVMs exacerbates the severity of bAVM hemorrhage.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Brain AVMs were induced in adult mice in which activin receptor\u2013like kinase 1 (<jats:italic>Alk1<\/jats:italic>, a gene that causes AVM) gene exons 4\u20136 were floxed by intrabasal ganglia injection of an adenoviral vector expressing Cre recombinase to induce <jats:italic>Alk1<\/jats:italic> mutation and an adeno-associated viral vector expressing human VEGF (AAV-VEGF) to induce angiogenesis. Two doses of AAV-VEGF (5 \u00d7 10<jats:sup>9<\/jats:sup> [high] or 2 \u00d7 10<jats:sup>9<\/jats:sup> [low]) viral genomes were used. In addition, the common carotid artery and external jugular vein were anastomosed in a group of mice treated with low-dose AAV-VEGF 6 weeks after the model induction to induce cerebral venous hypertension (VH), because VH increases the VEGF level in the brain. Brain samples were collected 8 weeks after the model induction. Hemorrhages in the bAVM lesions were quantified on brain sections stained with Prussian blue, which detects iron deposition. VEGF levels were quantified in bAVM tissue by enzyme-linked immunosorbent assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Compared to mice injected with a low dose of AAV-VEGF, the mice injected with a high dose had higher levels of VEGF (p = 0.003) and larger Prussian blue\u2013positive areas in the bAVM lesion at 8 or 9 weeks after model induction (p = 0.002). VH increased bAVM hemorrhage in the low-dose AAV-VEGF group. The overall mortality in the high-dose AAV-VEGF group was 26.7%, whereas no mouse died in the low-dose AAV-VEGF group without VH. In contrast, VH caused a mortality of 50% in the low-dose AAV-VEGF group.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Using mouse bAVM models, the authors provided direct evidence that elevation of the VEGF level increases bAVM hemorrhage and mouse mortality.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2019.1.jns183112","type":"journal-article","created":{"date-parts":[[2019,4,27]],"date-time":"2019-04-27T07:20:04Z","timestamp":1556349604000},"page":"1566-1573","source":"Crossref","is-referenced-by-count":36,"title":["Effect of elevation of vascular endothelial growth factor level on exacerbation of hemorrhage in mouse brain arteriovenous malformation"],"prefix":"10.3171","volume":"132","author":[{"given":"Philip","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, California;"},{"name":"Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People\u2019s Republic of China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonali","family":"Shaligram","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Espen J.","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Tai","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoliang","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, California;"},{"name":"Department of Neurological Surgery, University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Lawton","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1","series-title":"JAMA","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1001\/jama.2014.3200","article-title":"Outcome after conservative management or intervention for unruptured brain arteriovenous malformations","volume":"311","author":"Al-Shahi Salman R","year":"2014","unstructured":"Al-Shahi Salman R, White PM, Counsell CE, du Plessis J, van Beijnum J, Josephson CB, : Outcome after conservative management or intervention for unruptured brain arteriovenous malformations. JAMA 311:1661\u20131669, 201410.1001\/jama.2014.3200"},{"key":"b2","series-title":"Ophthalmology","doi-asserted-by":"publisher","first-page":"1695.e1","DOI":"10.1016\/j.ophtha.2006.05.064","article-title":"Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy","volume":"113","author":"Avery RL","year":"2006","unstructured":"Avery RL, Pearlman J, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, : Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology 113:1695.e1\u20131695.e15, 200610.1016\/j.ophtha.2006.05.064"},{"key":"b3","series-title":"World Neurosurg","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.wneu.2017.04.120","article-title":"Delayed venous drainage in ruptured arteriovenous malformations based on quantitative color-coded digital subtraction angiography","volume":"104","author":"Burkhardt JK","year":"2017","unstructured":"Burkhardt JK, Chen X, Winkler EA, Cooke DL, Kim H, Lawton MT: Delayed venous drainage in ruptured arteriovenous malformations based on quantitative color-coded digital subtraction angiography. World Neurosurg 104:619\u2013627, 201710.1016\/j.wneu.2017.04.12028457930"},{"key":"b4","series-title":"Transl Stroke Res","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1007\/s12975-014-0343-0","article-title":"Brain arteriovenous malformation modeling, pathogenesis, and novel therapeutic targets","volume":"5","author":"Chen W","year":"2014","unstructured":"Chen W, Choi EJ, McDougall CM, Su H: Brain arteriovenous malformation modeling, pathogenesis, and novel therapeutic targets. Transl Stroke Res 5:316\u2013329, 20142472325610.1007\/s12975-014-0343-0"},{"key":"b5","series-title":"Arterioscler Thromb Vasc Biol","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1161\/ATVBAHA.112.300485","article-title":"Reduced mural cell coverage and impaired vessel integrity after angiogenic stimulation in the Alk1-deficient brain","volume":"33","author":"Chen W","year":"2013","unstructured":"Chen W, Guo Y, Walker EJ, Shen F, Jun K, Oh SP, : Reduced mural cell coverage and impaired vessel integrity after angiogenic stimulation in the Alk1-deficient brain. Arterioscler Thromb Vasc Biol 33:305\u2013310, 20132324140710.1161\/ATVBAHA.112.300485"},{"key":"b6","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1161\/STROKEAHA.113.003655","article-title":"De novo cerebrovascular malformation in the adult mouse after endothelial Alk1 deletion and angiogenic stimulation","volume":"45","author":"Chen W","year":"2014","unstructured":"Chen W, Sun Z, Han Z, Jun K, Camus M, Wankhede M, : De novo cerebrovascular malformation in the adult mouse after endothelial Alk1 deletion and angiogenic stimulation. Stroke 45:900\u2013902, 201410.1161\/STROKEAHA.113.00365524457293"},{"key":"b7","series-title":"PLoS One","doi-asserted-by":"publisher","first-page":"e88511","DOI":"10.1371\/journal.pone.0088511","article-title":"Novel brain arteriovenous malformation mouse models for type 1 hereditary hemorrhagic telangiectasia","volume":"9","author":"Choi EJ","year":"2014","unstructured":"Choi EJ, Chen W, Jun K, Arthur HM, Young WL, Su H: Novel brain arteriovenous malformation mouse models for type 1 hereditary hemorrhagic telangiectasia. PLoS One 9:e88511, 201410.1371\/journal.pone.008851124520391"},{"key":"b8","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1161\/STROKEAHA.112.671974","article-title":"Endoglin deficiency in bone marrow is sufficient to cause cerebrovascular dysplasia in the adult mouse after vascular endothelial growth factor stimulation","volume":"44","author":"Choi EJ","year":"2013","unstructured":"Choi EJ, Walker EJ, Degos V, Jun K, Kuo R, Pile-Spellman J, : Endoglin deficiency in bone marrow is sufficient to cause cerebrovascular dysplasia in the adult mouse after vascular endothelial growth factor stimulation. Stroke 44:795\u2013798, 201310.1161\/STROKEAHA.112.67197423306322"},{"key":"b9","series-title":"Cerebrovasc Dis","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1159\/000337762","article-title":"Minimal homozygous endothelial deletion of Eng with VEGF stimulation is sufficient to cause cerebrovascular dysplasia in the adult mouse","volume":"33","author":"Choi EJ","year":"2012","unstructured":"Choi EJ, Walker EJ, Shen F, Oh SP, Arthur HM, Young WL, : Minimal homozygous endothelial deletion of Eng with VEGF stimulation is sufficient to cause cerebrovascular dysplasia in the adult mouse. Cerebrovasc Dis 33:540\u2013547, 201210.1159\/00033776222571958"},{"key":"b10","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1161\/STROKEAHA.112.652032","article-title":"A perfect storm: how a randomized trial of unruptured brain arteriovenous malformations\u2019 (ARUBA\u2019s) trial design challenges notions of external validity","volume":"43","author":"Cockroft KM","unstructured":"Cockroft KM, Jayaraman MV, Amin-Hanjani S, Derdeyn CP, McDougall CG, Wilson JA: A perfect storm: how a randomized trial of unruptured brain arteriovenous malformations\u2019 (ARUBA\u2019s) trial design challenges notions of external validity. Stroke 43:1979\u20131981, 20122266940610.1161\/STROKEAHA.112.652032"},{"key":"b11","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"e200","DOI":"10.1161\/STR.0000000000000134","article-title":"Management of brain arteriovenous malformations: a scientific statement for healthcare professionals from the American Heart Association\/American Stroke Association","volume":"48","author":"Derdeyn CP","year":"2017","unstructured":"Derdeyn CP, Zipfel GJ, Albuquerque FC, Cooke DL, Feldmann E, Sheehan JP, : Management of brain arteriovenous malformations: a scientific statement for healthcare professionals from the American Heart Association\/American Stroke Association. Stroke 48:e200\u2013e224, 20172864235210.1161\/STR.0000000000000134"},{"key":"b12","series-title":"Lancet","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/S0140-6736(02)07946-1","article-title":"Arteriovenous malformations","volume":"359","author":"Fleetwood IG","year":"2002","unstructured":"Fleetwood IG, Steinberg GK: Arteriovenous malformations. Lancet 359:863\u2013873, 200210.1016\/S0140-6736(02)07946-111897302"},{"key":"b13","series-title":"J Cereb Blood Flow Metab","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1038\/jcbfm.2009.67","article-title":"Nonischemic cerebral venous hypertension promotes a pro-angiogenic stage through HIF-1 downstream genes and leukocyte-derived MMP-9","volume":"29","author":"Gao P","year":"2009","unstructured":"Gao P, Zhu Y, Ling F, Shen F, Lee B, Gabriel RA, : Nonischemic cerebral venous hypertension promotes a pro-angiogenic stage through HIF-1 downstream genes and leukocyte-derived MMP-9. J Cereb Blood Flow Metab 29:1482\u20131490, 20091947127810.1038\/jcbfm.2009.67"},{"key":"b14","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1161\/STROKEAHA.111.647263","article-title":"Silent intralesional microhemorrhage as a risk factor for brain arteriovenous malformation rupture","volume":"43","author":"Guo Y","year":"2012","unstructured":"Guo Y, Saunders T, Su H, Kim H, Akkoc D, Saloner DA, : Silent intralesional microhemorrhage as a risk factor for brain arteriovenous malformation rupture. Stroke 43:1240\u20131246, 20122230825310.1161\/STROKEAHA.111.647263"},{"key":"b15","series-title":"Am J Physiol Heart Circ Physiol","doi-asserted-by":"publisher","first-page":"H2250","DOI":"10.1152\/ajpheart.00083.2008","article-title":"Increased tissue perfusion promotes capillary dysplasia in the ALK1-deficient mouse brain following VEGF stimulation","volume":"295","author":"Hao Q","year":"2008","unstructured":"Hao Q, Su H, Marchuk DA, Rola R, Wang Y, Liu W, : Increased tissue perfusion promotes capillary dysplasia in the ALK1-deficient mouse brain following VEGF stimulation. Am J Physiol Heart Circ Physiol 295:H2250\u2013H2256, 200810.1152\/ajpheart.00083.200818835925"},{"key":"b16","series-title":"Transl Stroke Res","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s12975-010-0020-x","article-title":"VEGF induces more severe cerebrovascular dysplasia in Endoglin\u00b1 than in Alk1\u00b1 mice","volume":"1","author":"Hao Q","year":"2010","unstructured":"Hao Q, Zhu Y, Su H, Shen F, Yang GY, Kim H, : VEGF induces more severe cerebrovascular dysplasia in Endoglin\u00b1 than in Alk1\u00b1 mice. Transl Stroke Res 1:197\u2013201, 201010.1007\/s12975-010-0020-x20640035"},{"key":"b17","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1097\/00006123-200010000-00022","article-title":"Abnormal pattern of Tie-2 and vascular endothelial growth factor receptor expression in human cerebral arteriovenous malformations","volume":"47","author":"Hashimoto T","year":"2000","unstructured":"Hashimoto T, Emala CW, Joshi S, Mesa-Tejada R, Quick CM, Feng L, : Abnormal pattern of Tie-2 and vascular endothelial growth factor receptor expression in human cerebral arteriovenous malformations. Neurosurgery 47:910\u2013919, 200010.1097\/00006123-200010000-0002211014431"},{"key":"b18","series-title":"Neurosurgery","first-page":"1058","article-title":"Coexpression of angiogenic factors in brain arteriovenous malformations","volume":"56","author":"Hashimoto T","year":"2005","unstructured":"Hashimoto T, Wu Y, Lawton MT, Yang GY, Barbaro NM, Young WL: Coexpression of angiogenic factors in brain arteriovenous malformations. Neurosurgery 56:1058\u20131065, 200515854255"},{"key":"b19","series-title":"Br J Neurosurg","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3109\/02688697.2013.815325","article-title":"Increased expression of vascular endothelial growth factor and its receptor in enlarging brain arteriovenous malformations\u2014a case report","volume":"28","author":"Kashiwazaki D","year":"2014","unstructured":"Kashiwazaki D, Kobayashi R, Houkin K, Kuroda S: Increased expression of vascular endothelial growth factor and its receptor in enlarging brain arteriovenous malformations\u2014a case report. Br J Neurosurg 28:119\u2013121, 201410.3109\/02688697.2013.815325"},{"key":"b20","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1097\/00006123-200005000-00032","article-title":"Expression of structural proteins and angiogenic factors in cerebrovascular anomalies","volume":"46","author":"Kili\u00e7 T","year":"2000","unstructured":"Kili\u00e7 T, Pamir MN, K\u00fcll\u00fc S, Eren F, Ozek MM, Black PM: Expression of structural proteins and angiogenic factors in cerebrovascular anomalies. Neurosurgery 46:1179\u20131192, 200010.1097\/00006123-200005000-0003210807251"},{"key":"b21","series-title":"Stroke: Pathophysiology, Diagnosis, and Management","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/B978-1-4160-5478-8.10012-0","article-title":"Genetics and vascular biology of brain vascular malformations (Chapter 12)","author":"Kim H","year":"2011","unstructured":"Kim H, Pawlikowska L, Young WL: Genetics and vascular biology of brain vascular malformations (Chapter 12), in Mohr JP, Wolf PA, Grotta JC,  (eds): Stroke: Pathophysiology, Diagnosis, and Management, ed 5. Philadelphia: Churchill Livingstone Elsevier, 2011, pp 169\u201318610.1016\/B978-1-4160-5478-8.10012-0"},{"key":"b22","series-title":"Neurosurgery","first-page":"117","article-title":"Expression of vascular endothelial growth factors and their receptors in and around intracranial arteriovenous malformations","volume":"50","author":"Koizumi T","year":"2002","unstructured":"Koizumi T, Shiraishi T, Hagihara N, Tabuchi K, Hayashi T, Kawano T: Expression of vascular endothelial growth factors and their receptors in and around intracranial arteriovenous malformations. Neurosurgery 50:117\u2013126, 200211844242"},{"key":"b23","series-title":"Eur Radiol","doi-asserted-by":"publisher","first-page":"2868","DOI":"10.1007\/s00330-016-4645-3","article-title":"Subsequent haemorrhage in children with untreated brain arteriovenous malformation: Higher risk with unbalanced inflow and outflow angioarchitecture","volume":"27","author":"Ma L","year":"2017","unstructured":"Ma L, Chen XL, Chen Y, Wu CX, Ma J, Zhao YL: Subsequent haemorrhage in children with untreated brain arteriovenous malformation: Higher risk with unbalanced inflow and outflow angioarchitecture. Eur Radiol 27:2868\u20132876, 201710.1007\/s00330-016-4645-327900505"},{"key":"b24","series-title":"Transl Stroke Res","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1007\/s12975-016-0478-2","article-title":"Integrin \u03b28 deletion enhances vascular dysplasia and hemorrhage in the brain of adult Alk1 heterozygous mice","volume":"7","author":"Ma L","year":"2016","unstructured":"Ma L, Shen F, Jun K, Bao C, Kuo R, Young WL, : Integrin \u03b28 deletion enhances vascular dysplasia and hemorrhage in the brain of adult Alk1 heterozygous mice. Transl Stroke Res 7:488\u2013496, 20162735286710.1007\/s12975-016-0478-2"},{"key":"b25","series-title":"Stroke","first-page":"e91","article-title":"Transgenic mouse model of hemorrhagic arteriovenous malformation in brain and spinal cord","volume":"42","author":"Milton I","year":"2011","unstructured":"Milton I, Seki T: Transgenic mouse model of hemorrhagic arteriovenous malformation in brain and spinal cord. Stroke 42:e91, 2011 (Abstract #163)"},{"key":"b26","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1161\/STROKEAHA.112.653584","article-title":"Hull down on the horizon: A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA) trial","volume":"43","author":"Mohr JP","year":"2012","unstructured":"Mohr JP, Moskowitz AJ, Parides M, Stapf C, Young WL: Hull down on the horizon: A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA) trial. Stroke 43:1744\u20131745, 20122266940510.1161\/STROKEAHA.112.653584"},{"key":"b27","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"e537","DOI":"10.1161\/STROKEAHA.110.580274","article-title":"The ARUBA trial: current status, future hopes","volume":"41","author":"Mohr JP","year":"2010","unstructured":"Mohr JP, Moskowitz AJ, Stapf C, Hartmann A, Lord K, Marshall SM, : The ARUBA trial: current status, future hopes. Stroke 41:e537\u2013e540, 201010.1161\/STROKEAHA.110.58027420634478"},{"key":"b28","series-title":"Lancet","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/S0140-6736(13)62302-8","article-title":"Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial","volume":"383","author":"Mohr JP","year":"2014","unstructured":"Mohr JP, Parides MK, Stapf C, Moquete E, Moy CS, Overbey JR, : Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet 383:614\u2013621, 201410.1016\/S0140-6736(13)62302-8"},{"key":"b29","series-title":"Blood","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1182\/blood-2007-08-107359","article-title":"ALK5- and TGFBR2-independent role of ALK1 in the pathogenesis of hereditary hemorrhagic telangiectasia type 2","volume":"111","author":"Park SO","year":"2008","unstructured":"Park SO, Lee YJ, Seki T, Hong KH, Fliess N, Jiang Z, : ALK5- and TGFBR2-independent role of ALK1 in the pathogenesis of hereditary hemorrhagic telangiectasia type 2. Blood 111:633\u2013642, 20081791138410.1182\/blood-2007-08-107359"},{"key":"b30","series-title":"Front Biosci","doi-asserted-by":"publisher","first-page":"3190","DOI":"10.2741\/2042","article-title":"Recombinant adeno-associated viral vector encoding human VEGF165 induces neomicrovessel formation in the adult mouse brain","volume":"11","author":"Shen F","year":"2006","unstructured":"Shen F, Su H, Liu W, Kan YW, Young WL, Yang GY: Recombinant adeno-associated viral vector encoding human VEGF165 induces neomicrovessel formation in the adult mouse brain. Front Biosci 11:3190\u20133198, 20061672038510.2741\/2042"},{"key":"b31","series-title":"J Cereb Blood Flow Metab","doi-asserted-by":"publisher","first-page":"2343","DOI":"10.1038\/jcbfm.2011.97","article-title":"Coexpression of angiopoietin-1 with VEGF increases the structural integrity of the blood-brain barrier and reduces atrophy volume","volume":"31","author":"Shen F","year":"2011","unstructured":"Shen F, Walker EJ, Jiang L, Degos V, Li J, Sun B, : Coexpression of angiopoietin-1 with VEGF increases the structural integrity of the blood-brain barrier and reduces atrophy volume. J Cereb Blood Flow Metab 31:2343\u20132351, 201110.1038\/jcbfm.2011.9721772310"},{"key":"b32","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"838","DOI":"10.3171\/jns.1996.85.5.0838","article-title":"Expression of vascular endothelial growth factor in pediatric and adult cerebral arteriovenous malformations: an immunocytochemical study","volume":"85","author":"Sonstein WJ","year":"1996","unstructured":"Sonstein WJ, Kader A, Michelsen WJ, Llena JF, Hirano A, Casper D: Expression of vascular endothelial growth factor in pediatric and adult cerebral arteriovenous malformations: an immunocytochemical study. J Neurosurg 85:838\u2013845, 199610.3171\/jns.1996.85.5.08388893722"},{"key":"b33","series-title":"Retina","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1097\/01.iae.0000238561.99283.0e","article-title":"Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration","volume":"26","author":"Spaide RF","year":"2006","unstructured":"Spaide RF, Laud K, Fine HF, Klancnik JM Jr, Meyerle CB, Yannuzzi LA, : Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration. Retina 26:383\u2013390, 20061660395510.1097\/01.iae.0000238561.99283.0e"},{"key":"b34","series-title":"Curr Opin Neurol","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1097\/01.wco.0000200546.14668.78","article-title":"Invasive treatment of unruptured brain arteriovenous malformations is experimental therapy","volume":"19","author":"Stapf C","year":"2006","unstructured":"Stapf C, Mohr JP, Choi JH, Hartmann A, Mast H: Invasive treatment of unruptured brain arteriovenous malformations is experimental therapy. Curr Opin Neurol 19:63\u201368, 20061641567910.1097\/01.wco.0000200546.14668.78"},{"key":"b35","series-title":"Proc Natl Acad Sci U S A","doi-asserted-by":"publisher","first-page":"13801","DOI":"10.1073\/pnas.250488097","article-title":"Adeno-associated viral vector-mediated vascular endothelial growth factor gene transfer induces neovascular formation in ischemic heart","volume":"97","author":"Su H","year":"2000","unstructured":"Su H, Lu R, Kan YW: Adeno-associated viral vector-mediated vascular endothelial growth factor gene transfer induces neovascular formation in ischemic heart. Proc Natl Acad Sci U S A 97:13801\u201313806, 20001109575110.1073\/pnas.250488097"},{"key":"b36","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"972","DOI":"10.3171\/jns.2001.94.6.0972","article-title":"Endothelial proliferation, neoangiogenesis, and potential de novo generation of cerebrovascular malformations","volume":"94","author":"Sure U","year":"2001","unstructured":"Sure U, Butz N, Schlegel J, Siegel AM, Wakat JP, Mennel HD, : Endothelial proliferation, neoangiogenesis, and potential de novo generation of cerebrovascular malformations. J Neurosurg 94:972\u2013977, 20011140952710.3171\/jns.2001.94.6.0972"},{"key":"b37","series-title":"JAMA","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1001\/jama.2011.1632","article-title":"Treatment of brain arteriovenous malformations: a systematic review and meta-analysis","volume":"306","author":"van Beijnum J","unstructured":"van Beijnum J, van der Worp HB, Buis DR, Al-Shahi Salman R, Kappelle LJ, Rinkel GJ, : Treatment of brain arteriovenous malformations: a systematic review and meta-analysis. JAMA 306:2011\u20132019, 201110.1001\/jama.2011.163222068993"},{"key":"b38","series-title":"Ann Neurol","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1002\/ana.22348","article-title":"Arteriovenous malformation in the adult mouse brain resembling the human disease","volume":"69","author":"Walker EJ","year":"2011","unstructured":"Walker EJ, Su H, Shen F, Choi EJ, Oh SP, Chen G, : Arteriovenous malformation in the adult mouse brain resembling the human disease. Ann Neurol 69:954\u2013962, 201110.1002\/ana.2234821437931"},{"key":"b39","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1161\/STROKEAHA.111.647982","article-title":"Bevacizumab attenuates VEGF-induced angiogenesis and vascular malformations in the adult mouse brain","volume":"43","author":"Walker EJ","year":"2012","unstructured":"Walker EJ, Su H, Shen F, Degos V, Amend G, Jun K, : Bevacizumab attenuates VEGF-induced angiogenesis and vascular malformations in the adult mouse brain. Stroke 43:1925\u20131930, 2012 (Erratum in Stroke 44: e21, 2013)10.1161\/STROKEAHA.111.64798222569934"},{"key":"b40","series-title":"J Vis Exp","first-page":"e50472","article-title":"Adult mouse venous hypertension model: common carotid artery to external jugular vein anastomosis","volume":"95","author":"Yang ST","year":"2015","unstructured":"Yang ST, Rodriguez-Hernandez A, Walker EJ, Young WL, Su H, Lawton MT: Adult mouse venous hypertension model: common carotid artery to external jugular vein anastomosis. J Vis Exp 95:e50472, 2015"},{"key":"b41","series-title":"J Clin Invest","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1172\/JCI9369","article-title":"VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain","volume":"106","author":"Zhang ZG","year":"2000","unstructured":"Zhang ZG, Zhang L, Jiang Q, Zhang R, Davies K, Powers C, : VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest 106:829\u2013838, 200010.1172\/JCI936911018070"},{"issue":"Suppl 1","key":"b42","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"A54","DOI":"10.1161\/str.47.suppl_1.54","article-title":"Soluble FLT1 gene therapy through systemic viral delivery reduces the severity of mouse brain arteriovenous malformation","volume":"47","author":"Zhu W","year":"2016","unstructured":"Zhu W, Shen F, Kang S, : Soluble FLT1 gene therapy through systemic viral delivery reduces the severity of mouse brain arteriovenous malformation. Stroke 47 (Suppl 1):A54, 2016 (Abstract)10.1161\/str.47.suppl_1.54"},{"key":"b43","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1161\/STROKEAHA.116.015713","article-title":"Soluble FLT1 gene therapy alleviates brain arteriovenous malformation severity","volume":"48","author":"Zhu W","year":"2017","unstructured":"Zhu W, Shen F, Mao L, Zhan L, Kang S, Sun Z, : Soluble FLT1 gene therapy alleviates brain arteriovenous malformation severity. Stroke 48:1420\u20131423, 20172832584610.1161\/STROKEAHA.116.015713"},{"key":"b44","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1227\/01.NEU.0000228962.68204.CF","article-title":"Expression of hypoxia-inducible factor-1 and vascular endothelial growth factor in response to venous hypertension","volume":"59","author":"Zhu Y","year":"2006","unstructured":"Zhu Y, Lawton MT, Du R, Shwe Y, Chen Y, Shen F, : Expression of hypoxia-inducible factor-1 and vascular endothelial growth factor in response to venous hypertension. Neurosurgery 59:687\u2013696, 200610.1227\/01.NEU.0000228962.68204.CF16955051"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/132\/5\/article-p1566.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/132\/5\/article-p1566.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/132\/5\/article-p1566.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T08:43:01Z","timestamp":1658738581000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/132\/5\/article-p1566.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5]]},"references-count":44,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.3171\/2019.1.jns183112","relation":{},"ISSN":["0022-3085","1933-0693"],"issn-type":[{"value":"0022-3085","type":"print"},{"value":"1933-0693","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5]]}}}