{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,4,16]],"date-time":"2023-04-16T04:15:14Z","timestamp":1681618514054},"reference-count":44,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec><jats:title>OBJECTIVE<\/jats:title><jats:p>To shed light on the role of relaxin in cerebral cavernous malformations (CCMs) in adults and children, the authors investigated endothelial cell (EC) expression of relaxin 1, 2, and 3; vascular endothelial growth factor receptor\u20131 and \u20132 (VEGFR-1 and -2); Ki-67; vascular geometry; and hemorrhage, as well as the clinical presentation of 32 patients with surgically resected lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Paraffin-embedded sections of 32 CCMs and 5 normal nonvascular lesion control (NVLC) brain tissue samples were immunohistochemically stained with antibodies to relaxin 1, 2, and 3; angiogenesis growth factor receptors Flt-1 (VEGFR-1) and Flk-1 (VEGFR-2); and proliferation marker Ki-67. For morphometric analysis, Elastica van Gieson stain was used, and for hemorrhage demonstration, Turnbull stain was used. Data from the pediatric and adult CCMs were compared with each other and with those obtained from the NVLCs. Statistical analyses were performed with Fisher\u2019s exact test, the chi-square test, the phi correlation coefficient, and the Student t-test. A p value &lt; 0.05 was considered significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Pediatric and adult cavernoma vessels did not significantly differ in diameter. Hemorrhage was observed in CCMs but not in NVLC samples (p &lt; 0.05). There was no difference in expression of Ki-67, VEGFR-1 and -2, and relaxin 1, 2, and 3 in the ECs of pediatric and adult CCMs. The ECs of CCMs were largely negative for relaxin 3 compared to NVLCs (p &lt; 0.05), whereas CCMs, compared to control brain tissue samples, more frequently expressed Flt-1 and relaxin 2 (p &lt; 0.05). Ki-67 was not expressed in the NVLCs, but the difference was not statistically significant. Relaxin 1 and 2 expression and increased expression of VEGFR-1 were associated with a supra- versus infratentorial location (p &lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Relaxin 1 and 2 and VEGFR-1 play a role in supratentorial cavernomas. Relaxin 3 may play a physiological role in normal brain vasculature. Relaxin 1 and 3 are also found in normal cerebral vasculature. Relaxin 1, 2, and 3 are associated with increased VEGFR-1 expression.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2019.9.peds19333","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T22:01:25Z","timestamp":1581112885000},"page":"144-150","source":"Crossref","is-referenced-by-count":0,"title":["Cerebral cavernomas in adults and children express relaxin"],"prefix":"10.3171","volume":"25","author":[{"given":"Caroline","family":"Gewiss","sequence":"first","affiliation":[{"name":"Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Hagel","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kara","family":"Krajewski","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Schleswig-Holstein, Campus L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1754","reference":[{"key":"b1","series-title":"Pediatr Neurosurg","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1159\/000209283","article-title":"Cavernous malformations of the central nervous system in the pediatric age group","volume":"45","author":"Acciarri N","year":"2009","unstructured":"Acciarri N, Galassi E, Giulioni M, Pozzati E, Grasso V, Palandri G, : Cavernous malformations of the central nervous system in the pediatric age group. Pediatr Neurosurg 45:81\u2013104, 20091930774310.1159\/000209283"},{"key":"b2","series-title":"Am J Pathol","first-page":"1367","article-title":"Relaxin protects against myocardial injury caused by ischemia and reperfusion in rat heart","volume":"152","author":"Bani D","year":"1998","unstructured":"Bani D, Masini E, Bello MG, Bigazzi M, Sacchi TB: Relaxin protects against myocardial injury caused by ischemia and reperfusion in rat heart. Am J Pathol 152:1367\u20131376, 19989588905"},{"key":"b3","series-title":"J Biol Chem","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1074\/jbc.M107882200","article-title":"Human relaxin gene 3 (H3) and the equivalent mouse relaxin (M3) gene. Novel members of the relaxin peptide family","volume":"277","author":"Bathgate RA","year":"2002","unstructured":"Bathgate RA, Samuel CS, Burazin TC, Layfield S, Claasz AA, Reytomas IG, : Human relaxin gene 3 (H3) and the equivalent mouse relaxin (M3) gene. Novel members of the relaxin peptide family. J Biol Chem 277:1148\u20131157, 20021168956510.1074\/jbc.M107882200"},{"key":"b4","series-title":"Am J Physiol Renal Physiol","doi-asserted-by":"publisher","first-page":"F1121","DOI":"10.1152\/ajprenal.00042.2014","article-title":"The renal circulation in normal pregnancy and preeclampsia: is there a place for relaxin?","volume":"306","author":"Conrad KP","year":"2014","unstructured":"Conrad KP, Davison JM: The renal circulation in normal pregnancy and preeclampsia: is there a place for relaxin? Am J Physiol Renal Physiol 306:F1121\u2013F1135, 201410.1152\/ajprenal.00042.2014"},{"key":"b5","series-title":"Neurol Sci","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s10072-009-0157-0","article-title":"Treatment and outcome of children with cerebral cavernomas: a survey on 32 patients","volume":"31","author":"Consales A","year":"2010","unstructured":"Consales A, Piatelli G, Ravegnani M, Pavanello M, Striano P, Zoli ML, : Treatment and outcome of children with cerebral cavernomas: a survey on 32 patients. Neurol Sci 31:117\u2013123, 201010.1007\/s10072-009-0157-019834644"},{"key":"b6","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.3171\/2015.1.JNS141452","article-title":"Characterization of radiation-induced cavernous malformations and comparison with a nonradiation cavernous malformation cohort","volume":"122","author":"Cutsforth-Gregory JK","year":"2015","unstructured":"Cutsforth-Gregory JK, Lanzino G, Link MJ, Brown RD Jr, Flemming KD: Characterization of radiation-induced cavernous malformations and comparison with a nonradiation cavernous malformation cohort. J Neurosurg 122:1214\u20131222, 201510.3171\/2015.1.JNS14145225699412"},{"key":"b7","series-title":"Science","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1126\/science.1312256","article-title":"The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor","volume":"255","author":"de Vries C","year":"1992","unstructured":"de Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT: The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 255:989\u2013991, 1992131225610.1126\/science.1312256"},{"key":"b8","series-title":"Ann Neurol","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1002\/ana.410040410","article-title":"Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights","volume":"4","author":"Dekaban AS","year":"1978","unstructured":"Dekaban AS: Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights. Ann Neurol 4:345\u2013356, 197810.1002\/ana.410040410727739"},{"key":"b9","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"702","DOI":"10.3171\/jns.1991.75.5.0702","article-title":"An analysis of the natural history of cavernous angiomas","volume":"75","author":"Del Curling O Jr","year":"1991","unstructured":"Del Curling O Jr, Kelly DL Jr, Elster AD, Craven TE: An analysis of the natural history of cavernous angiomas. J Neurosurg 75:702\u2013708, 1991191969110.3171\/jns.1991.75.5.0702"},{"key":"b10","series-title":"J Neurosurg","first-page":"167","article-title":"Radiation-induced cavernous malformation","volume":"89","author":"Detwiler PW","year":"1998","unstructured":"Detwiler PW, Porter RW, Zabramski JM, Spetzler RF: Radiation-induced cavernous malformation. J Neurosurg 89:167\u2013169, 19989647193"},{"key":"b11","series-title":"Acta Neurochir (Wien)","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1007\/BF01411054","article-title":"Cavernomas of the central nervous system in children. A report of 22 cases","volume":"138","author":"Di Rocco C","year":"1996","unstructured":"Di Rocco C, Iannelli A, Tamburrini G: Cavernomas of the central nervous system in children. A report of 22 cases. Acta Neurochir (Wien) 138:1267\u20131274, 199610.1007\/BF01411054"},{"key":"b12","series-title":"J Cell Sci","first-page":"701","article-title":"Cerebral cavernous malformation proteins at a glance","volume":"127","author":"Draheim KM","year":"2014","unstructured":"Draheim KM, Fisher OS, Boggon TJ, Calderwood DA: Cerebral cavernous malformation proteins at a glance. J Cell Sci 127:701\u2013707, 2014"},{"key":"b13","series-title":"J Cell Mol Med","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1111\/j.1582-4934.2007.00111.x","article-title":"Paracrine effects of transplanted myoblasts and relaxin on post-infarction heart remodelling","volume":"11","author":"Formigli L","year":"2007","unstructured":"Formigli L, Perna AM, Meacci E, Cinci L, Margheri M, Nistri S, : Paracrine effects of transplanted myoblasts and relaxin on post-infarction heart remodelling. J Cell Mol Med 11:1087\u20131100, 20071797988410.1111\/j.1582-4934.2007.00111.x"},{"issue":"1","key":"b14","series-title":"Neurosurg Focus","doi-asserted-by":"publisher","first-page":"e6","DOI":"10.3171\/foc.2006.21.1.7","article-title":"Are cavernous sinus hemangiomas and cavernous malformations different entities?","volume":"21","author":"Gonzalez LF","year":"2006","unstructured":"Gonzalez LF, Lekovic GP, Eschbacher J, Coons S, Porter RW, Spetzler RF: Are cavernous sinus hemangiomas and cavernous malformations different entities? Neurosurg Focus 21(1):e6, 20061685925910.3171\/foc.2006.21.1.7"},{"key":"b15","series-title":"Cancer","doi-asserted-by":"publisher","first-page":"3285","DOI":"10.1002\/cncr.10596","article-title":"Radiation-induced cavernous hemangiomas of the brain: a late effect predominantly in children","volume":"94","author":"Heckl S","year":"2002","unstructured":"Heckl S, Aschoff A, Kunze S: Radiation-induced cavernous hemangiomas of the brain: a late effect predominantly in children. Cancer 94:3285\u20133291, 200210.1002\/cncr.1059612115362"},{"key":"b16","series-title":"Mol Endocrinol","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1210\/mend.14.8.0510","article-title":"The three subfamilies of leucine-rich repeat-containing G protein-coupled receptors (LGR): identification of LGR6 and LGR7 and the signaling mechanism for LGR7","volume":"14","author":"Hsu SY","year":"2000","unstructured":"Hsu SY, Kudo M, Chen T, Nakabayashi K, Bhalla A, van der Spek PJ, : The three subfamilies of leucine-rich repeat-containing G protein-coupled receptors (LGR): identification of LGR6 and LGR7 and the signaling mechanism for LGR7. Mol Endocrinol 14:1257\u20131271, 20001093554910.1210\/mend.14.8.0510"},{"key":"b17","series-title":"Science","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1126\/science.1065654","article-title":"Activation of orphan receptors by the hormone relaxin","volume":"295","author":"Hsu SY","year":"2002","unstructured":"Hsu SY, Nakabayashi K, Nishi S, Kumagai J, Kudo M, Sherwood OD, : Activation of orphan receptors by the hormone relaxin. Science 295:671\u2013674, 200210.1126\/science.106565411809971"},{"key":"b18","series-title":"Dev Med Child Neurol","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1111\/j.1469-8749.1990.tb16956.x","article-title":"Late childhood changes in brain morphology observable with MRI","volume":"32","author":"Jernigan TL","year":"1990","unstructured":"Jernigan TL, Tallal P: Late childhood changes in brain morphology observable with MRI. Dev Med Child Neurol 32:379\u2013385, 1990235475110.1111\/j.1469-8749.1990.tb16956.x"},{"key":"b19","series-title":"Surg Neurol","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.surneu.2008.09.014","article-title":"There are no estrogen and progesterone receptors in cerebral cavernomas: a preliminary immunohistochemical study","volume":"72","author":"Kaya AH","year":"2009","unstructured":"Kaya AH, Ulus A, Bayri Y, Topal A, Gun S, Kandemir B, : There are no estrogen and progesterone receptors in cerebral cavernomas: a preliminary immunohistochemical study. Surg Neurol 72:263\u2013265, 20091914718910.1016\/j.surneu.2008.09.014"},{"key":"b20","series-title":"BioMed Res Int 2014","article-title":"Upregulation of relaxin after experimental subarachnoid hemorrhage in rabbits","volume":"836397","author":"Kikkawa Y","year":"2014","unstructured":"Kikkawa Y, Matsuo S, Kurogi R, Nakamizo A, Mizoguchi M, Sasaki T: Upregulation of relaxin after experimental subarachnoid hemorrhage in rabbits. BioMed Res Int 2014:836397, 2014"},{"key":"b21","series-title":"Neurosci Biobehav Rev","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1016\/j.neubiorev.2006.06.001","article-title":"Brain development in children and adolescents: insights from anatomical magnetic resonance imaging","volume":"30","author":"Lenroot RK","year":"2006","unstructured":"Lenroot RK, Giedd JN: Brain development in children and adolescents: insights from anatomical magnetic resonance imaging. Neurosci Biobehav Rev 30:718\u2013729, 200610.1016\/j.neubiorev.2006.06.00116887188"},{"key":"b22","series-title":"Neuroscience","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.neuroscience.2006.08.072","article-title":"Relaxin-3 in GABA projection neurons of nucleus incertus suggests widespread influence on forebrain circuits via G-protein-coupled receptor-135 in the rat","volume":"144","author":"Ma S","year":"2007","unstructured":"Ma S, Bonaventure P, Ferraro T, Shen PJ, Burazin TC, Bathgate RA, : Relaxin-3 in GABA projection neurons of nucleus incertus suggests widespread influence on forebrain circuits via G-protein-coupled receptor-135 in the rat. Neuroscience 144:165\u2013190, 20071707100710.1016\/j.neuroscience.2006.08.072"},{"issue":"1","key":"b23","series-title":"Neurosurg Focus","doi-asserted-by":"publisher","first-page":"e3","DOI":"10.3171\/foc.2006.21.1.4","article-title":"Clinical progression and familial occurrence of cerebral cavernous angiomas: the role of angiogenic and growth factors","volume":"21","author":"Maiuri F","year":"2006","unstructured":"Maiuri F, Cappabianca P, Gangemi M, De Caro Mdel B, Esposito F, Pettinato G, : Clinical progression and familial occurrence of cerebral cavernous angiomas: the role of angiogenic and growth factors. Neurosurg Focus 21(1):e3, 20061685925610.3171\/foc.2006.21.1.4"},{"key":"b24","series-title":"Endocrinology","doi-asserted-by":"publisher","first-page":"4713","DOI":"10.1210\/endo.138.11.5520","article-title":"Relaxin counteracts myocardial damage induced by ischemia-reperfusion in isolated guinea pig hearts: evidence for an involvement of nitric oxide","volume":"138","author":"Masini E","year":"1997","unstructured":"Masini E, Bani D, Bello MG, Bigazzi M, Mannaioni PF, Sacchi TB: Relaxin counteracts myocardial damage induced by ischemia-reperfusion in isolated guinea pig hearts: evidence for an involvement of nitric oxide. Endocrinology 138:4713\u20134720, 1997934819810.1210\/endo.138.11.5520"},{"key":"b25","series-title":"Sci STKE 2001","article-title":"VEGF receptor signal transduction","volume":"re21","author":"Matsumoto T","year":"2001","unstructured":"Matsumoto T, Claesson-Welsh L: VEGF receptor signal transduction. Sci STKE 2001:re21, 2001"},{"key":"b26","series-title":"FASEB J","doi-asserted-by":"publisher","first-page":"2352","DOI":"10.1096\/fj.06-6263com","article-title":"Evidence for local relaxin ligand-receptor expression and function in arteries","volume":"20","author":"Novak J","year":"2006","unstructured":"Novak J, Parry LJ, Matthews JE, Kerchner LJ, Indovina K, Hanley-Yanez K, : Evidence for local relaxin ligand-receptor expression and function in arteries. FASEB J 20:2352\u20132362, 20061707731210.1096\/fj.06-6263com"},{"key":"b27","series-title":"Childs Nerv Syst","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1007\/s00381-007-0322-9","article-title":"Incidence of vascular malformations in spontaneous intra-cerebral haemorrhage in children","volume":"23","author":"Papadias A","year":"2007","unstructured":"Papadias A, Taha A, Sgouros S, Walsh AR, Hockley AD: Incidence of vascular malformations in spontaneous intra-cerebral haemorrhage in children. Childs Nerv Syst 23:881\u2013886, 200710.1007\/s00381-007-0322-917450369"},{"key":"b28","series-title":"Neurosurg Clin N Am","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.nec.2010.03.011","article-title":"Normal and abnormal embryology and development of the intracranial vascular system","volume":"21","author":"Raybaud C","year":"2010","unstructured":"Raybaud C: Normal and abnormal embryology and development of the intracranial vascular system. Neurosurg Clin N Am 21:399\u2013426, 201010.1016\/j.nec.2010.03.01120561492"},{"issue":"Pt B","key":"b29","series-title":"Int J Biochem Cell Biol","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.biocel.2016.09.011","article-title":"Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: two sides of the same coin","volume":"81","author":"Retta SF","year":"2016","unstructured":"Retta SF, Glading AJ: Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: two sides of the same coin. Int J Biochem Cell Biol 81 (Pt B):254\u2013270, 20162763968010.1016\/j.biocel.2016.09.011"},{"key":"b30","series-title":"N Engl J Med","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1056\/NEJM198808113190605","article-title":"Cerebral cavernous malformations. Incidence and familial occurrence","volume":"319","author":"Rigamonti D","year":"1988","unstructured":"Rigamonti D, Hadley MN, Drayer BP, Johnson PC, Hoenig-Rigamonti K, Knight JT, : Cerebral cavernous malformations. Incidence and familial occurrence. N Engl J Med 319:343\u2013347, 1988339319610.1056\/NEJM198808113190605"},{"key":"b31","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1097\/00006123-199605000-00011","article-title":"Expression of angiogenic factors and structural proteins in central nervous system vascular malformations","volume":"38","author":"Rothbart D","year":"1996","unstructured":"Rothbart D, Awad IA, Lee J, Kim J, Harbaugh R, Criscuolo GR: Expression of angiogenic factors and structural proteins in central nervous system vascular malformations. Neurosurgery 38:915\u2013925, 199610.1097\/00006123-199605000-000118727816"},{"key":"b32","series-title":"Endocr Rev","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1210\/er.2003-0013","article-title":"Relaxin\u2019s physiological roles and other diverse actions","volume":"25","author":"Sherwood OD","year":"2004","unstructured":"Sherwood OD: Relaxin\u2019s physiological roles and other diverse actions. Endocr Rev 25:205\u2013234, 200410.1210\/er.2003-001315082520"},{"key":"b33","series-title":"J Comp Neurol","doi-asserted-by":"publisher","first-page":"4016","DOI":"10.1002\/cne.22442","article-title":"Distribution of relaxin-3 and RXFP3 within arousal, stress, affective, and cognitive circuits of mouse brain","volume":"518","author":"Smith CM","year":"2010","unstructured":"Smith CM, Shen PJ, Banerjee A, Bonaventure P, Ma S, Bathgate RA, : Distribution of relaxin-3 and RXFP3 within arousal, stress, affective, and cognitive circuits of mouse brain. J Comp Neurol 518:4016\u20134045, 20102073759810.1002\/cne.22442"},{"key":"b34","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"342","DOI":"10.3171\/jns.2005.102.2.0342","article-title":"Biological activity of adult cavernous malformations: a study of 56 patients","volume":"102","author":"Sure U","year":"2005","unstructured":"Sure U, Freman S, Bozinov O, Benes L, Siegel AM, Bertalanffy H: Biological activity of adult cavernous malformations: a study of 56 patients. J Neurosurg 102:342\u2013347, 20051573956410.3171\/jns.2005.102.2.0342"},{"key":"b35","series-title":"Lancet","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0140-6736(12)61855-8","article-title":"Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial","volume":"381","author":"Teerlink JR","year":"2013","unstructured":"Teerlink JR, Cotter G, Davison BA, Felker GM, Filippatos G, Greenberg BH, : Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet 381:29\u201339, 201310.1016\/S0140-6736(12)61855-823141816"},{"key":"b36","series-title":"Eur J Heart Fail","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1002\/ejhf.830","article-title":"Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX-AHF-2 study","volume":"19","author":"Teerlink JR","year":"2017","unstructured":"Teerlink JR, Voors AA, Ponikowski P, Pang PS, Greenberg BH, Filippatos G, : Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX-AHF-2 study. Eur J Heart Fail 19:800\u2013809, 201710.1002\/ejhf.83028452195"},{"key":"b37","series-title":"Childs Nerv Syst","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1007\/s00381-006-0044-4","article-title":"Biological activity of paediatric cerebral cavernomas: an immunohistochemical study of 28 patients","volume":"22","author":"Tirakotai W","year":"2006","unstructured":"Tirakotai W, Fremann S, Soerensen N, Roggendorf W, Siegel AM, Mennel HD, : Biological activity of paediatric cerebral cavernomas: an immunohistochemical study of 28 patients. Childs Nerv Syst 22:685\u2013691, 20061648947410.1007\/s00381-006-0044-4"},{"key":"b38","series-title":"J Biol Chem","doi-asserted-by":"publisher","first-page":"10681","DOI":"10.1016\/S0021-9258(18)87000-4","article-title":"Relaxin modulates synthesis and secretion of procollagenase and collagen by human dermal fibroblasts","volume":"265","author":"Unemori EN","year":"1990","unstructured":"Unemori EN, Amento EP: Relaxin modulates synthesis and secretion of procollagenase and collagen by human dermal fibroblasts. J Biol Chem 265:10681\u201310685, 199010.1016\/S0021-9258(18)87000-42162358"},{"key":"b39","series-title":"Hum Reprod","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1093\/humrep\/14.3.800","article-title":"Relaxin stimulates expression of vascular endothelial growth factor in normal human endometrial cells in vitro and is associated with menometrorrhagia in women","volume":"14","author":"Unemori EN","year":"1999","unstructured":"Unemori EN, Erikson ME, Rocco SE, Sutherland KM, Parsell DA, Mak J, : Relaxin stimulates expression of vascular endothelial growth factor in normal human endometrial cells in vitro and is associated with menometrorrhagia in women. Hum Reprod 14:800\u2013806, 199910.1093\/humrep\/14.3.80010221717"},{"key":"b40","series-title":"Wound Repair Regen","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1111\/j.1524-475X.2000.00361.x","article-title":"Relaxin induces vascular endothelial growth factor expression and angiogenesis selectively at wound sites","volume":"8","author":"Unemori EN","year":"2000","unstructured":"Unemori EN, Lewis M, Constant J, Arnold G, Grove BH, Normand J, : Relaxin induces vascular endothelial growth factor expression and angiogenesis selectively at wound sites. Wound Repair Regen 8:361\u2013370, 20001118612510.1111\/j.1524-475X.2000.00361.x"},{"key":"b41","series-title":"Neurosurgery","first-page":"359","article-title":"Expression of endothelial cell angiogenesis receptors in human cerebrovascular malformations","volume":"48","author":"Uranishi R","year":"2001","unstructured":"Uranishi R, Baev NI, Ng PY, Kim JH, Awad IA: Expression of endothelial cell angiogenesis receptors in human cerebrovascular malformations. Neurosurgery 48:359\u2013368, 200111220380"},{"key":"b42","series-title":"Pharmacotherapy","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/phar.1548","article-title":"Relaxin: a novel agent for the treatment of acute heart failure","volume":"35","author":"Wilson SS","year":"2015","unstructured":"Wilson SS, Ayaz SI, Levy PD: Relaxin: a novel agent for the treatment of acute heart failure. Pharmacotherapy 35:315\u2013327, 201510.1002\/phar.154825759289"},{"key":"b43","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.3171\/2017.6.JNS17860","article-title":"Reductions in brain pericytes are associated with arteriovenous malformation vascular instability","volume":"129","author":"Winkler EA","year":"2018","unstructured":"Winkler EA, Birk H, Burkhardt JK, Chen X, Yue JK, Guo D, : Reductions in brain pericytes are associated with arteriovenous malformation vascular instability. J Neurosurg 129:1464\u20131474, 201810.3171\/2017.6.JNS1786029303444"},{"key":"b44","series-title":"J Am Heart Assoc","doi-asserted-by":"publisher","first-page":"e002657","DOI":"10.1161\/JAHA.115.002657","article-title":"Age-related changes of normal cerebral and cardiac blood flow in children and adults aged 7 months to 61 years","volume":"5","author":"Wu C","year":"2016","unstructured":"Wu C, Honarmand AR, Schnell S, Kuhn R, Schoeneman SE, Ansari SA, : Age-related changes of normal cerebral and cardiac blood flow in children and adults aged 7 months to 61 years. J Am Heart Assoc 5:e002657, 201610.1161\/JAHA.115.00265726727967"}],"container-title":["Journal of Neurosurgery: Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-pediatr\/25\/2\/article-p144.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-pediatr\/25\/2\/article-p144.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-pediatr\/25\/2\/article-p144.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,15]],"date-time":"2023-04-15T19:54:50Z","timestamp":1681588490000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-pediatr\/25\/2\/article-p144.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2]]},"references-count":44,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3171\/2019.9.peds19333","relation":{},"ISSN":["1933-0707","1933-0715"],"issn-type":[{"value":"1933-0707","type":"print"},{"value":"1933-0715","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2]]}}}