{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T01:44:54Z","timestamp":1780105494168,"version":"3.54.0"},"reference-count":29,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2011,7]]},"abstract":"\nObject<\/jats:title>\nCystathionine \u03b2-synthase (CBS) is an enzyme that metabolizes homocysteine to form H2<\/jats:sub>S in the brain. Hydrogen sulfide functions as a vasodilator as well as a regulator of neuronal ion channels and multiple intracellular signaling pathways. Given the myriad effects of H2<\/jats:sub>S, the authors hypothesized that patients possessing gain-of-function polymorphisms of the CBS gene will experience a decreased incidence of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH).<\/jats:p><\/jats:sec>\n\nMethods<\/jats:title>\nPatients were enrolled in a prospective observational database of aSAH outcomes. DNA was extracted from buccal swabs and sequenced for 3 functional polymorphisms of the CBS gene (699C\u2192T, 844ins68, and 1080C\u2192T) by polymerase chain reaction. Serum homocysteine levels (\u03bcmol\/L) were assayed. Multivariate analysis was used to determine the relationship between CBS genotype and occurrence of both angiographic vasospasm and DCI.<\/jats:p><\/jats:sec>\n\nResults<\/jats:title>\nThere were 87 patients included in the study. None of the polymorphisms investigated were significantly associated with the incidence of angiographic vasospasm. However, after controlling for admission hypertension, patients with the gain-of-function 844 WT\/ins genotypes were less likely to experience DCI relative to those with the 844 WT\/WT genotype (86 patients, p = 0.050), while the decrease-in-function genotype 1080 TT was more likely to experience DCI relative to those with 1080 CC and CT genotypes (84 patients, p = 0.042). Serum homocysteine levels did not correlate with the extent of either angiographic vasospasm or DCI in this analysis.<\/jats:p><\/jats:sec>\n\nConclusions<\/jats:title>\nPolymorphisms of the CBS gene that impart gain-of-function may be associated with a reduced risk of DCI after aSAH, independent of serum homocysteine. Signaling through H2<\/jats:sub>S may mediate protection from DCI following aSAH through a mechanism that does not involve macrovascular vasodilation.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2011.2.jns101414","type":"journal-article","created":{"date-parts":[[2011,3,18]],"date-time":"2011-03-18T14:24:28Z","timestamp":1300458268000},"page":"101-107","source":"Crossref","is-referenced-by-count":17,"title":["Gain-of-function polymorphisms of cystathionine \u03b2-synthase and delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage"],"prefix":"10.3171","volume":"115","author":[{"given":"Bartosz T.","family":"Grobelny","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, New York University Medical Center; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F.","family":"Ducruet","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"DeRosa","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan S.","family":"Kotchetkov","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad E.","family":"Zacharia","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary L.","family":"Hickman","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Neurology, Columbia University College of Physicians and Surgeons, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reshma","family":"Narula","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Claassen","sequence":"additional","affiliation":[{"name":"Neurology, Columbia University College of Physicians and Surgeons, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiwon","family":"Lee","sequence":"additional","affiliation":[{"name":"Neurology, Columbia University College of Physicians and Surgeons, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj","family":"Badjatia","sequence":"additional","affiliation":[{"name":"Neurology, Columbia University College of Physicians and Surgeons, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan A.","family":"Mayer","sequence":"additional","affiliation":[{"name":"Neurology, Columbia University College of Physicians and Surgeons, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Sander","family":"Connolly","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-jns101414","series-title":"J Neurosci","first-page":"1066","article-title":"The possible role of hydrogen sulfide as an endogenous neuromodulator","volume":"16","author":"Abe","year":"1996"},{"key":"b2-jns101414","series-title":"J Cereb Blood Flow Metab","first-page":"978","article-title":"Nitric oxide scavenging by hemoglobin or nitric oxide synthase inhibition by N-nitro-L-arginine induces cortical spreading ischemia when K+ is increased in the subarachnoid space","volume":"18","author":"Dreier","year":"1998"},{"key":"b3-jns101414","series-title":"Hum Mutat","first-page":"856","article-title":"Large-scale population-based metabolic phenotyping of thirteen genetic polymorphisms related to one-carbon metabolism","volume":"28","author":"Fredriksen","year":"2007"},{"key":"b4-jns101414","series-title":"Stroke","first-page":"1963","article-title":"Defining vasospasm after subarachnoid hemorrhage: what is the most clinically relevant definition?","volume":"40","author":"Frontera","year":"2009"},{"key":"b5-jns101414","series-title":"Pain","first-page":"74","article-title":"Hydrogen sulfide as a novel nociceptive messenger","volume":"132","author":"Kawabata","year":"2007"},{"key":"b6-jns101414","series-title":"Stroke","first-page":"200","article-title":"Predictors of cognitive dysfunction after subarachnoid hemorrhage","volume":"33","author":"Kreiter","year":"2002"},{"key":"b7-jns101414","series-title":"Mol Genet Metab","first-page":"53","article-title":"Polymorphisms in the CBS gene associated with decreased risk of coronary artery disease and increased responsiveness to total homocysteine lowering by folic acid","volume":"70","author":"Kruger","year":"2000"},{"key":"b8-jns101414","series-title":"Neurochem Int","first-page":"214","article-title":"Homocysteine decreases blood flow to the brain due to vascular resistance in carotid artery","volume":"53","author":"Kumar","year":"2008"},{"key":"b9-jns101414","series-title":"Stroke","first-page":"3216","article-title":"Homocysteine and pulsatility index of cerebral arteries","volume":"40","author":"Lim","year":"2009"},{"key":"b10-jns101414","series-title":"N Engl J Med","first-page":"1567","article-title":"Homocysteine lowering with folic acid and B vitamins in vascular disease","volume":"354","author":"Lonn","year":"2006"},{"key":"b11-jns101414","series-title":"Stroke","first-page":"3015","article-title":"Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial","volume":"39","author":"Macdonald","year":"2008"},{"key":"b12-jns101414","series-title":"Circulation","first-page":"888","article-title":"Hydrogen sulfide improves survival after cardiac arrest and cardiopulmonary resuscitation via a nitric oxide synthase 3-dependent mechanism in mice","volume":"120","author":"Minamishima","year":"2009"},{"key":"b13-jns101414","series-title":"Acta Neurochir (Wien)","first-page":"137","article-title":"Delayed cerebral ischaemia: the pathological substrate","volume":"131","author":"Neil-Dwyer","year":"1994"},{"key":"b14-jns101414","series-title":"Stroke","first-page":"1292","article-title":"Nitric oxide modulates spreading depolarization threshold in the human and rodent cortex","volume":"39","author":"Petzold","year":"2008"},{"key":"b15-jns101414","series-title":"Clin Chem","first-page":"290","article-title":"Rapid and accurate HPLC assay for plasma total homocysteine and cysteine in a clinical laboratory setting","volume":"45","author":"Pfeiffer","year":"1999"},{"key":"b16-jns101414","series-title":"Neurol Res","first-page":"151","article-title":"Cerebral vasospasm following subarachnoid hemorrhage: time for a new world of thought","volume":"31","author":"Pluta","year":"2009"},{"key":"b17-jns101414","series-title":"Stroke","first-page":"889","article-title":"Hydrogen sulfide is a mediator of cerebral ischemic damage","volume":"37","author":"Qu","year":"2006"},{"key":"b18-jns101414","series-title":"J Neurosurg","first-page":"55","article-title":"Endothelin concentrations in patients with aneurysmal subarachnoid hemorrhage. Correlation with cerebral vasospasm, delayed ischemic neurological deficits, and volume of hematoma","volume":"82","author":"Seifert","year":"1995"},{"key":"b19-jns101414","series-title":"Am J Physiol Cell Physiol","first-page":"C1779","article-title":"Cystathionine-beta-synthase gene transfer and 3-deazaadenosine ameliorate inflammatory response in endothelial cells","volume":"293","author":"Sen","year":"2007"},{"key":"b20-jns101414","series-title":"Biospectroscopy","first-page":"311","article-title":"Orientation of the heme vinyl groups in the hydrogen sulfide-binding hemoglobin I from Lucina pectinata","volume":"4","author":"Silfa","year":"1998"},{"key":"b21-jns101414","series-title":"Pfl\u00fcgers Arch","first-page":"389","article-title":"Hydrogen sulfide increases calcium-activated potassium (BK) channel activity of rat pituitary tumor cells","volume":"459","author":"Sitdikova","year":"2010"},{"key":"b22-jns101414","series-title":"J Cereb Blood Flow Metab","first-page":"1204","article-title":"Endothelial nitric oxide synthase gene single-nucleotide polymorphism predicts cerebral vasospasm after aneurysmal subarachnoid hemorrhage","volume":"28","author":"Starke","year":"2008"},{"key":"b23-jns101414","series-title":"Neurosurgery","first-page":"781","article-title":"Thromboembolism and delayed cerebral ischemia after subarachnoid hemorrhage: an autopsy study","volume":"59","author":"Stein","year":"2006"},{"issue":"12 Suppl","key":"b24-jns101414","series-title":"Stroke","first-page":"IV85","article-title":"Prevention and treatment of delayed ischemic dysfunction in patients with aneurysmal subarachnoid hemorrhage","volume":"21","author":"Tettenborn","year":"1990"},{"issue":"Suppl 1","key":"b25-jns101414","series-title":"Neurochirurgia (Stuttg)","first-page":"84","article-title":"Blood pressure and heart rate during treatment with nimodipine in patients with subarachnoid hemorrhage","volume":"28","author":"Tettenborn","year":"1985"},{"key":"b26-jns101414","series-title":"JAMA","first-page":"565","article-title":"Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial","volume":"291","author":"Toole","year":"2004"},{"key":"b27-jns101414","series-title":"Am J Physiol Regul Integr Comp Physiol","first-page":"R1930","article-title":"Reappraisal of H2S\/sulfide concentration in vertebrate blood and its potential significance in ischemic preconditioning and vascular signaling","volume":"294","author":"Whitfield","year":"2008"},{"key":"b28-jns101414","series-title":"Science","first-page":"587","article-title":"H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase","volume":"322","author":"Yang","year":"2008"},{"key":"b29-jns101414","series-title":"EMBO J","first-page":"6008","article-title":"The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener","volume":"20","author":"Zhao","year":"2001"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/115\/1\/article-p101.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/115\/1\/article-p101.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/115\/1\/article-p101.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T03:08:22Z","timestamp":1679886502000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/115\/1\/article-p101.xml"}},"subtitle":["Clinical article"],"short-title":[],"issued":{"date-parts":[[2011,7]]},"references-count":29,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.3171\/2011.2.jns101414","relation":{},"ISSN":["0022-3085","1933-0693"],"issn-type":[{"value":"0022-3085","type":"print"},{"value":"1933-0693","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,7]]}}}