{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:37:01Z","timestamp":1790138221791,"version":"4.0.1"},"reference-count":56,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,6]]},"abstract":"<jats:p content-type=\"fine-print\"><jats:italic>Object.<\/jats:italic> Stilbazulenyl nitrone (STAZN) is a second-generation azulenyl nitrone that has markedly enhanced antioxidant properties compared with those of conventional alpha-phenyl nitrones. In this study, the authors assessed the potential efficacy of STAZN in a rodent model of fluid-percussion brain injury, which results in a consistent cortical contusion.<\/jats:p>\n<jats:p content-type=\"fine-print\"><jats:italic>Methods.<\/jats:italic> After anesthesia had been induced in normothermic Sprague\u2014Dawley rats (brain temperature 36\u201336.5\u00b0C) by halothane\u2014nitrous oxide, the animals were subjected to a right parietooccipital parasagittal fluid-percussion injury (1.5\u20132 atm). The agent (STAZN, 30 mg\/kg; eight animals) or vehicle (dimethyl sulfoxide; eight animals) was administered intraperitoneally at 5 minutes and 4 hours after trauma. The neurological status of each rat was evaluated on Days 1, 2, and 7 postinjury (normal score 0, maximum injury 12). Seven days after trauma, the rat brains were perfusion fixed, coronal sections at various levels were digitized, and areas of contusion were measured. Treatment with STAZN significantly improved neurological scores on Days 2 and 7 postinjury compared with vehicle-treated rats. Administration of STAZN also significantly reduced the total contusion area by 63% (1.8 \u00b1 0.5 mm<jats:sup>2<\/jats:sup> in STAZN-treated animals compared with 4.8 \u00b1 2.1 mm<jats:sup>2<\/jats:sup> in vehicle-treated animals; p = 0.04) and the deep cortical contusion area by 60% (1.2 \u00b1 0.2 mm<jats:sup>2<\/jats:sup> in STAZN-treated animals compared with 2.9 \u00b1 1.2 mm<jats:sup>2<\/jats:sup> in vehicle-treated animals; p = 0.03). By contrast, hippocampal cell loss in the CA3 sector was unaffected by STAZN treatment.<\/jats:p>\n<jats:p content-type=\"fine-print\"><jats:italic>Conclusions.<\/jats:italic> Therapy with STAZN, a novel potent antioxidant, administered following traumatic brain injury, markedly improves neurological and histological outcomes. Azulenyl nitrones appear to represent a promising class of neuroprotective agents for combating this devastating condition.<\/jats:p>","DOI":"10.3171\/jns.2002.96.6.1077","type":"journal-article","created":{"date-parts":[[2009,5,13]],"date-time":"2009-05-13T17:44:46Z","timestamp":1242236686000},"page":"1077-1083","source":"Crossref","is-referenced-by-count":20,"title":["Stilbazulenyl nitrone, a novel azulenyl nitrone antioxidant, improved neurological deficit and reduced contusion size after traumatic brain injury in rats"],"prefix":"10.3171","volume":"96","author":[{"given":"Ludmila","family":"Belayev","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofelia F.","family":"Alonso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Busto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Ley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myron D.","family":"Ginsberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1","series-title":"Free Radic Biol Med","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1016\/S0891-5849(97)00338-9","article-title":"Azulenyl nitrones: colorimetric detection of oxyradical end products and neuroprotection in the gerbil transient forebrain ischemia\/reperfusion model.","volume":"24","author":"Althaus","year":"1998"},{"key":"b2","series-title":"Surg Neurol","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/S0090-3019(96)00461-2","article-title":"Oxidative stress following traumatic brain injury in rats.","volume":"47","author":"Awasthi","year":"1997"},{"key":"b3","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1089\/neu.2000.17.1029","article-title":"Postinjury treatment with magnesium chloride attenuates cortical damage after traumatic brain injury in rats.","volume":"17","author":"Bareyre","year":"2000"},{"key":"b4","series-title":"Organic Synthesis: Theory and Applications.","first-page":"155","article-title":"Aspects of the chemistry and biology of azulenyl nitrones, a newly synthesized class of spin-trapping agents","volume":"4","author":"Becker","year":"1998"},{"key":"b5","series-title":"Cell Mol Life Sci","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1007\/s000180050457","article-title":"Diagnostic and therapeutic applications of azulenyl nitrone spin traps.","volume":"56","author":"Becker","year":"1999"},{"key":"b6","series-title":"J Am Chem Soc","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1021\/ja952895z","article-title":"Highly sensitive colorimetric detection and facile isolation of diamagnetic free radical adducts of novel chromotropic nitrone spin trapping agents readily derived from guaiazulene.","volume":"118","author":"Becker","year":"1996"},{"key":"b7","series-title":"JCS Perkin Trans","first-page":"1289","article-title":"Redox behavior of azulenyl nitrones: fully reversible one electron oxidation by cyclic voltammetry at potentials in the range of biological antioxidants.","volume":"2","author":"Becker","year":"1998"},{"key":"b8","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1161\/01.STR.17.3.472","article-title":"Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination.","volume":"17","author":"Bederson","year":"1986"},{"key":"b9","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1161\/01.STR.27.9.1616","article-title":"Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model.","volume":"27","author":"Belayev","year":"1996"},{"key":"b10","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1089\/neu.1999.16.445","article-title":"with high-dose albumin reduces histopathological damage and improves neurological deficit following fluid percussion brain injury in rats.","volume":"16","author":"Belayev","year":"1999"},{"key":"b11","series-title":"Neuroreport","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1097\/00001756-199612200-00012","article-title":"Bilateral ischemic tolerance of rat hippocampus induced by prior unilateral transient focal ischemia: relationship to c-fos mRNA expression.","volume":"8","author":"Belayev","year":"1996"},{"key":"b12","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1089\/08977150151070919","article-title":"Infusion of prostacyclin following experimental brain injury in the rat reduces cortical lesion volume.","volume":"18","author":"Bentzer","year":"2001"},{"key":"b13","series-title":"Ann Neurol","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1002\/ana.410150507","article-title":"Regional blood flow in compression-induced brain edema in rats: effect of dietary vitamin E.","volume":"15","author":"Busto","year":"1984"},{"key":"b14","series-title":"Brain Res","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/0006-8993(94)91689-6","article-title":"\u03b1-Phenyl-tert-butyl-nitrone reduces cortical infarct and edema in rats subjected to focal ischemia.","volume":"644","author":"Cao","year":"1994"},{"key":"b15","series-title":"J Mol Neurosci","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/BF02896848","article-title":"Protection against oxidative damage to CNS by alpha-phenyl-tert-butyl nitrone (PBN) and other spin-trapping agents: a novel series of nonlipid free radical scavengers.","volume":"3","author":"Carney","year":"1991"},{"key":"b16","series-title":"Neuroscience","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/S0306-4522(99)00138-4","article-title":"An optimal redox status for the survival of axotomized ganglion cells in the developing retina.","volume":"93","author":"Castagne","year":"1999"},{"key":"b17","series-title":"J Cereb Blood Flow Metab","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1097\/00004647-200101000-00002","article-title":"Reactive oxygen radicals in signaling and damage in the ischemic brain.","volume":"21","author":"Chan","year":"2001"},{"key":"b18","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1161\/01.STR.20.10.1383","article-title":"Photochemical stroke model: flunarizine prevents sensorimotor deficits after neocortical infarcts in rats.","volume":"20","author":"De Ryck","year":"1989"},{"key":"b19","series-title":"Acta Neuropathol","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1007\/BF00296740","article-title":"Post-traumatic brain hypothermia reduces histopathological damage following concussive brain injury in the rat.","volume":"87","author":"Dietrich","year":"1994"},{"key":"b20","series-title":"Trends Pharmacol Sci","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/0165-6147(92)90013-V","article-title":"Pharmacological strategies in CNS trauma.","volume":"13","author":"Faden","year":"1992"},{"key":"b21","series-title":"Resuscitation","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S0300-9572(00)00321-X","article-title":"Severe traumatic brain injury.","volume":"48","author":"Finfer","year":"2001"},{"key":"b22","series-title":"Proc Natl Acad Sci USA","doi-asserted-by":"publisher","first-page":"5057","DOI":"10.1073\/pnas.92.11.5057","article-title":"N-tert-butyl-alphaphenylnitrone improves recovery of brain energy state in rats following transient focal ischemia.","volume":"92","author":"Folbergrova","year":"1995"},{"key":"b23","series-title":"Acta Physiol Scand","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1046\/j.1365-201x.2000.00657.x","article-title":"The effect of alpha-phenyl-tertbutyl nitrone (PBN) on free radical formation in transient focal ischaemia measured by microdialysis and 3,4-dihydroxybenzoate formation.","volume":"168","author":"Gido","year":"2000"},{"key":"b24","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"499","DOI":"10.3171\/jns.2001.94.3.0499","article-title":"Diminution of metabolism\/blood flow uncoupling following traumatic brain injury in rats in response to high-dose human albumin treatment.","volume":"94","author":"Ginsberg","year":"2001"},{"key":"b25","series-title":"J Neurochem","first-page":"1704","article-title":"Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia.","volume":"65","author":"Globus","year":"1995"},{"key":"b26","series-title":"Acta Neurochir","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1007\/s007010050445","article-title":"Age and outcome after severe head injury.","volume":"142","author":"Gomez","year":"2000"},{"key":"b27","series-title":"Cerebrovascular Disease: Pathophysiology, Diagnosis, and Management.","first-page":"710","article-title":"Antioxidant pharmacotherapy","author":"Hall","year":"1998"},{"key":"b28","series-title":"Free Radical Damage and its Control.","first-page":"217","article-title":"Free radicals in central nervous system injury","author":"Hall","year":"1994"},{"key":"b29","series-title":"Int Rev Neurobiol","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0074-7742(08)60725-4","article-title":"Nitrone-based free radical traps as neuroprotective agents in cerebral ischaemia and other pathologies.","volume":"40","author":"Hensley","year":"1997"},{"key":"b30","series-title":"Brain Res","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/0006-8993(94)91601-2","article-title":"Kynurenate is neuroprotective following experimental brain injury in the rat.","volume":"655","author":"Hicks","year":"1994"},{"key":"b31","series-title":"J Neurol Neurosurg Psychiatry","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1136\/jnnp.60.4.362","article-title":"Epidemiology of head injury.","volume":"60","author":"Jennett","year":"1996"},{"key":"b32","series-title":"Exp Neurol","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1006\/exnr.1998.6824","article-title":"Azulenyl nitrone spin traps protect against MPTP neurotoxicity.","volume":"152","author":"Klivenyi","year":"1998"},{"key":"b33","series-title":"Neurobiol Dis","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1006\/nbdi.1996.0015","article-title":"Delayed treatment with alpha-phenyl-N-tert-butyl nitrone (PBN) attenuates secondary mitochondrial dysfunction after transient focal cerebral ischemia in the rat.","volume":"3","author":"Kuroda","year":"1996"},{"key":"b34","series-title":"J Cereb Blood Flow Metab","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1097\/00004647-199907000-00008","article-title":"Neuroprotective effects of a novel nitrone, NXY-059, after transient focal cerebral ischemia in the rat.","volume":"19","author":"Kuroda","year":"1999"},{"key":"b35","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1161\/01.STR.32.3.675","article-title":"Tolerability and pharmacokinetics of the nitrone NXY-059 in patients with acute stroke.","volume":"32","author":"Lees","year":"2001"},{"key":"b36","series-title":"Neurosci Lett","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/0304-3940(90)90731-N","article-title":"Decreases in tissue levels of ubiquinol-9 and -10, ascorbate and alpha-tocopherol following spinal cord impact trauma in rats.","volume":"108","author":"Lemke","year":"1990"},{"key":"b37","series-title":"Exp Neurol","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1006\/exnr.2000.7513","article-title":"NPS 1506 attenuates cognitive dysfunction and hippocampal neuron death following brain trauma in the rat.","volume":"166","author":"Leoni","year":"2000"},{"key":"b38","series-title":"J Neurotrauma","first-page":"S359","article-title":"Neurobehavioral recovery.","volume":"9","author":"Levin","year":"1992"},{"key":"b39","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1089\/neu.1998.15.521","article-title":"Involvement of reactive oxygen species in membrane phospholipid breakdown and energy perturbation after traumatic brain injury in the rat.","volume":"15","author":"Lewen","year":"1998"},{"key":"b40","series-title":"Acta Neurochir","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s007010170141","article-title":"\u03b2-Phenyl-tert-N-butyl nitrone (PBN) improves functional and morphological outcome after cortical contusion injury in the rat.","volume":"143","author":"Marklund","year":"2001"},{"key":"b41","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1161\/01.STR.32.1.190","article-title":"NXY-059, a free radical\u2014trapping agent, substantially lessens the functional disability resulting from cerebral ischemia in a primate species.","volume":"32","author":"Marshall","year":"2001"},{"key":"b42","series-title":"Neurosurgery","first-page":"546","article-title":"Head injury: recent past, present, and future.","volume":"47","author":"Marshall","year":"2000"},{"key":"b43","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1089\/neu.1998.15.731","article-title":"Novel pharmacologic strategies in the treatment of experimental traumatic brain injury: 1998.","volume":"15","author":"McIntosh","year":"1998"},{"key":"b44","series-title":"NIH Consens Statement","first-page":"1","article-title":"Rehabilitation of persons with traumatic brain injury.","volume":"16","year":"1998"},{"key":"b45","series-title":"Free Radic Res Commun","doi-asserted-by":"publisher","first-page":"321","DOI":"10.3109\/10715768609080971","article-title":"Phenyl-T-butyl-nitrone is active against traumatic shock in rats.","volume":"1","author":"Novelli","year":"1986"},{"key":"b46","series-title":"Am J Physiol Heart Circ Physiol","doi-asserted-by":"publisher","first-page":"H924","DOI":"10.1152\/ajpheart.2000.279.3.H924","article-title":"Chronic metabolic sequelae of traumatic brain injury: prolonged suppression of somatosensory activation.","volume":"279","author":"Passineau","year":"2000"},{"key":"b47","series-title":"Neuropharmacology","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/S0028-3908(00)00170-2","article-title":"Efficacy of disodium 4-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059), a free radical trapping agent, in a rat model of hemorrhagic stroke.","volume":"40","author":"Peeling","year":"2001"},{"key":"b48","series-title":"Neurosci Lett","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/0304-3940(90)90093-O","article-title":"Protection from cerebral ischemic injury in gerbils with the spin trap agent N-tert-butyl-alpha-phenylnitrone (PBN).","volume":"116","author":"Phillis","year":"1990"},{"key":"b49","series-title":"Hum Cell","first-page":"345","article-title":"The role of oxygen radicals in the pathobiology of traumatic brain injury.","volume":"5","author":"Povlishock","year":"1992"},{"key":"b50","series-title":"Free Radic Biol Med","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/0891-5849(94)90183-X","article-title":"\u03b1-Phenyl-tert-butyl-nitrone inhibits free radical release in brain concussion.","volume":"16","author":"Sen","year":"1994"},{"key":"b51","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1089\/neu.1993.10.109","article-title":"A nonpsychotropic cannabinoid, HU-211, has cerebroprotective effects after closed head injury in the rat.","volume":"10","author":"Shohami","year":"1993"},{"key":"b52","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1089\/neu.1999.16.471","article-title":"Expression of brain-derived neurotrophic factor, nerve growth factor, and heat shock protein HSP70 following fluid percussion brain injury in rats.","volume":"16","author":"Truettner","year":"1999"},{"key":"b53","series-title":"J Neurosci Res","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1002\/(SICI)1097-4547(19980501)52:3<342::AID-JNR10>3.0.CO;2-8","article-title":"Riluzole attenuates cortical lesion size, but not hippocampal neuronal loss, following traumatic brain injury in the rat.","volume":"52","author":"Zhang","year":"1998"},{"key":"b54","series-title":"Acta Physiol Scand","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1111\/j.1748-1716.1994.tb09816.x","article-title":"Delayed treatment with the spin trap alpha-phenyl-N-tert-butyl nitrone (PBN) reduces infarct size following transient middle cerebral artery occlusion in rats.","volume":"152","author":"Zhao","year":"1994"},{"key":"b55","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"510","DOI":"10.3171\/jns.1999.90.3.0510","article-title":"Influence of early posttraumatic hypothermia therapy on local cerebral blood flow and glucose metabolism after fluid-percussion brain injury.","volume":"90","author":"Zhao","year":"1999"},{"key":"b56","series-title":"Ann Emerg Med","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1067\/mem.2001.113505","article-title":"Traumatic brain injury outcome: concepts for emergency care.","volume":"37","author":"Zink","year":"2001"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/96\/6\/article-p1077.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/96\/6\/article-p1077.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/96\/6\/article-p1077.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,26]],"date-time":"2023-03-26T21:40:42Z","timestamp":1679866842000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/96\/6\/article-p1077.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,6]]},"references-count":56,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.3171\/jns.2002.96.6.1077","relation":{},"ISSN":["0022-3085"],"issn-type":[{"value":"0022-3085","type":"print"}],"subject":[],"published":{"date-parts":[[2002,6]]}}}