NXY-059 is a neuroprotective free radical trapping agent that reduces oxidative damage by neutralizing free radicals, while also mitigating neuroinflammation by protecting the integrity of the blood-brain barrier[1-2]. NXY-059 is applicable for research related to acute ischemic stroke[3-4].
In vitro, NXY-059 (250μM) was applied to a co-culture model of bovine brain capillary endothelial cells and glial cells under oxygen-glucose deprivation (OGD) conditions. NXY-059 significantly inhibited the OGD-induced increase in sucrose permeability and reduced the abnormal transcellular transport of tissue-type plasminogen activator (tPA) from the luminal to the brain side [5]. NXY-059 (300μM) pretreated N1E-115 neuroblastoma cells for 30 minutes. NXY-059 failed to inhibit cell death induced by sodium nitroprusside (SNP; 100μM)[6].
In vivo, NXY-059 (3, 10, and 30mg/kg/h) was intravenously infused in a rat model of transient middle cerebral artery occlusion, starting 2.25 hours after occlusion and continuing for 21.75 hours. NXY-059 significantly reduced neurological deficits and histologically measured infarct volume, with the protective effect linearly correlating with plasma concentration[7]. NXY-059 (3 or 10mg/kg) was intravenously administered in a transient focal cerebral ischemia model in Sprague-Dawley rats, with injections at 0 and 30 minutes after occlusion. NXY-059 significantly reduced cortical infarct volume, decreased the number of apoptotic cells, and suppressed ischemia-induced cell death[8].
References:
[1] Fong JJ, Rhoney DH. NXY-059: review of neuroprotective potential for acute stroke. Ann Pharmacother. 2006 Mar;40(3):461-71.
[2] Wang CX, Shuaib A. NXY-059: a neuroprotective agent in acute stroke. Int J Clin Pract. 2004 Oct;58(10):964-9.
[3] Maples KR, Green AR, Floyd RA. Nitrone-related therapeutics: potential of NXY-059 for the treatment of acute ischaemic stroke. CNS Drugs. 2004;18(15):1071-84.
[4] Lees KR, Zivin JA, Ashwood T, et al. NXY-059 for acute ischemic stroke. N Engl J Med. 2006 Feb 9;354(6):588-600.
[5] Culot M, Mysiorek C, Renftel M, et al. Cerebrovascular protection as a possible mechanism for the protective effects of NXY-059 in preclinical models: an in vitro study. Brain Res. 2009 Oct 19;1294:144-52.
[6] Hainsworth AH, Bhuiyan N, Green AR. The nitrone disodium 2,4-sulphophenyl-N-tert-butylnitrone is without cytoprotective effect on sodium nitroprusside-induced cell death in N1E-115 neuroblastoma cells in vitro. J Cereb Blood Flow Metab. 2008 Jan;28(1):24-8.
[7] Sydserff SG, Borelli AR, Green AR, et al. NXY-059 on infarct volume after transient or permanent middle cerebral artery occlusion in the rat; studies on dose, plasma concentration and therapeutic time window. Br J Pharmacol. 2002 Jan;135(1):103-12.
[8] Takizawa S, Izuhara Y, Kitao Y, et al. A novel inhibitor of advanced glycation and endoplasmic reticulum stress reduces infarct volume in rat focal cerebral ischemia. Brain Res. 2007 Dec 5;1183:124-37.
NXY-059具有神经保护活性的自由基捕获剂，NXY-059可中和自由基来减少氧化损伤，同时通过保护血脑屏障完整性以减轻神经炎症[1-2]。NXY-059可用于急性缺血性中风的相关研究[3-4]。
在体外，NXY-059（250μM）在氧糖剥夺（OGD）条件下作用于牛脑毛细血管内皮细胞与胶质细胞共培养模型时，NXY-059显著抑制OGD诱导的蔗糖通透性增加，并降低组织型纤溶酶原激活剂（tPA）从管腔侧向脑侧的异常转运 [5]。NXY-059（300μM）预处理N1E-115神经母细胞瘤细胞30分钟，NXY-059未能抑制由硝普钠（SNP；100μM）诱导的细胞死亡 [6]。
在体内，NXY-059（3，10和30mg/kg/h）静脉输注大鼠短暂性大脑中动脉闭塞模型，从闭塞后2.25小时开始给药持续21.75小时，NXY-059显著减少神经功能缺损和组织学测量的梗死体积，且保护作用与血浆浓度线性相关[7]。NXY-059（3或10mg/kg）静脉注射短暂性局灶性缺血SD大鼠中，分别在闭塞后0和30分钟给药，NXY-059显著降低皮质梗死体积，并减少凋亡细胞数量，抑制缺血诱导的细胞死亡[8]。