NOX2 inhibition with apocynin worsens stroke outcome in aged rats.
NOX2 inhibition with apocynin worsens stroke outcome in aged rats.
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DOI：
10.1016/j.brainres.2009.07.052
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发表时间：
2009-10-06
期刊：
影响因子：
2.9
通讯作者：
Huber JD
中科院分区：
文献类型：
--
作者：
Kelly KA;Li X;Tan Z;VanGilder RL;Rosen CL;Huber JD
本研究用组织纤溶酶原激活剂(TPA)阻断大脑中动脉(MCAO)，观察NOX2亚型NADPH氧化酶对老龄大鼠脑损伤和功能恢复的抑制作用。观察NOX2对幼年和老年大鼠大脑中动脉闭塞和tPA再灌流后脑损伤程度和功能恢复的影响。大鼠在MCAO前30min给予载脂蛋白(NOX2抑制剂，5 mg/kg)或生理盐水。在MCAO后24小时，检测血脑屏障通透性(BBB)、卒中梗死体积、水肿形成和氧化损伤。老年大鼠服用apocynin可增加死亡率，但未能改善功能结局、总梗塞体积、水肿形成和血脑屏障通透性。与年轻成年大鼠相比，老年大鼠在MCAO后对侧大脑半球的血脑屏障对蔗糖的通透性增加，大脑的抗氧化能力减弱。我们的结论是，在老年大鼠中抑制NOX2会加重中风损伤并降低功能结局。这些结果表明，年龄是卒中损害的一个重要因素，必须对载脂蛋白作为卒中治疗药物进行更严格的检查。
This study utilized middle cerebral artery occlusion (MCAO) with tissue plasminogen activator (tPA) to assess inhibition of the NOX2 isoform of NADPH oxidase on brain injury and functional recovery in aged rats. Effects of NOX2 on the degree of brain injury and functional recovery following MCAO and tPA reperfusion was assessed in young adult and aged rats. Rats received apocynin (NOX2 inhibitor; 5 mg/kg) or saline 30 min prior to MCAO. At 24 h following MCAO, blood-brain barrier permeability (BBB), stroke infarct volume, edema formation, and oxidative damage were measured. Apocynin treatment in aged rats increased mortality rate and failed to improve functional outcome, total infarct volume, edema formation, and BBB permeability. Aged rats displayed increased BBB permeability to sucrose in the contralateral hemisphere following MCAO and diminished antioxidant capacity in the brain as compared to young adult rats. We conclude that inhibition of NOX2 in the aged rat exacerbates stroke injury and diminishes functional outcome. These results suggest age is an important factor in stroke damage and more rigorous examination of apocynin as a therapeutic agent for treatment of stroke must be done.
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