Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai, 200040, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200032, China.
Brain Res. 2013 Nov 13;1538:93-103. doi: 10.1016/j.brainres.2013.09.036. Epub 2013 Sep 29.
Increasing evidence shows that exposure to an enriched environment (EE) after cerebral ischemia/reperfusion injury is neuroprotective in animal models. Recent studies have demonstrated that animals housed in an enriched environment condition after an experimental stroke obtained a better functional outcome than those housed in a standard condition. However, little is known about the underlying mechanisms of neuroprotective effects of enriched environment exposure prior to injury. The current study examined the neuroprotective effects of prior enriched environment exposure after transient middle cerebral artery occlusion (MCAO) in rats. Male Sprague Dawley (SD) rats, weighing 55-65g at the beginning of the experiment, were randomly assigned to a pre-ischemic enriched environment (PIEE) or pre-ischemic standard condition (PISC) group for 1 month. They were weighed on days1, 7, 18, and 28, and their locomotor activity was tracked during the period between 9:00am and 3:00pm daily. After 1 month, ischemia was induced by occluding the middle cerebral artery for 90min, followed by reperfusion. After approximately 24h of the operation, functional outcomes were assessed using the beam-walking test and a neurological evaluation scale in all rats. We measured the expression of extracellular signal regulated protein kinases1/2 (ERK1/2) by western blotting and gene expression levels of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthasen (iNOS) by Real-Time PCR in the cortical area affected by ischemia. Finally, we measured the level of malondialdehyde (MDA) content, which is a biomarker of oxidative stress. The results showed that rats in the PIEE group had lighter weight than those in the PISC group. The functional outcomes of rats in the PIEE group were better than those in the PISC group, and substances associated with inflammation, such as MDA, nNOS, iNOS, and phospho-ERK1/2, were lower in the PIEE group compared with the PISC group. These results indicate that enriched environment may provide neuroprotection via ischemic preconditioning and enhance resilience to cerebral ischemia.
越来越多的证据表明，在脑缺血/再灌注损伤后暴露于丰富环境（EE）对动物模型具有神经保护作用。最近的研究表明，在实验性中风后生活在丰富环境条件下的动物比生活在标准环境条件下的动物获得更好的功能结果。然而，对于损伤前丰富环境暴露的神经保护作用的潜在机制知之甚少。本研究探讨了在大鼠短暂性大脑中动脉闭塞（MCAO）后预先暴露于丰富环境对神经的保护作用。雄性 Sprague Dawley（SD）大鼠，在实验开始时体重为 55-65g，随机分为缺血前丰富环境（PIEE）或缺血前标准条件（PISC）组，进行 1 个月。在第 1、7、18 和 28 天称重，并在每天上午 9:00 至下午 3:00 期间跟踪其运动活动。1 个月后，通过阻断大脑中动脉 90min 诱导缺血，然后再灌注。手术后大约 24h，通过在所有大鼠中进行行走束试验和神经学评估量表来评估功能结果。我们通过蛋白质印迹法测量了细胞外信号调节蛋白激酶 1/2（ERK1/2）的表达，并通过实时 PCR 测量了受缺血影响的皮质区神经元型一氧化氮合酶（nNOS）和诱导型一氧化氮合酶（iNOS）的基因表达水平。最后，我们测量了丙二醛（MDA）含量的水平，MDA 是氧化应激的生物标志物。结果表明，PIEE 组大鼠的体重比 PISC 组大鼠轻。PIEE 组大鼠的功能结果优于 PISC 组，且 PIEE 组大鼠的 MDA、nNOS、iNOS 和磷酸化 ERK1/2 等与炎症相关的物质低于 PISC 组。这些结果表明，丰富的环境可能通过缺血预处理提供神经保护作用，并增强对脑缺血的抵抗力。
