Duszczyk Malgorzata, Ziembowicz Apolonia, Gadamski Roman, Wieronska Joanna M, Smialowska Maria, Lazarewicz Jerzy W
Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego Street, Warsaw 02-106, Poland.
Neuropeptides. 2009 Feb;43(1):31-9. doi: 10.1016/j.npep.2008.09.008. Epub 2008 Nov 13.
Preconditioning with sublethal ischemia or hypoxia may reduce the high susceptibility of CA1 pyramidal neurons to ischemic injury. In this study, we tested the hypothesis that enhanced level of neuropeptide Y (NPY) might play a role in the mechanisms responsible for this induced tolerance. Changes in NPY immunoreactivity in the hippocampal formation of preconditioned Mongolian gerbils were compared with the level of tolerance to test ischemia. Tolerance was induced by preconditioning with 2-min of ischemia or with three trials of mild hypobaric hypoxia (360 Torr, 2 h), separated by 24 h, that were completed 48 h before the 3-min test ischemia. The number of NPY-positive neurons in the gerbil hippocampal formation was assessed 2, 4 and 7 days after preconditioning. Survival of the CA1 pyramidal neurons was examined 14 days after the insult. Our experiments demonstrated that ischemic and hypoxic preconditioning produced equal attenuation of the damage evoked by 3-min ischemia, although the pattern of NPY immunoreactivity in the hippocampus differed. Preconditioning ischemia resulted in a 20% rise in the number of NPY-positive neurons 2 days later that disappeared 4 days after the ischemic episode, while mild hypobaric hypoxia induced a twofold increase in the number of NPY-positive neurons that lasted for at least 7 days. Although induced tolerance to ischemia 2 days after ischemic or hypoxic preconditioning was accompanied by increased immunoreactivity of NPY, there was no correlation between its intensity and the level of neuroprotection.
用亚致死性缺血或缺氧进行预处理可能会降低CA1锥体神经元对缺血性损伤的高度易感性。在本研究中，我们检验了这样一个假设，即神经肽Y（NPY）水平的升高可能在这种诱导耐受性的机制中发挥作用。将预处理的蒙古沙鼠海马结构中NPY免疫反应性的变化与对试验性缺血的耐受水平进行比较。通过2分钟的缺血预处理或三次轻度低压缺氧试验（360托，2小时）诱导耐受性，每次试验间隔24小时，在3分钟试验性缺血前48小时完成。在预处理后2、4和7天评估沙鼠海马结构中NPY阳性神经元的数量。在损伤后14天检查CA1锥体神经元的存活情况。我们的实验表明，缺血和缺氧预处理对3分钟缺血引起的损伤产生了同等程度的减轻，尽管海马中NPY免疫反应性的模式有所不同。预处理缺血导致2天后NPY阳性神经元数量增加20%，在缺血发作后4天消失，而轻度低压缺氧诱导NPY阳性神经元数量增加两倍，持续至少7天。尽管缺血或缺氧预处理后2天诱导的对缺血的耐受性伴随着NPY免疫反应性的增加，但其强度与神经保护水平之间没有相关性。
