Zorina I I, Fokina E A, Zakharova I O, Bayunova L V, Shpakov A O
I.M.Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, 44 pr. Toreza, St. Petersburg 194223, Russian Federation, e-mail:
Adv Gerontol. 2019;32(6):941-947.
The success of preclinical neuroprotection studies depends on the model used in animal research. The methodological approaches developed on young animals and widely used for modeling cerebral ischemia/reperfusion injury may not be so effective or not suitable for its modeling on senescent animals, which usage is recommended for preclinical trials. The aim of this study was to investigate the age-related features on the effect of brain reperfusion with different duration (1 and 3 h) after 2-vessel forebrain ischemia on the level of lipid peroxidation (LPO) products and on the activity of Na+/K+-ATPase in the cerebral cortex of rats aged 22-24 months. We found a later accumulation of LPO products (3 h instead of 1 h after blood recirculation), specifically triene conjugates and Schiff bases, and a decrease in the activity of Na+/K+-ATPase in the cerebral cortex of aged rats compared to young animals. The data obtained reveal the difference in the molecular and physiological mechanisms of the development of disorders in the brain during ischemia/reperfusion in aged and young animals. The revealed differences in these mechanisms should be consider in developing and testing compounds, which will be further used for the treatment of elderly patients with stroke and ischemic brain damage.
临床前神经保护研究的成功取决于动物研究中所使用的模型。在幼龄动物上开发并广泛用于模拟脑缺血/再灌注损伤的方法，可能对老龄动物并不那么有效或不适用于老龄动物的模型构建，而老龄动物模型在临床前试验中是推荐使用的。本研究的目的是调查在22 - 24月龄大鼠的大脑前脑双血管缺血后，不同时长（1小时和3小时）的脑再灌注对脂质过氧化（LPO）产物水平以及大脑皮层中Na⁺/K⁺ - ATP酶活性的影响的年龄相关特征。我们发现，与幼龄动物相比，老龄大鼠大脑皮层中LPO产物（再灌注后3小时而非1小时），特别是三烯共轭物和席夫碱的积累延迟，以及Na⁺/K⁺ - ATP酶活性降低。所获得的数据揭示了老龄和幼龄动物在缺血/再灌注期间大脑功能障碍发展的分子和生理机制的差异。在开发和测试将进一步用于治疗老年中风和缺血性脑损伤患者的化合物时，应考虑这些机制上揭示出的差异。
