Karimi Narges, Haghani Masoud, Noorafshan Ali, Moosavi Seyed Mostafa Shid
Department of Physiology, The Medical School, Shiraz University of Medical Sciences, Shiraz 71365-1689, Iran.
Department of Physiology, The Medical School, Shiraz University of Medical Sciences, Shiraz 71365-1689, Iran; Histomorphometry and Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz 71365-1689, Iran.
Neuroscience. 2017 Sep 1;358:238-248. doi: 10.1016/j.neuroscience.2017.06.058. Epub 2017 Jul 4.
Recent evidence suggests that ischemia/reperfusion (I/R) in an organ may have distance effect on the brain. In this study, the effects of renal I/R, limb I/R or both together on the structural and function of hippocampus were evaluated and compared. Hence, rats were subjected to 2-h bilateral lower limb ischemia, 45-min bilateral renal ischemia, or combined limb and renal ischemia followed by 1-day reperfusion. At 22-h reperfusion, each rat was fixed on a stereotaxic apparatus for performing electrophysiological study on the hippocampus. The long-term potentiation (LTP) was induced by high-frequency stimulation (HFS), and paired-pulse ratio (PPR) was also monitored before and after HFS delivery. After taking blood sample and sacrificing animal, its brain was removed and preserved for stereological study. The limb I/R reduced plasma osmolality that led to synaptic excitement in the hippocampus, where there was a considerable loss of pyramidal cells and markedly impaired short- and long-term synaptic plasticity. The renal I/R largely increased plasma creatinine that might excite basal synaptic transmission. In the rats with combined limb and renal I/R, the hippocampal neuronal loss and impaired synaptic plasticity were the same as those with limb I/R, but basal synaptic transmission was lowered. In conclusion, the 2-h lower limb ischemia compared to 45-min renal ischemia induced more injurious distant effects on the hippocampus after 1-day reperfusion. The combination of renal and limb I/R did not add or potentiate hippocampal neuronal loss and synaptic plasticity impairment, whereas it decreased the basal synaptic transmission with respect to each one alone.
最近的证据表明,器官中的缺血/再灌注(I/R)可能对大脑产生远程影响。在本研究中,评估并比较了肾I/R、肢体I/R或两者共同作用对海马结构和功能的影响。因此,将大鼠进行2小时的双侧下肢缺血、45分钟的双侧肾缺血,或肢体与肾联合缺血,随后再灌注1天。在再灌注22小时时,将每只大鼠固定在立体定位仪上,对海马进行电生理研究。通过高频刺激(HFS)诱导长时程增强(LTP),并在HFS刺激前后监测配对脉冲比率(PPR)。采集血样并处死动物后,取出其大脑并保存用于体视学研究。肢体I/R降低了血浆渗透压,导致海马中的突触兴奋,其中锥体细胞大量丢失,短期和长期突触可塑性明显受损。肾I/R使血浆肌酐大幅升高,这可能会激发基础突触传递。在肢体与肾联合I/R的大鼠中,海马神经元丢失和突触可塑性受损与肢体I/R的大鼠相同,但基础突触传递降低。总之,与45分钟的肾缺血相比,2小时的下肢缺血在再灌注1天后对海马产生了更具损伤性的远程影响。肾与肢体I/R的联合作用并未增加或增强海马神经元丢失和突触可塑性损伤,而相对于单独的每种情况,它降低了基础突触传递。