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下肢和肾脏缺血/再灌注后海马体的结构和功能障碍。

Structural and functional disorders of hippocampus following ischemia/reperfusion in lower limbs and kidneys.

作者信息

Karimi Narges, Haghani Masoud, Noorafshan Ali, Moosavi Seyed Mostafa Shid

机构信息

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.

出版信息

Neuroscience. 2017 Sep 1;358:238-248. doi: 10.1016/j.neuroscience.2017.06.058. Epub 2017 Jul 4.

Abstract

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.

摘要

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。

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