Comparative Biochemistry and Physiology A: Molecular & Integrative Physiology ( IF 2.1 ) Pub Date : 2020-08-15 , DOI: 10.1016/j.cbpa.2020.110792 Tina H Wang 1 , Liam Eaton 1 , Matthew E Pamenter 2
Reactive nitrogen species (RNS), including nitric oxide (NO), are important cellular messengers when tightly regulated, but unregulated production of RNS during hypoxia or ischemia and reoxygenation is deleterious to hypoxia-intolerant brain. Therefore, maintaining NO homeostasis during hypoxia/ischemia and reoxygenation may be a hallmark of hypoxia-tolerant brain. Unlike most mammals, naked mole-rats (NMRs; Heterocephalus glaber) are tolerant of repeated bouts of hypoxia in vivo. Although there is some evidence that NMR brain is tolerant of hypoxia/ischemia, little is known about the underlying neuroprotective mechanism(s), and their tolerance to reoxygenation injury has not been examined. We hypothesized that NMR brain would maintain NO homeostasis better than hypoxia-intolerant mouse brain during hypoxic/ischemic stresses and following reoxygenation. To test this, we exposed adult NMR and mouse cortical slices to transitions from normoxia (21% O2) to hypoxia (< 1% O2) or ischemia (oxygen glucose deprivation, OGD), followed by reoxygenation, while measuring neuronal NO production. We report that NMR cortical neurons maintain NO homeostasis during hypoxia/OGD and avoid bursts of NO upon reoxygenation. Conversely, mouse cortical neurons maintain NO homeostasis in OGD but not hypoxia and exhibit a burst of NO upon reperfusion. This suggests that maintenance of NO homeostasis during fluctuating O2 availability may be a contributing neuroprotective mechanism against hypoxia/ischemia and reoxygenation injury in hypoxia-tolerant NMR brain.
中文翻译:
一氧化氮的稳态过程在急性体外低氧期间和裸鼠模型中复氧后得以维持,但在小鼠皮层神经元中则没有。
当严格调节时,反应性氮素(RNS),包括一氧化氮(NO),是重要的细胞信使,但在缺氧或局部缺血和再氧化期间RNS的产生不受调节,这对不耐缺氧的大脑有害。因此,在缺氧/缺血和复氧过程中保持NO稳态可能是耐缺氧大脑的标志。与大多数哺乳动物不同,裸mole鼠(NMRs; Heterocephalus glaber)能够耐受体内反复缺氧。尽管有一些证据表明NMR脑可以耐受缺氧/缺血,但对于潜在的神经保护机制知之甚少,尚未研究其对复氧损伤的耐受性。我们假设在缺氧/缺血性应激以及复氧后,NMR脑比缺氧耐缺氧的小鼠脑更好地维持NO稳态。为了测试这一点,我们将成人NMR和小鼠皮质切片暴露于从正常氧(21%O 2)到缺氧(<1%O 2)或缺血(缺氧葡萄糖,OGD),然后再充氧,同时测量神经元NO的产生。我们报告说,核磁共振皮质神经元在缺氧/ OGD期间保持NO稳态,并避免在复氧时NO爆发。相反,小鼠皮层神经元在OGD中维持NO稳态,但没有缺氧,并且在再灌注时表现为NO爆发。这表明在波动的O 2利用率期间维持NO稳态可能是针对耐缺氧NMR脑的缺氧/缺血和复氧损伤的神经保护机制。