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As a general anesthesia drug, sevoflurane has been found to be potentially neurotoxic to the developing brain. Neuroglobin (Ngb) is a novel oxygen-carrying globulin that has been demonstrated to have neuroprotective effects in a variety of central nervous system disorders. However, it is unclear whether Ngb has a protective effect on nerve damage caused by sevoflurane. Therefore, this study was designed to investigate the effect and related mechanisms of Ngb on neural injury induced by sevoflurane. Pregnant rats on gestational day 20 (G20) were exposed to 3.5% sevoflurane for two hours, which led to an increase of Ngb on the 0-1st day after birth and decreased significantly on the 3rd day, while Cytochrome c increased from the 1 st day until the 7th day of offspring rats. Meanwhile, sevoflurane reduced Bcl-2 and Hif-1αand increased Bax and cleaved-caspase 3 in the third day after birth. Hemin inhibits endogenous apoptosis by increasing Ngb and Hif-1α. And increased Ngb improved the damage of long-term learning and memory induced by sevoflurane and increased the number of neurons in the hippocampus. We concluded that Ngb can improve the neuronal injury induced by sevoflurane exposure by inhibiting apoptosis and increasing the number of neurons. And this protective effect of Ngb may be related to Hif-1α signaling pathway. This finding may provide a novel therapeutic approach for sevoflurane -induced nerve damage., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Exploring the effective therapy for neonatal hypoxic-ischemic brain injury is an important goal. This study was designed to investigate how dexmedetomidine (DEX) contribute to hypoxic brain injury. Methods: Developing Sprague-Dawley rat models of hypoxia/reoxygenation (H/R) injury were constructed to simulate neonatal hypoxic brain injury for DEX treatment. Immunohistochemistry and western blot were performed to measure neuroglobin (Ngb) protein expression in hippocampal tissues. Hippocampal neuron injury and apoptosis were detected by Nissl staining and TUNEL assay, respectively. A Morris water maze (MWM) test was performed to evaluate the long-term learning and memory function. Results: The expression of Ngb was increased following H/R model establishment and up-regulated by medium and high doses of DEX, but not up-regulated by low doses of DEX. Medium and high doses of DEX alleviated the H/R injury as well as induced the reduction of Nissl bodies and apoptosis. Besides, medium and high doses of DEX down-regulated cytosolic Cyt-c, Apaf-1, and caspase-3 in H/R injury model. MWM test showed that medium and high doses of DEX significantly shortened the escape latency and enhanced the number of platform crossings. However, low doses of DEX have no effect on Nissl bodies, mitochondrial apoptosis, expression of apoptosis-related proteins and long-term learning functions. Conclusions: DEX induced Ngb expression in H/R rat models. The neuroprotection of DEX-mediated Ngb up-regulation may be achieved by inhibiting neuronal apoptosis through the mitochondrial pathway. Findings indicated that DEX may be useful as an effective therapy for neonatal hypoxic brain injury. [ABSTRACT FROM AUTHOR]

To observe the effect of dexmedetomidine (DEX) on mitochondrial apoptosis of hippocampal neurons in hypoxia/reoxygenation (H/R) brain injury in developing rats, and to investigate its regulatory mechanism on HIF-1α/p53 signaling pathway. Hypoxia/reoxygenation model was used in this study. TUNEL assay was performed to detect cell apoptosis. Immunohistochemical analysis and Western-blotting analysis were conducted to detect Cytochrome-C (Cyt-c), APAF-1, Caspase-3, Neuroglobin (Ngb), HIF-1α and p53 expression. After 28 days, Morris water maze (MWM) was performed. 50 μg/kg DEX improved H/R-induced brain injury and inhibited mitochondrial apoptosis in rats. Western-blotting and Immunohistochemical results demonstrated that DEX could up-regulate Ngb through α 2 receptor to inhibit H/R-induced mitochondrial apoptosis. In addition, by adding inhibitors yohimbine and 2-methoxyestradiol (2ME2), we found that DEX could activate HIF-1α/p53 signaling pathway. MWM test showed that DEX could enhance long-term learning and memory of H/R brain injury rats. DEX alleviates H/R-induced brain injury and mitochondrial apoptosis in developing rats through α 2 receptor, which may be related to activation of HIF-1α/p53 signaling pathway to up-regulate the expression of Ngb. [ABSTRACT FROM AUTHOR]