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| Instantaneous firing of hippocampal neurons can be affected by the ambient oxygen level in the hypoxic cycle. (A) The time period during which the ambient O 2 level was above the mean (15.5%) was regarded as high supply of O 2 , while the time period during which the O 2 was below the mean was designated as lower supply of O 2. In the first 5 min of intermittent hypoxia (IH), the level of oxygen supply had no clear effect on the firing of both the putative pyramidal neurons (B) and the putative interneurons (C). However, in the last 5 min of 8 h IH treatment, both putative pyramidal neurons (D) and putative interneurons (E) tended to fire more during the period of higher oxygen supply. The data were from 50 putative pyramidal neurons and 12 putative interneurons (six rats). Wilcoxon's paired signed rank test for pyramidal neurons; Paired Student's t-test for interneurons; *P < 0.05.
Source publication
Chronic intermittent hypoxia (CIH) occurs in obstructive sleep apnea (OSA), a common sleep-disordered breathing associated with malfunctions in multiple organs including the brain. How OSA-associated CIH impacts on brain activities and functions leading to neurocognitive impairment is virtually unknown. Here, by means of in vivo electrophysiologica...
Contexts in source publication
Context 1
... rates of the recorded neurons when the oxygen level was above mean level (15.5%) with those below the mean level (Figure 4A), no differences were detected after 5 min of intermittent hypoxia (Figures 4B,C). The only exception was found at the times when the overall firing rates were elevated after 8 h of intermittent hypoxia in the first week (Figures 4D,E). ...
Context 2
... rates of the recorded neurons when the oxygen level was above mean level (15.5%) with those below the mean level (Figure 4A), no differences were detected after 5 min of intermittent hypoxia (Figures 4B,C). The only exception was found at the times when the overall firing rates were elevated after 8 h of intermittent hypoxia in the first week (Figures 4D,E). ...
Context 3
... rates of the recorded neurons when the oxygen level was above mean level (15.5%) with those below the mean level (Figure 4A), no differences were detected after 5 min of intermittent hypoxia (Figures 4B,C). The only exception was found at the times when the overall firing rates were elevated after 8 h of intermittent hypoxia in the first week (Figures 4D,E). Under this condition, in both pyramidal neurons and interneurons, the mean firing rates were lower when the ambient oxygen level was below the mean, that is, when there was a relatively low supply of oxygen. ...
Context 4
... average firing rate of all pyramidal neurons recorded in the phase of relatively high oxygen level (2.27 ± 0.27 spikes/s in day 1, n = 50 cells; 3.10 ± 0.42 spikes/s in day 2, n = 50 cells; 3.88 ± 0.64 spikes/s in day 3, n = 50 cells; 3.45 ± 0.62 spikes/s in day 5, n = 50 cells) was significantly higher than that in the phase of lower oxygen level (2.02 ± 0.26 spikes/s in day 1, n = 50 cells ; 2.53 ± 0.32 spikes/s in day 2, n = 50 cells; 3.49 ± 0.63 spikes/s in day 3, n = 50 cells; 3.12 ± 0.54 spikes/s in day 5, n = 50 cells; P < 0.05). Although real-time pO 2 or SaO 2 values were not monitored in the freely moving rats, such cyclic changes in neuronal activities with an interval of 90s could be very obvious in some neurons (Supplementary Figure 4), consistent with the effect of the cyclic IH. ...
Citations
... Chronic hypoxia has been linked to seizures 58 . Intermittent hypoxia has been shown to increase muscle sympathetic nerve activity 59 and motoneuronal output 60 , and caused hyperexcitability in pyramidal neurons and interneurons in the hippocampus 61 . Thus, the origin of the transient Connectivity. ...
Resting state networks (RSN), which show the connectivity in the brain in the absence of any stimuli, are increasingly important to assess brain function. Here, we investigate the changes in RSN as well as the hemodynamic changes during acute, global hypoxia. Mice were imaged at different levels of oxygen (21, 12, 10 and 8%) over the course of 10 weeks, with hypoxia and normoxia acquisitions interspersed. Simultaneous GCaMP and intrinsic optical imaging allowed tracking of both neuronal and hemodynamic changes. During hypoxic conditions, we found a global increase of both HbO and HbR in the brain. The saturation levels of blood dropped after the onset of hypoxia, but surprisingly climbed back to levels similar to baseline within the 10-min hypoxia period. Neuronal activity also showed a peak at the onset of hypoxia, but dropped back to baseline as well. Despite regaining baseline sO2 levels, changes in neuronal RSN were observed. In particular, the connectivity as measured with GCaMP between anterior and posterior parts of the brain decreased. In contrast, when looking at these same connections with HbO measurements, an increase in connectivity in anterior–posterior brain areas was observed suggesting a potential neurovascular decoupling.
... Obstructive sleep apnoea (OSA) is an increasingly common sleep-breathing disorder accompanied by upper airway obstruction and arousal during sleep. 1 OSA is associated with malfunctions in multiple physiological functions, including cognition. 2 The adverse outcomes of cognitive domains manifest as daytime sleepiness, lower attention, poor episodic memory, reduced responsiveness and working memory, behavioral problems, etc. 3,4 Currently, the OSA population is increasing, and this disorder is becoming a global health problem. 5 However, most individuals remain unaware of the health problem, and 80% do not receive a diagnosis and treatment. ...
Background
Chronic intermittent hypoxia (CIH) could cause neuronal damage, accelerating the progression of dementia. However, safe and effective therapeutic drugs and delivery are needed for successful CIH therapy.
Purpose
To investigate the neuroprotective effect of Huperzine A (HuA) packaged with nanoliposomes (HuA-LIP) on neuronal damage induced by CIH.
Methods
The stability and release of HuA-LIP in vitro were identified. Mice were randomly divided into the Control, CIH, HuA-LIP, and HuA groups. The mice in the HuA and HuA-LIP groups received HuA (0.1 mg/kg, i.p.), and HuA-LIP was administered during CIH exposure for 21 days. HuA-LIP contains the equivalent content of HuA.
Results
We prepared a novel formulation of HuA-LIP that had good stability and controlled release. First, HuA-LIP significantly ameliorated cognitive dysfunction and neuronal damage in CIH mice. Second, HuA-LIP elevated T-SOD and GSH-Px abilities and decreased MDA content to resist oxidative stress damage induced by CIH. Furthermore, HuA-LIP reduced brain iron levels by downregulating TfR1, hepcidin, and FTL expression. In addition, HuA-LIP activated the PKAα/Erk/CREB/BDNF signaling pathway and elevated MAP2, PSD95, and synaptophysin to improve synaptic plasticity. Most importantly, compared with HuA, HuA-LIP showed a superior performance against neuronal damage induced by CIH.
Conclusion
HuA-LIP has a good sustained-release effect and targeting ability and efficiently protects against neural injury caused by CIH.
... For instance, the central nervous system was found to suffer a severe functional impairment after blocking the oxygen supply to the brain for 5 s [2]. Functional and structural injuries were observed in central neurons when chronic intermittent hypoxia occurred in obstructive sleep apnea [3]. Some estimates have demonstrated that almost half of all neonatal encephalopathies might be attributed to hypoxia-ischemia [4]. ...
Isoflavones are a class of major phenolic compounds, derived from soybeans, that possess unique therapeutic and biological properties. The possible mechanisms of isoflavone-mediated protection of neuronal PC12 cells against hypoxic damage was investigated in this study. Isoflavones showed potential neuroprotective effects by increasing cell viability, decreasing the level of reactive oxygen species (ROS), and inhibiting apoptosis and cell cycle arrest in cobalt chloride (CoCl2)-induced hypoxic damage. A Western blot analysis indicated that isoflavones decreased apoptosis by up-regulating the Bcl-xL protein and down-regulating the Bax protein. They further reduced the S-phase fraction of the cell cycle by down-regulating the p21 protein and up-regulating the cyclin A protein levels. Additionally, isoflavones activated Nrf2 protein translocation and inhibited the p38 MAPK and AKT–mTOR pathways. A molecular docking analysis further revealed that isoflavones displayed a potential competitive interaction with the Nrf2 protein for Keap1. Our findings suggest that isoflavones could be a potent neuroprotective phytochemical in soybeans and their products.
