Delayed Hyperbaric Oxygen Therapy Promotes Neurogenesis Through Reactive Oxygen Species/Hypoxia-Inducible Factor-1α/β-Catenin Pathway in Middle Cerebral Artery Occlusion Rats

Hu, Qin; Liang, Xiping; Chen, Di; Chen, Yujie; Doycheva, Desislava; Tang, Juan; Tang, Jiping; Zhang, Junyi

doi:10.1161/strokeaha.114.005116

Cited by 73 publications

(66 citation statements)

References 36 publications

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“…This is a radial effect of stroke that triggers neural repair. Free radicals generated in penumbra and in peri-infarct tissue are part of the stimulus for neurogenesis [20,21]; cytokines activate astrocytes, promote angiogenesis, and induce axonal sprouting [19,22,23]; and synchronized neuronal activity induces axonal sprouting and the formation of new connections (Fig. 1) [24].…”

Section: Radial Stroke: Triggers For Neural Repairmentioning

confidence: 99%

“…Free radicals also directly activate neural stem cells through induction of growth factor signaling pathways [20]. Through these systems, free radical generation after stroke is one of the signals of poststroke neurogenesis [21,44]. Immature neurons in the largest germinal matrix, the subventricular zone (SVZ), respond to the stroke, migrate to the area of damage, and may participate in Fig.…”

Section: Radial Stroke: Triggers For Neural Repairmentioning

confidence: 99%

“…1 Stroke progresses in time from initial to secondary injury and to tissue repair as a continuum in which the initial pathological events trigger later regenerative events neural repair [30,45]. Blocking free radical generation, such as with an antioxidant, reduces poststroke neurogenesis [21]. It appears that free radical generation in peri-infarct tissue is one of the signals to multipotent neural stem cells and their progeny in the SVZ, together with other cytokines and growth factors activated in peri-infarct cortex [27,30,45].…”

Section: Radial Stroke: Triggers For Neural Repairmentioning

confidence: 99%

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The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

Carmichael

2016

Neurotherapeutics

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Stroke not only causes initial cell death, but also a limited process of repair and recovery. As an overall biological process, stroke has been most often considered from the perspective of early phases of ischemia, how these inter-relate and lead to expansion of the infarct. However, just as the biology of later stages of stroke becomes better understood, the clinical realities of stroke indicate that it is now more a chronic disease than an acute killer. As an overall biological process, it is now more important to understand how early cell death leads to the later, limited recovery so as develop an integrative view of acute to chronic stroke. This progression from death to repair involves sequential stages of primary cell death, secondary injury events, reactive tissue progenitor responses, and formation of new neuronal circuits. This progression is radial: from the tissue that suffers the infarct secondary injury signals, including free radicals and inflammatory cytokines, radiate out from the stroke core to trigger later regenerative events. Injury and repair processes occur not just in the local stroke site, but are also triggered in the connected networks of neurons that had existed in the stroke center: damage signals are relayed throughout a brain network. From these relayed, distributed damage signals, reactive astrocytosis, inflammatory processes, and the formation of new connections occur in distant brain areas. In short, emerging data in stroke cell death studies and the development of the field of stroke neural repair now indicate a continuum in time and in space of progressive events that can be considered as the 3 Rs of stroke biology: radial, relayed, and regenerative.

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Section: Radial Stroke: Triggers For Neural Repairmentioning

confidence: 99%

Section: Radial Stroke: Triggers For Neural Repairmentioning

confidence: 99%

Section: Radial Stroke: Triggers For Neural Repairmentioning

confidence: 99%

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The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

Carmichael

2016

Neurotherapeutics

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“…Under hypoxic conditions, HIF-1α is capable of regulating anaerobic metabolism by inducing the expression of its target gene, and promoting angiogenesis and an increase of erythropoietin, which ensures that the hypoxic tissues and cells maintain at a certain oxygen concentration and tolerate the hypoxic environment (25,26). Previous studies have demonstrated that, when cerebral ischemia occurs, HIF-1α-induced gene expression may promote reperfusion of the ischemic penumbra area, thus improving glucose transport, which helps to mediate the ability of cells to tolerate hypoxia and has an important protective role for ischemic and hypoxic neurons (27,28). Following mild transient ischemia and hypoxia, HIF-1α expression levels are increased, which induces ischemic and hypoxic tolerance and demonstrates the neuroprotective effect of HIF-1α against ischemia and hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective mechanism of HIF-1α overexpression in the early stage of acute cerebral infarction in rats

Sun

Geng

2016

Experimental and Therapeutic Medicine

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Abstract. The present study aimed to explore the expression and neuroprotective mechanism of hypoxia inducible factor (HIF-1α) in the brain tissue of a rat model of early acute cerebral infarction. A total of 64 Sprague Dawley rats were randomly divided into surgery and sham groups and the model of focal cerebral infarction was established by the suture-occluded method. In the sham group, blood vessels were separated but not occluded. Rats in the surgery and sham groups were subdivided into eight groups (n=4/group). Blood samples was collected at 8 time points including 30 min and 1, 3, 6, 12, 48, 24 and 72 h, respectively, and HIF-1α content was detected using ELISA. Brain tissues of rats in all groups were harvested following blood collection. HIF-1α protein expression was detected by immunohistochemistry and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling was used to analyze the brain cell apoptosis index. ELISA results demonstrated that rats in the surgery group began to express HIF-1α within 30 min, and HIF-1α expression levels gradually increased, peaking at 12 h. HIF-1α expression levels were significantly increased in the surgery group at all time points, as compared with the sham group (P<0.05). The concentration of HIF-1α decreased rapidly in 12 h. At various time points, HIF-1α protein expression in the brain tissue of rats in the sham group was negative. HIF-1α protein expression was significantly increased in the surgery group (P<0.05), peaking at 12 h, and decreasing after this point. As compared with the sham group, the apoptosis indices of the brain tissue of rats in the surgery group exhibited a gradual increasing trend with significant decreases observed after 12 h (P<0.05). Intra-group comparison of all indices in the surgery group, indicated that there was a statistically significant difference between postoperative 12 h and other time points (P<0.05).In conclusion, the present study demonstrated that HIF-1α was highly expressed in the brain tissue of rat models of early acute cerebral infarction. The results also indicated that HIF-1α significantly reduced the apoptosis of infarcted cells, suggesting that HIF-1α may have a neuroprotective role in early acute cerebral infarction.

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“…The actual evidence for this concept is limited, though. In addition to some studies showing no effect on surrogate markers of ROS production in experimental cerebral ischemia [35,36], a recent study suggested that delayed HBO therapy had a beneficial effect after cerebral ischemia as it promoted production of reactive oxygen species [37].…”

Section: Discussionmentioning

confidence: 99%