Oxygen-glucose deprivation in neurons: implications for cell transplantation therapies

Rizzo, Sebastiano Antonio; Bartley, Oliver; Rosser, Anne Elizabeth; Newland, Ben

doi:10.1016/j.pneurobio.2021.102126

Cited by 8 publications

(4 citation statements)

References 97 publications

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“…Liu et al found that small compound inhibitors of basal glucose transport inhibit cell proliferation and induce apoptosis in cancer cells via glucose-deprivation-like mechanisms [ 43 ]. Rizzo et al studied the mechanisms of neuronal death in ischemic stroke by establishing an in vitro model of oxygen and glucose deprivation and found that continuous oxygen and glucose deprivation significantly reduced neuronal activity and increased neuronal death [ 44 ]. It has been reported that type 2 diabetes rats have impaired learning and memory function due to apoptosis of hippocampal neurons.…”

Section: Discussionmentioning

confidence: 99%

Alpha-Ketoglutarate Alleviates Neuronal Apoptosis Induced by Central Insulin Resistance through Inhibiting S6K1 Phosphorylation after Subarachnoid Hemorrhage

Ding

Sheng

et al. 2022

Oxidative Medicine and Cellular Longevity

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Neuronal apoptosis after subarachnoid hemorrhage (SAH) is believed to play an important role in early brain injury after SAH. The energy metabolism of neuron is closely related to its survival. The transient hyperglycemia caused by insulin resistance (IR) after SAH seriously affects the prognosis of patients. However, the specific mechanisms of IR after SAH are still not clear. Studies have shown that α-KG takes part in the regulation of IR and cell apoptosis. In this study, we aim to investigate whether α-KG can reduce IR after SAH, improve the disorder of neuronal glucose metabolism, alleviate neuronal apoptosis, and ultimately play a neuroprotective role in SAH-induced EBI. We first measured α-KG levels in the cerebrospinal fluid (CSF) of patients with SAH. Then, we established a SAH model through hemoglobin (Hb) stimulation with HT22 cells for further mechanism research. Furthermore, an in vivo SAH model in mice was established by endovascular perforation. Our results showed that α-KG levels in CSF significantly increased in SAH patients and could be used as a potential prognostic biomarker. In in vitro model of SAH, we found that α-KG not only inhibited IR-induced reduction of glucose uptake in neurons after SAH but also alleviated SAH-induced neuronal apoptosis. Mechanistically, we found that α-KG inhibits neuronal IR by inhibiting S6K1 activation after SAH. Moreover, neuronal apoptosis significantly increased when glucose uptake was reduced. Furthermore, our results demonstrated that α-KG could also alleviate neuronal apoptosis in vivo SAH model. In conclusion, our study suggests that α-KG alleviates apoptosis by inhibiting IR induced by S6K1 activation after SAH.

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Section: Discussionmentioning

confidence: 99%

Alpha-Ketoglutarate Alleviates Neuronal Apoptosis Induced by Central Insulin Resistance through Inhibiting S6K1 Phosphorylation after Subarachnoid Hemorrhage

Ding

Sheng

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…FGF2 is interesting in the regeneration field as one of the main inducers of vascularization together with VEGF 42 , as vascularization is key to replenish the site with oxygen and nutrients and is often the first hurdle to overcome for a successful graft 43 . This well-defined model system, using a biomaterial with a known elastin sequence in combination with synthetic glycosaminoglycans, opens for the possibility to test for inhibitors and activators of vascularization that otherwise might already be present in undefined ECM hydrogels such as Matrigel 6 .…”

Section: Discussionmentioning

confidence: 99%

Controlled release of growth factors using synthetic glycosaminoglycans in a modular macroporous scaffold for tissue regeneration

et al. 2022

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Healthy regeneration of tissue relies on a well-orchestrated release of growth factors. Herein, we show the use of synthetic glycosaminoglycans for controlled binding and release of growth factors to induce a desired cellular response. First, we screened glycosaminoglycans with growth factors of interest to determine kon (association rate constant), koff (dissociation rate constant), and Kd (equilibrium rate constant). As proof-of-concept, we functionalized an elastin-like recombinamer (ELR) hydrogel with a synthetic glycosaminoglycan and immobilized fibroblast growth factor 2 (FGF2), demonstrating that human umbilical vein endothelial cells cultured on top of ELR hydrogel differentiated into tube-like structures. Taking this concept further, we developed a tunable macroporous ELR cryogel material, containing a synthetic glycosaminoglycan and FGF2 that showed increased blood vessel formation and reduced immune response compared to control when implanted in a subcutaneous mouse model. These results demonstrated the possibility for specific release of desired growth factors in/from a modular 3D scaffold in vitro and in vivo.

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“…Moreover, configured MSC products usually suspend cells in normal saline, in a typical oxygen–glucose deprivation (OGD) microenvironment. Currently, the in vitro OGD model is often used to mimic the interruption of the supply of oxygen and metabolic fuel to the cells and tissues that occurs during an ischemic event and has been extensively developed to elucidate the role of key cellular and molecular mechanisms underlying ischemia-induced injury in the heart and brain, mainly including myocardial infarct, ischemic stroke, and cardiac arrest 19 , 20 . As both oxygen and glucose are critical to cell survival, the duration of OGD is positively correlated with reduced cell viability in a variety of in vitro models.…”

Section: Introductionmentioning

confidence: 99%

“…As both oxygen and glucose are critical to cell survival, the duration of OGD is positively correlated with reduced cell viability in a variety of in vitro models. Accordingly, it has been demonstrated that under hypoxic conditions, glucose deprivation accounts for the widespread loss of neurons seen in OGD and reperfusion 19 . However, Kanazawa et al indicated that both microglia and peripheral blood mononuclear cells (PBMCs) pretreated by optimal OGD might be novel therapeutic strategies against ischemic stroke 21,22 .…”

Section: Introductionmentioning

confidence: 99%

Nonfreezing Low Temperature Maintains the Viability of Menstrual Blood–Derived Endometrial Stem Cells Under Oxygen–Glucose Deprivation Through the Sustained Release of Autophagy-Produced Energy

et al. 2022

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Between the completion of the mesenchymal stem cell (MSCs) preparation and the transplantation into the patient, there is a time interval during which the quality control and transport of MSC products occur, which usually involves suspending the cells in normal saline in an oxygen–glucose deprivation (OGD) microenvironments. Thus, how to effectively maintain MSC viability during the abovementioned time interval is bound to play a significant role in the therapeutic effect of MSC-based therapies. Recently, menstrual blood–derived endometrial stem cells (MenSCs) have attracted extensive attention in regenerative medicine due to their superior biological characteristics, including noninvasive protocols for their collection, abundant source material, stable donation, and autotransplantation. Therefore, this study aimed to mainly determine the effect of storage temperature on the maintenance of MenSC viabilities in an OGD microenvironment, and to preliminarily explore its potential mechanism. Simultaneously, the effects of solvents commonly used in the clinic on MenSC viability were also examined to support the clinical application of MenSCs. Consequently, our results demonstrated that in the OGD microenvironment, a nonfreezing low temperature (4°C) was suitable and cost-effective for MenSC storage, and the maintenance of MenSC viability stored at 4°C was partly contributed by the sustained releases of autophagy-produced energy. Furthermore, the addition of human serum albumin effectively inhibited the cell sedimentations in the MenSC suspension. These results provide support and practical experience for the extensive application of MenSCs in the clinic.

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Oxygen-glucose deprivation in neurons: implications for cell transplantation therapies

Cited by 8 publications

References 97 publications

Alpha-Ketoglutarate Alleviates Neuronal Apoptosis Induced by Central Insulin Resistance through Inhibiting S6K1 Phosphorylation after Subarachnoid Hemorrhage

Alpha-Ketoglutarate Alleviates Neuronal Apoptosis Induced by Central Insulin Resistance through Inhibiting S6K1 Phosphorylation after Subarachnoid Hemorrhage

Controlled release of growth factors using synthetic glycosaminoglycans in a modular macroporous scaffold for tissue regeneration

Nonfreezing Low Temperature Maintains the Viability of Menstrual Blood–Derived Endometrial Stem Cells Under Oxygen–Glucose Deprivation Through the Sustained Release of Autophagy-Produced Energy

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