scholarly journals Neuroprotective Effects of GV1001 in Animal Stroke Model and Neural Cells Subject to Oxygen-Glucose Deprivation/Reperfusion Injury

2021 ◽  
Vol 23 (3) ◽  
pp. 420-436
Author(s):  
Hyuk Sung Kwon ◽  
Ye Eun Kim ◽  
Hyun-Hee Park ◽  
Jeong-Woo Son ◽  
Hojin Choi ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Cortical Neurons ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Neural Cells ◽  
Lesion Volume ◽  
Stroke Model ◽  
Neuroprotective Effects ◽  
Neurobehavioral Function

Background and Purpose Previous studies have revealed the diverse neuroprotective effects of GV1001. In this study, we investigated the effects of GV1001 on focal cerebral ischemia-reperfusion injury (IRI) in rats and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in neural stem cells (NSCs) and cortical neurons. Methods Focal cerebral IRI was induced by transient middle cerebral artery occlusion (MCAO). Brain diffusion-weighted imaging (DWI) was performed 2 hours after occlusion, and a total of 37 rats were treated by reperfusion with GV1001 or saline 2 hours after occlusion. Fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging, immunohistochemistry, and neurobehavioral function analyses were performed. Additionally, OGD/R-injured NSCs and cortical neurons were treated with different GV1001 concentrations. Cell viability, proliferation, migration, and oxidative stress were determined by diverse molecular analyses. Results In the stroke model, GV1001 protected neural cells against IRI. The most effective dose of GV1001 was 60 μM/kg. The infarct volume on FLAIR 48 hours after MCAO compared to lesion volume on DWI showed a significantly smaller ratio in the GV1001-treated group. GV1001-treated rats exhibited better behavioral functions than the saline-treated rats. Treatment with GV1001 increased the viability, proliferation, and migration of the OGD/R-injured NSCs. Free radicals were significantly restored by treatment with GV1001. These neuroprotective effects of GV1001 have also been demonstrated in OGD/R-injured cortical neurons. Conclusions The results suggest that GV1001 has neuroprotective effects against IRI in NSCs, cortical neurons, and the rat brain. These effects are mediated through the induction of cellular proliferation, mitochondrial stabilization, and anti-apoptotic, anti-aging, and antioxidant effects.

scholarly journals Metformin Protects Neurons against Oxygen-Glucose Deprivation/Reoxygenation -Induced Injury by Down-Regulating MAD2B

2016 ◽  
Vol 40 (3-4) ◽  
pp. 477-485 ◽  
Author(s):  
Xianfang Meng ◽  
Guangpin Chu ◽  
Zhihua Yang ◽  
Ping Qiu ◽  
Yue Hu ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Cyclin B1 ◽  
Oxygen Glucose Deprivation ◽  
Neuroprotective Effects ◽  
Histone 3

Background/Aims: Metformin, the common medication for type II diabetes, has protective effects on cerebral ischemia. However, the molecular mechanisms are far from clear. Mitotic arrest deficient 2-like protein 2 (MAD2B), an inhibitor of the anaphase-promoting complex (APC), is widely expressed in hippocampal and cortical neurons and plays an important role in mediating high glucose-induced neurotoxicity. The present study investigated whether metformin modifies the expression of MAD2B and to exert its neuroprotective effects in primary cultured cortical neurons during oxygen-glucose deprivation/reoxygenation (OGD/R), a widely used in vitro model of ischemia/reperfusion. Methods: Primary cortical neurons were cultured, deprived of oxygen-glucose for 1 h, and then recovered with oxygen-glucose for 12 h and 24 h. Cell viability was measured by detecting the levels of lactate dehydrogenase (LDH) in culture medium. The levels of MAD2B, cyclin B and p-histone 3 were measured by Western blot. Results: Cell viability of neurons was reduced under oxygen-glucose deprivation/reoxygenation (OGD/R). The expression of MAD2B was increased under OGD/R. The levels of cyclin B1, which is a substrate of APC, were also increased. Moreover, OGD/R up-regulated the phosphorylation levels of histone 3, which is the induction of aberrant re-entry of post-mitotic neurons. However, pretreatment of neurons with metformin alleviated OGD/R-induced injury. Metformin further decreased the expression of MAD2B, cyclin B1 and phosphorylation levels of histone 3. Conclusion: Metformin exerts its neuroprotective effect through regulating the expression of MAD2B in neurons under OGD/R.

scholarly journals Combination of mild hypothermia with neuroprotectants has greater neuroprotective effects during oxygen-glucose deprivation and reoxygenation-mediated neuronal injury

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Xiao-Ya Gao ◽  
Jian-Ou Huang ◽  
Ya-Fang Hu ◽  
Yong Gu ◽  
Shu-Zhen Zhu ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Mild Hypothermia ◽  
Neuronal Damage ◽  
Combined Treatment ◽  
Neuronal Injury ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Single Treatment ◽  
Neuroprotective Effects ◽  
Apoptosis Pathway

Abstract Co-treatment of neuroprotective reagents may improve the therapeutic efficacy of hypothermia in protecting neurons during ischemic stroke. This study aimed to find promising drugs that enhance the neuroprotective effect of mild hypothermia (MH). 26 candidate drugs were selected based on different targets. Primary cultured cortical neurons were exposed to oxygen-glucose deprivation and reoxygenation (OGD/R) to induce neuronal damage, followed by either single treatment (a drug or MH) or a combination of a drug and MH. Results showed that, compared with single treatment, combination of MH with brain derived neurotrophic factor, glibenclamide, dizocilpine, human urinary kallidinogenase or neuroglobin displayed higher proportion of neuronal cell viability. The latter three drugs also caused less apoptosis rate in combined treatment. Furthermore, co-treatment of those three drugs and MH decreased the level of reactive oxygen species (ROS) and intracellular calcium accumulation, as well as stabilized mitochondrial membrane potential (MMP), indicating the combined neuroprotective effects are probably via inhibiting mitochondrial apoptosis pathway. Taken together, the study suggests that combined treatment with hypothermia and certain neuroprotective reagents provide a better protection against OGD/R-induced neuronal injury.

Berberine Preconditioning Protects Neurons Against Ischemia via Sphingosine-1-Phosphate and Hypoxia-Inducible Factor-1α

2016 ◽  
Vol 44 (05) ◽  
pp. 927-941 ◽  
Author(s):  
Qichun Zhang ◽  
Huimin Bian ◽  
Liwei Guo ◽  
Huaxu Zhu
Keyword(s):  
Cortical Neurons ◽  
Ischemia Reperfusion ◽  
Hypoxia Inducible Factor ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Cerebral Injury ◽  
Male Rats ◽  
Neuroprotective Effects ◽  
Sphingosine 1 Phosphate ◽  
Cerebral Ischemic

Berberine exerts neuroprotective and modulates hypoxia inducible factor-1-alpha (HIF-1[Formula: see text]. Based on the role of HIF-1[Formula: see text] in hypoxia preconditioning and association between HIF-1[Formula: see text] and sphingosine-1-phosphate (S1P), we hypothesized that berberine preconditioning (BP) would ameliorate the cerebral injury induced by ischemia through activating the system of HIF-1[Formula: see text] and S1P. Adult male rats with middle cerebral artery occlusion (MCAO) and rat primary cortical neurons treated with oxygen and glucose deprivation (OGD) with BP at 24[Formula: see text]h (40[Formula: see text]mg/kg) and 2[Formula: see text]h (10[Formula: see text][Formula: see text]mol/L), respectively, were used to determine the neuroprotective effects. The HIF-1[Formula: see text] accumulation, and S1P metabolism were assayed in the berberine-preconditioned neurons, and the HIF-1[Formula: see text]-mediated transcriptional modulation of sphingosine kinases (Sphk) 1 and 2 was analyzed using chromatin immunoprecipitation and real-time polymerase chain reaction. BP significantly prevented cerebral ischemic injury in the MCAO rats at 24[Formula: see text]h and 72[Formula: see text]h following ischemia/reperfusion. In OGD-treated neurons, BP enhanced HIF-1[Formula: see text] accumulation with activation of PI3K/Akt, and induced S1P production by activating Sphk2 via the promotion of HIF-1[Formula: see text]-mediated Sphk2 transcription. In conclusion, BP activated endogenous neuroprotective mechanisms associated with the S1P/HIF-1 pathway and helped protect neuronal cells against hypoxia/ischemia.

scholarly journals rLj-RGD3, a Novel Three-RGD-Motif-Containing Recombinant Protein fromLampetra japonica, Protects PC12 Cells from Injury Induced by Oxygen-Glucose Deprivation and Reperfusion

2016 ◽  
Vol 2016 ◽  
pp. 1-9
Author(s):  
Li Lv ◽  
Qian Lu ◽  
Fangyu Shao ◽  
Weiping Li ◽  
Qin Zhou ◽  
...  
Keyword(s):  
Recombinant Protein ◽  
Protein Expression ◽  
Pc12 Cells ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
High Dose ◽  
Neuroprotective Effects ◽  
Tumour Metastasis

rLj-RGD3 is a 14.5 kDa recombinant protein with 3 RGD (Arg-Gly-Asp) motifs from the salivary gland secretions ofLampetra japonica, which is a histidine-rich and arginine-rich protein. Previous reports indicated that rLj-RGD3 has typical functions of RGD-toxin protein, such as platelet aggregation suppression tumour metastasis and angiogenesis inhibition. Because histidine and arginine have cerebral ischemia-reperfusion and neuroprotective functions, we investigated whether rLj-RGD3 has such activities and studied the mechanism. The effects of rLj-RGD3 on neuroprotection and antiapoptosis were determined. The expression level of focal adhesion kinase (FAK), p-FAK, Caspase-3, and Bcl-2 after oxygen-glucose deprivation and reperfusion (OGD-R) was examined. The viability of PC12 cells incubated with rLj-RGD3 at high concentrations (16 μmol/L) increased significantly due to its ability to protect the cells from apoptosis after OGD-R-induced injury. Furthermore, rLj-RGD3 attenuated the damage due to OGD-R. Most of the PC12 cells were apoptotic after OGD-R. In contrast, the number of apoptotic PC12 cells was significantly decreased in the group treated with a high-dose of rLj-RGD3. In addition, rLj-RGD3 activated FAK and p-FAK protein. rLj-RGD3 inhibited Caspase-3 and upregulated Bcl-2 protein expression in PC12 cells after OGD-R. The study provides the first evidence for neuroprotective effects of rLj-RGD3 in ischemic injury that may be partly mediated through inhibition of Caspase-3 and upregulation of Bcl-2, FAK, and p-FAK protein expression.

scholarly journals Suppression of lncRNA RMRP ameliorates oxygen-glucose deprivation/re-oxygenation-induced neural cells injury by inhibiting autophagy and PI3K/Akt/mTOR-mediated apoptosis

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Zheyi Zhou ◽  
Hong Xu ◽  
Baozhu Liu ◽  
Linglu Dun ◽  
Changjun Lu ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Neural Cells ◽  
Aberrant Expression ◽  
Invasion And Migration ◽  
Cycle Arrest ◽  
Apoptosis Pathways ◽  
And Migration

Abstract The aberrant expression of lncRNAs has been inferred to be closely related with the progression of neural ischemia/reperfusion (I/R) injury. RMRP is an lncRNA associated with I/R injury. In order to determine the role of RMRP in I/R injury, the effects of RMRP knockdown on oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced injury in SH-SY5Y cells were evaluated. The effect of OGD/R administration on the expression of RMRP and apoptosis in SH-SY5Y cells, and the effect of RMRP suppression by siRNA on the impairments of cells proliferation and mobility potential due to OGD/R administration were assessed in the current study. At the molecular level, the current study detected the expressions of indicators involved in autophagy and PI3K/Akt/mTOR-mediated apoptosis pathways. The OGD/R administration induced the expression of RMRP and apoptosis in SH-SY5Y cells. After RMRP knockdown, the proliferation potential of SH-SY5Y cells was restored, and apoptosis and cell cycle arrest were inhibited. Moreover, RMRP inhibition also increased the invasion and migration of SH-SY5Y cells which were treated with OGD/R. The effects of RMRP suppression on the phenotypes of SH-SY5Y were associated with the inhibition of LC3II, p-PI3K, p-Akt, and p-mTOR as well as the induction of P62 and Bcl-2. Inhibition of RMRP contributed to the improvement of OGD/R-induced neuronal injury, which might be mediated through the inhibition of autophagy and apoptosis pathways.

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