scholarly journals Glycine Protects against Hypoxic-Ischemic Brain Injury by Regulating Mitochondria-Mediated Autophagy via the AMPK Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-29 ◽  
Author(s):  
Chen-chen Cai ◽  
Jiang-hu Zhu ◽  
Li-xia Ye ◽  
Yuan-yuan Dai ◽  
Ming-chu Fang ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Adenosine Monophosphate ◽  
Ischemic Brain Injury ◽  
Hypoxic Stress ◽  
Ischemic Brain ◽  
Ampk Pathway ◽  
Amp Activated Protein Kinase ◽  
Ischemic Encephalopathy

Hypoxic-ischemic encephalopathy (HIE) is detrimental to newborns and is associated with high mortality and poor prognosis. Thus, the primary aim of the present study was to determine whether glycine could (1) attenuate HIE injury in rats and hypoxic stress in PC12 cells and (2) downregulate mitochondria-mediated autophagy dependent on the adenosine monophosphate- (AMP-) activated protein kinase (AMPK) pathway. Experiments conducted using an in vivo HIE animal model and in vitro hypoxic stress to PC12 cells revealed that intense autophagy associated with mitochondrial function occurred during in vivo HIE injury and in vitro hypoxic stress. However, glycine treatment effectively attenuated mitochondria-mediated autophagy. Additionally, after identifying alterations in proteins within the AMPK pathway in rats and PC12 cells following glycine treatment, cyclosporin A (CsA) and 5-aminoimidazole-4-carboxamide-1-b-4-ribofuranoside (AICAR) were administered in these models and indicated that glycine protected against HIE and CoCl2 injury by downregulating mitochondria-mediated autophagy that was dependent on the AMPK pathway. Overall, glycine attenuated hypoxic-ischemic injury in neurons via reductions in mitochondria-mediated autophagy through the AMPK pathway both in vitro and in vivo.

scholarly journals Intranasal Administration of Human MSC for Ischemic Brain Injury in the Mouse: In Vitro and In Vivo Neuroregenerative Functions

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112339 ◽  
Author(s):  
Vanessa Donega ◽  
Cora H. Nijboer ◽  
Luca Braccioli ◽  
Ineke Slaper-Cortenbach ◽  
Annemieke Kavelaars ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intranasal Administration ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

scholarly journals Loss of AMP-Activated Protein Kinase Induces Mitochondrial Dysfunction and Proinflammatory Response in Unstimulated Abcd1-Knockout Mice Mixed Glial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Jaspreet Singh ◽  
Hamid Suhail ◽  
Shailendra Giri
Keyword(s):  
Protein Kinase ◽  
Mitochondrial Dysfunction ◽  
Glial Cells ◽  
Adenosine Monophosphate ◽  
Proinflammatory Response ◽  
Inflammatory Protein ◽  
Lower Oxygen ◽  
Amp Activated Protein Kinase

X-linked adrenoleukodystrophy (X-ALD) is caused by mutations and/or deletions in the ABCD1 gene. Similar mutations/deletions can give rise to variable phenotypes ranging from mild adrenomyeloneuropathy (AMN) to inflammatory fatal cerebral adrenoleukodystrophy (ALD) via unknown mechanisms. We recently reported the loss of the anti-inflammatory protein adenosine monophosphate activated protein kinase (AMPKα1) exclusively in ALD patient-derived cells. X-ALD mouse model (Abcd1-knockout (KO) mice) mimics the human AMN phenotype and does not develop the cerebral inflammation characteristic of human ALD. In this study we document that AMPKα1 levelsin vivo(in brain cortex and spinal cord) andin vitroin Abcd1-KO mixed glial cells are similar to that of wild type mice. Deletion of AMPKα1 in the mixed glial cells of Abcd1-KO mice induced spontaneous mitochondrial dysfunction (lower oxygen consumption rate and ATP levels). Mitochondrial dysfunction in ALD patient-derived cells and in AMPKα1-deleted Abcd1-KO mice mixed glial cells was accompanied by lower levels of mitochondrial complex (1-V) subunits. More importantly, AMPKα1 deletion induced proinflammatory inducible nitric oxide synthase levels in the unstimulated Abcd1-KO mice mixed glial cells. Taken together, this study provides novel direct evidence for a causal role for AMPK loss in the development of mitochondrial dysfunction and proinflammatory response in X-ALD.

scholarly journals β-Estradiol Protects Against Acidosis-Mediated and Ischemic Neuronal Injury by Promoting ASIC1a (Acid-Sensing Ion Channel 1a) Protein Degradation

Stroke ◽  
2019 ◽  
Vol 50 (10) ◽  
pp. 2902-2911 ◽  
Author(s):  
Renpeng Zhou ◽  
Tiandong Leng ◽  
Tao Yang ◽  
Feihu Chen ◽  
Wei Hu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Protein Expression ◽  
Ion Channel ◽  
Ischemic Brain Injury ◽  
Estradiol Treatment ◽  
Ischemic Brain ◽  
Intracellular Ca ◽  
Ischemic Neuronal Injury

Background and Purpose— Sex differences in the incidence and outcome of stroke have been well documented. The severity of stroke in women is, in general, significantly lower than that in men, which is mediated, at least in part, by the protective effects of β-estradiol. However, the detailed mechanisms underlying the neuroprotection by β-estradiol are still elusive. Recent studies have demonstrated that activation of ASIC1a (acid-sensing ion channel 1a) by tissue acidosis, a common feature of brain ischemia, plays an important role in ischemic brain injury. In the present study, we assessed the effects of β-estradiol on acidosis-mediated and ischemic neuronal injury both in vitro and in vivo and explored the involvement of ASIC1a and underlying mechanism. Methods— Cultured neurons and NS20Y cells were subjected to acidosis-mediated injury in vitro. Cell viability and cytotoxicity were measured by methylthiazolyldiphenyl-tetrazolium bromide and lactate dehydrogenase assays, respectively. Transient (60 minutes) focal ischemia in mice was induced by suture occlusion of the middle cerebral artery in vivo. ASIC currents were recorded using whole-cell patch-clamp technique while intracellular Ca 2+ concentration was measured with fluorescence imaging using Fura-2. ASIC1a expression was detected by Western blotting and quantitative real-time polymerase chain reaction. Results— Treatment of neuronal cells with β-estradiol decreased acidosis-induced cytotoxicity. ASIC currents and acid-induced elevation of intracellular Ca 2+ were all attenuated by β-estradiol treatment. In addition, we showed that β-estradiol treatment reduced ASIC1a protein expression, which was mediated by increased protein degradation, and that estrogen receptor α was involved. Finally, we showed that the level of ASIC1a protein expression in brain tissues and the degree of neuroprotection by ASIC1a blockade were lower in female mice, which could be attenuated by ovariectomy. Conclusions— β-estradiol can protect neurons against acidosis-mediated neurotoxicity and ischemic brain injury by suppressing ASIC1a protein expression and channel function. Visual Overview— An online visual overview is available for this article.

Neuroprotective effects of topiramate and memantine in combination with hypothermia in hypoxic-ischemic brain injury in vitro and in vivo

2018 ◽  
Vol 668 ◽  
pp. 103-107 ◽  
Author(s):  
Elisa Landucci ◽  
Luca Filippi ◽  
Elisabetta Gerace ◽  
Serena Catarzi ◽  
Renzo Guerrini ◽  
...  
Keyword(s):  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Neuroprotective Effects ◽  
Ischemic Brain ◽  
Hypoxic Ischemic Brain Injury

scholarly journals Neuroprotective Effects of Resveratrol in Ischemic Brain Injury

NeuroSci ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 305-319
Author(s):  
Noelia D. Machado ◽  
Gorka Villena Armas ◽  
Mariana A. Fernández ◽  
Santiago Grijalvo ◽  
David Díaz Díaz
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
De Novo ◽  
Neuroprotective Effect ◽  
Ischemic Brain Injury ◽  
In Vivo Models ◽  
Ischemic Brain ◽  
Number Of Patients

Cerebral ischemia represents the third cause of death and the first cause of disability in adults. This process results from decreasing cerebral blood flow levels as a result of the occlusion of a major cerebral artery. This restriction in blood supply generates low levels of oxygen and glucose, which leads to a decrease in the energy metabolism of the cell, producing inflammation, and finally, neurological deterioration. Currently, blood restoration of flow is the only effective approach as a therapy in terms of ischemic stroke. However, a significant number of patients still have a poor prognosis, probably owing to the increase in the generation of reactive oxygen species (ROS) during the reperfusion of damaged tissue. Oxidative stress and inflammation can be avoided by modulating mitochondrial function and have been identified as potential targets for the treatment of cerebral ischemia. In recent years, the beneficial actions of flavonoids and polyphenols against cerebrovascular diseases have been extensively investigated. The use of resveratrol (RSV) has been shown to markedly decrease brain damage caused by ischemia in numerous studies. According to in vitro and in vivo experiments, there is growing evidence that RSV is involved in several pathways, including cAMP/AMPK/SIRT1 regulation, JAK/ERK/STAT signaling pathway modulation, TLR4 signal transduction regulation, gut/brain axis modulation, GLUT3 up-regulation inhibition, neuronal autophagy activation, and de novo SUR1 expression inhibition. In this review, we summarize the recent outcomes based on the neuroprotective effect of RSV itself and RSV-loaded nanoparticles in vitro and in vivo models focusing on such mechanisms of action as well as describing the potential therapeutic strategies in which RSV plays an active role in cases of ischemic brain injury.

scholarly journals Predicting a Potential Link to Antidepressant Effect: Neuroprotection of Zhi-zi-chi Decoction on Glutamate-induced Cytotoxicity in PC12 Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Yin Zhang ◽  
Yusha Luo ◽  
Dongqi Zhang ◽  
Bo Pang ◽  
Jun Wen ◽  
...  
Keyword(s):  
Cell Viability ◽  
Pc12 Cells ◽  
Synergistic Effects ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Antidepressant Effects

Zhi-zi-chi Decoction (ZZCD), composed of Fructus Gardeniae (Zhizi in Chinese, ZZ in brief) and Semen sojae praeparatum (Dandouchi in Chinese, DDC in brief), has been used as a drug therapy for depression for thousands of years in China. However, the antidepressant mechanism of ZZCD still remains unknown. This study was aimed at exploring antidepressant effects of ZZCD from the aspect of neuroprotection based on herb compatibility. Glutamate-treated PC12 cells and chronic unpredictable mild stress (CUMS)-induced rats were established as models of depression in vitro and in vivo respectively. Cell viability, lactate dehydrogenase (LDH), apoptosis rate, reactive oxygen species (ROS), glutathione reductase (GR) and superoxide dismutase (SOD), and the expressions of Bax, Bcl-2 and cyclic adenosine monophosphate-response element binding protein (CREB) were measured to compare neuroprotection among single herbs and the formula in vitro. Behavior tests were conducted to validate antidepressant effects of ZZCD in vivo. Results showed that the compatibility of ZZ and DDC increased cell viability and activities of GR and SOD, and decreased the levels of LDH, apoptosis cells and ROS. Besides, the expressions of Bcl-2 and CREB were up-regulated while that of Bax was down-regulated by ZZCD. Furthermore, the compatibility of ZZ and DDC reversed abnormal behaviors in CUMS-induced rats and displayed higher efficacy than any of the single herbs. This study revealed that the antidepressant effects of ZZCD were closely associated with neuroprotection and elucidated synergistic effects of the compatibility of ZZ and DDC based on it.

scholarly journals In Vivo and in Vitro Evaluation of the Anti-inflammatory Effect of Thymoquinone Toward Ischemic Brain Injury Alleviation via Nrf2/HO-1 Pathway

2020 ◽  
Author(s):  
Nashwa Amin ◽  
Xiaoxue Du ◽  
Shijia Chen ◽  
Qiannan Ren ◽  
Azhar Badry ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Brain Damage ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Chronic Dose ◽  
The Brain

Abstract Background - In recent years, considerable efforts have been devoted to exploring effective therapy for cerebral ischemia. Reactive oxygen species (ROS) mediated - inflammation plays a crucial role in ischemic brain injury. Triptolide (TP) has been widely used for ischemic therapy although administrating a chronic dose of this therapy may cause serious drawbacks and higher liver toxicity. Considering these critical side effects, here we demonstrate the employment of thymoquinone (TQ) as a new alternative drug for alleviating ischemic brain damage via suppression of inflammatory cytokines by inducing Nrf2/HO-1 under a chronic dose without toxicity. Methods- We assessed a photo-thrombosis mouse model of focal cerebral ischemia to investigate the impact of the chronic dose of TQ to alleviates ischemic brain damage, meanwhile, we used Pc12 to determine the efficiency of TQ to attenuate the OGD/R induces cell death. Results- Our in vivo and in vitro results indicate that the administration of TQ drug can sufficiently mitigate the brain damage after stroke by increasing the Nrf2/HO-1 expression and thereby modulate the cell death and inflammation resulting from cerebral ischemia. The observation based on YFP mice elucidates the role of TQ therapy in recovering the brain status after injury through increasing the dendrite spines density and the ratio of YFP reporter cells with NeuN expression. Conclusions- Our study is the first to focus on the crucial role of the Nrf2/HO-1 pathway as a promising ischemic therapy under a chronic dose of TQ by increasing proliferating protein expression, decreasing inflammation and neuronal cell death as well as controlling the autophagy process.

scholarly journals Electroacupuncture Attenuates Inflammatory Pain by Activating AMPK/autophagy and Inhibiting iNOS and IL-1β in Inflamed Tissues

2021 ◽  
Author(s):  
Hongchun Xiang ◽  
Guowei Cai ◽  
Liang Hu ◽  
Yuye Lan ◽  
Tao Weng ◽  
...  
Keyword(s):  
Inflammatory Pain ◽  
Thermal Hyperalgesia ◽  
Adenosine Monophosphate ◽  
Peripheral Tissues ◽  
Analgesic Effects ◽  
Substrate Protein ◽  
Compound C ◽  
Amp Activated Protein Kinase

Abstract BackgroundElectroacupuncture (EA) produces analgesic effects on inflammatory pain partially via activating adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in the spinal cord. However, it is unclear whether EA activates AMPK in peripheral tissues in inflammatory pain. This study was aimed at determining whether EA promotes autophagy by activating AMPK to inhibit the expression of inflammatory mediators IL-1β and iNOS in inflamed skin tissues. MethodsIn CFA-induced inflammatory pain in mice, mechanical allodynia and thermal hyperalgesia were tested 2 hours after EA treatment. The AMPK antagonist Compound C was injected intraperitoneally 30 minutes before EA treatment. The analgesic effects of AMPK activator 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) were determined and its effects on autophagy, IL-1β and iNOS expression were detected. Also, the effects of the autophagy inhibitor 3-methyladenine (3-MA) on EA analgesia and iNOS/IL-1β expression in inflamed skin tissues were examined. The phosphorylation of AMPK (Thr172) and total AMPK proteins, LC3BII/I, autophagy substrate protein p62, IL-1β and iNOS were detected using Western blotting. Co-labeling of macrophages (CD68) with IL-1β and iNOS was detected using immunofluorescence. In addition, after NR8383 macrophages were treated with CFA, the effects of AICAR and Compound C on autophagy were determined using stubRFP-sensGFP-LC3 Lentivirus..ResultsEA reduced CFA-induced inflammatory pain, activated AMPK and autophagy, and inhibited iNOS and IL-1β expression in inflamed skin tissues. AICAR also attenuated CFA-induced hyperalgesia, promoted autophagy and inhibited iNOS and IL-1β expression in vivo and in vitro. In addition, the AMPK inhibitor Compound C reversed the effect of EA on autophagy. Pretreatment with 3-MA, an inhibitor of autophagy, inhibited the effect of EA on inflammatory pain and expression of iNOS and IL-1β in inflamed skin tissues. ConclusionsEA treatment alleviated inflammatory pain by activation of AMPK, enhancing autophagy, and inhibiting iNOS and IL-1β expression in the inflamed skin tissues.

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