scholarly journals Degradation of TRPML1 in Neurons Reduces Neuron Survival in Transient Global Cerebral Ischemia

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yang Wang ◽  
Shao-wei Jiang ◽  
Xuan Liu ◽  
Lei Niu ◽  
Xiao-li Ge ◽  
...  
Keyword(s):  
Neuronal Damage ◽  
Infarct Volume ◽  
Global Ischemia ◽  
Neurological Dysfunction ◽  
Global Cerebral Ischemia ◽  
Primary Neurons ◽  
Ischemic Reperfusion ◽  
Transient Global Ischemia

Postcardiac arrest syndrome yields poor neurological outcomes, but the mechanisms underlying this condition remain poorly understood. Autophagy plays an important role in neuronal apoptosis induced by ischemia. However, whether autophagy is involved in neuron apoptosis induced by cardiac arrest has been less studied. This study found that TRPML1 participates in cerebral ischemic reperfusion injury. Primary neurons were isolated and treated with mucolipin synthetic agonist 1 (ML-SA1), as well as infected with the recombinant lentivirus TRPML1 overexpression vector in vitro. ML-SA1 was delivered intracerebroventricularly in transient global ischemia model. Protein expression levels were determined by western blot. Neurological deficit score and the infarct volume were analyzed for the detection of neuronal damage. We found that TRPML1 was significantly downregulated in vivo and in vitro ischemic reperfusion model. We also observed that TRPML1 overexpression or treatment with the ML-SA1 attenuated neuronal death in primary neurons and ameliorated neurological dysfunction in vivo. Our findings suggested that autophagy and apoptosis were activated after transient global ischemia. Administration of ML-SA1 before transient global ischemia ameliorated neurological dysfunction possibly through the promotion of autophagy and the inhibition of apoptosis.

1,8-cineole ameliorates ischaemic brain damage via TRPC6/CREB pathways in rats

2021 ◽  
Author(s):  
Chen Meng ◽  
Wenjing Zeng ◽  
Jing Lv ◽  
Yu Wang ◽  
Meiling Gao ◽  
...  
Keyword(s):  
Brain Damage ◽  
Transient Receptor Potential ◽  
Infarct Volume ◽  
Glucose Deprivation ◽  
Neurological Dysfunction ◽  
Male Rats ◽  
Neuroprotective Effects ◽  
Ischaemic Brain

Abstract Objectives A previous in vitro study reported that the monoterpene oxide 1,8-cineole (cineole) attenuates neuronal caused by oxygen–glucose deprivation/reoxygenation in culture. However, to date, there is no in vivo evidence showing neuroprotective effects of cineole against stroke. This study aimed to investigate whether cineole attenuates cerebral ischaemic damage in rats. Methods A rat model of middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion was applied. Male rats were treated with oral cineole (100 mg/kg) for 7 consecutive days, then subjected to MCAO surgery. Infarct volume, neurologic deficits, apoptosis and expression levels of all-spectrin breakdown products of 145 kDa (SBDP145), transient receptor potential canonical (subtype) 6 (TRPC6) and phosphorylated CREB (p-CREB) were measured in ischaemic brain tissues. Key findings Cineole treatment significantly reduced infarct volume, neurological dysfunction, neuronal apoptosis, SBDP145 formation and TRPC6 degradation and enhanced p-CREB expression in MCAO rats compared with vehicle treatment. These neuroprotective effects were markedly suppressed by pharmacological inhibition of MEK or CaMKIV signalling. Conclusions Our study provides in vivo evidence demonstrating that cineole pretreatment attenuates ischaemic stroke-induced brain damage, mainly through blocking calpain-induced TRPC6 degradation and activating CREB via MEK/CREB and CaMKIV/CREB signalling pathways.

scholarly journals Inhibition of microRNA-181 Reduces Forebrain Ischemia-Induced Neuronal Loss

2013 ◽  
Vol 33 (12) ◽  
pp. 1976-1982 ◽  
Author(s):  
Jeong-mi Moon ◽  
Lijun Xu ◽  
Rona G Giffard
Keyword(s):  
Cell Death ◽  
Neuronal Survival ◽  
Infarct Volume ◽  
Glutamate Transporter ◽  
Neuronal Loss ◽  
Male Rats ◽  
Global Cerebral Ischemia ◽  
Forebrain Ischemia

MicroRNA (miRNA), miR-181a, is enriched in the brain, and inhibition of miR-181a reduced astrocyte death in vitro and infarct volume after stroke in vivo. This study investigated the role of miR-181a in neuronal injury in vitro and hippocampal neuronal loss in vivo after forebrain ischemia. miR-181a levels were altered by transfection with mimic or antagomir. N2a cells subjected to serum deprivation and oxidative stress showed less cell death when miR-181a was reduced and increased death when miR-181a increased; protection was associated with increased Bcl-2 protein. In contrast, transfected primary neurons did not show altered levels of cell death when miR-181a levels changed. Naive male rats and rats stereotactically infused with miR-181a antagomir or control were subjected to forebrain ischemia and cornus ammonis (CA)1 neuronal survival and protein levels were assessed. Forebrain ischemia increased miR-181a expression and decreased Bcl-2 protein in the hippocampal CA1 region. miR-181a antagomir reduced miR-181a levels, reduced CA1 neuronal loss, increased Bcl-2 protein, and significantly prevented the decrease of glutamate transporter 1. Thus, miR-181a antagomir reduced evidence of astrocyte dysfunction and increased CA1 neuronal survival. miR-181a inhibition is thus a potential target in the setting of forebrain or global cerebral ischemia as well as focal ischemia.

scholarly journals Propofol Exerts Greater Neuroprotection with Disodium Edetate than without It

2007 ◽  
Vol 28 (2) ◽  
pp. 354-366 ◽  
Author(s):  
Yoshinori Kotani ◽  
Yoshimi Nakajima ◽  
Tatsuya Hasegawa ◽  
Masahiko Satoh ◽  
Hisamitsu Nagase ◽  
...  
Keyword(s):  
Neuronal Damage ◽  
Cell Damage ◽  
Infarct Volume ◽  
Zinc Homeostasis ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Causal Mechanism ◽  
Neuroprotective Effects ◽  
Disodium Edetate

The main objective of this study, on mice, was to compare the neuroprotective effects of propofol with those of propofol plus disodium edetate (propofol EDTA). We also administered propofol EDTA (0.005% (w/v) EDTA) to mice intravenously, and measured the changes in zinc concentrations occurring after permanent middle cerebral artery occlusion. In the in vivo study, propofol EDTA displayed stronger neuroprotective effects than propofol alone. Furthermore, we examined the neuroprotective effects of EDTA administered alone, and found that EDTA Na significantly reduced the infarct volume. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive cells in the ischemic penumbra was reduced more by propofol EDTA than by propofol alone. We performed in the in vitro study in five groups (aerobic, vehicle (control), propofol, EDTA, and propofol plus EDTA). Propofol and EDTA each protected PC12 cells against oxygen—glucose deprivation-induced cell damage, and the effect of propofol was increased by adding EDTA. Because the chelating action of EDTA was a potential causal mechanism, we examined the effect of propofol EDTA on intracerebral zinc homeostasis. When propofol EDTA was given intravenously 10 mins before cerebral ischemia, the zinc concentration decreased significantly in the cortical area, but not in the subcortex. In conclusion, (a) propofol provides neuroprotection against both in vivo and in vitro ischemic damage, and its effects are enhanced when EDTA is added; and (b) EDTA itself protects against ischemic neuronal damage, possibly, owing to its zinc-chelating action.

scholarly journals Systemic Administration of Mesenchymal Stem Cells Increases Neuron Survival after Global Cerebral Ischemia In Vivo (2VO)

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Luisa Perasso ◽  
Carla Emilia Cogo ◽  
Debora Giunti ◽  
Carlo Gandolfo ◽  
Piero Ruggeri ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cerebral Ischemia ◽  
Brain Damage ◽  
Focal Cerebral Ischemia ◽  
Global Ischemia ◽  
Global Cerebral Ischemia ◽  
Hippocampal Damage ◽  
Sprague Dawley ◽  
Transient Global Ischemia

Although many studies have shown that administration of stem cells after focal cerebral ischemia improves brain damage, very little data are available concerning the damage induced by global cerebral ischemia. The latter causes neuronal death in selectively vulnerable areas, including the hippocampal CA1 region. We tested the hypothesis that intravenous infusion of bone marrowderived stromal cells (mesenchimal stem cells, MSC) reduce brain damage after transient global ischemia. In adult male Sprague-Dawley rats transient global ischemia was induced using bilateral common carotid artery occlusion for 20 min in addition to controlled hypotension. Five days after, the animals were anaesthetized with urethane and the brain was fixed, sectioned and stained with hematoxylin-eosin to investigate histological damage. MSC did not fully protect against ischemic damage, as the number of viable neurons in this group was lower than in normal (sham-operated) rats. However, in MSC-treated rats the number of viable CA1 pyramidal neurons was significally higher than in rats that had been subjected to ischemia but not treated with MSC. We conclude that intravenous administration of MSC after transient global ischemia reduces hippocampal damage.

scholarly journals A Potent Protective Role of Lysophospholipids against Global Cerebral Ischemia and Glutamate Excitotoxicity in Neuronal Cultures

2002 ◽  
Vol 22 (7) ◽  
pp. 821-834 ◽  
Author(s):  
Nicolas Blondeau ◽  
Inger Lauritzen ◽  
Catherine Widmann ◽  
Michel Lazdunski ◽  
Catherine Heurteaux
Keyword(s):  
Neuroprotective Effect ◽  
Primary Cultures ◽  
Global Ischemia ◽  
Glutamate Excitotoxicity ◽  
Global Cerebral Ischemia ◽  
In Vivo Model ◽  
Neuronal Cultures

Lysophospholipids (LPLs) are important intermediates in the synthesis and degradation of membrane phospholipids. Here we show that certain LPLs, particularly lysophosphatidylcholine and lysophosphatidylinositol, prevent neuronal death both in an in vivo model of transient global ischemia and in an in vitro model of excitotoxicity using primary cultures of cerebellar granule cells exposed to high extracellular concentrations of glutamate (20–40 μmol/L). The intravenous injection of lysophosphatidylcholine or lysophosphatidylinositol at a concentration of 200 nmol/kg induced a survival of CA1 pyramidal neurons as high as approximately 95%, even when the treatment was started 30 minutes after 15-minute global ischemia. In contrast, lysophosphatidic acid induced no protection. This work also provides evidence that a pretreatment with lysophosphatidylcholine or lysophosphatidylinositol (200 nmol/kg) injected as long as 3 days before a severe 6-minute ischemia provided a potent tolerance against neurodegeneration. Neuroprotection was also observed in in vitro experiments with LPLs. Taken together, in vivo and in vitro data suggest a potential therapeutic use of LPLs as antiischemic compounds. The potential role of 2P-domain K+ channels as targets of LPLs in this potent neuroprotective effect is discussed.

scholarly journals Glycolic acid protects neurons against ischemia in vitro and in two animal models of stroke

2020 ◽  
Author(s):  
Alexandra Chovsepian ◽  
Daniel Berchtold ◽  
Katarzyna Winek ◽  
Uta Mamrak ◽  
Inés Ramírez Álvarez ◽  
...  
Keyword(s):  
Glycolic Acid ◽  
Neuronal Damage ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Global Cerebral Ischemia ◽  
C Elegans ◽  
The One

ABSTRACTStroke is the second leading cause of death and disability worldwide. Current treatments, like pharmacological thrombolysis or mechanical thrombectomy, re-open occluded arteries but do not protect against ischemia-induced damage caused before reperfusion or ischemia/reperfusion-induced neuronal damage. It has been shown that knocking out djr-1.1 and djr-1.2 or glod-4 results in a decreased tolerance to anhydrobiosis in C elegans dauer larva and that Glycolic Acid (GA) can rescue this phenotype. During the process of desiccation/rehydration, a metabolic stop/start similar to the one observed during ischemia/reperfusion occurs. In this study we tested the protective effect of GA against ischemia in three different models (oxygen-glucose deprivation in vitro and Global cerebral ischemia as well as Middle Cerebral Artery Occlusion in vivo). Our results show that GA, given during reperfusion, strongly protects against ischemia-induced neuronal death, reduces the mortality in mice with large infarcts, significantly reduces the ischemic area in the brain and improves the functional outcome. The effect of GA is stronger when the substance is applied near the damaged tissue (i.e. directly to the neurons in vitro or intra-arterially via the internal carotid artery in vivo). These results suggest that GA treatment has the potential to dramatically reduce the mortality and disability caused by stroke in patients.

Amiloride Alleviates Neurological Deficits Following Transient Global Ischemia and Engagement of Central IL-6 and TNF-α Signal

2019 ◽  
Vol 19 (8) ◽  
pp. 597-604
Author(s):  
Li Pang ◽  
Shouqin Ji ◽  
Jihong Xing
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Caspase 3 ◽  
Global Ischemia ◽  
Neurological Deficits ◽  
Global Cerebral Ischemia ◽  
Caspase 9 ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Transient Global Ischemia

Background: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine if blocking acid sensing ion channels (ASICs) using amiloride in the Central Nervous System can alleviate neurological deficits after the induction of CA and further examine the participation of PIC signal in the hippocampus for the effects of amiloride. Methods: CA was induced by asphyxia and then cardiopulmonary resuscitation was performed in rats. Western blot analysis and ELISA were used to determine the protein expression of ASIC subunit ASIC1 in the hippocampus, and the levels of PICs. As noted, it is unlikely that this procedure is clinically used although amiloride and other pharmacological agents were given into the brain in this study. Results: CA increased ASIC1 in the hippocampus of rats in comparison with control animals. This was associated with the increase in IL-1β, IL-6 and TNF-α together with Caspase-3 and Caspase-9. The administration of amiloride into the lateral ventricle attenuated the upregulation of Caspase-3/Caspase-9 and this further alleviated neurological severity score and brain edema. Inhibition of central IL-6 and TNF-α also decreased ASIC1 in the hippocampus of CA rats. Conclusion: Transient global ischemia induced by CA amplifies ASIC1a in the hippocampus likely via PIC signal. Amiloride administered into the Central Nervous System plays a neuroprotective role in the process of global ischemia. Thus, targeting ASICs (i.e., ASIC1a) is suggested for the treatment and improvement of CA-evoked global cerebral ischemia.

scholarly journals Dangguijakyak-San Protects against 1-Methyl-4-phenyl-1,2,3,6,-tetrahydropyridine-Induced Neuronal Damage via Anti-Inflammatory Action

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Deok-Sang Hwang ◽  
Hyo Geun Kim ◽  
Jun-Bock Jang ◽  
Myung Sook Oh
Keyword(s):  
Neuronal Damage ◽  
Cell Damage ◽  
Substantia Nigra Pars Compacta ◽  
Inflammatory Factors ◽  
Dopaminergic Cell ◽  
Therapeutic Implications ◽  
Anti Inflammatory ◽  
Inflammatory Action

Dangguijakyak-san (DJS), a famous traditional Korean multiherbal medicine, has been used to treat gynecological and neuro-associated disease. Recent studies demonstrated that DJS has multiple bioactivities including neuroprotection. In the present study, we were to investigate the effect of DJS and its mechanism in anin vitroandin vivomodel of Parkinson’s disease (PD). In primary mesencephalic culture system, DJS attenuated the dopaminergic cell damage induced by 1-methyl-4-phenylpyridine toxicity, and it inhibited production of inflammatory factors such as tumor necrosis factorα(TNF-α), nitric oxide (NO), and activation of microglial cells. Then, we confirmed the effect of DJS in a mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the pole test, DJS at 50 mg/kg/day for 5 days showed increase of motor activity showing shortened time to turn and locomotor activity compared with the MPTP only treated mice. In addition, DJS significantly protected nigrostriatal dopaminergic neuron from MPTP stress. Moreover, DJS showed inhibition of gliosis in the substantia nigra pars compacta. These results have therapeutic implications for DJS in the treatment of PD via anti-inflammatory effects.

scholarly journals Neuroprotection by Brazilian Green Propolis againstIn vitroandIn vivoIschemic Neuronal Damage

2005 ◽  
Vol 2 (2) ◽  
pp. 201-207 ◽  
Author(s):  
Masamitsu Shimazawa ◽  
Satomi Chikamatsu ◽  
Nobutaka Morimoto ◽  
Satoshi Mishima ◽  
Hiroichi Nagai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Brain Infarction ◽  
Folk Medicine ◽  
Neuroprotective Function ◽  
Brazilian Green Propolis

We examined whether Brazilian green propolis, a widely used folk medicine, has a neuroprotective functionin vitroand/orin vivo.In vitro, propolis significantly inhibited neurotoxicity induced in neuronally differentiated PC12 cell cultures by either 24 h hydrogen peroxide (H2O2) exposure or 48 h serum deprivation. Regarding the possible underlying mechanism, propolis protected against oxidative stress (lipid peroxidation) in mouse forebrain homogenates and scavenged free radicals [induced by diphenyl-p-picrylhydrazyl (DPPH). In micein vivo, propolis [30 or 100 mg/kg; intraperitoneally administered four times (at 2 days, 1 day and 60 min before, and at 4 h after induction of focal cerebral ischemia by permanent middle cerebral artery occlusion)] reduced brain infarction at 24 h after the occlusion. Thus, a propolis-induced inhibition of oxidative stress may be partly responsible for its neuroprotective function againstin vitrocell death andin vivofocal cerebral ischemia.

scholarly journals Nitrous Oxide Plus Isoflurane Induces Apoptosis and Increases β-Amyloid Protein Levels

2009 ◽  
Vol 111 (4) ◽  
pp. 741-752 ◽  
Author(s):  
Yu Zhen ◽  
Yuanlin Dong ◽  
Xu Wu ◽  
Zhipeng Xu ◽  
Yan Lu ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Amyloid Precursor Protein ◽  
Caspase 3 ◽  
Precursor Protein ◽  
Primary Neurons ◽  
Gamma Secretase ◽  
Protein Levels ◽  
Secretase Inhibitor

Background Some anesthetics have been suggested to induce neurotoxicity, including promotion of Alzheimer's disease neuropathogenesis. Nitrous oxide and isoflurane are common anesthetics. The authors set out to assess the effects of nitrous oxide and/or isoflurane on apoptosis and beta-amyloid (Abeta) levels in H4 human neuroglioma cells and primary neurons from naïve mice. Methods The cells or neurons were exposed to 70% nitrous oxide and/or 1% isoflurane for 6 h. The cells or neurons and conditioned media were harvested at the end of the treatment. Caspase-3 activation, apoptosis, processing of amyloid precursor protein, and Abeta levels were determined. Results Treatment with a combination of 70% nitrous oxide and 1% isoflurane for 6 h induced caspase-3 activation and apoptosis in H4 naïve cells and primary neurons from naïve mice. The 70% nitrous oxide plus 1% isoflurane, but neither alone, for 6 h induced caspase-3 activation and apoptosis, and increased levels of beta-site amyloid precursor protein-cleaving enzyme and Abeta in H4-amyloid precursor protein cells. In addition, the nitrous oxide plus isoflurane-induced Abeta generation was reduced by a broad caspase inhibitor, Z-VAD. Finally, the nitrous oxide plus isoflurane-induced caspase-3 activation was attenuated by gamma-secretase inhibitor L-685,458, but potentiated by exogenously added Abeta. Conclusion These results suggest that the common anesthetics nitrous oxide plus isoflurane may promote neurotoxicity by inducing apoptosis and increasing Abeta levels. The generated Abeta may further potentiate apoptosis to form another round of apoptosis and Abeta generation. More studies, especially the in vivo confirmation of these in vitro findings, are needed.

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