Protective effects of Antrodia camphorata extract against hypoxic cell injury and ischemic stroke brain damage

2020 ◽  
Author(s):  
Zwe‐Ling Kong ◽  
Ya‐Ting Hsu ◽  
Athira Johnson ◽  
Tung‐Han Tsai ◽  
Song Miao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Cell Injury ◽  
Hypoxic Cell ◽  
Protective Effects ◽  
Antrodia Camphorata

scholarly journals Parkin Protects against Oxygen-Glucose Deprivation/Reperfusion Insult by Promoting Drp1 Degradation

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Jiayu Tang ◽  
Zhiping Hu ◽  
Jieqiong Tan ◽  
Sonlin Yang ◽  
Liuwang Zeng
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Protein Level ◽  
Ischemia Reperfusion Injury ◽  
Mitochondrial Dynamics ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Ubiquitin Proteasome System ◽  
Oxygen Glucose Deprivation ◽  
Protective Effects

Ischemic stroke results in severe brain damage and remains one of the leading causes of death and disability worldwide. Effective neuroprotective therapies are needed to reduce brain damage resulting from ischemic stroke. Mitochondria are crucial for cellular energy production and homeostasis. Modulation of mitochondrial function mediates neuroprotection against ischemic brain damage. Dynamin-related protein 1 (Drp1) and parkin play a key role in regulating mitochondrial dynamics. They are potential therapeutic targets for neuroprotection in ischemic stroke. Protective effects of parkin-Drp1 pathway on mitochondria were assessed in a cellular ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a) cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. OGDR induces mitochondrial fragmentation. The expression of Drp1 protein is increased after OGDR insult, while the parkin protein level is decreased. The altered protein level of Drp1 after OGDR injury is mediated by parkin through ubiquitin proteasome system (UPS). Drp1 depletion protects against OGDR induced mitochondrial damage and apoptosis. Meanwhile, parkin overexpression protects against OGDR induced apoptosis and mitochondrial dysfunction, which is attenuated by increased expression of Drp1. Our data demonstrate that parkin protects against OGDR insult through promoting degradation of Drp1. This neuroprotective potential of parkin-Drp1 pathway against OGDR insult will pave the way for developing novel neuroprotective agents for cerebral ischemia-reperfusion related disorders.

Abstract WP315: Neuroprotective Effects of Endogenous Adropin in Experimental Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Changjun Yang ◽  
Brian D Sanz ◽  
Kelly M DeMars ◽  
Andrew A Butler ◽  
Eduardo Candelario-Jalil
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Energy Homeostasis ◽  
Infarct Volume ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Male And Female ◽  
Enos Phosphorylation

Adropin is an endogenous peptide highly expressed in the brain and is encoded by the energy homeostasis-associated gene, Enho . We recently found that treatment with synthetic adropin peptide reduces infarct volume in ischemic stroke. This protection by exogenous adropin is associated with a significant increase in endothelial nitric oxide synthase (eNOS) phosphorylation (Ser 1176 ) and reduction of blood-brain barrier (BBB) permeability. However, it is not known whether endogenous adropin modulates ischemic brain damage. We hypothesize that lack of brain adropin increases stroke damage by exacerbating neurovascular dysfunction, while overexpression of this peptide decreases ischemic brain injury. We measured infarct size and BBB damage in male and female adropin overexpressing transgenics (AdrTg), adropin knockout ( Enho -/- ), and corresponding wild-type (WT) control mice subjected to permanent middle cerebral artery occlusion (pMCAO). At 48h after stroke, infarct volume was significantly smaller in AdrTg mice of both sexes compared to WT controls, while stroke resulted in a much larger infarction in both male and female Enho -/- compared to Enho +/+ mice. Brain levels of IgG and albumin, two sensitive markers of BBB disruption, were significantly reduced in AdrTg mice compared to the WT group, while the levels of these two plasma proteins in the ischemic brain of Enho -/- mice were dramatically increased compared to Enho +/+ animals after stroke. Latex vessel casting showed no differences in cerebrovascular anatomy or the diameter of the main brain arteries between Enho -/- , AdrTg and their respective WT controls. In AdrTg mice, we found a positive correlation between brain adropin levels and eNOS phosphorylation. These data suggest that increased eNOS phosphorylation by adropin is a potential mechanism underlying its protective effects in stroke. Consistent with this hypothesis, the protective effects of adropin were completely abolished in eNOS knockout (eNOS -/- ) mice subjected to pMCAO. Taken together, our findings show for the first time that endogenous adropin is a neuroprotective peptide in ischemic stroke. Understanding adropin signaling and function could offer a novel therapeutic strategy for the treatment of ischemic brain damage.

scholarly journals Notoginseng Leaf Triterpenes Ameliorates OGD/R-Induced Neuronal Injury via SIRT1/2/3-Foxo3a-MnSOD/PGC-1α Signaling Pathways Mediated by the NAMPT-NAD Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Weijie Xie ◽  
Ting Zhu ◽  
Ping Zhou ◽  
Huibo Xu ◽  
Xiangbao Meng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Energy Metabolism ◽  
Signaling Pathways ◽  
Cell Injury ◽  
Drug Candidate ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Mitochondrial Functions

Background. Cerebral ischemic stroke (CIS) is a common cerebrovascular disease whose main risks include necrosis, apoptosis, and cerebral infarction. But few therapeutic advances and prominent drugs seem to be of value for ischemic stroke in the clinic yet. In the previous study, notoginseng leaf triterpenes (PNGL) from Panax notoginseng stem and leaf have been confirmed to have neuroprotective effects against mitochondrial damages caused by cerebral ischemia in vivo. However, the potential mechanisms of mitochondrial protection have not been fully elaborated yet. Methods. The oxygen and glucose deprivation and reperfusion (OGD/R)-induced SH-SY5Y cells were adopted to explore the neuroprotective effects and the potential mechanisms of PNGL in vitro. Cellular cytotoxicity was measured by MTT, viable mitochondrial staining, and antioxidant marker detection in vitro.Mitochondrial functions were analyzed by ATP content measurement, MMP determination, ROS, NAD, and NADH kit in vitro. And the inhibitor FK866 was adopted to verify the regulation of PNGL on the target NAMPT and its key downstream. Results. In OGD/R models, treatment with PNGL strikingly alleviated ischemia injury, obviously preserved redox balance and excessive oxidative stress, inhibited mitochondrial damage, markedly alleviated energy metabolism dysfunction, improved neuronal mitochondrial functions, obviously reduced neuronal loss and apoptosis in vitro, and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL markedly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions and OGD/R-induced SH-SY5Y cells and regulated the downstream SIRT1/2-Foxo3a and SIRT1/3-MnSOD/PGC-1α pathways. And FK866 further verified that the protective effects of PNGL might be mediated by the NAMPT in vitro. Conclusions. The mitochondrial protective effects of PNGL are, at least partly, mediated via the NAMPT-NAD+ and its downstream SIRT1/2/3-Foxo3a-MnSOD/PGC-1α signaling pathways. PNGL, as a new drug candidate, has a pivotal role in mitochondrial homeostasis and energy metabolism therapy via NAMPT against OGD-induced SH-SY5Y cell injury.

Intracellular EDEMA does not adversely affect the ability to cryopreserve intact hearts

1993 ◽  
Vol 51 ◽  
pp. 278-279
Author(s):  
CL Hastings ◽  
RD Carlton ◽  
FG Lightfoot ◽  
AF Tryka
Keyword(s):  
Cell Injury ◽  
Median Sternotomy ◽  
Left Ventricular ◽  
Ventricular Free Wall ◽  
Hypoxic Cell ◽  
Free Wall ◽  
Sprague Dawley ◽  
Left Ventricular Free Wall ◽  
Sprague Dawley Rats

The earliest ultrastructural manifestation of hypoxic cell injury is the presence of intracellular edema. Does this intracellular edema affect the ability to cryopreserve intact myocardium? To answer this guestion, a model for anoxia induced intracellular edema (IE) was designed based on clinical intraoperative myocardial preservation protocol. The aortas of 250 gm male Sprague-Dawley rats were cannulated and a retrograde flush of Plegisol at 8°C was infused over 90 sec. The hearts were excised and placed in a 28°C bath of Lactated Ringers for 1 h. The left ventricular free wall was then sliced and the myocardium was slam frozen. Control rats (C) were anesthetized, the hearts approached by median sternotomy, and the left ventricular free wall frozen in situ immediately after slicing. The slam frozen samples were obtained utilizing the DDK PS1000, which was precooled to -185°C in liguid nitrogen. The tissue was in contact with the metal mirror for a dwell time of 20 sec, and stored in liguid nitrogen until freeze dry processing (Lightfoot, 1990).

scholarly journals Development of a photochemical thrombosis investigation system to obtain a rabbit ischemic stroke model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoonhee Kim ◽  
Yoon Bum Lee ◽  
Seung Kuk Bae ◽  
Sung Suk Oh ◽  
Jong-ryul Choi
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Rabbit Model ◽  
Specific Area ◽  
Brain Atlas ◽  
Rabbit Brain ◽  
Stroke Model ◽  
Triphenyltetrazolium Chloride ◽  
Induction System

AbstractPhotochemical thrombosis is a method for the induction of ischemic stroke in the cerebral cortex. It can generate localized ischemic infarcts in the desired region; therefore, it has been actively employed in establishing an ischemic stroke animal model and in vivo assays of diagnostic and therapeutic techniques for stroke. To establish a rabbit ischemic stroke model and overcome the shortcoming of previous studies that were difficult to build a standardized photothrombotic rabbit model, we developed a photochemical thrombosis induction system that can produce consistent brain damage on a specific area. To verify the generation of photothrombotic brain damage using the system, longitudinal magnetic resonance imaging, 2,3,5-triphenyltetrazolium chloride staining, and histological staining were applied. These analytical methods have a high correlation for ischemic infarction and are appropriate for analyzing photothrombotic brain damage in the rabbit brain. The results indicated that the photothrombosis induction system has a main advantage of being accurately controlled a targeted region of photothrombosis and can produce cerebral hemisphere lesions on the target region of the rabbit brain. In conjugation with brain atlas, it can induce photochemical ischemic stroke locally in the part of the brain that is responsible for a particular brain function and the system can be used to develop animal models with degraded specific functions. Also, the photochemical thrombosis induction system and a standardized rabbit ischemic stroke model that uses this system have the potential to be used for verifications of biomedical techniques for ischemic stroke at a preclinical stage in parallel with further performance improvements.

Nitric oxide preconditioning regulates endothelial monolayer integrity via the heat shock protein 90-soluble guanylate cyclase pathway

2007 ◽  
Vol 292 (2) ◽  
pp. H893-H903 ◽  
Author(s):  
Galina N. Antonova ◽  
Connie M. Snead ◽  
Alexander S. Antonov ◽  
Christiana Dimitropoulou ◽  
Richard C. Venema ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Injury ◽  
Soluble Guanylate Cyclase ◽  
Heat Shock Protein 90 ◽  
Protective Effects ◽  
No Donor ◽  
Spermine Nonoate

Large (pathological) amounts of nitric oxide (NO) induce cell injury, whereas low (physiological) NO concentrations often ameliorate cell injury. We tested the hypotheses that pretreatment of endothelial cells with low concentrations of NO (preconditioning) would prevent injury induced by high NO concentrations. Apoptosis, induced in bovine aortic endothelial cells (BAECs) by exposing them to either 4 mM sodium nitroprusside (SNP) or 0.5 mM N-(2-aminoethyl)- N-(2-hydroxy-2-nitrosohydrazino)-1,2-ethylenediamine (spermine NONOate) for 8 h, was abolished by 24-h pretreatment with either 100 μM SNP, 10 μM spermine NONOate, or 100 μM 8-bromo-cGMP (8-Br-cGMP). Repair of BAECs following wounding, measured as the recovery rate of transendothelial electrical resistance, was delayed by 8-h exposure to 4 mM SNP, and this delay was significantly attenuated by 24-h pretreatment with 100 μM SNP. NO preconditioning produced increased association and expression of soluble guanyl cyclase (sGC) and heat shock protein 90 (HSP90). The protective effect of NO preconditioning, but not the injurious effect of 4 mM SNP, was abolished by either a sGC activity inhibitor 1H-[1,2,4]oxadiazolo-[4,3- a]quinoxalin-1-one (ODQ) or a HSP90 binding inhibitor (radicicol) and was mimicked by 8-Br-cGMP. We conclude that preconditioning with a low dose of NO donor accelerates repair and maintains endothelial integrity via a mechanism that includes the HSP90/sGC pathway. HSP90/sGC may thus play a role in the protective effects of NO-generating drugs from injurious stimuli.

Protective effects of agrimonolide on hypoxia‐induced H9c2 cell injury by maintaining mitochondrial homeostasis

2021 ◽  
Author(s):  
Cheng Wang ◽  
Changxi Qi ◽  
Mingchao Liu ◽  
Lumei Wang ◽  
Guodong Cheng ◽  
...  
Keyword(s):  
Cell Injury ◽  
H9c2 Cell ◽  
Protective Effects ◽  
Mitochondrial Homeostasis
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