Gasdermin D serves as a key executioner of pyroptosis in experimental cerebral ischemia and reperfusion model both in vivo and in vitro

2019 ◽  
Vol 97 (6) ◽  
pp. 645-660 ◽  
Author(s):  
Dongping Zhang ◽  
Jinhong Qian ◽  
Peng Zhang ◽  
Haiying Li ◽  
Haitao Shen ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia And Reperfusion ◽  
Cerebral Ischemia And Reperfusion ◽  
Experimental Cerebral Ischemia

scholarly journals Simultaneous Detection of Blood Volume, Oxygenation, and Intracellular Calcium Changes during Cerebral Ischemia and Reperfusion in vivo Using Diffuse Reflectance and Fluorescence

2005 ◽  
Vol 25 (8) ◽  
pp. 1078-1092 ◽  
Author(s):  
Congwu Du ◽  
Alan P Koretsky ◽  
Igor Izrailtyan ◽  
Helene Benveniste
Keyword(s):  
Cerebral Ischemia ◽  
Intracellular Calcium ◽  
Blood Volume ◽  
Simultaneous Detection ◽  
Xenon Lamp ◽  
Ischemia And Reperfusion ◽  
Cerebral Ischemia And Reperfusion ◽  
Hemoglobin Oxygenation ◽  
Concentration Changes

We describe an approach to measure changes in intracellular calcium along with changes in blood volume and oxygenation directly from the exposed rat cortex in vivo during cerebral ischemia and reperfusion. Measurements were made using a catheter-based optical system. The endface of a Y-shaped bifurcated fiber optic bundle was mounted on the cortical surface. It delivered the light at three wavelengths of 548, 555, and 572 nm to the brain through a fast monochromator coupled to a xenon lamp, and collected the calcium-dependent fluorescence emission from Rhod2 at 589 nm (excited at 548 nm) along with the diffuse reflections at the wavelengths of 555 and 572 nm to determine the changes in blood volume and hemoglobin oxygenation. The feasibility of this approach was experimentally examined by inducing transient cerebral ischemia and reperfusion in the rat. The ischemia induced an 8.5%±1.7% fluorescence increase compared with the preischemic control values. Blood volume and tissue hemoglobin oxygenation decreased by 57.4%±12.6% and 47.3%±12.5%, respectively. All signals normalized on reperfusion. The ischemia-induced change in Rhod2-Ca2+ fluorescence was blocked using a calcium channel blocker, nimodipine, confirming that intracellular changes in calcium were responsible for the fluorescence changes. Thus, changes in cerebral hemodynamics and intracellular calcium concentration changes were measured simultaneously, facilitating future studies of the interrelationship between neuronal activation and metabolic and vascular processes in normal and diseased brain.

Abstract P801: Impact of Oxidized Phospholipids on Outcomes From Cerebral Ischemia and Reperfusion Injury

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Jin Yu ◽  
Hong Zhu ◽  
Calvin Yeang ◽  
Joseph L Witztum ◽  
Sotirios Tsimikas ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemia And Reperfusion ◽  
Oxidized Phospholipids ◽  
Ischemia And Reperfusion Injury ◽  
Cerebral Ischemia And Reperfusion ◽  
The Brain

The mechanisms leading to oxidative stress and cellular dysfunction during stroke are not well understood. To test the hypothesis that transient cerebral artery occlusion (MCAo) in mice results in the generation of oxidized phospholipids (oxPLs) that contribute to neuronal cell death and glial activation. Both in vitro and in vivo cerebral ischemia and reperfusion injury (IRI) resulted in the elevation of specific oxPLs. Neuronal cell death was determined in the presence of oxPLs and the natural oxPL E06 antibody protected the cells from the toxic effects. IRI in mice gave rise to increased immunoreactivity of oxPLs in the brain. E06 reduced inflammatory markers in the brain following IRI, including iba-1, GFAP and inflammatory cytokines. In addition, oxPLs gave rise to M1 and Mox microglial phenotypes which was reversed in the presence of E06 and elicited a more M2 phenotype. Nrf2 deficient mice show increased infarct volumes and microglia from Nrf2 -/- mice show a reduction in Mox gene expression, and E06 protects both mice and cells from the Nrf2 deficit. Cerebral IRI generates oxPLs which triggers neuronal cell loss and inflammation and inactivation of oxPLs in vivo reduces infarct volume and improves outcomes.

scholarly journals HMGB1-triggered inflammation inhibition of notoginseng leaf triterpenes against cerebral ischemia and reperfusion injury via MAPK and NF-κB signaling pathways

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 512 ◽  
Author(s):  
Xie ◽  
Zhu ◽  
Dong ◽  
Nan ◽  
Meng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuronal Loss ◽  
Ischemia And Reperfusion ◽  
Protective Effects ◽  
Ischemia And Reperfusion Injury ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia And Reperfusion

Ischemic stroke is a clinically common cerebrovascular disease whose main risks include necrosis, apoptosis and cerebral infarction, all caused by cerebral ischemia and reperfusion (I/R) injury. This process has particular significance for the treatment of stroke patients. Notoginseng leaf triterpenes (PNGL), as a valuable medicine, have been discovered to have neuroprotective effects. However, it was not confirmed that whether PNGL may possess neuroprotective effects against cerebral I/R injury. To explore the neuroprotective effects of PNGL and their underlying mechanisms, a middle cerebral artery occlusion/reperfusion (MCAO/R) model was established. In vivo results suggested that in MCAO/R model rats, PNGL pretreatment (73.0, 146, 292 mg/kg) remarkably decreased infarct volume, reduced brain water content, and improved neurological functions; moreover, PNGL (73.0, 146, 292 mg/kg) significantly alleviated blood-brain barrier (BBB) disruption and inhibited neuronal apoptosis and neuronal loss caused by cerebral I/R injury, while PNGL with a different concertation (146, 292 mg/kg) significantly reduced the concentrations of IL-6, TNF-α, IL-1 β, and HMGB1 in serums in a dose-dependent way, which indicated that inflammation inhibition could be involved in the neuroprotective effects of PNGL. The immunofluorescence and western blot analysis showed PNGL decreased HMGB1 expression, suppressed the HMGB1-triggered inflammation, and inhibited microglia activation (IBA1) in hippocampus and cortex, thus dose-dependently downregulating inflammatory cytokines including VCAM-1, MMP-9, MMP-2, and ICAM-1 concentrations in ischemic brains. Interestingly, PNGL administration (146 mg/kg) significantly downregulated the levels of p-P44/42, p-JNK1/2 and p-P38 MAPK, and also inhibited expressions of the total NF-κB and phosphorylated NF-κB in ischemic brains, which was the downstream pathway triggered by HMGB1. All of these results indicated that the protective effects of PNGL against cerebral I/R injury could be associated with inhibiting HMGB1-triggered inflammation, suppressing the activation of MAPKs and NF-κB, and thus improved cerebral I/R-induced neuropathological changes. This study may offer insight into discovering new active compounds for the treatment of ischemic stroke.

In vivo measurement of cytosolic free calcium during cerebral ischemia and reperfusion

1988 ◽  
Vol 24 (3) ◽  
pp. 420-428 ◽  
Author(s):  
Daisuke Uematsu ◽  
Joel H. Greenberg ◽  
Marchtin Reivich ◽  
Andrea Karp
Keyword(s):  
Cerebral Ischemia ◽  
Free Calcium ◽  
Ischemia And Reperfusion ◽  
Cytosolic Free Calcium ◽  
In Vivo Measurement ◽  
Cerebral Ischemia And Reperfusion

scholarly journals Barbaloin Alleviates Cerebral Ischemia and Reperfusion Injury in Rats and Inhibits Lipopolysaccharide-stimulated Inflammatory Responses in BV2 Microglial Cells

2020 ◽  
Author(s):  
Lin Wang ◽  
Lijuan Zhang
Keyword(s):  
Cerebral Ischemia ◽  
Inflammatory Responses ◽  
Infarct Volume ◽  
Microglial Cells ◽  
Ischemia And Reperfusion ◽  
Ischemia And Reperfusion Injury ◽  
Neuroprotective Effects ◽  
Protein Levels ◽  
Cerebral Ischemia And Reperfusion

Abstract Background: Barbaloin (BAR) is a bioactive anthracycline derived from the leaf exudates of aloe plants with a variety of biological and pharmacological properties. The present study was performed to investigate the neuroprotective effects of BAR against cerebral ischemia and reperfusion (I/R) injury in rats as well as the possible underlying mechanisms. Middle cerebral artery occlusion followed by reperfusion was used to induce cerebral I/R injury in rats, and BAR was administered intraperitoneally after the onset of ischemia. Results: We found that BAR remarkably improved neurological scores, reduced brain infarct volume, and inhibited neuronal apoptosis in cerebral I/R rats. Furthermore, BAR up-regulated Bcl-2 protein levels and down-regulated Bax, active caspase-3, and inducible nitric oxide synthase (iNOS) in ischemic cortex. I/R injury-induced increases in malondialdehyde content and decreases in glutathione peroxidase, glutathione, and superoxide dismutase activities were significantly attenuated by BAR administration. In vitro, BAR pretreatment inhibited the contents of proinflammatory cytokines (tumor necrosis factor-α, iNOS, and interleukin-6) and reduced protein levels of iNOS and nuclear expression of nuclear factor-κB p65 in lipopolysaccharide-stimulated BV-2 microglial cells. Conclusion: Taken together, our data suggest that BAR possesses neuroprotective effects against cerebral I/R injury through anti-oxidative, anti-apoptotic, and anti-inflammatory activities.

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