scholarly journals Attenuation of p53 Expression Protects against Focal Ischemic Damage in Transgenic Mice

1994 ◽  
Vol 14 (6) ◽  
pp. 887-891 ◽  
Author(s):  
R. Christian Crumrine ◽  
Amy L. Thomas ◽  
Philip F. Morgan
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Infarct Size ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Control Group ◽  
Ischemic Damage ◽  
Wild Type ◽  
P53 Expression ◽  
Wild Type Control

Apoptosis or programmed cell death may be involved in neuronal death in the cerebral cortex after a permanent focal ischemic insult. Studies indicate that protein p53 is a major determinant of the cellular mechanism that leads to programmed cell death. Wild-type C57 mice and two groups of transgenic C57 mice, one homozygous and the other heterozygous for a p53 null gene, were subjected to middle cerebral artery occlusion. As expected, the wild-type mice had a large, consistent infarct volume (22.11 ± 4.59 mm3; n = 10). Both transgenic groups had significantly less ischemic damage than the wild-type control group. However, unexpectedly, the heterozygous group had the least amount of ischemic damage (16.12 ± 1.71 mm3, n = 11; 27% reduction in infarct size). The ischemic damage in the homozygous group (18.72 ± 3.48 mm3, n = 9) was significantly less than in the wild-type control (15% reduction in infarct size) but significantly more than in the heterozygous group. Thus, although the absence of p53 expression was protective, grater protection was afforded by reduced expression of p53. These data suggest that attenuated p53 expression may be protective after an ischemic event.

Abstract W MP81: Excess Salt Increases Infarct Size Produced by Photothrombotic Middle Cerebral Artery Occlusion Without Increasing Blood Pressure in Spontaneously Hypertensive Rats

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Hiroshi Yao ◽  
Toru Nabika
Keyword(s):  
Infarct Size ◽  
Brain Tissue ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Control Group ◽  
Salt Loading ◽  
Ischemic Brain ◽  
Spontaneously Hypertensive ◽  
Ischemic Brain Tissue ◽  
Cerebral Artery Occlusion

Background and Purpose: Cerebral circulation is known to be vulnerable to excess salt (e.g., impaired vasodilation, increased oxidative stress, accelerated spontaneous stroke, and enhanced blood-brain barrier [BBB] disruption). To our knowledge, however, no study has investigated the effects of excess salt on focal ischemic injury. Methods: After 14 days of salt loading or water, spontaneously hypertensive rats (SHR, Izumo strain, n=43) or normotensive Wistar-Kyoto rats (WKY, n=11) were subjected to photothrombotic middle cerebral artery occlusion (MCAO), and infarct volume was determined at 48 h after MCAO. Brain albumin and hemoglobin contents, as indices of BBB disruption, were determined with SELDI-TOF-MS in ischemic brain tissue. Effects of excess salt on the lower limits of cerebral blood flow (CBF) autoregulation were also determined. Results: Two-way analysis of variance confirmed a significant effect of saline on the volumes of drinking in SHR (p=0.000). Resting mean arterial blood pressure (BP) in SHR was 137±15 (S.D.) mmHg and 141±7 mmHg in the salt loading and control groups, respectively. After MCAO, regional CBF, determined with two ways of laser-Doppler flowmetry (one-point measurement or manual scanning), was more steeply decreased in the salt-loaded group than in the control group. In SHR, infarct volume in the salt-loaded group was 112±27 mm3, which was significantly larger than 77±12 mm3 in the control group (p=0.002), while albumin and hemoglobin levels in discrete brain regions were not different between the groups. In WKY, salt loading did not significantly increase infarct size. CBF response to hemorrhagic hypotension (i.e., autoregulation) was not affected by excess salt. Conclusions: We demonstrated that excess salt increased infarct size produced by photothrombotic MCAO without increasing BP in SHR but not in WKY. Excess salt did not deteriorate both vasogenic edema and hemorrhagic transformation of ischemic brain tissue after MCAO. The detrimental effects of excess salt were considered to be the result of compromised CBF in the ischemic brain tissue supplied by collateral circulation. A future study will investigate the mechanisms underlying the salt sensitivity to focal brain ischemia independent of BP changes.

scholarly journals Hyperglycaemia and Infarct Size in Animal Models of Middle Cerebral Artery Occlusion: Systematic Review and Meta-Analysis

2010 ◽  
Vol 31 (3) ◽  
pp. 807-818 ◽  
Author(s):  
Niall J J MacDougall ◽  
Keith W Muir
Keyword(s):  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Type I Diabetes ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Control Group ◽  
Type I ◽  
Cerebral Artery Occlusion

Poststroke hyperglycaemia (PSH) is common, has an unclear pathophysiology, and is associated with poor outcomes. Animal studies report conflicting findings. We systematically reviewed the effects of hyperglycaemia on infarct volume in middle cerebral artery occlusion (MCAO) models, generating weighted mean differences between groups using random effects models summarised as effect size (normalised to control group infarct volume as 100%) and 95% confidence interval. Of 72 relevant papers, 23 reported infarct volume. Studies involved 664 animals and 35 distinct comparisons. Hyperglycaemia was induced by either streptozotocin (STZ, 17 comparisons, n=303) or dextrose (18 comparisons, n=356). Hyperglycaemic animals had infarcts that were 94% larger, but STZ was associated with significantly greater increase in infarct volumes than dextrose infusion (140% larger versus 48% larger). In seven studies, insulin did not significantly reduce infarct size and results were heterogeneous. Although hyperglycaemia exacerbates infarct volume in MCAO models, studies are heterogeneous, and do not address the common clinical problem of PSH because they have used either the STZ model of type I diabetes or extremely high glucose loads. Insulin had a nonsignificant and significantly heterogeneous effect. Further studies with relevant models may inform clinical trial design.

scholarly journals Remote and Anesthetic-Induced Myocardial Preconditioning Is Preserved in Atherosclerotic LDL Receptor-/- Mice In Vivo

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Walter Petermichl ◽  
Kathrin Eglmeier ◽  
Henriette Hesse ◽  
Michael Gruber ◽  
Bernhard Graf ◽  
...  
Keyword(s):  
Infarct Size ◽  
Histopathological Examination ◽  
Ldl Receptor ◽  
Atherogenic Diet ◽  
Control Group ◽  
Myocardial Infarct Size ◽  
Ischemic Damage ◽  
Wild Type ◽  
High Fat

Introduction. In the animal model, preconditioning is a powerful weapon against ischemic damage. The reason why the human heart cannot be protected from ischemic damage by preconditioning remains unclear. There are assumptions that the lack of preconditioning in humans is caused by concomitant diseases such as dyslipoproteinemia and arteriosclerosis. This study investigates whether dyslipoproteinemia and the resulting arteriosclerosis can be a cause of a reduced precondition effect of heart in mice. Methods. LDL receptor-deficient mice were fed a long-term (14-16 weeks) high-fat atherogenic diet to induce arteriosclerosis. Arteriosclerosis was identified by histological examination and vessel contraction tests. LDLR-/- and wild-type mice were randomly assigned to anesthetic-induced, remote ischemic, or no preconditioning. All mice were subjected to 45 minutes of coronary artery occlusion and 180 minutes of reperfusion. The area at risk and infarct size were determined by Evans Blue and triphenyltetrazolium chloride staining. Results. Histopathological examination showed atherosclerosis in high-fat atherogenic fed LDLR-/- mice, and the vessel relaxation capacity was significantly reduced compared to wild-type mice. In the wild type, as expected, infarct size was significantly reduced by preconditioning compared to the control. In LDLR-/- mice, infarct size was significantly reduced by preconditioning compared to the control. Surprisingly, the LDLR-/- control group also had a significantly reduced infarct size compared to the wild-type control group. Conclusion. We were able to demonstrate that a high-fat diet morphologically and functionally triggered atherosclerosis in LDLR-/- mice. Interestingly, LDLR-/- mice with an atherogenic diet had smaller infarct sizes compared to wild-type mice. Moreover, preconditioning additionally reduced myocardial infarct size in LDLR-/- mice. A long-term high-fat atherogenic diet and preconditioning seem to result in additive cardioprotection in LDLR-/- mice.

scholarly journals Neuroprotective mechanisms of erythropoietin in a rat stroke model

2020 ◽  
Vol 11 (1) ◽  
pp. 48-59
Author(s):  
Martin Juenemann ◽  
Tobias Braun ◽  
Nadine Schleicher ◽  
Mesut Yeniguen ◽  
Patrick Schramm ◽  
...  
Keyword(s):  
Blood Flow ◽  
Infarct Size ◽  
Cerebral Edema ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Lesion Volume ◽  
Ischemic Lesion ◽  
Human Erythropoietin ◽  
Male Wistar Rats ◽  
Cerebral Artery Occlusion

AbstractObjectiveThis study was designed to investigate the indirect neuroprotective properties of recombinant human erythropoietin (rhEPO) pretreatment in a rat model of transient middle cerebral artery occlusion (MCAO).MethodsOne hundred and ten male Wistar rats were randomly assigned to four groups receiving either 5,000 IU/kg rhEPO intravenously or saline 15 minutes prior to MCAO and bilateral craniectomy or sham craniectomy. Bilateral craniectomy aimed at elimination of the space-consuming effect of postischemic edema. Diagnostic workup included neurological examination, assessment of infarct size and cerebral edema by magnetic resonance imaging, wet–dry technique, and quantification of hemispheric and local cerebral blood flow (CBF) by flat-panel volumetric computed tomography.ResultsIn the absence of craniectomy, EPO pretreatment led to a significant reduction in infarct volume (34.83 ± 9.84% vs. 25.28 ± 7.03%; p = 0.022) and midline shift (0.114 ± 0.023 cm vs. 0.083 ± 0.027 cm; p = 0.013). We observed a significant increase in regional CBF in cortical areas of the ischemic infarct (72.29 ± 24.00% vs. 105.53 ± 33.10%; p = 0.043) but not the whole hemispheres. Infarct size-independent parameters could not demonstrate a statistically significant reduction in cerebral edema with EPO treatment.ConclusionsSingle-dose pretreatment with rhEPO 5,000 IU/kg significantly reduces ischemic lesion volume and increases local CBF in penumbral areas of ischemia 24 h after transient MCAO in rats. Data suggest indirect neuroprotection from edema and the resultant pressure-reducing and blood flow-increasing effects mediated by EPO.

Proteome and metabolome profiling of wild-type and YCA1 -knock-out yeast cells during acetic acid-induced programmed cell death

2015 ◽  
Vol 128 ◽  
pp. 173-188 ◽  
Author(s):  
Valentina Longo ◽  
Maša Ždralević ◽  
Nicoletta Guaragnella ◽  
Sergio Giannattasio ◽  
Lello Zolla ◽  
...  
Keyword(s):  
Cell Death ◽  
Acetic Acid ◽  
Programmed Cell Death ◽  
Yeast Cells ◽  
Wild Type ◽  
Knock Out ◽  
Metabolome Profiling

scholarly journals Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta-analysis

BMJ ◽  
2018 ◽  
pp. k3529 ◽  
Author(s):  
Xian Shen ◽  
Bin Zhao
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Control Group ◽  
Controlled Trials ◽  
Clinical Benefits ◽  
American Society ◽  
Randomised Controlled ◽  
Expression Status

Abstract Objective To evaluate the relative efficacy of programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors versus conventional drugs in patients with cancer that were PD-L1 positive and PD-L1 negative. Design Meta-analysis of randomised controlled trials. Data sources PubMed, Embase, Cochrane database, and conference abstracts presented at the American Society of Clinical Oncology and European Society of Medical Oncology up to March 2018. Review methods Studies of PD-1 or PD-L1 inhibitors (avelumab, atezolizumab, durvalumab, nivolumab, and pembrolizumab) that had available hazard ratios for death based on PD-L1 positivity or negativity were included. The threshold for PD-L1 positivity or negativity was that PD-L1 stained cell accounted for 1% of tumour cells, or tumour and immune cells, assayed by immunohistochemistry staining methods. Results 4174 patients with advanced or metastatic cancers from eight randomised controlled trials were included in this study. Compared with conventional agents, PD-1 or PD-L1 inhibitors were associated with significantly prolonged overall survival in both patients that were PD-L1 positive (n=2254, hazard ratio 0.66, 95% confidence interval 0.59 to 0.74) and PD-L1 negative (1920, 0.80, 0.71 to 0.90). However, the efficacies of PD-1 or PD-L1 blockade treatment in patients that were PD-L1 positive and PD-L1 negative were significantly different (P=0.02 for interaction). Additionally, in both patients that were PD-L1 positive and PD-L1 negative, the long term clinical benefits from PD-1 or PD-L1 blockade were observed consistently across interventional agent, cancer histotype, method of randomisation stratification, type of immunohistochemical scoring system, drug target, type of control group, and median follow-up time. Conclusions PD-1 or PD-L1 blockade therapy is a preferable treatment option over conventional therapy for both patients that are PD-L1 positive and PD-L1 negative. This finding suggests that PD-L1 expression status alone is insufficient in determining which patients should be offered PD-1 or PD-L1 blockade therapy.

Abstract T P237: Effect of Danger Associated Molecular Pattern Receptor Complex Proteins CD24 and Siglec-G on Stroke Outcome and Microglial Responses

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Jonathan R Weinstein ◽  
Josiah Hanson ◽  
Lauren Hood ◽  
Diana Chao ◽  
Sean P Murphy ◽  
...  
Keyword(s):  
Infarct Volume ◽  
High Mobility ◽  
Artery Occlusion ◽  
Receptor Complex ◽  
Wild Type ◽  
Vessel Occlusion ◽  
Doppler Flowmetry ◽  
Cytokines And Chemokines ◽  
Molecular Pattern

Background: Both microglia and Toll-like receptors (TLRs) are critical in stroke pathophysiology. In ischemic brain, microglia sense endogenous TLR agonists (danger associated molecular patterns or DAMPs) and respond with varied immune reactions. CD24 and Siglec-G form a receptor complex that modulates TLR4 function and controls responses to DAMPs. The role of CD24 and Siglec-G in stroke is unknown. Methods: We performed 45 min middle cerebral artery occlusion (MCAO) on 12 - 14 week old wild-type, TLR4-/-, CD24-/- and Siglec-G-/- male mice and assessed total and regional adjusted infarct volumes at 48 hours with 2,3,5-triphenyltetrazolium staining. Number of mice per group was determined by power analysis. Cerebral blood flow was assessed with laser doppler flowmetry. In vitro, we examined the effects of endogenous TLR4 agonists heat shock protein-70 and high mobility group box 1 on cytokine (TNFα, IL-6) and chemokine (CXCL10, CCL5) release from microglia derived from wild-type, TLR4-/-, CD24-/- and Siglec-G-/- mice. Results: Following exclusions for weight, temperature and sub-optimal vessel occlusion/reperfusion, total infarct volumes (mean±SEM) were 51±8 mm3 (n = 21), 51±10 mm3 (n = 8), 28±8 mm3 (n = 13) and 54±8 mm3 (n = 19) in wild-type, TLR4-/-, CD24-/- and Siglec-G-/- mice, respectively (p>0.05, one-way ANOVA). Release of cytokines and chemokines was absent (as expected) in microglia from TLR4-/- mice and differentially regulated in microglia from CD24-/- and Siglec-G-/- mice. Conclusions: Genetic deficiency in TLR4, CD24 or Siglec-G modulated microglial response to endogenous TLR4 agonists but did not significantly alter post-stroke infarct volume.

Myocardial temperature in acute myocardial infarction: protection with mild regional hypothermia

1997 ◽  
Vol 273 (1) ◽  
pp. H220-H227 ◽  
Author(s):  
S. L. Hale ◽  
R. A. Kloner
Keyword(s):  
Infarct Size ◽  
Myocardial Infarct ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Control Group ◽  
Myocardial Infarct Size ◽  
Local Cooling ◽  
Risk Zone ◽  
Myocardial Temperature

This study tests the hypothesis that a 2-4 degrees C reduction in myocardial temperature, obtained by using topical regional hypothermia (TRH), reduces infarct size. Anesthetized rabbits received coronary artery occlusion and reperfusion. We cooled hearts in the TRH group by applying an ice bag directly over the risk zone; the control group received no intervention. Risk zone myocardial temperature (MT) in the TRH group was reduced at occlusion by 2 degrees C from baseline and after 5 min of occlusion by 3.6 degrees C. In the control group, MT in the risk region remained within 0.3 degree C of baseline. The ischemic area was similar in both groups, yet infarct size in the TRH group was reduced by an average of 65% compared with the control group. Infarct size closely correlated with MT in the risk region at the time of occlusion. In a second protocol in which all hearts were paced, infarct size was 21% of the risk region in TRH hearts compared with 44% in controls. These results strongly support the important role of MT in the progression of necrosis and demonstrate that the application of local cooling to the risk region profoundly reduces myocardial infarct size.

scholarly journals Comparative Effects of Verapamil, Nicardipine, and Nitroglycerin on Myocardial Ischemia/Reperfusion Injury

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Hitoshi Yui ◽  
Uno Imaizumi ◽  
Hisashi Beppu ◽  
Mitsuhiro Ito ◽  
Munetaka Furuya ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rabbit Model ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Control Group ◽  
Area At Risk ◽  
Group A

The aim of this experiment was to establish whether verapamil, nicardipine, and nitroglycerin have (1) infarct size-limiting effects and (2) antiarrhythmic effects inin vivorabbit hearts during ischemia/reperfusion. Rabbits received regional ischemia by 30 min of left anterior descending coronary artery occlusion followed by 3 hours of reperfusion under ketamine and xylazine anesthesia. The animals were randomly assigned to the following 4 treatment groups: a control group, a verapamil group, a nicardipine group, and a nitroglycerin group. A continuous infusion of verapamil, nicardipine, or nitroglycerin was initiated 5 min prior to ischemia. Infarct size/area at risk decreased in verapamil, and nitroglycerin. The incidence of ischemia-induced arrhythmia decreased in nicardipine, verapamil and nitroglycerin. The incidence of reperfusion-induced arrhythmias decreased in verapamil and nitroglycerin. From the present experimental results, verapamil and nitroglycerin rather than nicardipine did afford significant protection to the heart subjected to ischemia and reperfusion in a rabbit model.

Sign in / Sign up

Export Citation Format

Share Document