Abstract TP56: Insight Into Human Ischemia Reperfusion Injury in Acute Stroke: A Voxel-Based MRI Analysis of Tissue Fate

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
May Nour ◽  
Fabien Scalzo ◽  
Jeffery R Alger ◽  
Sidney Starkman ◽  
Latisha K Ali ◽  
...  
Keyword(s):  
Acute Stroke ◽  
Reperfusion Injury ◽  
Mechanical Thrombectomy ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Stroke Patients ◽  
Flair Imaging ◽  
Human Stroke ◽  
Iv Tpa

Background: Reperfusion is characterized by initial restriction of blood supply followed by subsequent vascular restoration and concomitant reoxygenation of downstream tissue. In spite of mitigating initial tissue hypoxia, exacerbation of tissue injury may occur. Animal models have delineated reperfusion injury on the cellular and molecular levels, yet, no study has quantified voxel-based analyses of tissue fate due to reperfusion injury in human stroke. Methods: Evaluation included 58 stroke patients with an age range of 65±18 years, 65% of whom were woman and 35% men. All patients presented with M1 MCA occlusion and a subset received mechanical thrombectomy (38) while another received intravenous tPA followed by mechanical thrombectomy (20). Serial perfusion MRI images were obtained on presentation as well as 3-6 hours following reperfusion and processed to extract Tmax parameters. These images were co-registered serially at the voxel level with tissue fate outcomes on FLAIR and GRE 4-5 days following presentation. Reperfusion was defined by serial changes observed in Tmax voxels. The volume of reperfusion, injury, as well as tissue fate relative to initial perfusion were calculated. Results: Hemorrhage was noted on GRE in 28.9% of the patients who received thrombectomy alone and in 20% of those who received IV tPA followed by thrombectomy. In pure thrombectomy cases without later hemorrhage, average voxel-based reperfusion was 72.3% with 18% demonstrating reperfusion injury and tissue death as assessed by FLAIR imaging 4-5 days following presentation, averaging 86.2%. In patients who received IV tPA followed by mechanical thrombectomy without any subsequent hemorrhage, average voxel-based reperfusion was 66.0% with 6.2% demonstrating reperfusion injury in reperfused voxels and tissue death as assessed by FLAIR imaging 4-5 following presentation, averaging 90.3%. Conclusions: Non-hemorrhagic forms of reperfusion injury are common in acute stroke patients treated with standard therapies. Despite reperfusion and irrespective of treatment modality, substantial amounts of tissue are destined to infarct. Voxel-based analyses of serial imaging studies may provide a framework to develop therapies for reperfusion injury.

scholarly journals Inhibition of leukocyte L-selectin function with a monoclonal antibody attenuates reperfusion injury to the rabbit ear

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2322-2328 ◽  
Author(s):  
D Mihelcic ◽  
B Schleiffenbaum ◽  
TF Tedder ◽  
SR Sharar ◽  
JM Harlan ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Arterial Blood Flow ◽  
Arterial Blood ◽  
Rabbit Ear ◽  
Adhesive Interactions

Abstract The leukocyte adhesion molecule L-selectin mediates neutrophil adhesive interactions with endothelial cells and is in part responsible for neutrophil rolling. We examined the role of L-selectin in ischemia- reperfusion injury of rabbit ears using a monoclonal antibody (MoAb) directed to a functional epitope of L-selectin. Arterial blood flow to the rabbit ear was occluded for six hours with ambient temperature at 23 degrees C to 24 degrees C. Rabbits were treated at reperfusion with saline (n = 8), the L-selectin function-blocking LAM1–3 MoAb (2 mg/kg), or the nonfunction-blocking LAM1–14 MoAb (2 mg/kg). Tissue injury was determined by measuring edema and necrosis. Edema in the LAM1–3 MoAb- treated group (peak = 25 +/- 4 mL) was significantly less (P < .05) than in saline-treated (peak = 40 +/- 8 mL) and LAM1–14 MoAb-treated (peak = 41 +/- 6 mL) groups. Tissue necrosis at 7 days was not observed in the LAM1–3 MoAb-treated group, whereas significant necrosis (P < .05) was seen in the saline- (8% +/- 3% necrosis) and LAM1–14 MoAb- treated (7% +/- 3% necrosis) group. We conclude that blocking L- selectin ameliorates necrosis and edema after ischemia and reperfusion in the rabbit ear, presumably by blocking neutrophil rolling.

scholarly journals Targeting HIF-1α to Prevent Renal Ischemia-Reperfusion Injury: Does It Work?

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Kapil Sethi ◽  
Kenny Rao ◽  
Damien Bolton ◽  
Oneel Patel ◽  
Joseph Ischia
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Arterial Occlusion ◽  
Small Animal ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Metabolic Adaptation ◽  
Critical Ischemia

Partial nephrectomy (open or minimally invasive) usually requires temporary renal arterial occlusion to limit intraoperative bleeding and improve access to intrarenal structures. This is a time-critical step due to the critical ischemia period of renal tissue. Prolonged renal ischemia may lead to irreversible nephron damage in the remaining tissue and, ultimately, chronic kidney disease. This is potentiated by the incompletely understood ischemia-reperfusion injury (IRI). A key mechanism in IRI prevention appears to be the upregulation of an intracellular transcription protein, Hypoxia-Inducible Factor (HIF). HIF mediates metabolic adaptation, angiogenesis, erythropoiesis, cell growth, survival, and apoptosis. Upregulating HIF-1α via ischemic preconditioning (IPC) or drugs that simulate hypoxia (hypoxia-mimetics) has been investigated as a method to reduce IRI. While many promising chemical agents have been trialed for the prevention of IRI in small animal studies, all have failed in human trials. The aim of this review is to highlight the techniques and drugs that target HIF-1α and ameliorate IRI associated with renal ischemia. Developing a technique or drug that could reduce the risk of acute kidney injury associated with renal IRI would have an immediate worldwide impact on multisystem surgeries that would otherwise risk ischemic tissue injury.

scholarly journals Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Ozkan Onal ◽  
Fahri Yetisir ◽  
A. Ebru Salman Sarer ◽  
N. Dilara Zeybek ◽  
C. Oztug Onal ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Intestinal Injury ◽  
Control Group ◽  
Injury Score ◽  
Tissue Samples ◽  
Intestinal Ischemia Reperfusion

Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine.Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF) intraperitoneally (ip) for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR) group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD), catalase (CAT), glutathioneperoxidase (GSH-Px), malondyaldehide (MDA), and protein carbonyl (PCO) were analyzed in tissue samples. Total oxidant status (TOS), and total antioxidant capacity (TAC) were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test.Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group.Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy prevented intestine from ischemia reperfusion injury. It is thought that the therapeutic effect of ozone is associated with increase in antioxidant enzymes and protection of cells from oxidation and inflammation.

Polymorphonuclear leukocyte infiltration into gastric mucosa after ischemia-reperfusion

1994 ◽  
Vol 266 (1) ◽  
pp. G48-G54 ◽  
Author(s):  
F. J. Andrews ◽  
C. Malcontenti-Wilson ◽  
P. E. O'Brien
Keyword(s):  
Gastric Mucosa ◽  
Reperfusion Injury ◽  
Polymorphonuclear Leukocytes ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Mucosal Injury ◽  
Immunoperoxidase Staining ◽  
Immunoperoxidase Technique ◽  
Gastric Ischemia

Polymorphonuclear leukocytes (PMN) have been implicated in the pathogenesis of ischemia-reperfusion injury. The objective of this study was to investigate PMN infiltration and distribution within the gastric mucosa of rats subjected to 30 min gastric ischemia followed by reperfusion. Sections of mucosa were stained for PMN using an immunoperoxidase technique, and injury was assessed by quantitative histology. In control animals, there were 4 +/- 2 PMN/mm2 in the superficial and 9 +/- 4 PMN/mm2 in the deep mucosa. This increased significantly to 67 +/- 9 PMN/mm2 (P < 0.05) and 160 +/- 53 PMN/mm2 (P < 0.01) respectively at 15 min of reperfusion. The percentage of these PMN which were extravasated was 83 +/- 4% in the superficial mucosa and 82 +/- 4% in the deep mucosa (P < 0.001 compared with control levels of 0% in superficial and 10% in deep mucosa). Significant PMN infiltration occurred before full expression of mucosal injury and treatment of rats with anti-PMN antisera blocked reperfusion injury (treated 10.7 +/- 1.4% mucosa damaged, controls 33.5 +/- 2.4%; P < 0.001). Treatment with allopurinol (100 mg/kg) significantly reduced the number of infiltrating PMN (superficial 7 +/- 1/mm2, deep 16 +/- 2/mm2; P < 0.01) and the percentage of extravasating PMN (superficial 40 +/- 10%, deep 30 +/- 15%; P < 0.01) while also significantly reducing tissue injury (21.9 +/- 1.9% mucosa damaged, P < 0.01 compared with controls). We conclude that the immunoperoxidase staining provides a simple means of identifying PMN in histological sections. Furthermore, our results support a role for PMN in gastric ischemia-reperfusion injury.

scholarly journals The Effect of Intravenous Anesthetics on Ischemia-Reperfusion Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ahmet Eroglu
Keyword(s):  
Reperfusion Injury ◽  
Clinical Studies ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Intravenous Anesthetics ◽  
The Future ◽  
Tissue Injuries

The effects of intravenous anesthetics on ischemia-reperfusion injury (IRI) have been investigated in both animals and clinical studies. The protective effects and the dosages of the intravenous anesthetics on IRI were discussed in this paper. The prevention of the tissue injury after the IRI was demonstrated with intravenous anesthetics in some studies. In the future, the studies should be focused on the dosage of the anesthetics related to diminishing the tissue injuries. Further studies might be required in order to investigate the effects of the anesthetics on molecular levels.

scholarly journals T cell–derived interleukin (IL)-21 promotes brain injury following stroke in mice

2014 ◽  
Vol 211 (4) ◽  
pp. 595-604 ◽  
Author(s):  
Benjamin D.S. Clarkson ◽  
Changying Ling ◽  
Yejie Shi ◽  
Melissa G. Harris ◽  
Aditya Rayasam ◽  
...  
Keyword(s):  
T Cells ◽  
Brain Injury ◽  
T Cell ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Cd4 T Cells ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Intracellular Cytokine Staining

T lymphocytes are key contributors to the acute phase of cerebral ischemia reperfusion injury, but the relevant T cell–derived mediators of tissue injury remain unknown. Using a mouse model of transient focal brain ischemia, we report that IL-21 is highly up-regulated in the injured mouse brain after cerebral ischemia. IL-21–deficient mice have smaller infarcts, improved neurological function, and reduced lymphocyte accumulation in the brain within 24 h of reperfusion. Intracellular cytokine staining and adoptive transfer experiments revealed that brain-infiltrating CD4+ T cells are the predominant IL-21 source. Mice treated with decoy IL-21 receptor Fc fusion protein are protected from reperfusion injury. In postmortem human brain tissue, IL-21 localized to perivascular CD4+ T cells in the area surrounding acute stroke lesions, suggesting that IL-21–mediated brain injury may be relevant to human stroke.

scholarly journals Polyethylene Glycol Preconditioning: An Effective Strategy to Prevent Liver Ischemia Reperfusion Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Mohamed Bejaoui ◽  
Eirini Pantazi ◽  
Maria Calvo ◽  
Emma Folch-Puy ◽  
Anna Serafín ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Rat Liver ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Water Soluble ◽  
Effective Strategy ◽  
Sprague Dawley ◽  
Hepatic Ischemia

Hepatic ischemia reperfusion injury (IRI) is an inevitable clinical problem for liver surgery. Polyethylene glycols (PEGs) are water soluble nontoxic polymers that have proven their effectiveness in variousin vivoandin vitromodels of tissue injury. The present study aims to investigate whether the intravenous administration of a high molecular weight PEG of 35 kDa (PEG 35) could be an effective strategy for rat liver preconditioning against IRI. PEG 35 was intravenously administered at 2 and 10 mg/kg to male Sprague Dawley rats. Then, rats were subjected to one hour of partial ischemia (70%) followed by two hours of reperfusion. The results demonstrated that PEG 35 injected intravenously at 10 mg/kg protected efficiently rat liver against the deleterious effects of IRI. This was evidenced by the significant decrease in transaminases levels and the better preservation of mitochondrial membrane polarization. Also, PEG 35 preserved hepatocyte morphology as reflected by an increased F-actin/G-actin ratio and confocal microscopy findings. In addition, PEG 35 protective mechanisms were correlated with the activation of the prosurvival kinase Akt and the cytoprotective factor AMPK and the inhibition of apoptosis. Thus, PEG may become a suitable agent to attempt pharmacological preconditioning against hepatic IRI.

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