Abstract 122: Selective Intra-Arterial Cooling (SI-AC) Improve Recovery in a Nonhuman Primate Model of Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Di Wu ◽  
Longfei Wu ◽  
Jian Chen ◽  
Yuchuan Ding ◽  
Xunming Ji
Keyword(s):  
Ischemic Stroke ◽  
Diffusion Tensor ◽  
Ischemia Reperfusion ◽  
Brain Network ◽  
Adjunctive Treatment ◽  
Large Animal Model ◽  
Large Animal ◽  
Primate Model ◽  
Stroke Models ◽  
Observation Period

Background and Purpose: Recent findings from our group prove that selective intra-arterial cooling (SI-AC) treatment leads to prominent and persistent functional improvements after stroke in both rodents and non-human primate (NHPs) stroke models. In this study, neuro-protective potentials of SI-AC treatment were further explored at brain network and histopathological levels in preclinical higher-order brains. Methods: Cerebral ischemia/reperfusion was induced by thrombus and thrombolysis (t-PA) in adult rhesus monkeys (n=10). SI-AC treatment was randomly given to 5 models. Conventional MRI and diffusion tensor imaging scans were performed 4 h, 7 and 30 days post focal ischemia. Effects on functional recovery were also assessed through longitudinal neurologic scores and behavior tests. Animals were euthanized after the final scan for histological analysis. Results: SI-AC treatment led to a higher rate of infarct reversal, significantly mitigated neurologic deficits, and more preserved dexterity when compared with those only receiving t-PA during a 30-day observation period. More fiber numbers, a higher FA values based on DTI analysis, and a higher integrity of white matter based on immunochemistry in ipsilateral side were observed in models receiving t-PA plus SI-AC during the same observation period. Histological findings, consistent with MRI images in the infarct size and reversal, indicated that myelin damage, spheroids, and spongiosis were significantly improved in models receiving SI-AC treatment than those with t-PA alone treatment. Conclusions: Our findings further supported that SI-AC as an adjunctive treatment could significantly improve neural tissue and functional preservation in a large animal model, suggesting its potential application in ischemic stroke treatments.

Large animal canine endovascular ischemic stroke models: A review

2016 ◽  
Vol 127 ◽  
pp. 134-140 ◽  
Author(s):  
Kunakorn Atchaneeyasakul ◽  
Luis Guada ◽  
Kevin Ramdas ◽  
Mitsuyoshi Watanabe ◽  
Pallab Bhattacharya ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Large Animal ◽  
Stroke Models

Abstract TP107: Midline Shift Predicts Functional Outcomes in Porcine Ischemic Stroke Model

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Samantha Spellicy ◽  
Erin Kaiser ◽  
Michael Bowler ◽  
Brian Jurgielewicz ◽  
Robin Webb ◽  
...  
Keyword(s):  
Animal Model ◽  
Ischemic Stroke ◽  
Functional Outcomes ◽  
Randomized Study ◽  
Large Animal Model ◽  
Control Group ◽  
Large Animal ◽  
Midline Shift ◽  
Post Stroke ◽  
Significant Difference

In this study, we sought to identify acute MRI parameters which are predictive of long-term functional outcomes as well as assess the effects of a neural stem cell extracellular vesicle (NSC EV) therapeutic in a large animal model of ischemic stroke. In this randomized study, stroke was induced through a permanent right-sided middle cerebral artery occlusion (MCAO) on 16 male landrace pigs, which were divided into either treatment or control group. NSC EVs or PBS was administered at 2, 14, and 24 hours, and MRI was conducted at day 1 and 84 post-stroke. Data on 65 gait and 25 behavior parameters were collected pre-stroke and at multiple timepoints over 84 days following MCAO. Of all 15 measured MRI parameters, axial and coronal midline shift (MLS), at day 1 post stroke, had the highest total number of significant correlations (52 parameters at p<0.05) to acute and chronic functional measurements in control animals such as step time in the left front limb (p=0.0322) and cycle time in the right hind limb (p=0.0011) respectively. This suggests MLS is the best overall predictor of specific functional deficits at both acute and chronic timepoints, which to our knowledge has never been shown in an animal model. Additionally, the parameters found to be correlated to MLS in control animals were not correlated in NSC EV-treated animals, suggesting NSC EV treatment disrupts this natural correlation between degree of MLS and functional outcomes. NSC EVs and control pigs were binned into either high or low MLS groups and their survival and recovery was assessed by the modified Rankin Scale (mRS). While there was a significant difference in mRS scores of control animals with high and low MLS at day 6 post-MCAO (p=0.0008), there was not in NSC EV-treated animals (p=0.6754). Further, there was a significant difference in survival of control animals with high and low axial MLS (p=0.0401), but not in the NSC EV group (p=0.4142). Additionally, mRNA expression of GFAP was significantly correlated with increasing MLS in non-treated but not NSC EV-treated animals. These findings show although NSC EV treatment does not significantly alter the degree of MLS 1-day post-MCAO, it does alter gene expression, increase survival, and improve functional recovery following large MLS alterations.

scholarly journals Cardiac Function in a Long-Term Follow-Up Study of Moderate and Severe Porcine Model of Chronic Myocardial Infarction

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Renate de Jong ◽  
Gerardus P. J. van Hout ◽  
Jaco H. Houtgraaf ◽  
S. Takashima ◽  
Gerard Pasterkamp ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Ischemia Reperfusion ◽  
Time Frame ◽  
Large Animal Model ◽  
Large Animal ◽  
Loop Analysis ◽  
Circumflex Artery ◽  
Left Circumflex Artery ◽  
2D Echocardiography

Background. Novel therapies need to be evaluated in a relevant large animal model that mimics the clinical course and treatment in a reasonable time frame. To reliably assess therapeutic efficacy, knowledge regarding the translational model and the course of disease is needed.Methods. Landrace pigs were subjected to a transient occlusion of the proximal left circumflex artery (LCx)(n=6)or mid-left anterior descending artery (LAD)(n=6)for 150 min. Cardiac function was evaluated before by 2D echocardiography or 3D echocardiography and pressure-volume loop analysis. At 12 weeks of follow-up the heart was excised for histological analysis and infarct size calculations.Results. Directly following AMI, LVEF was severely reduced compared to baseline in the LAD group-17.1±1.6%, P=0.009compared to only a moderate reduction in the LCx group-5.9±1.5%, P=0.02and this effect remained unchanged during 12 weeks of follow-up.Conclusion. Two models of chronic MI, representative for different patient groups, can reproducibly be created through clinically relevant ischemia-reperfusion of the mid-LAD and proximal LCx.

scholarly journals Adenosine A2a Receptor Stimulation Attenuates Ischemia-Reperfusion Injury and Improves Survival in A Porcine Model of DCD Liver Transplantation

2020 ◽  
Vol 21 (18) ◽  
pp. 6747
Author(s):  
Zoltan Czigany ◽  
Eve Christiana Craigie ◽  
Georg Lurje ◽  
Shaowei Song ◽  
Kei Yonezawa ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Adenosine A2a Receptor ◽  
Large Animal Model ◽  
Large Animal ◽  
Receptor Stimulation ◽  
A2a Receptor ◽  
Htk Solution ◽  
Adenosine A2a

Orthotopic liver transplantation (OLT) using allografts from donation after circulatory death (DCD) is potentially associated with compromised clinical outcomes due to ischemia-reperfusion injury (IRI)-induced organ damage and graft-related complications. The aim of this study was to provide in vivo data on the effects of adenosine A2a receptor stimulation in a clinically relevant large animal model of DCD liver transplantation. Cardiac arrest was induced in German Landrace pigs (n = 10; 20–25 kg). After 30 min of warm ischemia, the donor liver was retrieved following a cold flush with 3 L of histidine-tryptophan-ketoglutarate-HTK solution. Animals of the treatment group (n = 5/group) received a standard dose of the selective adenosine receptor agonist CGS 21680 added to the cold flush. All grafts were stored for 4.5 h at 4 °C in HTK-solution before OLT. Hepatocellular injury, apoptosis, protein kinase A-PKA activity, graft microcirculation, liver function, and animal survival were assessed. Compared to untreated livers, adenosine A2a receptor stimulation resulted in improved tissue microcirculation (103% ± 5% vs. 38% ± 4% compared to baseline; p < 0.05), accelerated functional recovery of the graft (indocyanine green-plasma disappearance rate (ICG-PDR) of 75% ± 18% vs. 40% ± 30% after 3 h), increased PKA activity ratio (56% ± 3% vs. 32% ± 3%; p < 0.001 after 1 h), and consequently reduced tissue necrosis and apoptosis. The potent protective effects were clinically manifested in significantly improved survival in the treatment group after 72 h (100% vs. 40%; p = 0.04). The ex vivo administration of adenosine A2a receptor agonist during the back-table flush mitigates IRI-mediated tissue damage and improves functional graft recovery and survival in a large animal model of DCD liver transplantation.

Hypoxemic Versus Normoxemic Reperfusion in a Large Animal Model of Severe Ischemia-Reperfusion Injury

2011 ◽  
Vol 166 (2) ◽  
pp. 194-198 ◽  
Author(s):  
Ryan K. Lehmann ◽  
Lionel R. Brounts ◽  
Kelly E. Lesperance ◽  
Matthew J. Eckert ◽  
Richard N. Lesperance ◽  
...  
Keyword(s):  
Animal Model ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Large Animal Model ◽  
Large Animal ◽  
Severe Ischemia

Inhibition of p38 reduces myocardial infarction injury in the mouse but not pig after ischemia-reperfusion

2005 ◽  
Vol 289 (6) ◽  
pp. H2747-H2751 ◽  
Author(s):  
Robert A. Kaiser ◽  
Jefferson M. Lyons ◽  
Jodie Y. Duffy ◽  
Connie J. Wagner ◽  
Kelly M. McLean ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Small Animal ◽  
Large Animal Model ◽  
Large Animal ◽  
Cellular Injury ◽  
P38 Inhibitor ◽  
Causative Effect ◽  
Sb 239063 ◽  
Potential Regulatory Role

The MAPK family member p38 is activated in the heart after ischemia-reperfusion (I/R) injury. However, the cardioprotective vs. proapoptotic effects associated with p38 activation in the heart after I/R injury remain unresolved. Another issue to consider is that the majority of past studies have employed the rodent as a model for assessing p38's role in cardiac injury vs. protection, while the potential regulatory role in a large animal model is even more uncertain. Here we performed a parallel study in the mouse and pig to directly compare the extent of cardiac injury after I/R at baseline or with the selective p38 inhibitor SB-239063. Infusion of SB-239063 5 min before ischemia in the mouse prevented ischemia-induced p38 activation, resulting in a 25% reduction of infarct size compared with vehicle-treated animals (27.9 ± 2.9% vs. 37.5 ± 2.7%). In the pig, SB-239063 similarly inhibited myocardial p38 activation, but there was no corresponding effect on the degree of infarction injury (43.6 ± 4.0% vs. 41.4 ± 4.3%). These data suggest a difference in myocardial responsiveness to I/R between the small animal mouse model and the large animal pig model, such that p38 activation in the mouse contributes to acute cellular injury and death, while the same activation in pig has no causative effect on these parameters.

scholarly journals Protective role of selectin ligand inhibition in a large animal model of kidney ischemia–reperfusion injury

2006 ◽  
Vol 69 (10) ◽  
pp. 1749-1755 ◽  
Author(s):  
C. Jayle ◽  
S. Milinkevitch ◽  
F. Favreau ◽  
C. Doucet ◽  
J.P. Richer ◽  
...  
Keyword(s):  
Animal Model ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Large Animal Model ◽  
Large Animal ◽  
Selectin Ligand ◽  
Kidney Ischemia
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