{"id":223,"date":"2020-10-02T14:51:00","date_gmt":"2020-10-02T18:51:00","guid":{"rendered":"http:\/\/site.caes.uga.edu\/tnrrl\/?page_id=223"},"modified":"2024-02-22T10:39:10","modified_gmt":"2024-02-22T15:39:10","slug":"ischemic-stroke","status":"publish","type":"page","link":"https:\/\/site.caes.uga.edu\/tnrrl\/preclinical-research\/ischemic-stroke\/","title":{"rendered":"Ischemic Stroke"},"content":{"rendered":"\n<p style=\"font-size:clamp(14px, 0.875rem + ((1vw - 3.2px) * 0.385), 17px);px\">Every year, approximately 795,000 people suffer from a stroke and more than 140,000 people die, thus making stroke the fifth leading cause of death in the United States<sup>1<\/sup>. Although hundreds of therapeutics have sought to mitigate patient morbidity and mortality, few Food and Drug Administration (FDA)-approved therapies are currently available to treat ischemic stroke patients. The limitations of these therapies have promoted the continued investigation of novel ischemic stroke therapies. <\/p>\n\n\n\n<p style=\"font-size:clamp(14px, 0.875rem + ((1vw - 3.2px) * 0.385), 17px);px\">In order to improve preclinical translation, the Stroke Therapy Academic Industry Roundtable (STAIR) and the Stem Cell Emerging Paradigm in Stroke (STEPS) consortiums strongly recommend testing in gyrencephalic, large animal models <sup>2,3<\/sup>. Consequently, the TNRR Laboratory has developed a pig ischemic stroke model with brain anatomy and pathophysiology similar to humans<sup>4<\/sup>. Our research has provided evidence that pigs and humans share the following stroke pathophysiologies:<\/p>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-28f84493 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<ul class=\"wp-block-list\">\n<li>Edema formation, hemispheric swelling, and midline shift as determined by T2Weighted (T2W, A) and T2Fluid Attenuated Inversion Recovery (T2F,<strong> <\/strong>B) images <sup>7<\/sup><\/li>\n\n\n\n<li>Lesion volumes as assessed via acute diffusion weighted imaging (DWI, C)<sup>6<\/sup><\/li>\n\n\n\n<li>Primary onset of cytotoxic edema followed by delayed vasogenic edema as assessed via apparent diffusion coefficient (ADC, D)<sup>5<\/sup><\/li>\n\n\n\n<li>Reductions in white matter integrity at acute and chronic time points as assessed by fractional anisotropy (FA, E) <sup>7,9<\/sup><\/li>\n\n\n\n<li>Cerebellar herniation<sup>8<\/sup><\/li>\n\n\n\n<li>Deteriorations in spatiotemporal and relative gait analyses including velocity, cadence, swing percent of cycle, stride length, cycle time, and mean pressure<sup>7,10<\/sup><\/li>\n<\/ul>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<figure class=\"wp-block-image size-large is-style-default\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"305\" src=\"https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/MRI-2-1024x305.jpg\" alt=\"\" class=\"wp-image-668\" srcset=\"https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/MRI-2-1024x305.jpg 1024w, https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/MRI-2-300x89.jpg 300w, https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/MRI-2-768x228.jpg 768w, https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/MRI-2.jpg 1200w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><figcaption class=\"wp-element-caption\"><em>Acute magnetic resonance assessment of our preclinical pig ischemic stroke model. <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31997796\/\">Kaiser et. al., 2020<\/a>.<\/em><\/figcaption><\/figure>\n<\/div>\n<\/div>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-28f84493 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p style=\"font-size:clamp(14px, 0.875rem + ((1vw - 3.2px) * 0.385), 17px);px\">Preservation of these pathologies is critical as they are frequently associated with poor neurological outcome, functional deficits, and premature mortality in patients<sup>11-14<\/sup>. Understanding how ischemia leads to these tissue-level changes and consequent cognitive and motor function deficits, preferably in models with comparable cerebral anatomy, is a research priority that will help advance strategies and preclinical testing of novel therapeutics for tissue repair and regeneration post-stroke. <a href=\"https:\/\/www.facebook.com\/UGACAES\/videos\/288102168768958\/\" data-type=\"link\" data-id=\"https:\/\/www.facebook.com\/UGACAES\/videos\/288102168768958\/\">Click here to watch a video on how the TNRR Laboratory is researching and treating ischemic stroke with regenerative cell therapies.<\/a><\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<figure class=\"wp-block-image aligncenter size-large is-style-default\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"318\" src=\"https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/DTI-2-1024x318.png\" alt=\"\" class=\"wp-image-557\" srcset=\"https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/DTI-2-1024x318.png 1024w, https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/DTI-2-300x93.png 300w, https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/DTI-2-768x239.png 768w, https:\/\/site.caes.uga.edu\/tnrrl\/files\/2020\/11\/DTI-2.png 1200w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><figcaption class=\"wp-element-caption\"><em>This 3D diffusion tensor imaging reveals a loss of myelinated white matter tracts following ischemic stroke. Reductions in cerebral white matter have been associated with contralateral deteriorations in patient motor function and are therefore an important therapeutic target. Image courtesy of Kelly Scheulin.<\/em><br><\/figcaption><\/figure>\n<\/div>\n<\/div>\n\n\n\n<ul class=\"wp-block-list\">\n<li><sup>1<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31992061\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31992061\/\" target=\"_blank\">Virani, S.S., et al., <em>Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association.<\/em> Circulation, 2020. <strong>141<\/strong>(9): p. e139-e596<\/a>. <\/li>\n\n\n\n<li><sup>2<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/21273569\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/21273569\/\" target=\"_blank\">Savitz, S.I., et al., <em>Stem Cell Therapy as an Emerging Paradigm for Stroke (STEPS) II.<\/em> Stroke, 2011. <strong>42<\/strong>(3): p. 825-9<\/a>.<\/li>\n\n\n\n<li><sup>3<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/12750546\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/12750546\/\" target=\"_blank\">Fisher, M. and R. Stroke Therapy Academic Industry, <em>Recommendations for advancing development of acute stroke therapies: Stroke Therapy Academic Industry Roundtable 3.<\/em> Stroke, 2003. <strong>34<\/strong>(6): p. 1539-46<\/a>.<\/li>\n\n\n\n<li><sup>4<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/24655785\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/24655785\/\" target=\"_blank\">Platt, S.R., et al., <em>Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model.<\/em> Exp Transl Stroke Med, 2014. <strong>6<\/strong>(1): p. 5<\/a>.<\/li>\n\n\n\n<li><sup>5<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32194080\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32194080\/\" target=\"_blank\">Kaiser, E.E., et al., <em>Characterization of tissue and functional deficits in a clinically translational pig model of acute ischemic stroke.<\/em> Brain Res, 2020. <strong>1736<\/strong>: p. 146778<\/a>.<\/li>\n\n\n\n<li><sup>6<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32194080\/\" target=\"_blank\">Kaiser E.E., W.F.D., <em>Large animal ischemic stroke models: replicating human stroke pathophysiology.<\/em> Neural Regen Res, 2019.<\/a><\/li>\n\n\n\n<li><sup>7<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/29650593\/\" target=\"_blank\">Webb, R.L., et al., <em>Human Neural Stem Cell Extracellular Vesicles Improve Recovery in a Porcine Model of Ischemic Stroke.<\/em> Stroke, 2018. <strong>49<\/strong>(5): p. 1248-1256.<\/a><\/li>\n\n\n\n<li><sup>8<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31811639\/\" target=\"_blank\">Spellicy S., K.E., Bowler M., Jurgielewicz B., Webb R., West F., Stice S., <em>Neural stem cell extracellular vesicles disrupt midline shift predictive outcomes in porcine ischemic stroke model.<\/em><\/a><\/li>\n\n\n\n<li><sup>9<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/28855627\/\" target=\"_blank\">Baker, E.W., et al., <em>Induced Pluripotent Stem Cell-Derived Neural Stem Cell Therapy Enhances Recovery in an Ischemic Stroke Pig Model.<\/em> Sci Rep, 2017. <strong>7<\/strong>(1): p. 10075.<\/a> <\/li>\n\n\n\n<li><sup>10<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/24286894\/\" target=\"_blank\">Duberstein, K.J., et al., <em>Gait analysis in a pre- and post-ischemic stroke biomedical pig model.<\/em> Physiol Behav, 2014. <strong>125<\/strong>: p. 8-16.<\/a><\/li>\n\n\n\n<li><sup>11<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/16941183\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/16941183\/\" target=\"_blank\">Sanak, D., et al., <em>Impact of diffusion-weighted MRI-measured initial cerebral infarction volume on clinical outcome in acute stroke patients with middle cerebral artery occlusion treated by thrombolysis.<\/em> Neuroradiology, 2006. <strong>48<\/strong>(9): p. 632-9<\/a>.<\/li>\n\n\n\n<li><sup>12<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/22807220\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/22807220\/\" target=\"_blank\">Gonzalez, R.G., <em>Clinical MRI of acute ischemic stroke.<\/em> J Magn Reson Imaging, 2012. <strong>36<\/strong>(2): p. 259-71<\/a>.<\/li>\n\n\n\n<li><sup>13<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/26322013\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/26322013\/\" target=\"_blank\">Ahmad, A.S., et al., <em>Considerations for the Optimization of Induced White Matter Injury Preclinical Models.<\/em> Front Neurol, 2015. <strong>6<\/strong>: p. 172<\/a>.<\/li>\n\n\n\n<li><sup>14<\/sup><a rel=\"noreferrer noopener\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/29201557\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/29201557\/\" target=\"_blank\">Lee, K.B., et al., <em>Brain lesions affecting gait recovery in stroke patients.<\/em> Brain Behav, 2017. <strong>7<\/strong>(11): p. e00868<\/a>.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Every year, approximately 795,000 people suffer from a stroke and more than 140,000 people die, thus making stroke the fifth leading cause of death in the United States1. Although hundreds of therapeutics have sought to mitigate patient morbidity and mortality, few Food and Drug Administration (FDA)-approved therapies are currently available to treat ischemic stroke patients. [&hellip;]<\/p>\n","protected":false},"author":722,"featured_media":0,"parent":14,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-223","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/pages\/223","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/users\/722"}],"replies":[{"embeddable":true,"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/comments?post=223"}],"version-history":[{"count":10,"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/pages\/223\/revisions"}],"predecessor-version":[{"id":1224,"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/pages\/223\/revisions\/1224"}],"up":[{"embeddable":true,"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/pages\/14"}],"wp:attachment":[{"href":"https:\/\/site.caes.uga.edu\/tnrrl\/wp-json\/wp\/v2\/media?parent=223"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}