<meta charset="utf8"></head><body>tMCAO 诱导的卒中中高血糖增强的出血转化

<ol>
	<li>Patel, P., Yavagal, D., Khandelwal, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperacute+management+of+ischemic+strokes:+JACC+focus+seminar.">Hyperacute management of ischemic strokes: JACC focus seminar.</a> J Am Coll Cardiol. 75 (15), 1844-1856 (2020).</li><li>Goncalves, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thrombolytic+tPA-induced+hemorrhagic+transformation+of+ischemic+stroke+is+mediated+by+PKC&#946;+phosphorylation+of+occludin.">Thrombolytic tPA-induced hemorrhagic transformation of ischemic stroke is mediated by PKC&#946; phosphorylation of occludin.</a> Blood. 140 (4), 388-400 (2022).</li><li>Adebayo, O. D., Culpan, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnostic+accuracy+of+computed+tomography+perfusion+in+the+prediction+of+hemorrhagic+transformation+and+patient+outcome+in+acute+ischaemic+stroke:+A+systematic+review+and+meta-analysis.">Diagnostic accuracy of computed tomography perfusion in the prediction of hemorrhagic transformation and patient outcome in acute ischaemic stroke: A systematic review and meta-analysis.</a> Eur Stroke J. 5 (1), 4-16 (2020).</li><li>Fluri, F., Schuhmann, M. K., Kleinschnitz, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+ischemic+stroke+and+their+application+in+clinical+research.">Animal models of ischemic stroke and their application in clinical research.</a> Drug Des Devel Ther. 9, 3445-3454 (2015).</li><li>Knight, R. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prediction+of+impending+hemorrhagic+transformation+in+ischemic+stroke+using+magnetic+resonance+imaging+in+rats.">Prediction of impending hemorrhagic transformation in ischemic stroke using magnetic resonance imaging in rats.</a> Stroke. 29 (1), 144-151 (1998).</li><li>Orset, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Combination+treatment+with+U0126+and+rt-PA+prevents+adverse+effects+of+the+delayed+rt-PA+treatment+after+acute+ischemic+stroke.">Combination treatment with U0126 and rt-PA prevents adverse effects of the delayed rt-PA treatment after acute ischemic stroke.</a> Sci Rep. 11 (1), 11993 (2021).</li><li>Kwon, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hemorrhagic+transformation+after+large+cerebral+infarction+in+rats+pretreated+with+dabigatran+or+warfarin.">Hemorrhagic transformation after large cerebral infarction in rats pretreated with dabigatran or warfarin.</a> Stroke. 48 (10), 2865-2871 (2017).</li><li>Mi, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Correlation+of+hyperglycemia+with+mortality+after+acute+ischemic+stroke.">Correlation of hyperglycemia with mortality after acute ischemic stroke.</a> Ther Adv Neurol Disord. 11, 1756285617731686 (2018).</li><li>Seners, P., Turc, G., Oppenheim, C., Baron, J. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Incidence,+causes+and+predictors+of+neurological+deterioration+occurring+within+24+following+acute+ischaemic+stroke:+A+systematic+review+with+pathophysiological+implications.">Incidence, causes and predictors of neurological deterioration occurring within 24 following acute ischaemic stroke: A systematic review with pathophysiological implications.</a> J Neurol Neurosurg Psychiatry. 86 (1), 87-94 (2015).</li><li>Reshi, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperglycemia+in+acute+ischemic+stroke:+Is+it+time+to+re-evaluate+our+understanding.">Hyperglycemia in acute ischemic stroke: Is it time to re-evaluate our understanding.</a> Med Hypotheses. 107, 78-80 (2017).</li><li>Graham, M. L., Schuurman, H. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Validity+of+animal+models+of+type+1+diabetes,+and+strategies+to+enhance+their+utility+in+translational+research.">Validity of animal models of type 1 diabetes, and strategies to enhance their utility in translational research.</a> Eur J Pharmacol. 759, 221-230 (2015).</li><li>Rehni, A. K., Liu, A., Perez-Pinzon, M. A., Dave, K. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diabetic+aggravation+of+stroke+and+animal+models.">Diabetic aggravation of stroke and animal models.</a> Exp Neurol. 292, 63-79 (2017).</li><li>Chiang, T., Messing, R. O., Chou, W. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+model+of+middle+cerebral+artery+occlusion.">Mouse model of middle cerebral artery occlusion.</a> J Vis Exp. 48, e2761 (2011).</li><li>Ma, F., Sun, P., Zhang, X., Hamblin, M. H., Yin, K. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endothelium-targeted+deletion+of+the+miR-15a/16-1+cluster+ameliorates+blood-brain+barrier+dysfunction+in+ischemic+stroke.">Endothelium-targeted deletion of the miR-15a/16-1 cluster ameliorates blood-brain barrier dysfunction in ischemic stroke.</a> Sci Signal. 13 (621), eaay5686 (2020).</li><li>Wanson, R. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+semiautomated+method+for+measuring+brain+infarct+volume.">A semiautomated method for measuring brain infarct volume.</a> J Cereb Blood Flow Metab. 10 (2), 290-293 (1990).</li><li>Friedl&#228;nder, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reliability+of+infarct+volumetry:+Its+relevance+and+the+improvement+by+a+software-assisted+approach.">Reliability of infarct volumetry: Its relevance and the improvement by a software-assisted approach.</a> J Cereb Blood Flow Metab. 37 (8), 3015-3026 (2017).</li><li>Wang, H. L., Lai, T. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optimization+of+Evans+blue+quantitation+in+limited+rat+tissue+samples.">Optimization of Evans blue quantitation in limited rat tissue samples.</a> Sci Rep. 4, 6588 (2014).</li><li>Wang, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Association+between+red+blood+cell+distribution+width+and+hemorrhagic+transformation+in+acute+ischemic+stroke+patients.">Association between red blood cell distribution width and hemorrhagic transformation in acute ischemic stroke patients.</a> Cerebrovasc Dis. 48 (3-6), 193-199 (2019).</li><li>Zhu, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stress+hyperglycemia+and+outcome+of+non-diabetic+patients+after+acute+ischemic+stroke.">Stress hyperglycemia and outcome of non-diabetic patients after acute ischemic stroke.</a> Front Neurol. 10, 1003 (2019).</li><li>Won, S. J., Tang, X. N., Suh, S. W., Yenari, M. A., Swanson, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperglycemia+promotes+tissue+plasminogen+activator-induced+hemorrhage+by+increasing+superoxide+production.">Hyperglycemia promotes tissue plasminogen activator-induced hemorrhage by increasing superoxide production.</a> Ann Neurol. 70 (4), 583-590 (2011).</li><li>Zhang, F. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rosiglitazone+attenuates+hyperglycemia-enhanced+hemorrhagic+transformation+after+transient+focal+ischemia+in+rats.">Rosiglitazone attenuates hyperglycemia-enhanced hemorrhagic transformation after transient focal ischemia in rats.</a> Neuroscience. 250, 651-657 (2013).</li><li>Soejima, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperbaric+oxygen+preconditioning+attenuates+hyperglycemia-enhanced+hemorrhagic+transformation+after+transient+MCAO+in+rats.">Hyperbaric oxygen preconditioning attenuates hyperglycemia-enhanced hemorrhagic transformation after transient MCAO in rats.</a> Med Gas Res. 2 (1), 9 (2012).</li><li>Chen, C., Ostrowski, R. P., Zhou, C., Tang, J., Zhang, J. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Suppression+of+hypoxia-inducible+factor-1alpha+and+its+downstream+genes+reduces+acute+hyperglycemia-enhanced+hemorrhagic+transformation+in+a+rat+model+of+cerebral+ischemia.">Suppression of hypoxia-inducible factor-1alpha and its downstream genes reduces acute hyperglycemia-enhanced hemorrhagic transformation in a rat model of cerebral ischemia.</a> J Neurosci Res. 88 (9), 2046-2055 (2010).</li><li>Lin, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Docosahexaenoic+acid+attenuates+hyperglycemia-enhanced+hemorrhagic+transformation+after+transient+focal+cerebral+ischemia+in+rats.">Docosahexaenoic acid attenuates hyperglycemia-enhanced hemorrhagic transformation after transient focal cerebral ischemia in rats.</a> Neuroscience. 301, 471-479 (2015).</li><li>MacDougal, E. L., Herman, W. H., Wing, J. J., Morgenstern, L. B., Lisabeth, L. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diabetes+and+ischaemic+stroke+outcome.">Diabetes and ischaemic stroke outcome.</a> Diabet Med. 35 (9), 1249-1257 (2018).</li><li>Yang, C., Hawkins, K. E., Dor&#233;, S., Candelario-Jalil, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuroinflammatory+mechanisms+of+blood-brain+barrier+damage+in+ischemic+stroke.">Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke.</a> Am J Physiol Cell Physiol. 316 (2), C135-C153 (2019).</li><li>Natarajan, R., Northrop, N., Yamamoto, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fluorescein+isothiocyanate+(FITC)-dextran+extravasation+as+a+measure+of+blood-brain+barrier+permeability.">Fluorescein isothiocyanate (FITC)-dextran extravasation as a measure of blood-brain barrier permeability.</a> Curr Protoc Neurosci. 79, 9.58.1-9.58.15 (2017).</li><li>Ahishali, B., Kaya, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+blood-brain+barrier+integrity+using+vascular+permeability+markers:+Evans+Blue,+Sodium+Fluorescein,+Albumin-Alexa+Fluor+conjugates,+and+Horseradish+Peroxidase.">Evaluation of blood-brain barrier integrity using vascular permeability markers: Evans Blue, Sodium Fluorescein, Albumin-Alexa Fluor conjugates, and Horseradish Peroxidase.</a> Methods Mol Biol. 2367, 87-103 (2021).</li><li>Kov&#225;cs, K. B., Bencs, V., Hud&#225;k, L., Ol&#225;h, L., Csiba, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hemorrhagic+transformation+of+ischemic+strokes.">Hemorrhagic transformation of ischemic strokes.</a> Int J Mol Sci. 24 (18), 14067 (2023).</li></ol>

<a href="https://appjove.unicartagenaproxy.elogim.com/t/6615">This corrects</a> the article <a href="https://dx.doi.org/10.3791/67371">10.3791/67371</a>

An erratum was issued for:&#160;<a href="https://jove.unicartagenaproxy.elogim.com/t/67371">A Mouse Model of Hemorrhagic Transformation Induced by Acute Hyperglycemia Combined with Transient Focal Ischemia</a>. The Protocol section was updated.

Erratum: A Mouse Model of Hemorrhagic Transformation Induced by Acute Hyperglycemia Combined with Transient Focal Ischemia

<table><tbody><tr><td>2,3,5-Triphenyltetrazolium Chloride (TTC)</td><td>Sigma-Aldrich</td><td>108380</td><td>The dye for TTC staining</td></tr><tr><td>24-well culture plate</td><td>Corning Incorporated</td><td>CLS3527</td><td>The vessel for TTC staining</td></tr><tr><td>30% glucose injection</td><td>Kelun Pharmaceutical</td><td>H42021188</td><td>Acute hyperglycemia induction</td></tr><tr><td>4% paraformaldehyde</td><td>Wuhan Servicebio Technology&lt;br/&gt; Co., Ltd.</td><td>G1101</td><td>Tissue fixation</td></tr><tr><td>5.0 Polyglycolic acid absorbable suture</td><td>Jinhuan Medical Co., Ltd</td><td>KCR531</td><td>Equipment for surgery</td></tr><tr><td>96-well culture plate</td><td>Corning Incorporated</td><td>CLS3596</td><td>EB content measuring</td></tr><tr><td>Anesthesia machine</td><td>Midmark Corporation</td><td>VMR</td><td>Anesthesia for animal</td></tr><tr><td>Antifade Mounting Medium with DAPI</td><td>Beyotime Biotech</td><td>P0131</td><td>Mount for tissue sections</td></tr><tr><td>Automation-tissue-dehydrating&amp;nbsp;&lt;br/&gt; machine</td><td>Leica Biosystems</td><td>TP1020</td><td>Dehydrate tissue</td></tr><tr><td>Confocal microscopy</td><td>Leica Biosystems</td><td>STELLARIS 5</td><td>Image acquisition</td></tr><tr><td>Diclofenac sodium gel</td><td>MaYinglong Pharmaceutical</td><td>H10950214</td><td>Analgesia for animal</td></tr><tr><td>Eosin staining solution</td><td>Servicebio Technology</td><td>G1001</td><td>The dye for H&amp;amp;E staining</td></tr><tr><td>Evans Blue</td><td>Aladdin</td><td>E104208</td><td>EB staining</td></tr><tr><td>Eye gel</td><td>Guangzhou Pharmaceutical</td><td>H44023098</td><td>Material for surgery</td></tr><tr><td>Fitc-dextran</td><td>Sigma-Aldrich</td><td>60842-46-8</td><td>BBB permeability assessing</td></tr><tr><td>Fluorescence microscope</td><td>Olympus</td><td>BX51</td><td>Image acquisition</td></tr><tr><td>Frozen microtome</td><td>Leica Biosystems</td><td>CM1900</td><td>Use for frozen sections</td></tr><tr><td>Glucometer</td><td>YuWell</td><td>580</td><td>Blood glucose measurement</td></tr><tr><td>Hematoxylin staining Solution</td><td>Servicebio</td><td>G1004</td><td>The dye for H&amp;amp;E staining</td></tr><tr><td>Iodine</td><td>Lircon</td><td>20020059</td><td>Material for surgery</td></tr><tr><td>Isoflurane</td><td>Rwd Life Science</td><td>R510-22-10</td><td>Anesthesia for animal</td></tr><tr><td>Laser doppler blood flow meter</td><td>Moor Instruments</td><td>moorVMS</td><td>Blood flow monitoring</td></tr><tr><td>MCAO Sutures</td><td>Rwd Life Science</td><td>907-00023-01</td><td>Material for surgery</td></tr><tr><td>Meloxicam</td><td>Boehringer-Ingelheim</td><td>J20160020</td><td>Analgesia for animal</td></tr><tr><td>Microsurgical instrument kit</td><td>Rwd Life Science</td><td>SP0003-M</td><td>Equipment for surgery</td></tr><tr><td>Microtome</td><td>Thermo Fisher Scientific</td><td>HM325</td><td>Tissue section production</td></tr><tr><td>Microtome blade</td><td>Leica Biosystems</td><td>819</td><td>Tissue section production</td></tr><tr><td>Mupirocin ointment</td><td>GlaxoSmithKline</td><td>H10930064</td><td>Anti-infection for animal</td></tr><tr><td>Neutral balsam</td><td>Absin Bioscience</td><td>abs9177</td><td>Seal for H&amp;amp;E staining</td></tr><tr><td>Paraffin embedding center</td><td>Thermo Fisher Scientific</td><td>EC 350</td><td>Produce paraffin blocks</td></tr><tr><td>Pentobarbital sodium</td><td>Sigma-Aldrich</td><td>P3761</td><td>Euthanasia for animal</td></tr><tr><td>Phosphate buffered saline</td><td>Beyotime Biotech</td><td>C0221A</td><td>Rinse for tissue section</td></tr><tr><td>Scanner</td><td>EPSON</td><td>V330</td><td>Tissue scanning</td></tr><tr><td>Shaver</td><td>Shenzhen Codos Electrical Appliances Co.,Ltd.</td><td>CP-9200</td><td>Equipment for surgery</td></tr><tr><td>Spectrophotometer</td><td>Thermo Fisher Scientific</td><td>1510-02362</td><td>EB content measuring</td></tr><tr><td>Sucrose solution</td><td>Shanghai Macklin Biochemical</td><td>57-50-1</td><td>Dehydration for tissue</td></tr><tr><td>Tissue-Tek O.C.T. Compound</td><td>Sakura</td><td>4583</td><td>Tissue embedding medium</td></tr><tr><td>Trichloroacetic acid</td><td>Sigma-Aldrich</td><td>T6399</td><td>EB content measuring</td></tr></tbody></table>

a mouse model of hemorrhagic transformation induced by acute hyperglycemia combined with transient focal ischemia

<meta charset="utf8"></head><body>急性高血糖合并短暂性局灶性缺血诱导的出血转化小鼠模型

急性高血糖合并短暂性局灶性缺血诱导的出血转化小鼠模型

Hemorrhagic transformation (HT) is a serious complication that can occur as a result of thrombolytic therapy following ischemic stroke (IS), and it poses ...

a-mouse-model-hemorrhagic-transformation-induced-acute-hyperglycemia

Universidad de Cartagena UDEC

Research

JoVE Journal

Medicine

A Mouse Model of Hemorrhagic Transformation Induced by Acute Hyperglycemia Combined with Transient Focal Ischemia

310 次观看.  Jianghan University. 本研究提出了一种方案，用于在患有急性高血糖症的 C57BL/6 小鼠中使用大脑中动脉闭塞/再灌注 （MCAO/R） 建立高度可重复的出血转化 （HT） 动物模型。

视频: 急性高血糖合并短暂性局灶性缺血诱导的出血转化小鼠模型

A Research Method For Detecting Transient Myocardial Ischemia In Patients With Suspected Acute Coronary Syndrome Using Continuous ST-segment Analysis

Each year, an estimated 785,000 Americans will have a new coronary attack, or acute coronary syndrome (ACS). The pathophysiology of ACS involves rupture of an atherosclerotic plaque; hence, treatment is aimed at plaque stabilization in order to prevent cellular death. However, there is considerable debate among clinicians, about which treatment pathway is best: early invasive using percutaneous coronary intervention (PCI/stent) when indicated or a conservative approach (i.e., medication only with PCI/stent if recurrent symptoms occur).
There are three types of ACS: ST elevation myocardial infarction (STEMI), non-ST elevation MI (NSTEMI), and unstable angina (UA). Among the three types, NSTEMI/UA is nearly four times as common as STEMI. Treatment decisions for NSTEMI/UA are based largely on symptoms and resting or exercise electrocardiograms (ECG). However, because of the dynamic and unpredictable nature of the atherosclerotic plaque, these methods often under detect myocardial ischemia because symptoms are unreliable, and/or continuous ECG monitoring was not utilized.
Continuous 12-lead ECG monitoring, which is both inexpensive and non-invasive, can identify transient episodes of myocardial ischemia, a precursor to MI, even when asymptomatic. However, continuous 12-lead ECG monitoring is not usual hospital practice; rather, only two leads are typically monitored. Information obtained with 12-lead ECG monitoring might provide useful information for deciding the best ACS treatment.
Purpose. Therefore, using 12-lead ECG monitoring, the COMPARE Study (electroCardiographic evaluatiOn of ischeMia comParing invAsive to phaRmacological trEatment) was designed to assess the frequency and clinical consequences of transient myocardial ischemia, in patients with NSTEMI/UA treated with either early invasive PCI/stent or those managed conservatively (medications or PCI/stent following recurrent symptoms). The purpose of this manuscript is to describe the methodology used in the COMPARE Study.
Method. Permission to proceed with this study was obtained from the Institutional Review Board of the hospital and the university. Research nurses identify hospitalized patients from the emergency department and telemetry unit with suspected ACS. Once consented, a 12-lead ECG Holter monitor is applied, and remains in place during the patient's entire hospital stay. Patients are also maintained on the routine bedside ECG monitoring system per hospital protocol. Off-line ECG analysis is done using sophisticated software and careful human oversight.

Continuous 12-lead electrocardiographic (ECG) monitoring can identify transient myocardial ischemia, even when asymptomatic, among patients with suspected acute coronary syndrome (ACS). In this article we describe our method for initiating patient monitoring using a Holter device, downloading the ECG data for off-line analysis, and how to utilize the ECG software to identify transient ischemia.

研究方法检测疑似急性冠脉综合征患者短暂心肌缺血的连续ST段分析

Each year, an estimated 785,000 Americans will have a new coronary attack, or acute coronary syndrome (ACS). The pathophysiology of ACS involves rupture ...

科研

医学

Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice

Ischemia-reperfusion induced acute kidney injury (IR-AKI) is widely used as a model of AKI in mice, but results are often quite variable with high, often unreported mortality rates that may confound analyses. Bilateral renal pedicle clamping is commonly used to induce IR-AKI, but differences between effective clamp pressures and/or renal responses to ischemia between kidneys often lead to more variable results. In addition, shorter clamp times are known to induce more variable tubular injury, and while mice undergoing bilateral injury with longer clamp times develop more consistent tubular injury, they often die within the first 3 days after injury due to severe renal insufficiency. To improve post-injury survival and obtain more consistent and predictable results, we have developed two models of unilateral ischemia-reperfusion injury followed by contralateral nephrectomy. Both surgeries are performed using a dorsal approach, reducing surgical stress resulting from ventral laparotomy, commonly used for mouse IR-AKI surgeries. For induction of moderate injury BALB/c mice undergo unilateral clamping of the renal pedicle for 26 min and also undergo simultaneous contralateral nephrectomy. Using this approach, 50-60% of mice develop moderate AKI 24 hr after injury but 90-100% of mice survive. To induce more severe AKI, BALB/c mice undergo renal pedicle clamping for 30 min followed by contralateral nephrectomy 8 days after injury. This allows functional assessment of renal recovery after injury with 90-100% survival. Early post-injury tubular damage as well as post injury fibrosis are highly consistent using this model.

We describe models of moderate and severe ischemia-reperfusion-induced kidney injury in which the mice undergo unilateral renal pedicle clamping followed by simultaneous or delayed contralateral nephrectomy, respectively. These models consistently give rise to renal dysfunction and post-injury fibrosis, but injury severity and survival are dependent on mouse background, age and surgical equipment.

急性肾损伤和伤后纤维化小鼠缺血再灌注模型

Ischemia-reperfusion induced acute kidney injury (IR-AKI) is widely used as a model of AKI in mice, but results are often quite variable with high, often ...

Reproducable Paraplegia by Thoracic Aortic Occlusion in a Murine Model of Spinal Cord Ischemia-reperfusion

Background 
Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered advancements to decrease the occurrence this injury.&#160;The current model demonstrates reproducible lower&#160;extremity paralysis following thoracic aortic occlusion.
Methods 
Adult male C57BL6 mice were anesthetized with isoflurane. Through a cervicosternal incision the aorta was exposed. The descending thoracic aorta and left subclavian arteries were identified without entrance into pleural space. Skeletonization of these arteries was followed by immediate closure (Sham) or occlusion for 4 min (moderate ischemia) or 8 min (prolonged ischemia). The sternotomy and skin were closed and the mouse was transferred to warming bed for recovery.&#160; Following recovery, functional analysis was obtained at 12 hr intervals until 48 hr.
Results 
Mice that underwent sham surgery showed no observable hind&#160;limb deficit. Mice subjected to moderate ischemia for 4 min had minimal functional deficit at 12 hr followed by progression to complete paralysis at 48 hr. Mice subjected to prolonged ischemia had an immediate paralysis with no observable hind-limb movement at any point in the postoperative period. There was no observed intraoperative or post&#160;operative mortality.
Conclusion 
Reproducible lower extremity paralysis whether immediate or delayed can be achieved in a murine model. Additionally, by using a median sternotomy and careful dissection, high survival rates, and reproducibility can be achieved.

The lack of mechanistic understanding of spinal cord ischemia-reperfusion injury has hindered further adjuncts to prevent paraplegia following high risk aortic operations. Thus, the development of animal models is imperative. This manuscript demonstrates reproducible lower extremity paralysis following thoracic aortic occlusion in a murine model.

可重放截瘫胸主动脉阻断脊髓缺血再灌注的小鼠模型

Background
Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered ...

Ischemic Tissue Injury in the Dorsal Skinfold Chamber of the Mouse: A Skin Flap Model to Investigate Acute Persistent Ischemia

Despite profound expertise and advanced surgical techniques, ischemia-induced complications ranging from wound breakdown to extensive tissue necrosis are still occurring, particularly in reconstructive flap surgery. Multiple experimental flap models have been developed to analyze underlying causes and mechanisms and to investigate treatment strategies to prevent ischemic complications. The limiting factor of most models is the lacking possibility to directly and repetitively visualize microvascular architecture and hemodynamics. The goal of the protocol was to present a well-established mouse model affiliating these before mentioned lacking elements. Harder et al. have developed a model of a musculocutaneous flap with a random perfusion pattern that undergoes acute persistent ischemia and results in ~50% necrosis after 10 days if kept untreated. With the aid of intravital epi-fluorescence microscopy, this chamber model allows repetitive visualization of morphology and hemodynamics in different regions of interest over time. Associated processes such as apoptosis, inflammation, microvascular leakage and angiogenesis can be investigated and correlated to immunohistochemical and molecular protein assays. To date, the model has proven feasibility and reproducibility in several published experimental studies investigating the effect of pre-, peri- and postconditioning of ischemically challenged tissue.

The window of the murine dorsal skinfold chamber presented visualizes a zone of acute persistent ischemia of a musculocutaneous flap. Intravital epi-fluorescence microscopy permits for direct and repetitive assessment of the microvasculature and quantification of hemodynamics. Morphologic and hemodynamic results can further be correlated with histological and molecular analyses.

在背皮褶商会鼠标的缺血性组织损伤:一个皮瓣模型，探讨急性缺血持续

Despite profound expertise and advanced surgical techniques, ischemia-induced complications ranging from wound breakdown to extensive tissue necrosis are ...

A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia

Stroke research has endured many setbacks in translating neuroprotective therapies into clinical practice. In contrast, the real-world therapy (tPA thrombolysis) rarely produces benefits in mechanical occlusion-based experimental models, which dominate preclinical stroke research. This split between the bench and bedside suggests the need to employ tPA-responsive models in preclinical stroke research. To this end, a simple and tPA-reactive thrombotic stroke model is invented and described here. This model consists of transient occlusion of the unilateral common carotid artery and delivery of 7.5% oxygen through a face mask in adult mice for 30 min, while maintaining the animal rectal temperature at 37.5 &#177; 0.5 &#176;C. Although reversible ligation of the unilateral carotid artery or hypoxia each suppressed cerebral blood flow only transiently, the combination of both insults caused lasting reperfusion deficits, fibrin and platelet deposition, and large infarct in the middle cerebral artery-supplied territory. Importantly, tail-vein injection of recombinant tPA at 0.5, 1, or 4 hr post-tHI (10 mg/kg) provided time-dependent reduction of the mortality rate and infarct size. This new stroke model is simple and can be standardized across laboratories to compare experimental results. Further, it induces thrombosis without craniectomy or introducing pre-formed emboli. Given these unique merits, the tHI model is a useful addition to the repertoire of preclinical stroke research.

Thromboembolic stroke models are vital tools for optimizing the recanalization therapy. Here we report a murine thrombotic stroke model based on transient cerebral hypoxic-ischemic (tHI) insult, which triggers thrombosis and infarction, and responds favorably to tissue plasminogen activator (tPA)-mediated fibrinolysis in a therapeutic window similar to those in stroke patients.

基于短暂性脑缺氧缺血性血栓性中风模型

Stroke research has endured many setbacks in translating neuroprotective therapies into clinical practice. In contrast, the real-world therapy (tPA ...

Photothrombosis-induced Focal Ischemia as a Model of Spinal Cord Injury in Mice

Spinal cord injury (SCI) is a devastating clinical condition causing permanent changes in sensorimotor and autonomic functions of the spinal cord (SC) below the site of injury. The secondary ischemia that develops following the initial mechanical insult is a serious complication of the SCI and severely impairs the function and viability of surviving neuronal and non-neuronal cells in the SC. In addition, ischemia is also responsible for the growth of lesion during chronic phase of injury and interferes with the cellular repair and healing processes. Thus there is a need to develop a spinal cord ischemia model for studying the mechanisms of ischemia-induced pathology. Focal ischemia induced by photothrombosis (PT) is a minimally invasive and very well established procedure used to investigate the pathology of ischemia-induced cell death in the brain. Here, we describe the use of PT to induce an ischemic lesion in the spinal cord of mice. Following retro-orbital sinus injection of Rose Bengal, the posterior spinal vein and other capillaries on the dorsal surface of SC were irradiated with a green light resulting in the formation of a thrombus and thus ischemia in the affected region. Results from histology and immunochemistry studies show that PT-induced ischemia caused spinal cord infarction, loss of neurons and reactive gliosis. Using this technique a highly reproducible and relatively easy model of SCI in mice can be achieved that would serve the purpose of scientific investigations into the mechanisms of ischemia induced cell death as well as the efficacy of neuroprotective drugs. This model will also allow exploration of the pathological changes that occur following SCI in live mice like axonal degeneration and regeneration, neuronal and astrocytic Ca2+ signaling using two-photon microscopy.

Photothrombosis is a minimally invasive and highly reproducible procedure to induce focal ischemia in the spinal cord and serves as a model of spinal cord injury in mice.

Photothrombosis引起的局部脑缺血脊髓损伤的小鼠模型

Spinal cord injury (SCI) is a devastating clinical condition causing permanent changes in sensorimotor and autonomic functions of the spinal cord (SC) ...

A Mouse Model for Laser-induced Choroidal Neovascularization

The mouse laser-induced choroidal neovascularization (CNV) model has been a crucial mainstay model for neovascular age-related macular degeneration (AMD) research. By administering targeted laser injury to the RPE and Bruch&#8217;s membrane, the procedure induces angiogenesis, modeling the hallmark pathology observed in neovascular AMD. 
First developed in non-human primates, the laser-induced CNV model has come to be implemented into many other species, the most recent of which being the mouse. Mouse experiments are advantageously more cost-effective, experiments can be executed on a much faster timeline, and they allow the use of various transgenic models. The miniature size of the mouse eye, however, poses a particular challenge when performing the procedure. Manipulation of the eye to visualize the retina requires practice of fine dexterity skills as well as simultaneous hand-eye-foot coordination to operate the laser. However, once mastered, the model can be applied to study many aspects of neovascular AMD such as molecular mechanisms, the effect of genetic manipulations, and drug treatment effects. 
The laser-induced CNV model, though useful, is not a perfect model of the disease. The wild-type mouse eye is otherwise healthy, and the chorio-retinal environment does not mimic the pathologic changes in human AMD. Furthermore, injury-induced angiogenesis does not reflect the same pathways as angiogenesis occurring in an age-related and chronic disease state as in AMD.
Despite its shortcomings, the laser-induced CNV model is one of the best methods currently available to study the debilitating pathology of neovascular AMD. Its implementation has led to a deeper understanding of the pathogenesis of AMD, as well as contributing to the development of many of the AMD therapies currently available.

Here, we present the mouse laser-induced choroidal neovascularization (CNV) protocol, an experimental model that re-creates the vascular hallmarks of neovascular age-related macular degeneration (AMD). Once mastered, it can reliably and effectively induce CNV as a model system to test various experimental measures.

小鼠模型的激光诱导脉络膜新生血管

The mouse laser-induced choroidal neovascularization (CNV) model has been a crucial mainstay model for neovascular age-related macular degeneration (AMD) ...

Diffuse Optical Spectroscopy for the Quantitative Assessment of Acute Ionizing Radiation Induced Skin Toxicity Using a Mouse Model

Acute skin toxicities from ionizing radiation (IR) are a common side effect from therapeutic courses of external beam radiation therapy (RT) and negatively impact patient quality of life and long term survival. Advances in the understanding of the biological pathways associated with normal tissue toxicities have allowed for the development of interventional drugs, however, current response studies are limited by a lack of quantitative metrics for assessing the severity of skin reactions. Here we present a diffuse optical spectroscopic (DOS) approach that provides quantitative optical biomarkers of skin response to radiation. We describe the instrumentation design of the DOS system as well as the inversion algorithm for extracting the optical parameters. Finally, to demonstrate clinical utility, we present representative data from a pre-clinical mouse model of radiation induced erythema and compare the results with a commonly employed visual scoring. The described DOS method offers an objective, high through-put evaluation of skin toxicity via functional response that is translatable to the clinical setting.

We present a diffuse optical spectroscopic (DOS) approach that provides quantitative optical biomarkers of skin response to radiation. We describe DOS instrumentation design, optical parameters extraction algorithms and the animal handling procedures required to yield representative data from a pre-clinical mouse model of radiation induced erythema.

弥漫性光学光谱治疗急性电离辐射引起的皮肤毒性的定量评价使用小鼠模型

Acute skin toxicities from ionizing radiation (IR) are a common side effect from therapeutic courses of external beam radiation therapy (RT) and ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

用线 Myography 测定小鼠肠系膜动脉的等轴收缩力

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish

Cisplatin is commonly used as chemotherapy. Although it has positive effects in cancer-treated individuals, cisplatin can easily accumulate in the kidney due to its low molecular weight. Such accumulation causes the death of tubular cells and can induce the development of Acute Kidney Injury (AKI), which is characterized by a quick decrease in kidney function, tissue damage, and immune cells infiltration. If administered in specific doses cisplatin can be a useful tool as an AKI inducer in animal models. The zebrafish has appeared as an interesting model to study renal function, kidney regeneration, and injury, as renal structures conserve functional similarities with mammals. Adult zebrafish injected with cisplatin shows decreased survival, kidney cell death, and increased inflammation markers after 24 h post-injection (hpi). In this model, immune cells infiltration and cell death can be assessed by flow cytometry and TUNEL assay. This protocol describes the procedures to induce AKI in adult zebrafish by intraperitoneal cisplatin injection and subsequently demonstrates how to collect the renal tissue for flow cytometry processing and cell death TUNEL assay. These techniques will be useful to understand the effects of cisplatin as a nephrotoxic agent and will contribute to the expansion of AKI models in adult zebrafish. This model can also be used to study kidney regeneration, in the search for compounds that treat or prevent kidney damage and to study inflammation in AKI. Moreover, the methods used in this protocol will improve the characterization of tissue damage and inflammation, which are therapeutic targets in kidney-associated comorbidities.

This protocol describes the procedures to induce Acute Kidney Injury (AKI) in adult zebrafish using cisplatin as a nephrotoxic agent. We detailed the steps to evaluate the reproducibility of the technique and two techniques to analyze inflammation and cell death in the renal tissue, flow cytometry and TUNEL, respectively.

成人斑马鱼中西斯铂诱导的急性肾损伤模型

Cisplatin is commonly used as chemotherapy. Although it has positive effects in cancer-treated individuals, cisplatin can easily accumulate in the kidney ...