הממומן על ידי איגוד הלב האמריקני ואת מצעד הפרוטות.

פרוטוקול זה אושר על ידי טיפול בבעלי חיים מוסדיים ועדת השתמש באוניברסיטת סטנפורד פועלת לפי המכון הלאומי לבריאות הנחיות לשימוש בחיות מעבדה. עכברוש ילודים HIE מודל <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> יום הודעה הלידה (PND) 7 Sprague-Dawley גורי חולדה (Charles River Laboratories, Inc, בווילמינגטון, MA) מורדמים באופן מלא עם isoflurane (Aerrane, בקסטר, Deerfield, IL;% 3-4 לזירוז ו 1-2% עבור תחזוקה). </li><li style=";text-align:right;direction:rtl"> חתך קטן עשה בצוואר (Extra Thin איריס מספריים # 14088-10, פיין למדע כלי Inc, פוסטר סיטי, קליפורניה) כדי לחשוף את עורק התרדמה השמאלי משותף (CCA). </li><li style=";text-align:right;direction:rtl"> המרכז לאמנות עכשווית הוא ligated עם תפר 5-0 משי (5-0 משי, Ethicon, סומר, NJ). </li><li style=";text-align:right;direction:rtl"> החתך נסגר עם דבק cyanoacrylate (Elmers מוצרים Inc, קולומבוס, OH). החתך מכוסה קלטת הרדמה היא נעצרה. הגורים הם חזרו אל הסכר שלהם מותר להתאושש במשך 1-2 שעות. </li><li style=";text-align:right;direction:rtl"> גורים ממוקמות אז בתא hypoxic המכיל חמצן 8% מאוזנת עם חנקן 92% עבור 100 דקות 37 ° C. 8 oxygen/92%% גז חנקן (Airgas, סקרמנטו, קליפורניה) זרימה דרך צינור לתוך הכלוב העכבר מצויד בכיסוי פלסטיק. הכיסוי עשוי להתאים לכלוב ויש לו שני חורים של 2 ס&quot;מ קוטר, אחד מהם לקבל את הצינור המחובר הטנק 8% חמצן גז אחר מאפשר הגז flowout. החדר ממוקם בתוך אמבט מים הוא התחמם לפני השימוש מדחום בתוכו חייב לרשום 37 ° C לפני תחילת היפוקסיה. </li><li style=";text-align:right;direction:rtl"> בתום 100 דקות של היפוקסיה, הגורים הם חזרו שוב אל סכר שלהם להחלמה. </li><li style=";text-align:right;direction:rtl"> 24 שעות לאחר סיומה של היפוקסיה, הגורים מומתים על ידי הרדמה עמוקה עם isoflurane. רקמת המוח היא perfused עם מלח רגיל קר, ואחריו פתרון של TTC 1% קר פוספט pH שנאגרו מלוחים, 7.4 (Sigma כימית Co, סנט לואיס, מיזורי). TTC חייב להישמר מפני אור. </li><li style=";text-align:right;direction:rtl"> המוח יוסרו מקורר למשך 1-2 דקות על קרח, לארבעה חלקים העטרה 3 מ&quot;מ זה מזה (רמות 1-4) נחתכים, החל rostrally ברמה של opticchiasm ו משפך, המתאים גבחת 1.8 ~ 2.0 מ&quot;מ רמת המוח עכבר מבוגר. </li><li style=";text-align:right;direction:rtl"> פרוסות המוח שקועים פתרון TTC וטופחו על 37 מעלות צלזיוס למשך 8 דקות, ואחריו קיבעון paraformaldehyde 4% / PBS לילה. מכיוון TTC אור רגישים, לשמור על פרוסות מן האור בתקופה זו. </li><li style=";text-align:right;direction:rtl"> סעיפים מוכתם TTC נסרקים ו דיגיטציה. באמצעות תמונה J (NIH, Bethesda, MD), את הדברים הבאים נמדדים עבור כל רמה: אזור של אוטם (אזור בלא כתם), שטח של חצי הכדור ipsilateral, ועל שטח של חצי הכדור הנגדי. אחוז infarcted שטח לכל פרוסה מחושב: (באזור של האוטם / שטח של חצי הכדור ipsilateral) או 1, 2, 3, 4. נפח אחוז האוטם מחושב כסכום (1 + 2 + 3 + 4) * 3mm. תחומי פגיעה בקליפת המוח או striatal ניתן לכמת בנפרד באופן דומה. </li></ol> נציג תוצאות <img src="/files/ftp_upload/old/955_2008_9_2_2/955_Fig-01.png" alt="איור 1" width="660" height="190" /> באיור 1. נציג HIE העטרה רמות 1-4 מוכתם TTC. סעיפים TTC העטרה מוכתם להפגין שטח של האוטם (בלבן).

<ol>
	<li>Rice, J. E., Vannucci, R. C., Brierley, J. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+influence+of+immaturity+on+hypoxic-ischemic+brain+damage+in+the+rat.">The influence of immaturity on hypoxic-ischemic brain damage in the rat.</a> Annals of neurology. 9 (2), 131-141 (1981).</li><li>Vannucci, R. C., Vannucci, S. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Perinatal+Hypoxic-Ischemic+Brain+Damage:+Evolution+of+an+Animal+Model.">Perinatal Hypoxic-Ischemic Brain Damage: Evolution of an Animal Model.</a> Dev Neurosci. 27 (2-4), 81-86 (2005).</li><li>Bona, E., Hagberg, H., Loberg, E. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Protective+effects+of+moderate+hypothermia+after+neonatal+hypoxia-ischemia:+short-+and+long-term+outcome.">Protective effects of moderate hypothermia after neonatal hypoxia-ischemia: short- and long-term outcome.</a> Pediatric research. 43 (6), 738-738 (1998).</li><li>Trescher, W. H., Ishiwa, S., Johnston, M. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+hypothermia+and+hyperthermia+on+attentional+and+spatial+learning+deficits+following+neonatal+hypoxia-ischemic+insult+in+rats.">Effects of hypothermia and hyperthermia on attentional and spatial learning deficits following neonatal hypoxia-ischemic insult in rats.</a> Behavioural brain research. 151 (1-2), 209-209 (2004).</li><li>Mishima, K., Ikeda, T., Yoshikawa, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Brief+post-hypoxic-ischemic+hypothermia+markedly+delays+neonatal+brain+injury.">Brief post-hypoxic-ischemic hypothermia markedly delays neonatal brain injury.</a> Brain development. 19 (5), 326-326 (1997).</li><li>Young, R. S., Olenginski, T. P., Yagel, S. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+graded+hypothermia+on+hypoxic-ischemic+brain+damage:+a+neuropathologic+study+in+the+neonatal+rat.">The effect of graded hypothermia on hypoxic-ischemic brain damage: a neuropathologic study in the neonatal rat.</a> Stroke; a journal of cerebral circulation. 14 (6), 929-929 (1983).</li><li>Bederson, J. B., Pitts, L. H., Germano, S. M., 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=Evaluation+of+2,3,5-triphenyltetrazolium+chloride+as+a+stain+for+detection+and+quantification+of+experimental+cerebral+infarction+in+rats.">Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats.</a> Stroke; a journal of cerebral circulation. 17 (6), 1304-1304 (1986).</li><li>Cai, J., Kang, Z., Liu, W. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hydrogen+therapy+reduces+apoptosis+in+neonatal+hypoxia-ischemia+rat+model.">Hydrogen therapy reduces apoptosis in neonatal hypoxia-ischemia rat model.</a> Neuroscience letters. 441 (2), 167-167 (2008).</li><li>Grow, J., Barks, J. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathogenesis+of+hypoxic-ischemic+cerebral+injury+in+the+term+infant:+current+concepts.">Pathogenesis of hypoxic-ischemic cerebral injury in the term infant: current concepts.</a> Clinics in perinatology. 29 (4), 585-585 (2002).</li><li>Aden, U., Halldner, L., Lagercrantz , 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=Aggravated+brain+damage+after+hypoxic+ischemia+in+immature+adenosine+A2A+knockout+mice.">Aggravated brain damage after hypoxic ischemia in immature adenosine A2A knockout mice.</a> Stroke; a journal of cerebral circulation. 34 (3), 739-739 (2003).</li></ol>

המודל הלידה מכרסם HIE הוא מודל נקבע כי משחזר היפוקסיה מוחית המתרחשים בתקופה פרי הלידה של ילודים. מחקרים נרחבים אפיון היסטולוגית ו immunocytochemical הראו כי מכרסמים בן 7 היום יש את הבגרות המוח מקביל מודל בשליש השלישי העובר האנושי 7. המודל HIE מכרסם כבר אינפורמטיבי מאוד להבנת המנגנונים...

<table><tbody><tr><td>Sprague-Dawley Rat Pups</td><td>Animal</td><td>Charles River Laboratories</td><td></td><td></td></tr><tr><td>Isoflurane</td><td>Surgery</td><td>Baxter Internationl Inc.</td><td></td><td></td></tr><tr><td>8% Oxygen/ 92% Nitrogen Gas</td><td>Surgery</td><td>Airgas</td><td></td><td></td></tr><tr><td>2,3,5-triphenyl tetrazolium chloride </td><td>Reagent</td><td>Sigma-Aldrich</td><td>T8877</td><td></td></tr><tr><td>Phosphate buffered saline (PBS) pH 7.4 </td><td>Reagent</td><td>GIBCO, by Life Technologies</td><td></td><td></td></tr><tr><td>Paraformaldehyde</td><td>Reagent</td><td>Sigma-Aldrich</td><td>P6148</td><td></td></tr></tbody></table>

the hypoxic ischemic encephalopathy model of perinatal ischemia

Hypoxic-איסכמי אנצפלופתיה (HIE) הוא תוצאה של חנק מערכתית המתרחשים בלידה. עשרים וחמישה אחוזים של יילודים עם HIE לפתח sequelae neuropsychological חמור וקבוע, כולל פיגור שכלי, שיתוק מוחין ואפילפסיה. התוצאות הן הרסניות של HIE וקבוע, מה שהופך אותו קריטי לזהות ולפתח אסטרטגיות טיפוליות כדי להפחית פגיעה מוחית בתינוקות עם HIE. לשם כך, המודל עכברוש בילוד לפגיעה hypoxic-איסכמי במוח פותחה מודל זה המצב האנושי. המודל HIE היה תוקף לראשונה על ידי ואנוצ&#39;י ואח&#39; 1 ומאז נעשה שימוש נרחב כדי לזהות את המנגנונים של פגיעה מוחית כתוצאה הלידה היפוקסיה איסכמיה-2 ו לבדוק התערבויות טיפוליות פוטנציאל 3,4. המודל HIE הוא תהליך דו שלב כרוך קשירת של עורק התרדמה השמאלי משותף ואחריו חשיפה לסביבה hypoxic. זרימת הדם במוח (CBF) בחצי הכדור ipsilateral על עורק הצוואר ligated אינו פוחת בגלל זרימת דם בטחונות דרך המעגל של ויליס, אולם עם מתח חמצן נמוך, CBF בחצי הכדור ipsilateral מקטין באופן משמעותי ותוצאות פגיעה איסכמי חד צדדית . השימוש כלוריד-2,3,5 triphenyltetrazolium (TTC) להכתים ולזהות רקמת מוח איסכמי פותחה במקור עבור דגמים הבוגרת של איסכמיה מכרסם מוחין 5, והוא משמש כדי להעריך את מידת infarctin מוחין בנקודות זמן מוקדם של עד 72 שעות לאחר האירוע איסכמי 6. בסרטון הזה, אנחנו מדגימים את המודל hypoxic-איסכמי פגיעה במוח חולדה הלידה ואת הערכה של גודל האוטם באמצעות מכתים TTC.

Watch this Scientific Journal Video about The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia at JoVE.com

The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia

המודל עכברוש הלידה לפגיעה hypoxic-איסכמי המוח הוא מודל ומבוססת של אנצפלופתיה הילוד האנושי איסכמי היפוקסי (HIE). במאמר זה, אנו מתארים את המודל של HIE ב שלאחר הלידה גורי חולדה.

מודל hypoxic אנצפלופתיה איסכמי של איסכמיה הלידה

Hypoxic-Ischemic Encephalopathy (HIE) is the consequence of systemic asphyxia occurring at birth. Twenty five percent of neonates with HIE develop severe ...

the-hypoxic-ischemic-encephalopathy-model-of-perinatal-ischemia

Research

JoVE Journal

Biology

35.6K Views.  Stanford University School of Medicine. המודל עכברוש הלידה לפגיעה hypoxic-איסכמי המוח הוא מודל ומבוססת של אנצפלופתיה הילוד האנושי איסכמי היפוקסי (HIE). במאמר זה, אנו מתארים את המודל של HIE ב שלאחר הלידה גורי חולדה.

Video: The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia

Mouse Models of Periventricular Leukomalacia

We describe a protocol for establishing mouse models of periventricular leukomalacia (PVL). PVL is the predominant form of brain injury in premature infants and the most common antecedent of cerebral palsy. PVL is characterized by periventricular white matter damage with prominent oligodendroglial injury. Hypoxia/ischemia with or without systemic infection/inflammation are the primary causes of PVL. We use P6 mice to create models of neonatal brain injury by the induction of hypoxia/ischemia with or without systemic infection/inflammation with unilateral carotid ligation followed by exposure to hypoxia with or without injection of the endotoxin lipopolysaccharide (LPS). Immunohistochemistry of myelin basic protein (MBP) or O1 and electron microscopic examination show prominent myelin loss in cerebral white matter with additional damage to the hippocampus and thalamus. Establishment of mouse models of PVL will greatly facilitate the study of disease pathogenesis using available transgenic mouse strains, conduction of drug trials in a relatively high throughput manner to identify candidate therapeutic agents, and testing of stem cell transplantation using immunodeficiency mouse strains.

We established mouse models of periventricular leukomalacia (PVL), the predominant brain injury in premature infants characterized by periventricular white matter lesions. Hypoxia/ischemia with/without systemic infection are the primary causes of PVL. Unilateral carotid ligation and hypoxia exposure with/without lipopolysaccharide injection creates PVL-like lesions in P6 mice.

עכבר מודלים של לויקומלציה periventricular

We describe a protocol for establishing mouse models of periventricular leukomalacia (PVL). PVL is the predominant form of brain injury in premature ...

Neuroscience

2-Vessel Occlusion/Hypotension: A Rat Model of Global Brain Ischemia

Cardiac arrest followed by resuscitation often results in dramatic brain damage caused by ischemia and subsequent reperfusion of the brain. Global brain ischemia produces damage to specific brain regions shown to be highly sensitive to ischemia 1. Hippocampal neurons have higher sensitivity to ischemic insults compared to other cell populations, and specifically, the CA1 region of the hippocampus is particularly vulnerable to ischemia/reperfusion 2.
The design of therapeutic interventions, or study of mechanisms involved in cerebral damage, requires a model that produces damage similar to the clinical condition and in a reproducible manner. Bilateral carotid vessel occlusion with hypotension (2VOH) is a model that produces reversible forebrain ischemia, emulating the cerebral events that can occur during cardiac arrest and resuscitation. We describe a model modified from Smith et al. (1984) 2, as first presented in its current form in Sanderson, et al. (2008) 3, which produces reproducible injury to selectively vulnerable brain regions 3-6. The reliability of this model is dictated by precise control of systemic blood pressure during applied hypotension, the duration of ischemia, close temperature control, a specific anesthesia regimen, and diligent post-operative care. An 8-minute ischemic insult produces cell death of CA1 hippocampal neurons that progresses over the course of 6 to 24 hr of reperfusion, while less vulnerable brain regions are spared. This progressive cell death is easily quantified after 7-14 days of reperfusion, as a near complete loss of CA1 neurons is evident at this time.
In addition to this brain injury model, we present a method for CA1 damage quantification using a simple, yet thorough, methodology. Importantly, quantification can be accomplished using a simple camera-mounted microscope, and a free ImageJ (NIH) software plugin, obviating the need for cost-prohibitive stereology software programs and a motorized microscopic stage for damage assessment.

Bilateral carotid occlusion coupled with systemic hypotension produces global brain ischemia in the rat, resulting in damage to the hippocampus with reproducible severity. Animal subjects are impaired with predictable patterns of brain damage, they recover expediently, and mortality rates are comparatively low.

ספיגה של 2 כלי השיט / תת לחץ דם: מודל עכברוש של איסכמיה המוח הגלובלית

Cardiac arrest followed by resuscitation often results in dramatic brain damage caused by ischemia and subsequent reperfusion of the brain. Global brain ...

Medicine

A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy

Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the world&#8217;s 2.9 million neonatal deaths. Animal models of HIE have contributed to the understanding of the pathophysiology in HIE, and have highlighted the dynamic process that occur in brain injury due to perinatal asphyxia. Thus, animal studies have suggested a time-window for post-insult treatment strategies. Hypothermia has been tested as a treatment for HIE in pdiglet models and subsequently proven effective in clinical trials. Variations of the model have been applied in the study of adjunctive neuroprotective methods and piglet studies of xenon and melatonin have led to clinical phase I and II trials1,2. The piglet HIE model is further used for neonatal resuscitation- and hemodynamic studies as well as in investigations of cerebral hypoxia on a cellular level. However, it is a technically challenging model and variations in the protocol may result in either too mild or too severe brain injury. In this article, we demonstrate the technical procedures necessary for establishing a stable piglet model of neonatal HIE. First, the newborn piglet (&#60; 24 hr old, median weight 1500 g) is anesthetized, intubated, and monitored in a setup comparable to that found in a neonatal intensive care unit. Global hypoxia-ischemia is induced by lowering the inspiratory oxygen fraction to achieve global hypoxia, ischemia through hypotension and a flat trace amplitude integrated EEG (aEEG) indicative of cerebral hypoxia. Survival is promoted by adjusting oxygenation according to the aEEG response and blood pressure. Brain injury is quantified by histopathology and magnetic resonance imaging after 72 hr.

Hypoxic-ischemic encephalopathy following perinatal asphyxia can be studied using animal models. We demonstrate the procedures necessary for establishing a piglet model of neonatal hypoxic-ischemic encephalopathy.

דגם חזרזיר של ילודים חוסר חמצן-איסכמי אנצפלופתיה

Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the ...

Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats

Encephalopathy of prematurity (EoP) is a term that encompasses the central nervous system (CNS) abnormalities associated with preterm birth. To best advance translational objectives and uncover new therapeutic strategies for brain injury associated with preterm birth, preclinical models of EoP must include similar mechanisms of prenatal global injury observed in humans and involve multiple components of the maternal-placental-fetal system. Ideally, models should produce a similar spectrum of functional deficits in the mature animal and recapitulate multiple aspects of the pathophysiology. To mimic human systemic placental perfusion defects, placental underperfusion and/or chorioamnionitis associated with pathogen-induced inflammation in early preterm birth, we developed a model of prenatal transient systemic hypoxia-ischemia (TSHI) combined with intra-amniotic lipopolysaccharide (LPS). In pregnant Sprague Dawley rats, TSHI via uterine artery occlusion on embryonic day 18 (E18) induces a graded placental underperfusion defect associated with increasing CNS damage in the fetus. When combined with intra-amniotic LPS injections, placental inflammation is increased and CNS damage is compounded with associated white matter, gait and imaging abnormalities. Prenatal TSHI and TSHI+LPS prenatal insults meet several of the criteria of an EoP model including recapitulating the intrauterine insult, causing loss of neurons, oligodendrocytes and axons, loss of subplate, and functional deficits in adult animals that mimic those observed in children born extremely preterm. Moreover, this model allows for the dissection of inflammation induced by divergent injury types.

Encephalopathy of prematurity encompasses the central nervous system abnormalities associated with injury from preterm birth. This report describes a clinically relevant rat model of in utero transient systemic hypoxia-ischemia and intra-amniotic lipopolysaccharide administration (LPS) that mimics chorioamnionitis, and the related impact of infectious stimuli and placental underperfusion on CNS development.

דוגמנות אנצפלופתיה של פגות שימוש בהריון היפוקסיה-איסכמיה עם lipopolysaccharide Intra-השפיר בחולדות

Encephalopathy of prematurity (EoP) is a term that encompasses the central nervous system (CNS) abnormalities associated with preterm birth. To best ...

Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury

We performed unilateral carotid artery occlusion on CD-1 mice to create a neonatal hypoxic-ischemic (HI) model and investigated the effects of neonatal HI brain injury by studying neurobehavioral functions in these mice compared to non-operated (i.e., normal) mice. During the study, Rice-Vannucci&#39;s method was used to induce neonatal HI brain damage in postnatal day 7-10 (P7-10) mice. The HI operation was performed on the pups by unilateral carotid artery ligation and exposure to hypoxia (8% O2 and 92% N2 for 90 min). One week after the operation, the damaged brains were evaluated with the naked eye through the semi-transparent skull and were categorized into subgroups based on the absence (&#34;no cortical injury&#34; group) or presence (&#34;cortical injury&#34; group) of cortical injury, such as a lesion in the right hemisphere. On week 6, the following neurobehavioral tests were performed to evaluate the cognitive and motor functions: passive avoidance task (PAT), ladder walking test, and grip strength test. These behavioral tests are helpful in determining the effects of neonatal HI brain injury and are used in other mouse models of neurodegenerative diseases. In this study, neonatal HI brain injury mice showed motor deficits that corresponded to right hemisphere damage. The behavioral test results are relevant to the deficits observed in human neonatal HI patients, such as cerebral palsy or neonatal stroke patients. In this study, a mouse model of neonatal HI brain injury was established and showed different degrees of motor deficits and cognitive impairment compared to non-operated mice. This work provides basic information on the HI mouse model. MRI images demonstrate the different phenotypes, separated according to the severity of brain damage by motor and cognitive tests.

We performed unilateral carotid artery occlusion on postnatal day 7-10 CD-1 mouse pups to create a neonatal hypoxic-ischemic (HI) model and investigated the effects of HI brain injury. We studied neurobehavioral functions in these mice compared to non-operated normal mice.

Neurobehavioral הערכות במודל של עכברים של פגיעה מוחית לפציעה Hypoxic-איסכמי Neonatal

We performed unilateral carotid artery occlusion on CD-1 mice to create a neonatal hypoxic-ischemic (HI) model and investigated the effects of neonatal HI ...

Transient Middle Cerebral Artery Occlusion Model of Neonatal Stroke in P10 Rats

A number of animal models have been used to study hypoxic-ischemic injury, traumatic injury, global hypoxia, or permanent ischemia in both the immature and mature brain. Stroke occurs commonly in the perinatal period in humans, and transient ischemia-reperfusion is the most common form of stroke in neonates. The reperfusion phase is a critical component of injury progression, which occurs over a period of days to weeks, and of the endogenous response to injury. This postnatal day 10 (p10) rat model of transient middle cerebral artery occlusion (tMCAO) creates a unilateral, non-hemorrhagic focal ischemia-reperfusion injury that can be utilized to study the mechanisms of focal injury and repair in the full-term-equivalent brain. The injury pattern that is produced by tMCAO is consistent and highly reproducible and can be confirmed with MRI or histological analyses. The severity of injury can be manipulated through changes in occlusion time and other methods that will be discussed.

Neonatal stroke is a significant cause of early brain injury requiring a translational model with consistent focal injury patterns and high reproducibility in order to enable study. This study describes the detailed surgical procedure for creating a non-hemorrhagic, unilateral focal ischemia-reperfusion injury in full-term-equivalent rodents.

עורקי חלוף דגם ספיג תיכון שיתוק של שבץ ילודים אצל חולדות P10

A number of animal models have been used to study hypoxic-ischemic injury, traumatic injury, global hypoxia, or permanent ischemia in both the immature ...

A Ferret Model of Inflammation-sensitized Late Preterm Hypoxic-ischemic Brain Injury

There is an ongoing need for clinically relevant models of perinatal infection and hypoxia-ischemia (HI) in which to test therapeutic interventions for infants with the neurological sequela of prematurity. Ferrets are ideal candidates for modeling the preterm human brain, as they are born lissencephalic and develop gyrencephalic brains postnatally. At birth, ferret brain development is similar to a 13 week human fetus, with postnatal-day (P) 17 kits considered to be equivalent to an infant at 32&#8211;36 weeks&#39; gestation. We describe an injury model in the P17 ferret, where lipopolysaccharide administration is followed by bilateral cerebral ischemia, hypoxia, and hyperoxia. This simulates the complex interaction of prolonged inflammation, ischemia, hypoxia, and oxidative stress experienced in a number of neonates who develop brain injury. Injured animals display a range of gross injury severity, with morphological changes in the brain including narrowing of multiple cortical gyri and associated sulci. Injured animals also show slowed reflex development, slower and more variable speed of locomotion in an automated catwalk, and decreased exploration in an open field. This model provides a platform in which to test putative therapies for infants with neonatal encephalopathy associated with inflammation and HI, study mechanisms of injury that affect cortical development, and investigate pathways that provide resilience in unaffected animals.

The method describes inflammation-sensitized hypoxic-ischemic and hyperoxic brain injury in the P17 ferret to model the complex interaction between prolonged inflammation and oxidative brain injury experienced in a number of late preterm infants.

מודל של החמוס של דלקת-מארוי מאוחר לטווח קדם-הסכמי פגיעה במוח

There is an ongoing need for clinically relevant models of perinatal infection and hypoxia-ischemia (HI) in which to test therapeutic interventions for ...

Continuous Video Electroencephalogram during Hypoxia-Ischemia in Neonatal Mice

Hypoxia ischemia is the most common cause of neonatal seizures. Animal models are crucial for understanding the mechanisms and physiology underlying neonatal seizures and hypoxia ischemia. This manuscript describes a method for continuous video electroencephalogram (EEG) monitoring in neonatal mice to detect seizures and analyze EEG background during hypoxia ischemia. Use of video and EEG in conjunction allows description of seizure semiology and confirmation of seizures. This method also allows analysis of power spectrograms and EEG background pattern trends over the experimental time period. In this hypoxia ischemia model, the method allows EEG recording prior to injury to obtain a normative baseline and during injury and recovery. Total monitoring time is limited by the inability to separate pups from the mother for longer than four hours. Although, we have used a model of hypoxic-ischemic seizures in this manuscript, this method for neonatal video EEG monitoring could be applied to diverse disease and seizure models in rodents.

This manuscript describes a method for continuous video EEG recordings using multiple depth electrodes in neonatal mice undergoing hypoxia-ischemia.

אלקטרואנצפלוגרמה וידאו רציפה במהלך היפוקסיה-איסכמיה בעכברים יילודים

Hypoxia ischemia is the most common cause of neonatal seizures. Animal models are crucial for understanding the mechanisms and physiology underlying ...

Early Pathological and Magnetic Resonance Detection of Cerebral Injury Using a Rat Model of Neonatal Hypoxic Ischemic Encephalopathy

Perinatal hypoxic-ischemic encephalopathy (HIE) is an acute disease that may afflict newborns, resulting in variable long- and short-term neurodevelopmental outcomes. Early diagnosis is critical to identifying infants who may benefit from intervention; however, early diagnosis relies heavily on clinical criteria. No molecular or radiological tests have shown promise in detecting early cerebral injury. Studies have shown that magnetic resonance imaging (MRI) can show changes in both blood flow/ischemia and metabolic disruption. However, they have all been used to evaluate the secondary phase of the disease (&gt;12 h) after the onset of the injury. Early diagnosis is critical to rapidly starting therapeutic hypothermia in eligible infants, which is currently recommended to be initiated within 6 h of birth. The rat model of hypoxic-ischemic injury was developed in 1981 and has been validated and used extensively to study changes in brain perfusion, cerebral injury markers, and morphology. However, it has primarily been used as a "late model", evaluating injury several days after the initial ischemic insult. The model has been known to have poor sensitivity in evaluating reliable and reproducible early cerebral changes. The objective of this study was to develop a reliable model to study early gross morphological and radiological markers of HIE using pathological staining and cerebral magnetic resonance imaging/magnetic resonance spectroscopy.

The present protocol describes a rodent model of newborn hypoxic-ischemic injury for identifying early changes in cerebral tissue by gross morphology and magnetic resonance imaging. This has benefits over existing models, which can be used to study late injury but do not allow the evaluation of reproducible early changes.

Perinatal hypoxic-ischemic encephalopathy (HIE) is an acute disease that may afflict newborns, resulting in variable long- and short-term ...

Establishing a Mouse Model of Neonatal Hypoxic-Ischemic Brain Injury

Source: Kim, M., et al. <a href="https://app.jove.com/v/55838">Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury.</a> J. Vis. Exp. (2017).
The video demonstrates the procedure for creating a mouse model to study neonatal hypoxic-ischemic brain injury. It outlines the steps for surgically inducing ischemia and subjecting the animal to hypoxia to exacerbate brain damage. Finally, it shows how to assess the resulting brain lesions, ensuring the mouse model is prepared for further scientific investigation.