scholarly journals Brief Update on Animal Models of Hypoxic-Ischemic Encephalopathy and Neonatal Stroke

ILAR Journal ◽  
2006 ◽  
Vol 47 (1) ◽  
pp. 32-38 ◽  
Author(s):  
F. J. Northington
Keyword(s):  
Animal Models ◽  
Hypoxic Ischemic Encephalopathy ◽  
Neonatal Stroke ◽  
Ischemic Encephalopathy

Animal models of hypoxic-ischemic encephalopathy: optimal choices for the best outcomes

2017 ◽  
Vol 28 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Lan Huang ◽  
Fengyan Zhao ◽  
Yi Qu ◽  
Li Zhang ◽  
Yan Wang ◽  
...  
Keyword(s):  
Animal Models ◽  
Small Animal ◽  
Underlying Disease ◽  
Therapeutic Interventions ◽  
Hypoxic Ischemic Encephalopathy ◽  
Large Animal ◽  
Large Animal Models ◽  
Neurological Research ◽  
Serious Disease ◽  
Ischemic Encephalopathy

AbstractHypoxic-ischemic encephalopathy (HIE), a serious disease leading to neonatal death, is becoming a key area of pediatric neurological research. Despite remarkable advances in the understanding of HIE, the explicit pathogenesis of HIE is unclear, and well-established treatments are absent. Animal models are usually considered as the first step in the exploration of the underlying disease and in evaluating promising therapeutic interventions. Various animal models of HIE have been developed with distinct characteristics, and it is important to choose an appropriate animal model according to the experimental objectives. Generally, small animal models may be more suitable for exploring the mechanisms of HIE, whereas large animal models are better for translational studies. This review focuses on the features of commonly used HIE animal models with respect to their modeling strategies, merits, and shortcomings, and associated neuropathological changes, providing a comprehensive reference for improving existing animal models and developing new animal models.

scholarly journals New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy

2021 ◽  
Author(s):  
Suresh Victor ◽  
Eridan Rocha-Ferreira ◽  
Ahad Rahim ◽  
Henrik Hagberg ◽  
David Edwards
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Therapeutic Hypothermia ◽  
Treatment Options ◽  
Standard Of Care ◽  
High Income ◽  
Hypoxic Ischemic Encephalopathy ◽  
Pharmacodynamic Modelling ◽  
Dose Ranging ◽  
Ischemic Encephalopathy

AbstractAround 0.75 million babies worldwide suffer from moderate or severe hypoxic-ischemic encephalopathy (HIE) each year resulting in around 400,000 babies with neurodevelopmental impairment. In 2010, neonatal HIE was associated with 2.4% of the total Global Burden of Disease. Therapeutic hypothermia (TH), a treatment that is now standard of care in high-income countries, provides proof of concept that strategies that aim to improve neurodevelopment are not only possible but can also be implemented to clinical practice. While TH is beneficial, neonates with moderate or severe HIE treated with TH still experience devastating complications: 48% (range: 44–53) combined death or moderate/severe disability. There is a concern that TH may not be effective in low- and middle-income countries. Therapies that further improve outcomes are desperately needed, and in high-income countries, they must be tested in conjunction with TH. We have in this review focussed on pharmacological treatment options (e.g. erythropoietin, allopurinol, melatonin, cannabidiol, exendin-4/exenatide). Erythropoietin and allopurinol show promise and are progressing towards the clinic with ongoing definitive phase 3 randomised placebo-controlled trials. However, there remain global challenges for the next decade. Conclusion: There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials to avoid exposure to harmful medications or abandoning putative treatments. What is Known:• Therapeutic hypothermia is beneficial in neonatal hypoxic-ischemic encephalopathy.• Neonates with moderate or severe hypoxic-ischemic encephalopathy treated with therapeutic hypothermia still experience severe sequelae. What is New:• Erythropoietin, allopurinol, melatonin, cannabidiol, and exendin-4/exenatide show promise in conjunction with therapeutic hypothermia.• There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials.

scholarly journals P.021 Esophageal cooling for hypoxic ischemic encephalopathy: a feasibility study

2019 ◽  
Vol 46 (s1) ◽  
pp. S19
Author(s):  
T Smith ◽  
P Couillard ◽  
P Hruska ◽  
P McBeth ◽  
J Kortbeek
Keyword(s):  
Cardiac Arrest ◽  
Animal Models ◽  
Feasibility Study ◽  
Primary Outcome ◽  
Hypoxic Ischemic Encephalopathy ◽  
Temperature Management ◽  
Target Temperature ◽  
Cooling Device ◽  
Icu Patients ◽  
Ischemic Encephalopathy

Background: Targeted temperature management (TTM) is a recognized treatment to decrease mortality and improve neurological functionin hypoxic ischemic encephalopathy (HIE). An esophageal cooling device (ECD) has been studied in animal models but human data is limited. ECD appear to offer similar benefits to intravascular cooling catheters with potentially less risk to the patient. We studied whether the ECD could act as a substitute for intravascular cooling catheters. Methods: Eight ICU patients admitted following cardiac arrest who required TTM were enrolled prospectively. The primary outcome measures were timeliness of insertion, ease of insertion, user Likert ratings, time to achieve a target temperature of 36˚C and time target temperature was maintained within 0.5˚C of the 36˚C goal for 24 hours using an ECD. Results: Time to reach target temperature 0 min to 540 min. ECD appeared to be effective at maintaining a target temperature of 36˚C for most patients. In general, the catheter was easy to insert and use. Conclusions: For patients requiring TTM, use of an ECDadequately allowed for TTM goalsto be achieved and maintained. Overall user evaluationwas positive.

scholarly journals Magnetic Resonance Imaging Findings of Term and Preterm Hypoxic-Ischemic Encephalopathy: A Review of Relevant Animal Models and Correlation to Human Imaging

2018 ◽  
Vol 12 (1) ◽  
pp. 55-65 ◽  
Author(s):  
Kyle A. Jisa ◽  
Dillon D. Clarey ◽  
Eric S. Peeples
Keyword(s):  
Magnetic Resonance Imaging ◽  
Brain Injury ◽  
Magnetic Resonance ◽  
Animal Models ◽  
Disease Process ◽  
Hypoxic Ischemic Encephalopathy ◽  
Imaging Findings ◽  
Resonance Imaging ◽  
Human Neonates ◽  
Ischemic Encephalopathy

Background:Neonatal hypoxic-ischemic encephalopathy is brain injury caused by decreased perfusion and oxygen delivery that most commonly occurs in the context of delivery complications such as umbilical cord compression or placental abruption. Imaging is a key component for guiding treatment and prediction of prognosis, and the most sensitive clinical imaging modality for the brain injury patterns seen in hypoxic-ischemic encephalopathy is magnetic resonance imaging.Objective:The goal of this review is to compare magnetic resonance imaging findings demonstrated in the available animal models of hypoxic-ischemic encephalopathy to those found in preterm (≤ 36 weeks) and term (>36 weeks) human neonates with hypoxic-ischemic encephalopathy, with special attention to the strengths and weaknesses of each model.Methods:A structured literature search was performed independently by two authors and the results of the searches were compiled. Animal model, human brain age equivalency, mechanism of injury, and area of brain injury were recorded for comparison to imaging findings in preterm and term human neonates with hypoxic-ischemic encephalopathy.Conclusion:Numerous animal models have been developed to better elicit the expected findings that occur after HIE by allowing investigators to control many of the clinical variables that result in injury. Although modeling the same disease process, magnetic resonance imaging findings in the animal models vary with the species and methods used to induce hypoxia and ischemia. The further development of animal models of HIE should include a focus on comparing imaging findings, and not just pathologic findings, to human studies.

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