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Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

Neural Regeneration Research 2025年第11期20卷 3144-3150页

作者： Holly Flyger Samantha j.Holdsworth alistair.j.gunn Laura Bennet Hamid Abbasi Mātai Medical Research Institute Tairāwhiti GisborneNew Zealand Department of Anatomy&Medical Imaging Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand Center for Brain Research The University of AucklandAucklandNew Zealand Auckland Bioengineering Institute The University of AucklandAucklandNew Zealand

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental *** assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and *** present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic *** review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent *** review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic *** challenges limit the timing consistency,particularly the need for intensive care and clinical ***,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after *** suggests that in the future it will be important to explore a wider range of times after hypo

关键词： magnetic resonance imaging neonatal hypoxic-ischemic encephalopathy neurodevelopmental outcomes prognostic biomarkers in neuroimaging scan timing therapeutic hypothermia

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Does MgSO_(4) protect the preterm brain?Dissecting its role in the pathophysiology of hypoxic ischemic encephalopathy

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Neural Regeneration Research 2024年第9期19卷 1861-1862页

作者： Robert Galinsky Laura Bennet alistair.j.gunn The Ritchie Centre Hudson Institute of Medical ResearchMelbourneVICAustralia Department of Obstetrics and Gynaecology Monash UniversityMelbourneVICAustralia Department of Physiology The University of AucklandAucklandNew Zealand

Mitigating preterm encephalopathy continues to be one of the greatest challenges in perinatal *** encephalopathy is associated with high mortality,serious morbidity,and significant socio-economic impacts on the individuals,their families,and public health sectors and welfare systems that last a *** cost of disability associated with preterm brain injury continues to *** of this injury,and disability,would significantly reduce this socioeconomic burden.

关键词： encephalopathy mortality hypoxic

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Challenges in developing therapeutic strategies for mild neonatal encephalopathy

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Neural Regeneration Research 2022年第2期17卷 277-282页

作者： Alice McDouall Guido Wassink Laura Bennet alistair.j.gunn joanne O.Davidson Department of Physiology The University of AucklandAucklandNew Zealand

There is increasing evidence that infants with mild neonatal encephalopathy(NE) have significant risks of mortality, brain injury and adverse neurodevelopmental outcomes. In the era of therapeutic hypothermia, infants need to be diagnosed within 6 hours of birth, corresponding with the window of opportunity for treatment of moderate to severe NE, compared to the retrospective grading over 2 to 3 days, typically with imaging and formal electroencephalographic assessment in the pre-hypothermia era. This shift in diagnosis may have increased the apparent prevalence of brain damage and poor neurological outcomes seen in infants with mild NE in the era of hypothermia. Abnormal short term outcomes observed in infants with mild NE include seizures, abnormal neurologic examination at discharge, abnormal brain magnetic resonance imaging and difficulty feeding. At 2 to 3 years of age, mild NE has been associated with an increased risk of autism, language and cognitive deficits. There are no approved treatment strategies for these infants as they were not included in the initial randomized controlled trials for therapeutic hypothermia. However, there is already therapeutic creep, with many centers treating infants with mild NE despite the limited evidence for its safety and efficacy. The optimal duration of treatment and therapeutic window of opportunity for effective treatment need to be specifically established for mild NE as the evolution of injury is likely to be slower, based on preclinical data. Randomized controlled trials of therapeutic hypothermia for infants with mild NE are urgently required to establish the safety and efficacy of treatment. This review will examine the evidence for adverse outcomes after mild NE and dissect some of the challenges in developing therapeutic strategies for mild NE, before analyzing the evidence for therapeutic hypothermia and other strategies for treatment of these infants.

关键词： asphyxia electroencephalogram erythropoietin mild hypoxic ischemic encephalopathy neonatal encephalopathy neurological examination neuroprotection Sarnat score therapeutic hypothermia

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Can we further optimize therapeutic hypothermia for hypoxic-ischemic encephalopathy?

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Neural Regeneration Research 2019年第10期14卷 1678-1683页

作者： Anthony Davies Guido Wassink Laura Bennet alistair.j.gunn joanne O.Davidson Department of Physiology The University of Auckland

Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and *** hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy;however,many infants still experience lifelong disabilities to movement,sensation and *** guidelines,based on strong clinical and preclinical evidence,recommend therapeutic hypothermia should be started within 6 hours of birth and continued for a period of 72 hours,with a target brain temperature of 33.5 ±0.5℃ for infants with moderate to severe hypoxic-ischemic *** clinical guidelines also recommend that infants be re warmed at a rate of 0.5℃ per hour,but this is not based on strong *** are no randomized controlled trials investigating the optimal rate of rewarming after therapeutic hypothermia for infants with hypoxic-ischemic *** studies of rewarming are conflicting and results were confounded by treatment with sub-optimal durations of *** this review,we evaluate the evidence for the optimal start time,duration and depth of hypothermia,and whether the rate of rewarming after treatment affects brain injury and neurological outcomes.

关键词： hypoxia-ischemia hypoxic-ischemic encephalopathy therapeutic hypothermia neuroprotection therapeutic strategies randomized controlled trials animal models fetal sheep piglets

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Glia and hemichannels: key mediators of perinatal encephalopathy

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Neural Regeneration Research 2018年第2期13卷 181-189页

作者： Robert Galinsky joanne O.Davidson justin M.Dean Colin R.Green Laura Bennet alistair.j.gunn Department of Physiology University of Auckland The Ritchie Centre Hudson Institute of Medical Research Department of Ophthalmology University of Auckland

Perinatal encephalopathy remains a major cause of disability, such as cerebral palsy. Therapeutic hypo- thermia is now well established to partially reduce risk of disability in late preterm/term infants. However, new and complementary therapeutic targets are needed to further improve outcomes. There is increasing evidence that glia play a key role in neural damage after hypoxia-ischemia and infection/inflammation. In this review, we discuss the role of astrocytic gap junction （connexin） hemichannels in the spread of neural injury after hypoxia-ischemia and/or infection/inflammation. Potential mechanisms of hemichannel medi- ated injury likely involve impaired intraceUular calcium handling, loss of blood-brain barrier integrity and release of adenosine triphosphate （ATP） resulting in over-activation of purinergic receptors. We propose the hypothesis that inflammation-induced opening of connexin hemichannels is a key regulating event that initiates a vicious cycle of excessive ATP release, which in turn propagates activation of purinergic receptors on microglia and astrocytes. This suggests that developing new neuroprotective strategies for preterm infants will benefit from a detailed understanding of glial and connexin hemichannel responses.

关键词： hypoxia-ischemia connexin hemichannels spreading injury connexin 43 astrocytes hypoxicischemic encephalopathy

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Diabetic retinopathy: recent advances towards understanding neurodegeneration and vision loss

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Science China(Life Sciences) 2015年第6期58卷 541-549页

作者： BARBER alistair j. Penn State Hershey Eye Center Penn State Hershey College of Medicine Milton S. Hershey Medical Center

Diabetic retinopathy （DR） is one of the most common retinal diseases world-wide. It has a complex pathology that involves the vasculature of the inner retina and breakdown of the blood-retinal barrier. Extensive research has determined that DR is not only a vascular disease but also has a neurodegenerative component and that essentially all types of ceils in the retina are affected, leading to chronic loss of visual function. A great deal of work using animal models of DR has established the loss of neurons and pathology of other cell types, including supporting glial cells. There has also been an increased emphasis on measuring retinal function in the models, as well as further validation and extension of the animal studies by clinical and translational research. This article will attempt to summarize the more recent developments in research towards understanding the complexities of retinal neurodegeneration and functional vision loss in DR.

关键词： retina diabetes neurodegeneration visual function vascular function apoptosis synapse dendrite

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Interleukin-1:an important target for perinatal neuroprotection?

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Neural Regeneration Research 2023年第1期18卷 47-50页

作者： Sharmony B.Kelly Elys Green Rod W.Hunt Claudia A.Nold-Petry alistair.j.gunn Marcel F.Nold Robert Galinsky The Ritchie Centre Hudson Institute of Medical ResearchMelbourneVictoriaAustralia Department of Obstetrics and Gynaecology Monash UniversityVictoriaAustralia Department of Pediatrics Monash UniversityVictoriaAustralia Monash Newborn Monash Children’s HospitalMelbourneAustralia Department of Physiology The University of AucklandAucklandNew Zealand

Perinatal inflammation is a significant risk factor for lifelong neurodevelopmental impairments such as cerebral *** clinical and preclinical evidence links the severity and pattern of perinatal inflammation to impaired maturation of white and grey matters and reduced brain *** pathways are involved in the pathogenesis of perinatal ***,studies of human and experimental perinatal encephalopathy have demonstrated a strong causative link between perinatal encephalopathy and excessive production of the pro-inflammatory effector cytokine *** this review,we summarize clinical and preclinical evidence that underpins interleukin-1 as a critical factor in initiating and perpatuating systemic and central nervous system inflammation and subsequent perinatal brain *** also highlight the important role of endogenous interleukin-1 receptor antagonist in mitigating interleukin-1-driven neuroinflammation and tissue damage,and summarize outcomes from clinical and mechanistic animal studies that establish the commercially available interleukin-1 receptor antagonist,anakinra,as a safe and effective therapeutic *** reflect on the evidence supporting clinical translation of interleukin-1 receptor antagonist for infants at the greatest risk of perinatal inflammation and impaired neurodevelopment,and suggest a path to advance interleukin-1 receptor antagonist along the translational path for perinatal neuroprotection.

关键词： brain inflammation interleukin-1 receptor antagonist interleukin-1 interleukin-1β neonatal encephalopathy neuroprotection preterm brain injury

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Paleobiological significance of the james Ross Basin

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Advances in Polar Science 2019年第3期30卷 186-198页

作者： j.alistair CRAME British Antarctic Survey High CrossMadingley RoadCambridge CB3 0ETUK

The extensive Late Mesozoic–Early Cenozoic sedimentary succession exposed within the james Ross Basin,Antarctica has huge potential to enhance paleobiological investigations into both the marine and terrestrial fossil *** excess of 7 km in total thickness and spanning the Early Cretaceous(Aptian)–Late Eocene in age,it represents an invaluable high-latitude(~65°S)site for comparison with lower latitude,tropical ones in an essentially greenhouse *** Early Cretaceous(Aptian–Albian)sequence is deep-water but there are indications of shallowing to inner shelf depths in both the Turonian and Coniacian *** first prolific shallow-water marine fauna occurs in the Santonian–Campanian Santa Marta Formation and this is followed by repeated occurrences through the later Campanian,Maastrichtian,Danian and Middle Eocene(Lutetian).In this study an attempt has been made to compare these Antarctic faunas directly with the well-known ones of the same age from the US Gulf *** comparisons made for three time slices,Late Maastrichtian,Danian and Middle Eocene,indicate that the Antarctic is characterised by both low taxonomic diversity and high levels of *** james Ross Basin is providing important evidence to indicate that the highest southern latitudes have always been characterised by a distinctive temperate biota,even on a pre-glacial *** roots of at least some elements of the modern Southern Ocean biota can be traced back to a Late Mesozoic–Early Cenozoic austral realm.

关键词： james Ross Basin biostratigraphy molluscan faunas US Gulf Coast biodiversity patterns evolutionof temperate biotas

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Chromodynamic Lattice Boltzmann Method for the Simulation of Drops,Erythrocytes,and other Vesicles

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Communications in Computational Physics 2023年第1期33卷 283-309页

作者： j.Spendlove X.Xu T.Schenkel j.P.gunn I.Halliday Department of Engineering and Mathematics Sheffield Hallam UniversityHoward StreetS11WBUK Materials&Engineering Research Institute Sheffield Hallam UniversityHoward StreetS11WBUK Department of Infection Immunity and Cardiovascular DiseaseThe Medical SchoolBeech Hill RoadSheffieldS102RXUK

Recently,we have validated a three-dimensional,single framework multicomponent lattice Boltzmann method,modified to generate vesicles(rather than drops)[“Three-dimensional single framework multicomponent lattice Boltzmann equation method for vesicle hydrodynamics,”*** 33,077110(2021)].This approach implements an immersed boundary force distribution,characterised by bending rigidity,surface tension,preferred curvature and conserved membrane area,in which work we successfully validated isolated vesicle flows against other methodologies and *** most immersed boundary algorithms,our method relies on numerical computation of high-order spatial derivatives and an intricate body force *** next step is to verify that it has sufficient numerical stability to address the anticipated application of high volume fraction flows of highly deformable objects in intimate *** is this in silico verification-of both the class of fluid object attainable and the stability of the later in strong,straining and shearing flows which is at issue,*** extend our method to simulate multiple variously deflated vesicles and multiple liquid droplets still within a single framework,from which our fluid objects emerge as particular *** present data from simulations containing up to four vesicles(five immiscible fluid species),which threshold verifies that simulations containing unlimited fluid objects are possible[“Modeling the flow of dense suspensions of deformable particles in three dimensions,”***.E 75,066707(2007)].These data also assure the ability of our immersed boundary forcing to preserve the character and integrity of fluid objects in interactions characterised by large local velocity gradients(intimate squeezing,shearing and elongational straining).Throughout,we take interfacial or membrane area,A,as a proxy for stability and physical veracity.

关键词： Lattice Boltzmann membranes vesicles

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A geocomputational analysis of Twitter activity around different world cities

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Geo-Spatial Information Science 2014年第3期17卷 145-152页

作者： Muhammad ADNAN alistair LEAK Paul LONGLEY Department of Geography University College LondonGower StreetLondon WC1E 6BTUK Department of Security and Crime Science University College London35 Tavistock SquareLondon WC1H 9EZUK

The penetration and use of social media services differs from city to *** paper is aimed to provide a comparison of the use of Twitter between different cities of the *** present a temporal analysis of activity on Twitter in 15 *** study consists of two parts:First,we created temporal graphs of the activity in the 15 cities,through which hours of high and low activity could be ***,we created heat map visualizations of the Twitter activities during the period of 19 September 2012–25 September *** heat map visualizations make the periods of intense and sparse activity apparent and provide a snapshot of the activity during the whole year.

关键词： Twitter temporal analysis heat map visualization activity patterns

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