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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

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

Amnion epithelial cells——a novel therapy for ischemic stroke?

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Neural Regeneration Research 2018年第8期13卷 1346-1349页

作者： Megan A.Evans Brad R.S.Broughton Grant R.Drummond Henry Ma Thanh G.Phan Euan M.Wallace Rebecca Lim Christopher G.Sobey Department of Physiology Anatomy & Microbiology La Trobe University Cardiovascular Disease Program Department of Pharmacology Biomedicine Discovery Institute Monash University Department of Medicine Monash University the ritchie centre Hudson Institute of Medical Research Department of Obstetrics and Gynaecology Monash University

Stroke is a leading cause of death and disability and new therapies are desperately needed. Given the complex nature of ischemic brain injury, it has been postulated that cell-based therapies may be useful. However, cell resources, invasive extraction procedures, immunological rejection, tumorigenesis and ethical challenges make it unlikely that many stem cell types could serve as a practical source for therapy. By contrast, these issues do not pertain to human amnion epithelial cells（h AECs）, which are placenta-derived stem cells. We recently assessed the effects of systemically delivered hAECs on stroke outcome using four animal models of stroke. We demonstrated that when injected intravenously after ischemia onset, hAECs migrate preferentially to the spleen and injured brain to limit apoptosis and inflammation, and attenuate early brain infiltration of immune cells, progression of infarction and systemic immunosuppression and to ultimately ameliorate functional deficits. When administration of hAECs is delayed by 1-3 days poststroke, long-term functional recovery can still be enhanced in young and aged mice of either sex. Moreover, our proof-of-principle findings suggest that h AECs are effective at limiting post-stroke infarct development in non-human primates. Overall, the results suggest that hAECs could be a viable clinical stroke therapy.

关键词： ischemic stroke cerebral infarction stem cells human amnion epithelial cells inflammation immunosuppression brain repair mouse non-human primate

Mesenchymal stem cell tracking in the intervertebral disc

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World Journal of Stem Cells 2015年第1期7卷 65-74页

作者： Charles Handley Tony Goldschlager David Oehme Peter Ghosh Graham Jenkin the ritchie centre Monash Institute of Medical Research Monash University Clayton VIC 3168 Australia Department of Neurosurgery Monash Medical Centre Clayton VIC 3168 Australia Department of Neurosurgery St Vincent’s Hospital Fitzroy VIC 3065 Australia Proteobioactives Research Laboratories Brookvale NSW 2100 Australia

Low back pain is a common clinical problem, which leads to significant social, economic and public health costs. Intervertebral disc(IVD) degeneration is accepted as a common cause of low back pain. Initially, this is characterized by a loss of proteoglycans from the nucleus pulposus resulting in loss of tissue hydration and hydrostatic pressure. Conservative management,including analgesia and physiotherapy often fails and surgical treatment, such as spinal fusion, is required. Stem cells offer an exciting possible regenerative approach to IVD disease. Preclinical research has demonstrated promising biochemical, histological and radiological results in restoring degenerate IVDs. Cell tracking provides an opportunity to develop an in-depth understanding of stem cell survival, differentiation and migration, enabling optimization of stem cell treatment. Magnetic Resonance Imaging(MRI) is a non-invasive, non-ionizing imaging modality with high spatial resolution, ideally suited for stem cell tracking. Furthermore, novel MRI sequences have the potential to quantitatively assess IVD disease, providing an improved method to review response to biological treatment. Superparamagnetic iron oxide nanoparticles have been extensively researched for the purpose of cell tracking. These particles are biocompatible, non-toxic and act as excellent MRI contrast agents. This review will explore recent advances and issues in stem cell tracking and molecular imaging in relation to the IVD.

关键词： Intervertebral disc Stem cells Cell tracking Magnetic resonance imaging Intervertebral disc degeneration

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

Thirteen years to get from b to a:one of the neglected isoforms of IL-37 enters the stage

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Cellular & Molecular Immunology 2024年第2期21卷 201-202页

作者： Steven X.Cho Ina Rudloff Andrew M.Ellisdon Claudia A.Nold-Petry Marcel F.Nold ritchie centre Hudson Institute of Medical ResearchMelbourneVICAustralia Department of Pediatrics Monash UniversityMelbourneVICAustralia Cancer Program Biomedicine Discovery InstituteMonash UniversityMelbourneVICAustralia Monash Newborn Monash Children’s HospitalMelbourneVICAustralia

Interleukin(IL)-37 is one of the few anti-inflammatory members of the predominantly pro-inflammatory IL-1 cytokine ***-37 possesses alarmin-like properties[1]and exerts its activities via intracellular[2]as well as cell surface receptor-dependent mechanisms,and the latter involves IL-1R8 and IL-18Rα[3].Because of its powerful and broad-spectrum“peacemaking”[4]functions,considerable efforts have been invested in developing IL-37-based anti-inflammatory therapeutics[5,6].

关键词： Interleukin neglected cytokine

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睡眠中婴儿对低氧的初始通气反应的变异性

世界核心医学期刊文摘（儿科学分册） 2006年第12期2卷 55-56页

作者： Richardson H.L. Parslow P.M. Walker A.M. R.S.C. Horne 王经纬 ritchie centre for Baby Health Research Monash Medical Centre246 Clayton RoadClaytonVic.3168Australia Dr.

Most of the available data on the hypoxic ventilatory response(HVR) in infants has been obtained in quiet sleep (QS),and only one study has made repeated tests in the same infant. We aimed to gain a more complete knowledge of the maturation and consistency of the initial phase of the HVR by performing multiple tests in both QS and active sleep (AS) over the first 6 mo of life in term infants. Fifteen healthy term infants were studied with daytime polysomnography longitudinally at 2-5 wk,2-3 mo,and 5-6 mo after birth. Each infant received multiple hypoxic(15%O2,balance N2) challenges (three or more) in bothAS and QS. In AS,infants consistently aroused to hypoxia; however,in QS,infants both aroused and failed to arouse. The initial phase of the HVR varied considerably between infants with the changes in ventilation/kg SD of inspired minute ventilation per kilogram of body weight ( /kg) being more variable during AS than QS at all three ages and overall decreasing with postnatal age in both sleep states. The variability between replicate VI·/kg measurements was also significantly greater in AS compared with QS at 2-5 wk postnatal age. There was no evidence of habituation to repeated hypoxic tests in either sleep *** study has demonstrated that the initial phase of the HVR is variable both between and within term infants in both AS and QS,with responses being markedly more variable during AS,and becoming more consistent with increasing postnatal *** performing only one test or by failing to account for arousal responses,previous studies may not have detected the natural variation of the infant HVR.

关键词：通气反应低氧睡眠状态初始反应多导睡眠图出生后自然变异变动性重复测定

Predictive models for mild cognitive impairment to Alzheimer's disease conversion

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Neural Regeneration Research 2021年第9期16卷 1766-1767页

作者： Konstantina Skolariki Graciella Muniz Terrera Samuel O.Danso Bioinformatics and Human Electrophysiology Laboratory Ionian UniversityCorfuGreece centre for Dementia Prevention University of EdinburghUK Division of Neuroimaging Centre for Clinical Brain Sciences and Edinburgh ImagingUniversity of EdinburghScotlandUK

Alzheimer's disease(AD) is an irreversible and progressive neurodegenerative disease as well as the most common form of dementia. It usually affects the older population, but early onset AD is still possible(ritchie e... 详细信息

关键词： Alzheimer al. impairment

Treatment review of sight threatening circumscribed choroidal haemangioma

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International Journal of Ophthalmology(English edition) 2010年第2期3卷 168-171页

作者： James FT Li Yim Teresa Sandinha Jan M Kerr Diana ritchie Ewan G Kemp Tennent Institute of Ophthalmology GlasgowScotlandUK Beatson Oncology centre GlasgowScotlandUK

AIMTo describe our clinical experience in treating circumscribed choroidal haemangioma (CCH) in a tertiary referral centre over a fifteen year period prior to photodynamic therapy.

关键词： circumscribed choroidal haemangioma plaque brachytherapy transpupillary thermotherapy