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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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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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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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