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postnatal hypoxia‐ischaemia

Yingying Hu, Zhouguang Wang, Shulin Pan, Hongyu Zhang, Mingchu Fang, Huai Jiang, Hao Zhang, Zhengzheng Gao, Kebin Xu, Zhenmao Li, Jian Xiao, Zhenlang Lin
Hypoxic-ischemic and inflammatory (HII) induces the disruption of blood-brain barrier (BBB) which leads to inflammatory responses and neuronal cell death, resulting in brain secondary damage. Previous studies showed that melatonin produced potent neuroprotective effects in neonatal hypoxic-ischaemic models. However, the relationship between BBB disruption and melatonin in HII was still unclear. The present study therefore investigated the beneficial effects of melatonin on BBB after HII and the underlying mechanisms...
May 9, 2017: Oncotarget
Thomas Wood, Catherine Hobbs, Mari Falck, Anne Charlotte Brun, Else Marit Løberg, Marianne Thoresen
BACKGROUND: Hyperthermia after hypoxia-ischaemia (HI) in newborn infants is associated with worse neurological outcomes. Loss of thermoregulation may also be associated with greater injury. METHODS: In the postnatal-day 7 (P7) rat, the effect of 5h of graded hyperthermia (38°C or 39°C) immediately after unilateral HI was compared to normothermia (NT, 37°C), and therapeutic hypothermia (TH, 32°C). Early (negative geotaxis) and late (staircase test) behavioural testing was performed, as well as neuropathology scoring in adulthood...
March 13, 2017: Pediatric Research
Patrícia Maidana Miguel, Bruna Ferrary Deniz, Iohanna Deckmann, Heloísa Deola Confortim, Ramiro Diaz, Daniela Pereira Laureano, Patrícia Pelufo Silveira, Lenir Orlandi Pereira
OBJECTIVES: The attention-deficit/hyperactivity disorder (ADHD) compromises the quality of life of individuals including adaptation to the social environment. ADHD aetiology includes perinatal conditions such as hypoxic-ischaemic events; preclinical studies have demonstrated attentional deficits and impulsive-hyperactive outcomes after neonatal hypoxic and/or ischaemic intervention, but data are missing to understand this relationship. Thus, the aim of this study was to evaluate executive function (EF) and impulsivity, and tissue integrity and dopaminergic function in the prefrontal cortex (PFC) of rats submitted to hypoxia-ischaemia (HI)...
January 20, 2017: World Journal of Biological Psychiatry
Thomas Wood, Damjan Osredkar, Maja Puchades, Elke Maes, Mari Falck, Torun Flatebø, Lars Walløe, Hemmen Sabir, Marianne Thoresen
Therapeutic hypothermia (HT) is standard care for moderate and severe neonatal hypoxic-ischaemic encephalopathy (HIE), the leading cause of permanent brain injury in term newborns. However, the optimal temperature for HT is still unknown, and few preclinical studies have compared multiple HT treatment temperatures. Additionally, HT may not benefit infants with severe encephalopathy. In a neonatal rat model of unilateral hypoxia-ischaemia (HI), the effect of five different HT temperatures was investigated after either moderate or severe injury...
March 21, 2016: Scientific Reports
Elisa Smit, Xun Liu, Hannah Gill, Sally Jary, Thomas Wood, Marianne Thoresen
AIM: Infants with birth asphyxia frequently require resuscitation. Current guidance is to start newborn resuscitation in 21% oxygen. However, infants with severe hypoxia-ischaemia may require prolonged resuscitation with oxygen. To date, no study has looked at the effect of resuscitation in 100% oxygen following a severe hypoxic-ischaemic insult. METHODS: Postnatal day 7 Wistar rats underwent a severe hypoxic-ischaemic insult (modified Vannucci unilateral brain injury model) followed by immediate resuscitation in either 21% or 100% oxygen for 30 min...
November 2015: Resuscitation
Damjan Osredkar, Hemmen Sabir, Mari Falck, Thomas Wood, Elke Maes, Torun Flatebø, Maja Puchades, Marianne Thoresen
INTRODUCTION: Bacterial lipopolysaccharide (LPS) injection prior to hypoxia-ischaemia significantly increases hypoxia-ischaemic brain injury in 7-day-old (P7) rats. In addition, therapeutic hypothermia (HT) is not neuroprotective in this setting. However, the mechanistic aspects of this therapeutic failure have yet to be elucidated. This study was designed to investigate the underlying cellular mechanisms in this double-hit model of infection-sensitised hypoxia-ischaemic brain injury...
2015: Developmental Neuroscience
R Wieczór, G Gadomska, B Góralczyk, K Stankowska, J Budzyński, J Fabisiak, K Suppan, G Pulkowski, D Rość
AIM: The number of people suffering from atherosclerosis-related complications such as peripheral arterial disease (PAD) ‑ including lower limbs PAD increases. Hypoxia and ischemia stimulate angiogenesis ‑ a postnatal multistage process in which new blood vessels form and the Vascular Endothelial Growth Factor (VEGF-A) is the key proangiogenic factor whereas its soluble receptors type 1 and type 2 (sVEGFR-1, sVEGFR-2) are regarded as inhibitory factors. The aim of this study was to assess the concentrations of VEGF-A, sVEGFR-1 and sVEGFR-2 in plasma of patients with symptomatic lower extremity PAD compared with selected clinical parameters (Ankle-Brachial Index, distance in walking test) and severity of PAD (according to the Fontaine classification)...
December 2015: International Angiology: a Journal of the International Union of Angiology
Shyama D Patel, Leslie Pierce, Amber J Ciardiello, Susan J Vannucci
Neonatal encephalopathy resulting from HI (hypoxia-ischaemia) continues to be a significant cause of mortality and morbidity in infants and children, affecting 1-2/1000 live term births and up to 60% of pre-term births. In order to understand the pathophysiology of this insult, as well as design therapeutic interventions, it is important to establish a relevant animal model for pre-clinical studies. One of the most frequently used models of HI-induced brain damage in immature animals is the unilateral carotid ligation/hypoxia model, initially developed in our laboratory more than 30 years ago...
April 2014: Biochemical Society Transactions
H E Reinebrant, J A Wixey, K M Buller
Neuronal losses have been shown to occur in the brainstem following a neonatal hypoxic-ischaemic (HI) insult. In particular serotonergic neurons, situated in the dorsal raphé nuclei, appear to be vulnerable to HI injury. Nonetheless the mechanisms contributing to losses of serotonergic neurons in the brainstem remain to be elucidated. One possible mechanism is that disruption of neural projections from damaged forebrain areas to dorsal raphé nuclei may play a role in the demise of serotonergic neurons. To test this, postnatal day 3 (P3) rat pups underwent unilateral common carotid artery ligation followed by hypoxia (6% O₂ for 30 min)...
September 17, 2013: Neuroscience
Himani S Ranasinghe, Arjan Scheepens, Ernest Sirimanne, Murray D Mitchell, Christopher E Williams, Mhoyra Fraser
Perinatal hypoxic ischemic (HI) brain injury is a leading cause of long-term neurological handicap in newborn babies. Recently, excessive activity of matrix metalloproteinases (MMPs), and in particular MMP-9, has been implicated in the aetiology of HI injuries to the immature brain. Our previous study suggested that MMP-9 may be involved in the development of the delayed injury processes following HI injury to the developing brain. Given this, we therefore propose that MMP-9 may be a useful target for rescue therapies in the injured developing brain...
2012: Developmental Neuroscience
Sylvie Girard, Hugues Sébire, Marie-Elsa Brochu, Sinziana Briota, Philippe Sarret, Guillaume Sébire
New therapeutic strategies are needed to protect neonates, especially premature newborns, against brain injury and associated neurobehavioral deficits. The role of pro-inflammatory cytokines, especially IL-1β, in the pathophysiological pathway leading to neonatal brain damage is increasingly recognized and represents an attractive therapeutic target. We investigated the therapeutic potential of postnatal systemic administration of the interleukin (IL)-1 receptor antagonist (IL-1Ra) in an animal model of perinatal brain injury using the insults most common to human neonates, i...
November 2012: Brain, Behavior, and Immunity
J W Finnie
Traumatic brain injury (TBI) is a frequent occurrence in veterinary medicine, but the mechanisms leading to brain damage after a head impact are incompletely understood, particularly in the postnatal immature and still developing nervous system. This paper reviews neurotrauma studies, largely in paediatric humans and experimental animal models, in order to outline the pathophysiological and biomechanical events likely to be operative in head trauma involving domestic animal species in the postnatal period, as there is almost no other information available in the veterinary literature...
August 2012: Australian Veterinary Journal
Bobbi Fleiss, Marie K L Nilsson, Klas Blomgren, Carina Mallard
BACKGROUND: Perinatal brain injury is complex and often associated with both inflammation and hypoxia-ischaemia (HI). In adult inflammatory brain injury models, therapies to increase acetylation are efficacious in reducing inflammation and cerebral injury. Our aim in the present study was to examine the neuropathological and functional effects of the histone deacetylase inhibitor (HDACi) trichostatin A (TSA) in a model of neonatal lipopolysaccharide (LPS)-sensitised HI. We hypothesised that, by decreasing inflammation, TSA would improve injury and behavioural outcome...
2012: Journal of Neuroinflammation
S Calkavur, M Akisu, O Olukman, Z Balim, A Berdeli, B Cakmak, O Koroglu, M Yalaz, N Kultursay
It is difficult to predict outcome in neonates that experience perinatal hypoxic ischaemia. Morbidity and mortality may be affected by genetic factors that augment inflammatory and coagulative responses. This prospective study analysed the effects of proinflammatory cytokine gene polymorphisms (tumour necrosis factor-α [TNFA] 308G>A and interleukin-6 [IL6] 174G>C) and prothrombotic factor gene mutations (prothrombin G20210A, factor V Leiden G1691A and methylenetetra hydrofolate reductase [MTHFR] C677T) on the early neurological prognosis in 40 term hypoxic ischaemic encephalopathic neonates...
2011: Journal of International Medical Research
Xiao-Feng Tian, Xiao-Bo Xia, Hui-Zhuo Xu, Si-Qi Xiong, Jian Jiang
BACKGROUND: Caveolin-1 expression correlates with the permeability of endothelial barriers and angiogenesis. However, the role of caveolin-1 in retinal neovascularization remains unknown. We evaluated the effect of caveolin-1 on the blood-retina barrier and retinal neovascularization in a murine model of oxygen-induced retinopathy. METHODS: Starting at postnatal day 7, mice were exposed to 75 ± 5% oxygen for 5 days and then returned to room air conditions to induce retinal neovascularization...
January 2012: Clinical & Experimental Ophthalmology
Ze D Jiang, Zeng Zang, Andrew R Wilkinson
AIM: To examine the influence of perinatal hypoxia-ischaemia (HI) or low Apgar scores on distortion product otoacoustic emissions (DPOAEs) in infants at 1 year and detect any postnatal changes. METHODS: Eighty-eight term infants born with perinatal HI or low Apgar scores alone were recruited at 1 year of age. The ears with type A tympanogram (normal) were studied with DPOAEs at 10 frequencies between 0.5 kHz and 10 kHz. RESULTS: DPOAE pass rates were decreased at all frequencies 1-10 kHz, particularly 1 and 2 kHz in both infants born with HI and those with low Apgar scores (χ(2) = 3...
February 2012: Journal of Paediatrics and Child Health
G W Schlager, E Griesmaier, K Wegleiter, V Neubauer, M Urbanek, U Kiechl-Kohlendorfer, U Felderhoff-Mueser, M Keller
Hypoxia-ischaemia (HI) is a major factor in the pathogenesis of developmental brain injury, leading to cognitive deficits and motor disabilities in preterm infants. The haematopoietic growth factor granulocyte colony-stimulating factor (G-CSF) has been shown to exert a neuroprotective activity in rodent models of ischaemic stroke and is currently subject to phase I/II clinical trials in adults. Results of studies examining the effect of G-CSF in perinatal brain damage have been contradictory. We have previously shown that G-CSF increases NMDAR-mediated excitotoxic brain injury in the neonatal mouse brain...
July 2011: Experimental Neurology
Małgorzata Beresewicz, Monika Majewska, Dorota Makarewicz, Steven Vayro, Barbara Zabłocka, Dariusz C Górecki
Insulin-like growth factor-1 (IGF-1) is a multifunctional peptide of which numerous isoforms exist. The predominant form, IGF-1Ea is involved in physiological processes while IGF-1Ec (mechano-growth factor, MGF) is expressed in response to a different set of stimuli. We have identified specific changes in the expression patterns of these IGF-1 variants in brain development in normal rats and following neonatal hypoxia-ischaemia (HI). Both IGF-1Ea and IGF-1Ec are expressed during normal postnatal brain development, albeit with highly specific temporal distributions...
February 2010: International Journal of Developmental Neuroscience
Zoe Ireland, Hayley Dickinson, Bobbi Fleiss, Lisa C Hutton, David W Walker
We have previously developed a model of near-term intra-uterine hypoxia producing significant neonatal mortality (37%) in a small laboratory animal - the spiny mouse - which has precocial offspring at birth. The aim of the present study was to determine if this insult resulted in the appearance of behavioural abnormalities in those offspring which survived the hypoxic delivery. Behavioural tests assessed gait (using footprint patterns), motor coordination and balance on an accelerating rotarod, and spontaneous locomotion and exploration in an open field...
2010: Neonatology
Sylvie Joriot-Chekaf, Rony Sfeir, Yvon Riou, Pierre Gressens, Louis Vallée, Régis Bordet, Joseph Vamecq
OBJECTIVES: Inhaled NO (INO), at 5-40 parts per million (ppm) in the air, is indicated for treating neonatal hypoxic respiratory failure. Whether these doses of INO are protective or toxic towards brain was here evaluated in laboratory animals. METHODS: In rat neonates (postnatal day 7), a brain injury based on permanent right carotid artery occlusion plus transient (90 min) respiratory hypoxia (8% O(2)) was challenged by two NO dosages (10 and 40 ppm) given either before, during or after transient hypoxia...
May 2010: Injury
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