Question: How can we further improve the neuroprotective effects of hypothermia in newborns with hypoxic-ischemic (HI) brain injury? Finding: Combination carnosine and hypothermia therapy effectively reduced brain damage in neonatal rats. The in situ zymography, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunofluorescence study results showed that neuroprotective effects were achieved with combination therapy only. Meaning: Carnosine and hypothermia have synergistic neuroprotective effects against brain damage following HI injury |
Question: What is the most important factor that increases mortality in infants with hypoxic-ischemic encephalopathy (HIE) who receive selective head cooling? Finding: All cases of neonatal mortality were severe HIE (stage 3), and a severely abnormal amplitude-integrated electroencephalography and mortality were increased with the need for advanced neonatal resuscitation upon delivery. Meaning: Advanced neonatal resuscitation affects HIE outcomes, and medical personnel should be prepared to provide the best intervention. |
Background: Sixty percent of infants with severe neonatal hypoxic-ischemic encephalopathy die, while most survivors have permanent disabilities. Treatment for neonatal hypoxic-ischemic encephalopathy is limited to therapeutic hypothermia, but it does not offer complete protection. Here, we investigated whether hypoxia-inducible factor (HIF) promotes cell survival and suggested neuroprotective strategies.
Purpose: HIF-1α-deficient mice have increased brain injury after neonatal hypoxia-ischemia (HI), and the... |
Hypoxic-ischemic encephalopathy is a significant cause of neonatal morbidity and mortality. Erythropoietin (EPO) is emerging as a therapeutic candidate for neuroprotection. Therefore, this study was designed to determine the neuroprotective role of recombinant human EPO (rHuEPO) and the possible mechanisms by which mitogen-activated protein kinase (MAPK) signaling pathway including extracellular signal-regulated kinase (ERK1/2), JNK, and p38 MAPK is modulated in... |
This study aimed to identify prognostic factors of neurological outcomes, including developmental delay, cerebral palsy and epilepsy in late-preterm and term infants with perinatal asphyxia. All late-preterm and term infants with perinatal asphyxia or hypoxic-ischemic insults who admitted the neonatal intensive care unit of Inje University Sanggye Paik Hospital between 2006 and 2014 and were followed up for at least 2... |
The aim of this study was to investigate the potential effects of mild hypoxia in the mature and immature brain. We prepared organotypic slice cultures of the hippocampus and used hippocampal tissue cultures at 7 and 14 days |
Hypoxic-ischemic encephalopathy is an important cause of neonatal mortality, as this brain injury disrupts normal mitochondrial respiratory activity. Carnitine plays an essential role in mitochondrial fatty acid transport and modulates excess acyl coenzyme A levels. In this study, we investigated whether treatment of primary cultures of rat cortical neurons with L-carnitine was able to prevent neurotoxicity resulting from oxygen-glucose deprivation... |
Purpose : Transforming growth factor (TGF)-β1 reportedly increases neuronal survival by inhibiting the induction of inducible nitric oxide synthase (NOS) in astrocytes and protecting neurons after excitotoxic injury. However, the neuroprotective mechanism of TGF-β1 on hypoxic-ischemic (HI) brain injury in neonatal rats is not clear. The aim of this study was to determine whether TGF-β1 has neuroprotective effects via a... |
Purpose : Perinatal asphyxia is an important cause of neonatal mortality and subsequent lifelong neurodevelopmental handicaps. Although many treatment strategies have been tested, there is currently no clinically effective treatment to prevent or reduce the harmful effects of hypoxia and ischemia in humans. Erythropoietin (Epo) has been shown to exert neuroprotective effects in various brain injury models although the exact... |
Purpose : The development of the corpus callosum occupies the entire period of cerebral formation. The myelination pattern on magnetic resonance imaging (MRI) is very useful to evaluate neurologic development and to predict neurologic outcome in high risk infants. The thickness of the corpus callosum is believed to depend on the myelination process. It is possible to calculate the length... |
Purpose : We intended to observe cell death and apoptotic changes in neurons in organotypic hippocampal slice cultures following oxygen-glucose deprivation (OGD), using propidium iodide (PI) uptake, Fluoro-Jade (FJ) staining, TUNEL staining and immunofluorescent staining for caspase-3. Methods : The hippocampus of 7-day-old rats was cut into 350 µm slices. The slices were cultured for 10 d (date in vitro, DIV... |
Pheochromocytoma is a rare tumor of childhood, arising from adrenal medullary and chromaffin tissue. Because chronic hypoxia may induce pheochromocytoma, there have been several reports of pheochromocytoma development in cyanotic patients after corrective or palliative cardiac surgery. The variable clinical presentation of pheochromocytoma is obscured by both underlying heart disease and medications. If sudden hypertension, aggravation of a heart condition,... |
Purpose : Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is a potent inhibitor of inosine-monophosphate dehydrogenase (IMPDH), a new immunosuppressive drug used. It was reported that MPA protected neurons after excitotoxic injury, induced apoptosis in microglial cells. However, the effects of MPA on hypoxic-ischemic (HI) brain injury has not been yet evaluated. Therefore, we examined whether MPA... |
Purpose : Fas is a cell surface receptor that transduces apoptotic death signals. Interaction of extracelluar domain of Fas with Fas ligand(FasL) triggers the apoptotic process in many diseases. We investigated the expression of Fas and FasL in the hippocampus of 7-day-old newborn rat brains following hypoxia-ischemia injury. Methods : The 7-days-old newborn rats were exposed to 8 percent oxygen... |
Purpose : Newborn brain tissue has to be dissociated into a single cell suspension for flow cytometric analysis of cell death during hypoxia-ischemia. Thus the development of a method to dissociate cells from the brain tissue with least damage and maintenance of membrane and antigen integrity remains the challenge for the in vivo application of this technique. We evaluated the... |
Purpose : Minocycline appears to reduce the mortality rate of patients with myocardial infarction. Therefore, the cardioprotective effects of minocycline through reduction of apoptosis were studied in a rat myocardiac cell culture induced by hypoxia. Methods : Cultured cells from the hearts of Sprague-Dawley rats were divided into two sets of groups : normoxia groups treated with 5% O2 and... |
Purpose : Our study was undertaken to discover whether a selective neuronal nitric oxide synthase inhibitor, 7-nitroindazole, influences brain cell membrane function and energy metabolism during and after transient global hypoxia-ischemia(HI) in newborn piglets. Methods : Cerebral HI was induced by temporary complete occlusion of bilateral common carotid arteries and simultaneous breathing with 8% oxygen for 30 minutes, followed by release... |
Purpose : In vivo, minocycline appears to be neuroprotective. Thus, the neuroprotective effects of minocycline were studied in a rat brain cortical cell culture induced by hypoxia. Methods : Cultured cells from the brains of Sprague-Dawley rats were divided into two sets of groups : normoxia groups treated with 5% CO2 and hypoxia groups treated with 1% CO2. After several... |
Purpose : Dexamethasone is frequently administered to prevent or treat chronic lung disease in human neonates who are also prone to hypoxic-ischemic(HI) insults. Recently, meta-analysis of the follow-up studies reveals a significantly increased odd ratio for the occurrence of cerebral palsy or an abnormal neurologic outcome, and there is conflicting evidence regarding the impact of dexamethasone exposure on HI brain... |
Purpose : We intended to evaluate the effect of hypoxia-ischemia on extracellular striatal monoamine metabolism in neonatal rat brains by in vivo microdialysis. Methods : The right common carotid arteries of five or six-day old rats were surgically ligated, and the probes for microdialysis were inserted into the right striatum with stereotaxic instrument. After stabilization for two hours, artificial cerebrospinal fluid... |
5% CO2-95% air atmosphere. The smooth muscle cells were confirmed by immunostaining with smooth muscle myosin and α-smooth muscle actin antibodies. The VEGF gene expression in the hypoxic group was compared with the one in control the group as well as the one in the starved group by RT-PCR and Northern blot hybridization. Results : There was no statistically significant difference... |
Purpose : Nuclear factor-κB(NF-κB) is now recognized as playing a potential role in programmed cell death and the adaptive response to various stress. Cellular hypoxia is a primary manifestation of many cardiovascular diseases. It seems that vascular endothelial growth factor (VEGF) and insulin like growth factor-I(IGF-I) have a function as a protective molecule in the heart against several stress including... |
Purpose : In order to evaluate the hypoxia-ischemia(H-I) induced neurotoxicity and the protective effect of xanthine oxidase(XO) inhibitor(allopurinol), cell number, cell viability, lactate dehydrogenase(LDH), protein synthesis(PS) and protein kinase C(PKC) activity were measured in cerebral neurons and astrocytes. Methods : Cytotoxic effect was measured by in vitro assay at 12-72 hours after H-I on cerebral neurons and astrocytes derived from 7-day... |
Purpose : This study was undertaken to determine whether any features of apoptosis would occur in the established model of cerebral hypoxia-ischemia in neonatal rats. It was also undertaken to evaluate the effect of post-insult hyperoxia on hypoxic ischemic cerebral injury. Methods : Seven-day-old neonatal rats underwent unilateral carotid artery dissection followed by 2 hours of hypoxia. To this end... |
Purpose : In order to evaluate the hypoxia-ischemia induced neurotoxic effect and the protective effect of vitamin E as an antioxidant, cell number and cell viability were measured in cerebral neurons and astrocytes derived in neonatal rats. Methods : 7-day old neonatal rats were subjected to unilateral common carotid artery occlusion, and exposed to hypoxic condition for 3 hours. The protective... |
Purpose : Cyanotic congenital heart diseases patients are in a state of hypoxia since birth. In general, hypoxia delays atrioventricular conduction. The atrioventricular node in such a hypoxic condition would have a different function, and some possibility for arrhythmia. The authors studied atrioventricular nodal function during hypoxia to elucidate the relationship between hypoxia and arrhythmia, including atrioventricular node in terms... |
Purpose : Brain damage resulting from a combination of hypoxia and ischemia in the newborn infant remains a major cause of perinatal death, cerebral palsy, mental retardation and epilepsy. Metabolic stress, including ischemia, hypoxia and seizures, induces the expression of a variety of stress proteins including nuclear proto-oncogene c-fos. The induction of c-fos can be considered a biomarker of events... |
Purpose : The mechanism of hypoxic damage is mainly intracellular influx of calcium ions through the glutamate ionotropic receptor. This study was performed to determine alterations in distribution and expression of kainate receptor subunits after 1 hour of moderate hypoxia in the newborn piglet brain, as in a condition of mild to moderate perinatal hypoxic-ischemic encephalopathy. Methods : Ten newborn piglets... |
Purpose : Recent studies suggest that nimodipine, a potent calcium-channel blocker, may improve neurological outcome after experimental hypoxia-ischemic brain injury. This study was conducted to evaluate the therapeutic effect of nimodipine on hypoxia-ischemia in immature rat brain. Methods : Seven-day postnatal rats were subjected to hypoxia-ischemia by unilateral common carotid artery occlusion combined with 2 hours of hypoxia(in 8% oxygen... |
Purpose : Perinatal asphyxia is an important cause of neurologic morbidity. Experiments in animal models of hypoxic-ischemic brain injury demonstrate that brain damage starts during hypoxia-ischemia. In order to evaluate the ischemic condition-induced neurotoxic effect in view of oxi- dative stress, we examined the cytotoxic effect in cultured cerebral neurons of neonatal mouse. Methods : Dissociated cell cultures were prepared... |