scholarly journals Antenatal dexamethasone before asphyxia promotes cystic neural injury in preterm fetal sheep by inducing hyperglycemia

2017 ◽  
Vol 38 (4) ◽  
pp. 706-718 ◽  
Author(s):  
Christopher A Lear ◽  
Joanne O Davidson ◽  
Georgia R Mackay ◽  
Paul P Drury ◽  
Robert Galinsky ◽  
...  
Keyword(s):  
Brain Injury ◽  
Perinatal Asphyxia ◽  
Brain Activity ◽  
Adverse Outcomes ◽  
Limited Information ◽  
Neurodevelopmental Outcomes ◽  
Neural Injury ◽  
Fetal Sheep ◽  
Glucose Levels ◽  
Diffuse Injury

Antenatal glucocorticoid therapy significantly improves the short-term systemic outcomes of prematurely born infants, but there is limited information available on their impact on neurodevelopmental outcomes in at-risk preterm babies exposed to perinatal asphyxia. Preterm fetal sheep (0.7 of gestation) were exposed to a maternal injection of 12 mg dexamethasone or saline followed 4 h later by asphyxia induced by 25 min of complete umbilical cord occlusion. In a subsequent study, fetuses received titrated glucose infusions followed 4 h later by asphyxia to examine the hypothesis that hyperglycemia mediated the effects of dexamethasone. Post-mortems were performed 7 days after asphyxia for cerebral histology. Maternal dexamethasone before asphyxia was associated with severe, cystic brain injury compared to diffuse injury after saline injection, with increased numbers of seizures, worse recovery of brain activity, and increased arterial glucose levels before, during, and after asphyxia. Glucose infusions before asphyxia replicated these adverse outcomes, with a strong correlation between greater increases in glucose before asphyxia and greater neural injury. These findings strongly suggest that dexamethasone exposure and hyperglycemia can transform diffuse injury into cystic brain injury after asphyxia in preterm fetal sheep.

Glycemic Control in Neurocritically Ill Patients

2019 ◽  
pp. 241-245
Author(s):  
Carla P. Venegas-Borsellino ◽  
Michael A. Pizzi ◽  
Santiago Naranjo-Sierra
Keyword(s):  
Traumatic Brain Injury ◽  
Ischemic Stroke ◽  
Blood Glucose ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Glycemic Control ◽  
Adverse Outcomes ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Poor Outcomes

Hyperglycemia, hypoglycemia, and variable blood glucose levels are associated with poor outcomes in critically ill patients. Patients with acute brain injury are sensitive to changes in glycemic levels because brain metabolism depends on a continuous, reliable supply of glucose. Numerous studies have shown that even moderate hypoglycemia may cause pronounced neuroglycopenia. Conversely hyperglycemia, which is prevalent in neurocritically ill patients, has been related to adverse outcomes after traumatic brain injury, ischemic stroke, intracranial hemorrhage, and subarachnoid hemorrhage.

scholarly journals Partial white and grey matter protection with prolonged infusion of recombinant human erythropoietin after asphyxia in preterm fetal sheep

2016 ◽  
Vol 37 (3) ◽  
pp. 1080-1094 ◽  
Author(s):  
Guido Wassink ◽  
Joanne O Davidson ◽  
Simerdeep K Dhillon ◽  
Mhoyra Fraser ◽  
Robert Galinsky ◽  
...  
Keyword(s):  
Recombinant Human Erythropoietin ◽  
Caspase 3 ◽  
Perinatal Asphyxia ◽  
Neuronal Loss ◽  
Prolonged Infusion ◽  
Neurodevelopmental Outcomes ◽  
Fetal Sheep ◽  
Spectral Edge Frequency ◽  
Human Erythropoietin ◽  
Medial Nucleus

Perinatal asphyxia in preterm infants remains a significant contributor to abnormal long-term neurodevelopmental outcomes. Recombinant human erythropoietin has potent non-haematopoietic neuroprotective properties, but there is limited evidence for protection in the preterm brain. Preterm (0.7 gestation) fetal sheep received sham asphyxia (sham occlusion) or asphyxia induced by umbilical cord occlusion for 25 min, followed by an intravenous infusion of vehicle (occlusion-vehicle) or recombinant human erythropoietin (occlusion-Epo, 5000 international units by slow push, then 832.5 IU/h), starting 30 min after asphyxia and continued until 72 h. Recombinant human erythropoietin reduced neuronal loss and numbers of caspase-3-positive cells in the striatal caudate nucleus, CA3 and dentate gyrus of the hippocampus, and thalamic medial nucleus ( P < 0.05 vs. occlusion-vehicle). In the white matter tracts, recombinant human erythropoietin increased total, but not immature/mature oligodendrocytes ( P < 0.05 vs. occlusion-vehicle), with increased cell proliferation and reduced induction of activated caspase-3, microglia and astrocytes ( P < 0.05). Finally, occlusion-Epo reduced seizure burden, with more rapid recovery of electroencephalogram power, spectral edge frequency, and carotid blood flow. In summary, prolonged infusion of recombinant human erythropoietin after severe asphyxia in preterm fetal sheep was partially neuroprotective and improved electrophysiological and cerebrovascular recovery, in association with reduced apoptosis and inflammation.

scholarly journals Increased Use of Therapeutic Hypothermia in Infants with Milder Neonatal Encephalopathy due to Presumed Perinatal Asphyxia

Neonatology ◽  
2020 ◽  
Vol 117 (4) ◽  
pp. 488-494
Author(s):  
Corline E.J. Parmentier ◽  
Linda S. de Vries ◽  
Mona C. Toet ◽  
Ingrid C. van Haastert ◽  
Corine Koopman ◽  
...  
Keyword(s):  
Therapeutic Hypothermia ◽  
Clinical Experience ◽  
Perinatal Asphyxia ◽  
Neurodevelopmental Outcome ◽  
Adverse Outcomes ◽  
Neonatal Encephalopathy ◽  
Neurodevelopmental Outcomes ◽  
Period 2 ◽  
Second Period

<b><i>Introduction:</i></b> Adverse outcomes have been reported in infants with mild neonatal encephalopathy (NE). Increasing clinical experience with the application of therapeutic hypothermia (TH) may have resulted in the treatment of newborns with milder NE during recent years. <b><i>Objective:</i></b> To determine whether infants treated with TH in the initial years following implementation had a higher degree of NE than infants treated during subsequent years. <b><i>Methods:</i></b> Infants with NE treated with TH from February 2008 until July 2017 were included. Thompson and Sarnat scores, amplitude-integrated electroencephalography (aEEG) background patterns before the start of TH, and neurodevelopmental outcome at 2 years were compared between infants treated from February 2008 until October 2012 (period 1) and infants treated from November 2012 until July 2017 (period 2). <b><i>Results:</i></b> 211 newborns with NE were treated with TH (period 1: <i>n</i> = 109, period 2: <i>n</i> = 102). Sarnat scores in period 1 and 2 were mild in 7.3 vs. 28.4%, moderate in 66.1 vs. 44.1%, and severe in 26.6 vs. 22.5%, respectively (<i>p</i> = 0.008). Thompson scores were lower in period 2 (median = 9, IQR 7–12) than in period 1 (median = 10, IQR 8.5–13.5, <i>p</i> = 0.018). The aEEGs and neurodevelopmental outcomes were comparable between the periods. <b><i>Conclusions:</i></b> Based on Thompson and Sarnat scores, but not aEEG background patterns, infants treated during the second period had milder NE than infants treated during the first years following implementation of TH. There was no difference in 2 years neurodevelopmental outcome. Further research is necessary to evaluate the value of TH for infants with clinically mild NE.

Short- and long-term outcomes of preterm spontaneous twin anemia-polycythemia sequence

2020 ◽  
Vol 48 (4) ◽  
pp. 329-334
Author(s):  
Soo Jin Han ◽  
Seung Mi Lee ◽  
Sohee Oh ◽  
Subeen Hong ◽  
Jeong Won Oh ◽  
...  
Keyword(s):  
Cord Blood ◽  
Neonatal Morbidity ◽  
Adverse Outcomes ◽  
Control Group ◽  
Long Term Outcomes ◽  
Neurodevelopmental Outcomes ◽  
Monochorionic Twin ◽  
Increased Risk ◽  
Study Population

AbstractBackgroundIn monochorionic twin pregnancy, placental anastomosis and inter-twin blood transfusion can result in specific complications, such as twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). It is well established that adverse outcomes are increased in TTTS, but reports on the neonatal and long-term outcomes of TAPS are lacking. The objective of this study was to evaluate the neonatal and neurodevelopmental outcomes in spontaneous TAPS.MethodsThe study population consisted of monochorionic twin pregnancies with preterm birth (24–37 weeks of gestation) between November 2003 and December 2016 and in which cord blood was taken at the time of delivery. According to the result of hemoglobin in cord blood, the study population was divided into two groups: a spontaneous TAPS group and a control group. Neonatal and neurodevelopmental outcomes were compared between the two groups.ResultsDuring the study period, 11 cases were diagnosed as spontaneous TAPS (6.4%). The TAPS group had lower gestational age at delivery and had a higher risk for cesarean delivery. However, neonates with TAPS were not at an increased risk for neonatal mortality and significant neonatal morbidity. In addition, the frequency of severe cerebral lesion during the neonatal period and the risk of cerebral palsy at 2 years of age were not different between the two groups.ConclusionThe spontaneous TAPS diagnosed by postnatal diagnostic criteria was not associated with the increased risk of adverse neonatal and neurodevelopmental outcomes. Further studies are needed to evaluate the morbidity of antenatally diagnosed TAPS.

scholarly journals Persistent inflammation worsens short-term outcomes in massive stroke patients

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Duanlu Hou ◽  
Chunjie Wang ◽  
Xiaofei Ye ◽  
Ping Zhong ◽  
Danhong Wu
Keyword(s):  
Blood Glucose ◽  
Pulmonary Infection ◽  
Laboratory Data ◽  
Adverse Outcomes ◽  
Imaging Data ◽  
Stroke Patients ◽  
Short Term ◽  
Glucose Levels ◽  
Logistic Analysis ◽  
Persistent Inflammation

Abstract Background Persistent inflammation is an important driver of disease progression and affects prognosis. Some indicators of inflammation predict short-term outcomes. The relationship between prognosis, especially mortality, and persistent inflammation in massive stroke has not been studied, and this has been the subject of our research. Methods From April 1, 2017 to February 1, 2020, consecutive patients were prospectively enrolled. Clinical data, laboratory data, imaging data and follow-up infections morbidity were compared between 2 groups according to modified Rankin scale (mRS) scores (mRS < 3 and ≥ 3) at 1 month. The binomial logistic analysis was used to determine independent factors of 1-month prognosis. Short-term functional outcome, mortality and infection rates in massive stroke with and without persistent inflammation were compared. Results One hundred thirty-nine patients with massive stroke were included from 800 patients. We found that admission blood glucose levels (p = 0.005), proportions of cerebral hemispheric (p = 0.001), posterior circulatory (p = 0.035), and lacunar (p = 0.022) ischemia were higher in poor outcome patients; neutrophil-to-lymphocyte ratio (odd ratio = 1.87, 95%CI 1.14–3.07, p = 0.013) and blood glucose concentrations (odd ratio = 1.34, 95%CI 1.01–1.79, p = 0.043) can independently predict the short-term prognosis in massive stroke patients. We also found that the incidence of pulmonary infection (p = 0.009), one-month mortality (p = 0.003) and adverse outcomes (p = 0.0005) were higher in patients with persistent inflammation. Conclusions This study suggested that persistent inflammation is associated with poor prognosis, 1-month mortality and the occurrence of in-hospital pulmonary infection and that higher baseline inflammation level predicts short-term poor outcomes in massive stroke.

Maternal Glycemia during pregnancy and Early Offspring Development: A Prospective Birth Cohort Study

2021 ◽  
Author(s):  
Peng Wang ◽  
Jun Xie ◽  
Xue-chun Jiao ◽  
Shuang-shuang Ma ◽  
Yang Liu ◽  
...  
Keyword(s):  
Cohort Study ◽  
Birth Cohort ◽  
Plasma Glucose ◽  
Birth Cohort Study ◽  
Neurodevelopmental Outcomes ◽  
Glucose Levels ◽  
Maternal Glucose Levels ◽  
Prospective Birth Cohort ◽  
Maternal Glucose ◽  
Prospective Birth Cohort Study

Abstract Context The association of maternal gestational diabetes mellitus (GDM) with neurodevelopmental outcomes remains controversial and evidence that maternal increasing levels of glucose during pregnancy associated with the risk for impaired neurodevelopment were limited. Objective To identify the continuous association of increasing maternal glucose levels with neurodevelopmental disorders in offspring and explore the potential contribution of cord metabolites to this association. Methods The prospective birth cohort study included 1036 mother-child pairs. Primary predictors were maternal exposure GDM and maternal glucose values at a 75-g oral-glucose-tolerance test (OGTT) at 24–28 weeks during pregnancy. Primary neurodevelopmental outcomes at 12 mo in offspring were assessed by the ASQ-3. Results Maternal GDM was associated with failing the communication domain in offspring in the adjusted models [RR with 95% CI: 1.97(1.11, 3.52)]. Increasing levels of fasting plasma glucose (FPG), 1 h plasma glucose (1-h PG) and 2 h plasma glucose (2-h PG) with one SD change were at higher risks in failing the personal social domain of ASQ [RRs with 95% CI for FPG: 1.49(1.09, 2.04); for 1-h PG: 1.70(1.27, 2.29); for 2-h PG: 1.36(1.01, 1.84)]. The linear association was also demonstrated. Compared with girls, boys exposed to higher maternal glucose levels were inclined to the failure of the personal social domain. Mediation analysis showed the contribution of maternal GDM to failure of communication domain mediated by C-peptide. Conclusions Maternal glucose levels below those diagnostic of diabetes are continuously associated with impaired neurodevelopment in offspring at 12 mo.

scholarly journals Humans with obesity have disordered brain responses to food images during physiological hyperglycemia

2018 ◽  
Vol 314 (5) ◽  
pp. E522-E529 ◽  
Author(s):  
Renata Belfort-DeAguiar ◽  
Dongju Seo ◽  
Cheryl Lacadie ◽  
Sarita Naik ◽  
Christian Schmidt ◽  
...  
Keyword(s):  
Brain Activity ◽  
Blood Oxygen Level Dependent ◽  
Normal Weight ◽  
Self Control ◽  
Food Cues ◽  
Brain Response ◽  
Glucose Levels ◽  
Hyperglycemic Clamp ◽  
Brain Responses ◽  
Food Images

Blood glucose levels influence brain regulation of food intake. This study assessed the effect of mild physiological hyperglycemia on brain response to food cues in individuals with obesity (OB) versus normal weight individuals (NW). Brain responses in 10 OB and 10 NW nondiabetic healthy adults [body mass index: 34 (3) vs. 23 (2) kg/m2, means (SD), P < 0.0001] were measured with functional MRI (blood oxygen level-dependent contrast) in combination with a two-step normoglycemic-hyperglycemic clamp. Participants were shown food and nonfood images during normoglycemia (~95 mg/dl) and hyperglycemia (~130 mg/dl). Plasma glucose levels were comparable in both groups during the two-step clamp ( P = not significant). Insulin and leptin levels were higher in the OB group compared with NW, whereas ghrelin levels were lower (all P < 0.05). During hyperglycemia, insula activity showed a group-by-glucose level effect. When compared with normoglycemia, hyperglycemia resulted in decreased activity in the hypothalamus and putamen in response to food images ( P < 0.001) in the NW group, whereas the OB group exhibited increased activity in insula, putamen, and anterior and dorsolateral prefrontal cortex (aPFC/dlPFC; P < 0.001). These data suggest that OB, compared with NW, appears to have disruption of brain responses to food cues during hyperglycemia, with reduced insula response in NW but increased insula response in OB, an area involved in food perception and interoception. In a post hoc analysis, brain activity in obesity appears to be associated with dysregulated motivation (striatum) and inappropriate self-control (aPFC/dlPFC) to food cues during hyperglycemia. Hyperstimulation for food and insensitivity to internal homeostatic signals may favor food consumption to possibly play a role in the pathogenesis of obesity.

scholarly journals Association between blood glucose levels and Glasgow Outcome Score in patients with traumatic brain injury: secondary analysis of a randomized trial

Trials ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Tao Yuan ◽  
Hongyu He ◽  
Yuepeng Liu ◽  
Jianwei Wang ◽  
Xin Kang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Blood Glucose ◽  
Brain Injury ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Threshold Effect ◽  
Glasgow Outcome Score ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Average Blood Glucose

Abstract Background Blood glucose levels that are too high or too low after traumatic brain injury (TBI) negatively affect patient prognosis. This study aimed to demonstrate the relationship between blood glucose levels and the Glasgow Outcome Score (GOS) in TBI patients. Methods This study was based on a randomized, dual-center, open-label clinical trial. A total of 208 patients who participated in the randomized controlled trial were followed up for 5 years. Information on the disease, laboratory examination, insulin therapy, and surgery for patients with TBI was collected as candidate variables according to clinical importance. Additionally, data on 5-year and 6-month GOS were collected as primary and secondary outcomes, respectively. For multivariate analysis, a generalized additive model (GAM) was used to investigate relationships between blood glucose levels and GOS. The results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). We further applied a two- piecewise linear regression model to examine the threshold effect of blood glucose level and GOS. Results A total of 182 patients were included in the final analysis. Multivariate GAM analysis revealed that a bell-shaped relationship existed between average blood glucose level and 5-year GOS score or 6-month GOS score. The inflection points of the average blood glucose level were 8.81 (95% CI: 7.43–9.48) mmol/L considering 5-year GOS as the outcome and were 8.88 (95% CI 7.43−9.74) mmol/L considering 6-month GOS score as the outcome. The same analysis revealed that there was also a bell relationship between average blood glucose levels and the favorable outcome group (GOS score ≥ 4) at 5 years or 6 months. Conclusion In a population of patients with traumatic brain injury, blood glucose levels were associated with the GOS. There was also a threshold effect between blood glucose levels and the GOS. A blood glucose level that is either too high or too low conveys a poor prognosis. Trial registration ClinicalTrials.gov NCT02161055. Registered on 11 June 2014.

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