Hypoxic-Ischemic Brain Injury: Potential Therapeutic Interventions for the Future

Muller, Aaron J.; Marks, Jeremy D.

doi:10.1542/neo.15-5-e177

Cited by 23 publications

(20 citation statements)

References 81 publications

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“…In a descriptive study conducted at the Cirena Neonatology Unit at Hospital Universitario del Valle in 2008, perinatal asphyxia prevalence was 19%, and the most frequent pathology in the mother was hypertensive disorder associated with pregnancy (36.1%). The highest mortality was evident in patients with Sarnat III hypoxic ischemic encephalopathy (71.4%) (19,20).…”

Section: Discussionmentioning

confidence: 99%

Risk factors associated with the development of perinatal asphyxia in neonates at Hospital Universitario del Valle, Cali, Colombia, 2010-2011

et al. 2016

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Introduction: Perinatal asphyxia is one of the main causes of perinatal mortality and morbidity worldwide and it generates high costs for health systems; however, it has modifiable risk factors. Objective: To identify the risk factors associated with the development of perinatal asphyxia in newborns at Hospital Universitario del Valle, Cali, Colombia. Materials and methods: Incident cases and concurrent controls were examined. Cases were defined as newborns with moderate to severe perinatal asphyxia who were older than or equal to 36 weeks of gestational age, needed advanced resuscitation and presented one of the following: early neurological disorders, multi-organ commitment or a sentinel event. The controls were newborns without asphyxia who were born one week apart from the case at the most and had a comparable gestational age. Patients with major congenital malformations and syndromes were excluded. Results: Fifty-six cases and 168 controls were examined. Premature placental abruption (OR=41.09; 95%CI: 4.61-366.56), labor with a prolonged expulsive phase (OR=31.76; 95%CI: 8.33-121.19), lack of oxytocin use (OR=2.57; 95% CI: 1.08 -6.13) and mothers without a partner (OR=2.56; 95% CI: 1.21-5.41) were risk factors for the development of perinatal asphyxia in the study population. Social difficulties were found in a greater proportion among the mothers of cases. Conclusions: Proper control and monitoring of labor, development of a thorough partograph, and active searches are recommended to ensure that all pregnant women have adequate prenatal care with the provision of social support to reduce the frequency and negative impact of perinatal asphyxia.

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Section: Discussionmentioning

confidence: 99%

Risk factors associated with the development of perinatal asphyxia in neonates at Hospital Universitario del Valle, Cali, Colombia, 2010-2011

et al. 2016

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“…Differentially expressed proteins were identified using iTRAQ and LC-MS/MS analysis on LTQ Orbitrap Velos mass spectrometer, by comparing hypoxia male (HM) vs normoxia male (NM) and hypoxia female (HF) vs normoxia female (NF) ( Fig 1A). 2,323 proteins were identified to be regulated differentially after the data analysis from experimental runs in triplicate. Majority (i.e.…”

Section: Resultsmentioning

confidence: 99%

“…Oxygenation in vertebrates is always life or -death necessity for any of the metabolic needs of cells and tissues [1]. Over the last decade, we have acquired adequate information of cellular and molecular mechanisms in hypoxic -ischemic injury, survival and death [2,3]. Hypoxic-ischemic neural injury continues to be the leading cause of death and disability worldwide [4].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia induced sex-difference in zebrafish brain proteome profile reveals the crucial role of H3K9me3 in recovery from acute hypoxia

Das¹,

Kamle

Kumar

et al. 2020

Preprint

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Understanding the molecular basis of sex differences in neural response to acute hypoxic insult has profound implications for the effective prevention and treatment of ischemic stroke. Global hypoxic-ischemic induced neural damage has been studied recently under the well-controlled, non-invasive, reproducible conditions using zebrafish model. Our earlier report on sex difference in global acute hypoxia induced neural damage and recovery in zebrafish prompted us for comprehensive study on the mechanisms underlying the recovery. An omics approach for studying quantitative changes in brain proteome upon hypoxia insult following recovery was undertaken using iTRAQ-based LC-MS/MS approach. The results shed light on altered expression of many regulatory proteins in zebrafish brain upon acute hypoxia following recovery. The sex difference in differentially expressed proteins along with the proteins expressed in uniform direction in both the sexes was studied. Core expression analysis by Ingenuity Pathway analysis (IPA) showed a distinct sex difference in the disease function heatmap. Most of the upstream regulators obtained through IPA were validated at the transcriptional level. Translational upregulation of H3K9me3 in male led us to elucidate the mechanism of recovery by confirming transcriptional targets through ChIP-qPCR. The upregulation of H3K9me3 level in male at 4 hr post-hypoxia appears to affect the early neurogenic markers nestin, klf4 and sox2, which might explain the late recovery in male, compared to female. Acute hypoxia-induced sex-specific comparison of brain proteome led us to 2 reveal many differentially expressed proteins, which can be further studied for the development of novel targets for better therapeutic strategy.

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“…Depletion of tissue energy reserves is followed by a secondary phase of acidosis, glutamate excitotoxicity, generation of reactive oxygen species and oxidative stress, followed by a prolonged period of delayed cell death or apoptosis, and inflammation (Vannucci & Hagberg, ). Therapeutic hypothermia (TH) is the only remedy currently employed in neonates with HIE (Muller & Marks, ) but an urgent need for adjuvant therapies remains. A better understanding of factors affecting the efficacy of TH will help in developing newer adjuvant therapies.…”

Section: Introductionmentioning

confidence: 99%

Intrauterine growth restriction and neonatal hypoxic ischemic brain injury causes sex‐specific long‐term neurobehavioral abnormalities in rats

Narang

Carter

Muncie

et al. 2019

J of Neuroscience Research

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There is a lack of knowledge of factors preventing an adequate response to moderate hypothermia after hypoxic ischemic (HI) brain injury. We hypothesized that growth restriction from reduced intrauterine perfusion would predispose neonatal rats to have a worse outcome with HI brain injury. IUGR was induced by placental insufficiency in dams at 14 days of gestation. HI was induced at postnatal day (P) 10 by permanent right carotid artery ligation followed by 90 min of hypoxia (8% oxygen). Tests for early brain injury and neurobehavioral outcomes were subsequently done. All statistical analysis was done using Two‐way ANOVA; post hoc Holm‐Sidak test. HI in control and IUGR groups decreased the success rate of the contralateral vibrissa‐elicited forelimb test, increased response latency in movement initiation test and increased the time to finish elevated beam walk test at P40 and P60. IUGR augmented HI‐induced abnormality in vibrissa‐elicited forelimb test at P40 but showed higher success rate when compared to HI only group at P60. IUGR’s negative effect on HI‐induced changes on the elevated beam walk test was sex‐specific and exaggerated in P60 males. Increased TUNEL positive cells in the cortex were noted at 72 h after in HI in control but not in IUGR groups. In conclusion, the consequences of IUGR on subsequent neonatal HI varied based on age, sex and outcomes examined, and overall, male sex and IUGR had worse effects on the long‐term neurobehavioral outcomes following HI.

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Hypoxic-Ischemic Brain Injury: Potential Therapeutic Interventions for the Future

Cited by 23 publications

References 81 publications

Risk factors associated with the development of perinatal asphyxia in neonates at Hospital Universitario del Valle, Cali, Colombia, 2010-2011

Risk factors associated with the development of perinatal asphyxia in neonates at Hospital Universitario del Valle, Cali, Colombia, 2010-2011

Hypoxia induced sex-difference in zebrafish brain proteome profile reveals the crucial role of H3K9me3 in recovery from acute hypoxia

Intrauterine growth restriction and neonatal hypoxic ischemic brain injury causes sex‐specific long‐term neurobehavioral abnormalities in rats

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