Correction: Impact of Perinatal Systemic Hypoxic–Ischemic Injury on the Brain of Male Offspring Rats: An Improved Model of Neonatal Hypoxic–Ischemic Encephalopathy in Early Preterm Newborns

Introduction. Birth hypoxia is a leading cause of perinatal mortality and neurological morbidity, resulting in central nervous system injury. Cerebral hypoxia and ischemia can produce a severe brain damage following a typical pattern, defined by selective vulnerability of the brain regions. The neonates are most prone to hypoxic-ischemic injuries due to the lack of efficient antioxidant defense. Neonatal hypoxia–ischemia (HI) in a 7-day-old rat HI model can produce cell death by apoptotic or necrotic mechanisms. The degree of apoptotic or necrotic mechanisms responsible for cell death in neonatal hypoxia–ischemia are not very clear as yet. The form of neuronal death may also depend on the severity of ischemic injury. Necrosis predominates in more severe cases, whereas apoptosis occurs in areas with milder ischemic injury. A human study demonstrated apoptotic and necrotic forms of cell death after hypoxic injury, whereas in some brains from stillbirths, only apoptotic figures were observed. The expression of activated caspase-3 reflects the role of apoptosis in neonatal hypoxic ischemic brain injury. Objectives. The aim of this study was to evaluate the possible neuroprotective effect of melatonin and hypothermia in hypoxic-ischemic encephalopathy in newborn rats. Local damages induced by hypoxia and ischemia were assessed by evaluating the changes in terms of histology and apoptosis. Methods. The experiment was conducted on 20 newborn Wistar rats premedicated for seven days with melatonin in a dose of 20 mg/kg/day. On the 7th postnatal day (P7), the newborn rats were exposed to ischemia (by clamping the right carotid artery) and hypobaric hypoxia (8% O2 for 90 minutes) and some groups to hypothermia. Results. In this experimental model of neonatal encephalopathy, melatonin, in a dose of 20 mg/kg/day has neuroprotective effect by reducing the number of cells expressing apoptosis in Cornu Ammonis (CA) (Ammon’s Horn) CA1, CA2, CA3 and dentate gyrus of the hippocampus when combined with hypothermia. Conclusion. The results of this study prove that melatonin is protective in ischemic-hypoxic brain injuries, but the protection is conditioned in most of the brain regions (excepting cerebral cortex) by conjugation with post-injury hypothermia treatment.

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Scutellarin ameliorates neonatal hypoxic-ischemic encephalopathy associated with GAP43-dependent signaling pathway

Chinese Medicine ◽

10.1186/s13020-021-00517-z ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Rui-Ze Niu ◽

Liu-Lin Xiong ◽

Hao-Li Zhou ◽

Lu-Lu Xue ◽

Qing-Jie Xia ◽

...

Keyword(s):

Neuronal Death ◽

Ischemic Injury ◽

Hypoxic Ischemic Encephalopathy ◽

Qrt Pcr ◽

Pharmacological Analysis ◽

Ischemic Encephalopathy ◽

Hypoxic Ischemic Injury

Abstract Background Neonatal hypoxic-ischemic encephalopathy (HIE) refers to the perinatal asphyxia caused by the cerebral hypoxic-ischemic injury. The current study was aimed at investigating the therapeutic efficacy of Scutellarin (Scu) administration on neurological impairments induced by hypoxic-ischemic injury and exploring the underlying mechanisms. Methods Primary cortical neurons were cultured and subjected to oxygen–glucose deprivation (OGD), and then treated with Scu administration. The growth status of neurons was observed by immunofluorescence staining of TUJ1 and TUNEL. Besides, the mRNA level of growth-associated protein 43 (GAP43) in OGD neurons with Scu treatment was detected by quantitative real-time polymerase chain reaction (qRT-PCR). To further verify the role of GAP43 in Scu treatment, GAP43 siRNA and knockout were applied in vitro and in vivo. Moreover, behavioral evaluations were performed to elucidate the function of GAP43 in the Scu-ameliorated long-term neurological impairments caused by HI insult. The underlying biological mechanism of Scu treatment was further elucidated via network pharmacological analysis. Finally, the interactive genes with GAP43 were identified by Gene MANIA and further validated by qRT-PCR. Results Our data demonstrated that Scu treatment increased the number of neurons and axon growth, and suppressed cell apoptosis in vitro. And the expression of GAP43 was downregulated after OGD, but reversed by Scu administration. Besides, GAP43 silencing aggravated the Scu-ameliorated neuronal death and axonal damage. Meanwhile, GAP43 knockout enlarged brain infarct area and deteriorated the cognitive and motor dysfunctions of HI rats. Further, network pharmacological analysis revealed the drug targets of Scu participated in such biological processes as neuronal death and regulation of neuronal death, and apoptosis-related pathways. GAP43 exhibited close relationship with PTN, JAK2 and STAT3, and GAP43 silencing upregulated the levels of PTN, JAK2 and STAT3. Conclusions Collectively, our findings revealed Scu treatment attenuated long-term neurological impairments after HI by suppressing neuronal death and enhancing neurite elongation through GAP43-dependent pathway. The crucial role of Scutellarin in neuroprotection provided a novel possible therapeutic agent for the treatment of neonatal HIE. Graphic abstract

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Pretreatment with Monosialoganglioside GM1 Protects the Brain of Fetal Sheep against Hypoxic-Ischemic Injury without Causing Systemic Compromise

Pediatric Research ◽

10.1203/00006450-199307000-00005 ◽

1993 ◽

Vol 34 (1) ◽

pp. 18-22 ◽

Cited By ~ 17

Author(s):

William K M Tan ◽

Chris E Williams ◽

Alistair J Gunn ◽

E Carina Mallard ◽

Peter D Gluckman

Keyword(s):

Ischemic Injury ◽

Fetal Sheep ◽

The Brain ◽

Hypoxic Ischemic Injury

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Fetal stress-mediated hypomethylation increases the brain susceptibility to hypoxic–ischemic injury in neonatal rats

Experimental Neurology ◽

10.1016/j.expneurol.2015.10.007 ◽

2016 ◽

Vol 275 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Yong Li ◽

Qingyi Ma ◽

Shina Halavi ◽

Katherine Concepcion ◽

Richard E. Hartman ◽

...

Keyword(s):

Ischemic Injury ◽

Neonatal Rats ◽

The Brain ◽

Hypoxic Ischemic Injury

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Preconditioning and Postinsult Therapies for Perinatal Hypoxic–Ischemic Injury at Term

Anesthesiology ◽

10.1097/aln.0b013e3181dc1b84 ◽

2010 ◽

Vol 113 (1) ◽

pp. 233-249 ◽

Cited By ~ 38

Author(s):

Robert D. Sanders ◽

Helen J. Manning ◽

Nicola J. Robertson ◽

Daqing Ma ◽

A. David Edwards ◽

...

Keyword(s):

Perinatal Period ◽

Rapid Identification ◽

Postnatal Period ◽

Hypoxic Ischemic Encephalopathy ◽

Current Status ◽

Neuroprotective Agents ◽

Period 2 ◽

Neuroprotective Strategies ◽

The Brain ◽

Ischemic Encephalopathy

Perinatal hypoxic-ischemic encephalopathy can be a devastating complication of childbirth. Herein, the authors review the pathophysiology of hypoxic-ischemic encephalopathy and the current status of neuroprotective strategies to ameliorate the injury centering on four themes: (1) monitoring in the perinatal period, (2) rapid identification of affected neonates to allow timely institution of therapy, (3) preconditioning therapy (a therapeutic that reduces the brain vulnerability) before hypoxic-ischemic encephalopathy, and (4) prompt institution of postinsult therapies to ameliorate the evolving injury. Recent clinical trials have demonstrated the significant benefit for hypothermic therapy in the postnatal period; furthermore, there is accumulating preclinical evidence that adjunctive therapies can enhance hypothermic neuroprotection. Advances in the understanding of preconditioning may lead to the administration of neuroprotective agents earlier during childbirth. Although most of these neuroprotective strategies have not yet entered clinical practice, there is a significant hope that further developments will enhance hypothermic neuroprotection.

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Evidence of Occurrence of Intradural and Subdural Hemorrhage in the Perinatal and Neonatal Period in the Context of Hypoxic Ischemic Encephalopathy: An Observational Study from Two Referral Institutions in the United Kingdom

Pediatric and Developmental Pathology ◽

10.2350/08-08-0509.1 ◽

2009 ◽

Vol 12 (3) ◽

pp. 169-176 ◽

Cited By ~ 38

Author(s):

Marta C. Cohen ◽

Irene Scheimberg

Keyword(s):

Thin Film ◽

Hypoxic Ischemic Encephalopathy ◽

Subdural Hemorrhage ◽

Intrauterine Death ◽

Venous Plexus ◽

Neonatal Deaths ◽

The United Kingdom ◽

Degrees Of Severity ◽

The Brain ◽

Ischemic Encephalopathy

The occurrence of subdural hemorrhage (SDH) on the convexities of the cerebral hemispheres is not an unusual finding in the setting of intrauterine, perinatal, or neonatal deaths, the hemorrhage usually presenting either as a thin film over the occipital poles or as a small infratentorial bleed. Working in 2 referral centers with over 30 000 deliveries per year, we routinely examine the dura macroscopically and histologically in nonmacerated fetuses over 24 weeks in gestation and in neonates. This paper describes our experience of intradural hemorrhage (IDH) and SDH associated with hypoxia. Our series comprises 25 fetuses and 30 neonates with obvious macroscopic intradural hemorrhage and hypoxia of varying degrees of severity diagnosed by systematic examination of the brain. Fetal gestational age ranged from 26–41/40 weeks (all no more than 24 hours from intrauterine death), while the 30 neonates lived for between 1 hour and 19 days. Simultaneously with IDH, frank SDH was seen in 2 of 3 of all cases (16 fetuses and 20 neonates). Intradural hemorrhage was more prominent in the posterior falx and tentorium, most likely because of the existence of 2 venous plexus at these sites. Our findings demonstrate that SDH and cerebral hypoxia are common associations of IDH and that SDH (often seen as a thin film of hemorrhage) almost always occurs in association with diffuse falcine IDH. Diffuse IDH with SDH are more frequently associated with severe or moderate hypoxic ischemic encephalopathy (HIE), while mild or early HIE is more common with focal IDH without SDH.

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NEUROSONOGRAPHIC STUDY OF CHILDREN WITH HYPOXIC-ISCHEMIC BRAIN IJURY

Science Review ◽

10.31435/rsglobal_sr/30042020/7050 ◽

2020 ◽

pp. 7-11

Author(s):

Volotko L. O.

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Brain Injury ◽

Brain Tissue ◽

Ischemic Injury ◽

Ischemic Brain ◽

Destructive Processes ◽

The Brain ◽

Hypoxic Ischemic Injury

The study is aimed at neurosonographic characteristics of brain injury in newborn patients with perinatal hypoxic-ischemic injury of central nervous system, complicated with inflectional process (meningitis, ventriculitis). It is settled that brain immaturity, hydrocephalic syndrome, ischemia of the brain tissue and intraventricular hemorrhages are found 2 times more often in infants with perinatal hypoxic-ischemic injury of central nervous system, complicated with inflectional process. This fact generally characterizes disorders of the hemato-encephalic barrier and the development of destructive processes in the tissue of the brain.

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Lipid Profiles from Dried Blood Spots Reveal Lipidomic Signatures of Newborns Undergoing Mild Therapeutic Hypothermia after Hypoxic-Ischemic Encephalopathy

Nutrients ◽

10.3390/nu13124301 ◽

2021 ◽

Vol 13 (12) ◽

pp. 4301

Author(s):

Rebekah Nixon ◽

Ting Hin Richard Ip ◽

Benjamin Jenkins ◽

Ping K. Yip ◽

Paul Clarke ◽

...

Keyword(s):

Therapeutic Hypothermia ◽

Peripheral Blood ◽

Univariate Analysis ◽

Dried Blood Spots ◽

Hypoxic Ischemic Encephalopathy ◽

Perinatal Brain Injury ◽

Blood Spots ◽

Lipid Species ◽

The Brain ◽

Ischemic Encephalopathy

Hypoxic-ischemic encephalopathy (HIE) is associated with perinatal brain injury, which may lead to disability or death. As the brain is a lipid-rich organ, various lipid species can be significantly impacted by HIE and these correlate with specific changes to the lipidomic profile in the circulation. Objective: To investigate the peripheral blood lipidomic signature in dried blood spots (DBS) from newborns with HIE. Using univariate analysis, multivariate analysis and sPLS-DA modelling, we show that newborns with moderate–severe HIE (n = 46) who underwent therapeutic hypothermia (TH) displayed a robust peripheral blood lipidomic signature comprising 29 lipid species in four lipid classes; namely phosphatidylcholine (PC), lysophosphatidylcholine (LPC), triglyceride (TG) and sphingomyelin (SM) when compared with newborns with mild HIE (n = 18). In sPLS-DA modelling, the three most discriminant lipid species were TG 50:3, TG 54:5, and PC 36:5. We report a reduction in plasma TG and SM and an increase in plasma PC and LPC species during the course of TH in newborns with moderate–severe HIE, compared to a single specimen from newborns with mild HIE. These findings may guide the research in nutrition-based intervention strategies after HIE in synergy with TH to enhance neuroprotection.

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Abstract 13824: Computerized Tomography vs Ultrasound Imaging for Detecting Hypoxic-Ischemic Brain Injury

Circulation ◽

10.1161/circ.144.suppl_2.13824 ◽

2021 ◽

Vol 144 (Suppl_2) ◽

Author(s):

Benjamin Karfunkle ◽

Pavitra Kotini-shah ◽

Richard Gordon ◽

Jing Li ◽

Misha Granado ◽

...

Keyword(s):

Brain Injury ◽

Hospital Discharge ◽

Computerized Tomography ◽

Point Of Care ◽

Ischemic Injury ◽

Ct Head ◽

Ct Brain ◽

Initial Imaging ◽

The Brain ◽

Hypoxic Ischemic Injury

Introduction: After an out-of-hospital cardiac arrest (OHCA), the resulting hypoxic-ischemic injury (HII) to the brain remains the main cause of mortality. Standardized approaches for measuring the extent of injury and monitoring of changes are lacking and continue to be a critical barrier to progress in improving neurological survival. Objective: We sought to characterize the prevalence of HII detected on computerized tomography of the brain and its correlation to point-of-care optic nerve sheath diameter (ONSD) measurements as an alternative modality for detecting brain injury. Methods: Adult OHCA patients at an urban academic ED were included in this study on a convenience sample basis from 2018-2019. The patients were grouped by findings of hypoxic-ischemic injury (HII) on both initial and subsequent CT brain imaging performed after ROSC in respective groups. CT Brain findings were compared to ONSD measurements as performed with point-of-care ultrasound by fellowship-trained emergency physicians within one hour of hospital arrival and at 6 hours, after return of spontaneous circulation (ROSC) and to cerebral performance category (CPC) at hospital discharge. Results: 76 patients enrolled in the study had a median age was 59, 49% were female, and 37% survived to hospital discharge. 58 patients had CT head performed, 40 had ONSD measured within one hour, and 27 patients had both. Of that 27, 9 (33%) had evidence of HII on initial imaging and 15 (55%) had evidence of HII on subsequent imaging for a total of 20 unique patients. The average ONSD within 1 hour of ROSC for those with no HII on any imaging was 0.59 cm, and for those without HII on initial imaging but with HII on subsequent imaging was 0.67 cm, and this difference was statistically significant (p< 0.05). Of the 20 patients with HI, 14 (70%) patients died and 6 (30%) survived with a CPC of 4. The average time to first CT head was 4 hours and 45 mins and the average time to subsequent imaging was 97 hours and 45 mins. Conclusion: After an OHCA, early time point ONSD measurements can potentially indicate brain injury within 1 hour of ROSC even in those without initial evidence of HII on CT imaging.

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