A physiologically-validated rat model of term birth asphyxia with seizure generation after, not during, brain hypoxia

ABSTRACTBirth asphyxia (BA) is often associated with seizures which emerge during the recovery and may exacerbate the ensuing hypoxic-ischemic encephalopathy. In rodent models of BA, exposure to hypoxia is used to evoke seizures, which commence already during the insult. Here, we introduce a term-equivalent model of BA, in which seizures are triggered after, not during, brain hypoxia. Postnatal day 11-12 rat pups were exposed either to steady asphyxia (15 min; 5 % O2 + 20 % CO2) or to intermittent asphyxia (30 min; three 5+5 min cycles of 9 % and 5 % O2 at constant 20 % CO2). Cortical activity and seizures were recorded in freely-behaving animals. Simultaneous electrode measurements of cortical local field potentials (LFP) and intracortical pH and Po2 were made under urethane-anesthesia. Both protocols decreased blood pH to <7.0 and base excess by 20 mmol/l, and evoked an increase in plasma copeptin (0.2 to 5 nM). Clonic and tonic convulsions were triggered after intermittent but not steady asphyxia, and they were tightly associated with electrographic seizures. During intermittent asphyxia LFP activity was suppressed as brain pH decreased from 7.3 to 6.7. Brain Po2 fell below detection level in 5 % ambient O2 but returned to the baseline level during steps to 9 % O2. Neuronal hyperexcitability and seizures were suppressed in all types of experiments when the post-asphyxia brain pH recovery was slowed down by 5 % CO2. Our data suggest that the recurring hypoxic episodes during intermittent asphyxia promote neuronal excitability, which becomes established as hyperexcitability and seizures only after the suppressing effect of the hypercapnic acidosis is relieved. The present rodent model of BA is to our knowledge the first one in which, consistent with clinical BA, robust behavioral and electrographic seizures are triggered after and not during the BA-mimicking insult.

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Study of Myocardial Dysfunction in Perinatal Asphyxia Field

Journal of Medical Research and Innovation ◽

10.15419/jmri.127 ◽

2018 ◽

Vol 2 (S1) ◽

pp. e000127

Author(s):

Kushali Tanna ◽

K M Mehariya ◽

Suchita Munsi ◽

Charul Pujani

Keyword(s):

Troponin I ◽

Heart Diseases ◽

Perinatal Asphyxia ◽

Myocardial Dysfunction ◽

Birth Asphyxia ◽

Serum Levels ◽

Spontaneous Respiration ◽

Term Neonates ◽

Myocardial Involvement ◽

Ischemic Encephalopathy

Aims and Objectives: To study an incidence of myocardial dysfunction in neonates admitted with perinatal asphyxia, to find out its correlation with severity of birth asphyxia and its outcome. Methods: This prospective study was conducted among 40 term neonates admitted in NICU of Civil Hospital Ahmedabad who had suffered with perinatal asphyxia (defined by WHO ), resuscitated as per NRP guidelines-2015 including both intramural and extramural admissions and who developed to hypoxic ischemic encephalopathy as defined by Levene staging. Neonates with congenital heart diseases, major central nervous system malformations and neonatal sepsis were excluded. Myocardial involvement was assessed by clinical evaluation, ECG, Creatinine Kinase Total (25-200IU/L), CK-MB (0-25IU/L) and Troponin I (0-0.03ug/L) measurements. Results: Among 40 cases, 10(25%) neonates had moderate birth asphyxia while 30(75%) had severe birth asphyxia. Respiratory distress was observed in 34(77.5%), poor spontaneous respiration 4(10%),shock in 14(35%),CCF 19(47.5%) while ECG was abnormal in 30(76.7%). Serum levels of CPK Total, CPK- MB and Troponin I were raised in 34(85%), 32(80%) and 28 (70%) neonates, respectively. Conclusion: There was a direct correlation between ECG changes and enzymatic levels which showed increasing abnormalities with increasing with severity of HIE.

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Therapeutic Hypothermia in Neonatal Hypoxic Ischemic Encephalopathy: Electrographic Seizures and Magnetic Resonance Imaging Evidence of Injury

The Journal of Pediatrics ◽

10.1016/j.jpeds.2013.01.041 ◽

2013 ◽

Vol 163 (2) ◽

pp. 465-470 ◽

Cited By ~ 65

Author(s):

Preethi Srinivasakumar ◽

John Zempel ◽

Michael Wallendorf ◽

Russell Lawrence ◽

Terrie Inder ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Therapeutic Hypothermia ◽

Hypoxic Ischemic Encephalopathy ◽

Resonance Imaging ◽

Magnetic Resonance Imaging Evidence ◽

Electrographic Seizures ◽

Ischemic Encephalopathy

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MRI IN HYPOXIC ISCHEMIC ENCEPHALOPATHY WITH CLINICAL FOLLOW UP

10.36106/ijar/7611680 ◽

2021 ◽

pp. 43-48

Author(s):

M R Shashikumar ◽

Narasipur Lingaiah Rajendrakumar ◽

Sanjay P ◽

Nanjaraj Chakenalli Puttaraj ◽

Shruti Shruti ◽

...

Keyword(s):

Clinical Outcome ◽

Mr Imaging ◽

Developmental Disorders ◽

Brain Mri ◽

Birth Asphyxia ◽

Hypoxic Ischemic Encephalopathy ◽

Preterm Neonates ◽

Diffusion Restriction ◽

Ischemic Encephalopathy

Introduction: HIE is often clinically suspected in the setting of a known perinatal stress event arising from a complicated or difcult delivery. The most sensitive and specic imaging technique for examining infants with suspected hypoxicischemic brain injury is MR imaging. It also gives information about the timing and specic patterns of injury and also suggest diagnoses other than HIE such as metabolic disorders and developmental disorders of the brain. MRI is also a useful tool in the determination of prognosis and also follow-up of HIE. Aim: This study was undertaken to evaluate the various MRI appearances of hypoxic ischemic encephalopathy in term and preterm neonates and to correlate the MRI appearances with clinical outcome. Materials and Methods: All neonates with history of birth asphyxia, referred for MRI examination to the Department of Radio-Diagnosis, K. R. Hospital attached to Mysore Medical College and Research Institute, during January 2018 to January 2019. All MRI scans were performed on GE optima MR360 1.5 Tesla. Sequences used were T1W axial, T1 FLAIR axial, T2W axial, T2 FLAIR axial, T1W sag, T2W coronal, T2W GRE axial, DWI axial and ADC maps. Results: 30 babies with clinically suspicion of HIE and positive ndings on MR imaging were evaluated in our study. Out of 30 babies, 18 were term and 12 babies were preterm. Periventricular luecomalacia is most common MRI pattern in preterm and central pattern in term neonates. 16 babies had abnormal developmental outcome at 6 months follow up study. 16 babies with diffusion restriction in corpus callosum, 12 had abnormal outcome. 7 out of 10 babies with loss of normal signal in internal capsule had abnormal outcome. Babies with diffusion restriction in basal ganglia had gross developmental delay. Conclusion: MRI is the modality of choice for evaluation of HIE because of excellent gray – white matter resolution, well-depiction of myelination pattern and multi-planar imaging capabilities. There is a strong relation between the MRI appearances of birth asphyxia and the clinical outcome. Therefore MRI has a strong role in prognosticating lesions.

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Hypoxic Ischemic Encephalopathy in Neonates with Birth Asphyxia - A Hospital Based Study

Journal of Nepalgunj Medical College ◽

10.3126/jngmc.v18i2.38878 ◽

2021 ◽

Vol 18 (2) ◽

pp. 22-26

Author(s):

Jyoti Adhikari ◽

Deepak Paudel

Keyword(s):

Birth Asphyxia ◽

College Teaching ◽

Hypoxic Ischemic Encephalopathy ◽

Obstructed Labor ◽

Female Ratio ◽

Live Births ◽

Normal Birth ◽

Risk Pregnancy ◽

Clinical Presentations ◽

Ischemic Encephalopathy

Introduction: Each year approximately 4 million babies are born asphyxiated, which results in 1 million deaths and an equal number of serious neurological sequelae. One of the commonest organs involved in birth asphyxia is brain which may lead to a syndrome of clinical manifestation called Hypoxic Ischemic Encephalopathy (HIE). Aims: To find out possible maternal and neonatal risk factors for Hypoxic Ischemic Encephalopathy, to analyze clinical presentations and outcome of HIE in asphyxiated newborns. Methods: Hospital based observational study was carried out among fifty newborns with Apgar score less than 7 at 1 minute of life admitted in Nepalgunj Medical College Teaching Hospital, Kohalpur, Banke. Results: The incidence of birth asphyxia and birth asphyxia with HIE were 37.2 per 1000 live births and 14 per 1000 live births with male: female ratio of 1.27:1. Most of the neonates 22(44%) were in HIE stage II. Meconium stained amniotic fluid 18 (36%) was the most common intrapartum risk factor followed by maternal use of intrapartum medications 14 (28%), Premature Rupture of Membrane (PROM) 8 (16%), prolonged labor 5 (10%) and obstructed labor 6 (12%). Four (8%) asphyxiated neonates with HIE had cord prolapse and 7 (14%) had cord around the neck. The most common resuscitation done was bag and mask ventilation (56%) (P<0.05). Majority of the studied neonates were of normal birth weight (76%) and head circumference (84%) (P<0.05) with clinical presentations of respiratory distress (88%), seizures (44%), apnea (22%), bradycardia (8%), tachycardia (6%) and bulged anterior fontanel (6%). The overall mortality of neonates with HIE was 20% of which most were of HIE stage III. Conclusion: Certain measures could be taken to prevent birth asphyxia: early detection and intervention of high risk pregnancy, prompt and effective resuscitation of asphyxiates newborns.

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Clinical Profile of Hypoxic- Ischemic Encephalopathy in Neonates with Birth Asphyxia in a Rural Tertiary Care Hospital in Central India

Pediatric Education and Research ◽

10.21088/per.2321.1644.6218.6 ◽

2018 ◽

Vol 6 (2) ◽

pp. 80-86

Author(s):

Kher Anjali M. ◽

◽

Singh Kuldeep ◽

Vagha Jayant ◽

◽

...

Keyword(s):

Tertiary Care Hospital ◽

Tertiary Care ◽

Birth Asphyxia ◽

Central India ◽

Clinical Profile ◽

Hypoxic Ischemic Encephalopathy ◽

Care Hospital ◽

Ischemic Encephalopathy

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Analysis of umbilical cord blood gas in term and near term asphyxiated newborn babies

Journal of Patan Academy of Health Sciences ◽

10.3126/jpahs.v4i2.24555 ◽

2017 ◽

Vol 4 (2) ◽

pp. 3-8

Author(s):

Amrit Ghimire ◽

Laxman Shrestha ◽

Merina Shrestha

Keyword(s):

Cord Blood ◽

Umbilical Cord ◽

Apgar Score ◽

Perinatal Asphyxia ◽

Birth Asphyxia ◽

Gas Analysis ◽

Blood Gas ◽

Cross Sectional ◽

Maternal Risk ◽

Blood Ph

Introductions: Birth asphyxia is failure breathing causing severe consequences or death. This study aims to determine the incidence of perinatal asphyxia in neonates with low Apgar and Hypoxic Ischemic Encephalopathy (HIE) in asphyxiated babies. Methods: This was a cross sectional study from November 1, 2010 to July 30, 2011. Babies with Apgar score of less than seven at five minute were enrolled in the study. Blood was drawn from umbilical cord artery for blood gas analysis. Neonates were followed up in every six hours for at least 48 hours. Staging of HIE according to Sarnat staging was done in babies with Apgar score of <7 at five minutes within 24 hours of birth. Data was analysed using SPSS version 16.0. Results: Total of 2,425 live births, 56 (2.30%) were born with an Apgar of < 7 at five minute, six were excluded (due to set exclusion criteria) and remaining 50 were analysed. Thirty-four (68% of 50) of babies with low Apgar score had maternal risk factors – meconium stained liquor being the commonest risk factor. Majority (46%) had cord blood pH of >7.2, 40% had between 7.1 to 7.2, 12% between 7 to 7.1 and remaining 2% had pH < 7. HIE developed in 22% (11/50) of the asphyxiated babies. Conclusions: More than 1/3rd (46%) of babies with low Apgar had low cord blood pH, 1/4th (26%) had base excess, and 22% developed features of HIE. Cord blood pH were better predictors than Apgar in asphyxiated babies.

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American alligator (Alligator mississippiensis) embryos tightly regulate intracellular pH during a severe acidosis

Canadian Journal of Zoology ◽

10.1139/cjz-2017-0249 ◽

2018 ◽

Vol 96 (7) ◽

pp. 723-727 ◽

Cited By ~ 6

Author(s):

R.B. Shartau ◽

D.A. Crossley ◽

Z.F. Kohl ◽

R.M. Elsey ◽

C.J. Brauner

Keyword(s):

Intracellular Ph ◽

Ph Regulation ◽

Alligator Mississippiensis ◽

American Alligator ◽

Acid Base ◽

Tissue Ph ◽

Snapping Turtle ◽

Blood Ph ◽

Brain Ph

Crocodilian nests naturally experience high CO2 (hypercarbia), which leads to increased blood Pco2 and reduced blood pH (pHe) in embryos; their response to acid–base challenges is not known. During acute hypercarbia, snapping turtle embryos preferentially regulate tissue pH (pHi) against pHe reductions. This is proposed to be associated with CO2 tolerance in reptilian embryos and is not found in adults. In the present study, we investigated pH regulation in American alligator (Alligator mississippiensis (Daudin, 1802)) embryos exposed to 1 h of hypercarbia hypoxia (13 kPa Pco2, 9 kPa Po2). Hypercarbia hypoxia reduced pHe by 0.42 pH unit, while heart and brain pHi increased, with no change in the pHi of other tissues. The results indicate that American alligator embryos preferentially regulate pHi, similar to snapping turtle embryos, which represents a markedly different strategy of acid–base regulation than what is observed in adult reptiles. These findings suggest that preferential pHi regulation may be a strategy of acid–base regulation used by embryonic reptiles.

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