Brain Alkalosis Causes Birth Asphyxia Seizures, Suggesting Therapeutic Strategy

Mohamed Mustafa Mahmoud Helmy, Else Tolner, Sampsa Vanhatalo, Juha Voipio, Kai Kaila

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

Objective: The mechanisms whereby birth asphyxia leads to generation of seizures remain unidentified. To study the
possible role of brain pH changes, we used a rodent model that mimics the alterations in systemic CO2 and O2
levels during and after intrapartum birth asphyxia.
Methods: Neonatal rat pups were exposed for 1 hour to hypercapnia (20% CO2 in the inhaled gas), hypoxia (9%
O2), or both (asphyxic conditions). CO2 levels of 10% and 5% were used for graded restoration of normocapnia.
Seizures were characterized behaviorally and utilizing intracranial electroencephalography. Brain pH and oxygen were
measured with intracortical microelectrodes, and blood pH, ionized calcium, carbon dioxide, oxygen, and lactate
with a clinical device. The impact of the postexposure changes in brain pH on seizure burden was assessed during 2
hours after restoration of normoxia and normocapnia. N-methyl-isobutyl-amiloride, an inhibitor of Naþ/Hþ exchange,
was given intraperitoneally.
Results: Whereas hypercapnia or hypoxia alone did not result in an appreciable postexposure seizure burden,
recovery from asphyxic conditions was followed by a large seizure burden that was tightly paralleled by a rise in
brain pH, but no change in brain oxygenation. By graded restoration of normocapnia after asphyxia, the alkaline
shift in brain pH and the seizure burden were strongly suppressed. The seizures were virtually blocked by
preapplication of N-methyl-isobutyl-amiloride.
Interpretation: Our data indicate that brain alkalosis after recovery from birth asphyxia plays a key role in the
triggering of seizures. We question the current practice of rapid restoration of normocapnia in the immediate
postasphyxic period, and suggest a novel therapeutic strategy based on graded restoration of normocapnia.
Alkuperäiskielienglanti
LehtiAnnals of Neurology
Vuosikerta69
Numero3
Sivut493-500
Sivumäärä8
ISSN0364-5134
DOI - pysyväislinkit
TilaJulkaistu - 2011
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 3112 Neurotieteet

Lainaa tätä

Helmy, Mohamed Mustafa Mahmoud ; Tolner, Else ; Vanhatalo, Sampsa ; Voipio, Juha ; Kaila, Kai. / Brain Alkalosis Causes Birth Asphyxia Seizures, Suggesting Therapeutic Strategy. Julkaisussa: Annals of Neurology. 2011 ; Vuosikerta 69, Nro 3. Sivut 493-500.
@article{9fcf016a0428453ab611b4323d6b003c,
title = "Brain Alkalosis Causes Birth Asphyxia Seizures, Suggesting Therapeutic Strategy",
abstract = "Objective: The mechanisms whereby birth asphyxia leads to generation of seizures remain unidentified. To study thepossible role of brain pH changes, we used a rodent model that mimics the alterations in systemic CO2 and O2levels during and after intrapartum birth asphyxia.Methods: Neonatal rat pups were exposed for 1 hour to hypercapnia (20{\%} CO2 in the inhaled gas), hypoxia (9{\%}O2), or both (asphyxic conditions). CO2 levels of 10{\%} and 5{\%} were used for graded restoration of normocapnia.Seizures were characterized behaviorally and utilizing intracranial electroencephalography. Brain pH and oxygen weremeasured with intracortical microelectrodes, and blood pH, ionized calcium, carbon dioxide, oxygen, and lactatewith a clinical device. The impact of the postexposure changes in brain pH on seizure burden was assessed during 2hours after restoration of normoxia and normocapnia. N-methyl-isobutyl-amiloride, an inhibitor of Na{\th}/H{\th} exchange,was given intraperitoneally.Results: Whereas hypercapnia or hypoxia alone did not result in an appreciable postexposure seizure burden,recovery from asphyxic conditions was followed by a large seizure burden that was tightly paralleled by a rise inbrain pH, but no change in brain oxygenation. By graded restoration of normocapnia after asphyxia, the alkalineshift in brain pH and the seizure burden were strongly suppressed. The seizures were virtually blocked bypreapplication of N-methyl-isobutyl-amiloride.Interpretation: Our data indicate that brain alkalosis after recovery from birth asphyxia plays a key role in thetriggering of seizures. We question the current practice of rapid restoration of normocapnia in the immediatepostasphyxic period, and suggest a novel therapeutic strategy based on graded restoration of normocapnia.",
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author = "Helmy, {Mohamed Mustafa Mahmoud} and Else Tolner and Sampsa Vanhatalo and Juha Voipio and Kai Kaila",
year = "2011",
doi = "10.1002/ANA.22223",
language = "English",
volume = "69",
pages = "493--500",
journal = "Annals of Neurology",
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Brain Alkalosis Causes Birth Asphyxia Seizures, Suggesting Therapeutic Strategy. / Helmy, Mohamed Mustafa Mahmoud; Tolner, Else; Vanhatalo, Sampsa; Voipio, Juha; Kaila, Kai.

julkaisussa: Annals of Neurology, Vuosikerta 69, Nro 3, 2011, s. 493-500.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Brain Alkalosis Causes Birth Asphyxia Seizures, Suggesting Therapeutic Strategy

AU - Helmy, Mohamed Mustafa Mahmoud

AU - Tolner, Else

AU - Vanhatalo, Sampsa

AU - Voipio, Juha

AU - Kaila, Kai

PY - 2011

Y1 - 2011

N2 - Objective: The mechanisms whereby birth asphyxia leads to generation of seizures remain unidentified. To study thepossible role of brain pH changes, we used a rodent model that mimics the alterations in systemic CO2 and O2levels during and after intrapartum birth asphyxia.Methods: Neonatal rat pups were exposed for 1 hour to hypercapnia (20% CO2 in the inhaled gas), hypoxia (9%O2), or both (asphyxic conditions). CO2 levels of 10% and 5% were used for graded restoration of normocapnia.Seizures were characterized behaviorally and utilizing intracranial electroencephalography. Brain pH and oxygen weremeasured with intracortical microelectrodes, and blood pH, ionized calcium, carbon dioxide, oxygen, and lactatewith a clinical device. The impact of the postexposure changes in brain pH on seizure burden was assessed during 2hours after restoration of normoxia and normocapnia. N-methyl-isobutyl-amiloride, an inhibitor of Naþ/Hþ exchange,was given intraperitoneally.Results: Whereas hypercapnia or hypoxia alone did not result in an appreciable postexposure seizure burden,recovery from asphyxic conditions was followed by a large seizure burden that was tightly paralleled by a rise inbrain pH, but no change in brain oxygenation. By graded restoration of normocapnia after asphyxia, the alkalineshift in brain pH and the seizure burden were strongly suppressed. The seizures were virtually blocked bypreapplication of N-methyl-isobutyl-amiloride.Interpretation: Our data indicate that brain alkalosis after recovery from birth asphyxia plays a key role in thetriggering of seizures. We question the current practice of rapid restoration of normocapnia in the immediatepostasphyxic period, and suggest a novel therapeutic strategy based on graded restoration of normocapnia.

AB - Objective: The mechanisms whereby birth asphyxia leads to generation of seizures remain unidentified. To study thepossible role of brain pH changes, we used a rodent model that mimics the alterations in systemic CO2 and O2levels during and after intrapartum birth asphyxia.Methods: Neonatal rat pups were exposed for 1 hour to hypercapnia (20% CO2 in the inhaled gas), hypoxia (9%O2), or both (asphyxic conditions). CO2 levels of 10% and 5% were used for graded restoration of normocapnia.Seizures were characterized behaviorally and utilizing intracranial electroencephalography. Brain pH and oxygen weremeasured with intracortical microelectrodes, and blood pH, ionized calcium, carbon dioxide, oxygen, and lactatewith a clinical device. The impact of the postexposure changes in brain pH on seizure burden was assessed during 2hours after restoration of normoxia and normocapnia. N-methyl-isobutyl-amiloride, an inhibitor of Naþ/Hþ exchange,was given intraperitoneally.Results: Whereas hypercapnia or hypoxia alone did not result in an appreciable postexposure seizure burden,recovery from asphyxic conditions was followed by a large seizure burden that was tightly paralleled by a rise inbrain pH, but no change in brain oxygenation. By graded restoration of normocapnia after asphyxia, the alkalineshift in brain pH and the seizure burden were strongly suppressed. The seizures were virtually blocked bypreapplication of N-methyl-isobutyl-amiloride.Interpretation: Our data indicate that brain alkalosis after recovery from birth asphyxia plays a key role in thetriggering of seizures. We question the current practice of rapid restoration of normocapnia in the immediatepostasphyxic period, and suggest a novel therapeutic strategy based on graded restoration of normocapnia.

KW - 3112 Neurosciences

U2 - 10.1002/ANA.22223

DO - 10.1002/ANA.22223

M3 - Article

VL - 69

SP - 493

EP - 500

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 3

ER -