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 the possible role of brain pH changes, we used a rodent model that mimics the alterations in systemic CO(2) and O(2) levels during and after intrapartum birth asphyxia.
  
  
  METHODS
  Neonatal rat pups were exposed for 1 hour to hypercapnia (20% CO(2) in the inhaled gas), hypoxia (9% O(2)), or both (asphyxic conditions). CO(2) 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 Na(+) /H(+) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biosciences, University of Helsinki, Finland.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Helmy
authors.forename: Else A
authors.initials: EA
authors.lastname: Tolner
authors.forename: Sampsa
authors.initials: S
authors.lastname: Vanhatalo
authors.forename: Juha
authors.initials: J
authors.lastname: Voipio
authors.forename: Kai
authors.initials: K
authors.lastname: Kaila
mesh_terms: D000471:Alkalosis / Q000150:complications*; D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000150:complications*; D004195:Disease Models, Animal; D004569:Electroencephalography; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000209:etiology*