Seizure susceptibility during recovery from hypercapnia in neonatal dogs

Yoshioka, Hiroshi; Nioka, Shoko; Miyake, Hidenori; Zaman, Aziza; Sawada, Tadashi; Chance, Britton

doi:10.1016/0887-8994(96)00116-6

Cited by 10 publications

(9 citation statements)

References 13 publications

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“…There is evidence indicating that both the amplitude and the rate of alkaline recovery of brain tissue pH boost neuronal excitability and the triggering of seizures. 29,30 Thus, we examined the efficacy of graded restoration of normocapnia (GRN) 31 in suppressing seizures by exposing the rat pups to 5% CO 2 in air for 30 min immediately after intermittent asphyxia. Here, rapid restoration of normocapnia (RRN) refers to the bulk of experiments in which the animals were promptly re-exposed to room air after asphyxia.…”

Section: Behavioral Seizures Emerge Following Intermittent Asphyxiamentioning

confidence: 99%

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

et al. 2020

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Objective Birth asphyxia (BA) is often associated with seizures that may exacerbate the ensuing hypoxic–ischemic encephalopathy. In rodent models of BA, exposure to hypoxia is used to evoke seizures, that commence already during the insult. This is in stark contrast to clinical BA, in which seizures are typically seen upon recovery. Here, we introduce a term‐equivalent rat model of BA, in which seizures are triggered after exposure to asphyxia. Methods Postnatal day 11–12 male rat pups were exposed to steady asphyxia (15 min; air containing 5% O2 + 20% CO2) or to intermittent asphyxia (30 min; three 5 + 5‐min cycles of 9% and 5% O2 at 20% CO2). Cortical activity and electrographic seizures were recorded in freely behaving animals. Simultaneous electrode measurements of intracortical pH, Po2, and local field potentials (LFPs) were made under urethane anesthesia. Results Both protocols decreased blood pH to <7.0 and brain pH from 7.3 to 6.7 and led to a fall in base excess by 20 mmol·L–1. Electrographic seizures with convulsions spanning the entire Racine scale were triggered after intermittent but not steady asphyxia. In the presence of 20% CO2, brain Po2 was only transiently affected by 9% ambient O2 but fell below detection level during the steps to 5% O2, and LFP activity was nearly abolished. Post‐asphyxia seizures were strongly suppressed when brain pH recovery was slowed down by 5% CO2. Significance The rate of brain pH recovery has a strong influence on post‐asphyxia seizure propensity. The recurring hypoxic episodes during intermittent asphyxia promote neuronal excitability, which leads to seizures only after the suppressing effect of the hypercapnic acidosis is relieved. The present rodent model of BA is to our best knowledge the first one in which, consistent with clinical BA, behavioral and electrographic seizures are triggered after and not during the BA‐mimicking insult.

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Section: Behavioral Seizures Emerge Following Intermittent Asphyxiamentioning

confidence: 99%

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

et al. 2020

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“…5). There is evidence indicating that both the amplitude and the rate of alkaline recovery of brain tissue pH, boosts neuronal excitability and the triggering of seizures (Woodbury et al, 1957;Yoshioka et al, 1996). Thus, we examined the efficacy of Graded Restoration of Normocapnia (GRN), a putative therapeutic maneuver which slows down the rate of alkaline recovery (Helmy et al, 2011), in suppressing seizures in the intermittent asphyxia model.…”

Section: Behavioral Seizures Emerge Following Intermittent Asphyxia mentioning

confidence: 99%

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

Ala-Kurikka

Pospelov

Summanen

et al. 2020

Preprint

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Birth asphyxia (BA) is a pathologic condition that arises from severe perinatal hypoxia and hypercapnia.Recovery following BA is often associated with seizures which may exacerbate the ensuing hypoxicischemic encephalopathy (HIE). Drugs used to treat post-BA seizures are often ineffective and there are concerns over their safety. Therefore, novel seizure-suppressing therapies are urgently needed. Most rodent models of BA-induced seizures are based on exposing neonatal rats or mice to hypoxia (or hypoxiaischemia), and overlook the fact that the hypercapnic acidosis linked to asphyxia has brain-sparing effects by suppressing neuronal excitability and enhancing cerebral blood flow. Thus, the aim of the present study was to investigate the dependence of asphyxia-induced seizures on brain pH and oxygen (Po 2 ) levels in a rodent model of term BA based on postnatal day 11-12 rat pups. Cortical activity and electrographic seizures were recorded in freely-behaving animals using epidural electrodes. Simultaneous measurements of cortical local field potentials as well as intracortical pH and Po 2 were made using microelectrodes and microsensors in urethane-anesthesized animals. The pups were exposed either to steady asphyxia (duration 15 min; with ambient air containing 5 % O 2 plus 20 % CO 2 ) or to intermittent asphyxia (30 min; with repetitive 5 min steps from 9 % to 5 % O 2 at constant 20 % CO 2 ). Both protocols led to acidemia (blood pH <7.0) coupled to a fall in base excess by 20 mmol/l, and to a large increase in plasma copeptin (from 0.2 nM to about 5 nM), a biomarker of BA. Brain pH decreased from 7.3 to 6.7 by the end of intermittent asphyxia.Brain Po 2 was only transiently affected by 9% ambient O 2 , but it fell below the level of detection with steps to 5 % O 2 , during which neuronal activity was near-abolished. The Po 2 steps to 9% were associated with a moderate increase in pH (0.12 units) and a slight recovery (~10 % of baseline) in ongoing neuronal activity.Behavioral seizures spanning the entire Racine scale were triggered after intermittent but not steady asphyxia, and they were tightly associated with neocortical electrographic seizures. The seizures were strongly suppressed when the post-asphyxia brain pH recovery was slowed down by a low level (5 %) of ambient CO 2 . The post-asphyxia overshoot in brain Po 2 (from 30 to 85 mmHg) had no discernible effect on neuronal activity. Our data suggest that the recurring hypoxic episodes during intermittent asphyxia promote neuronal excitability, which becomes established as hyperexcitability and seizures once the suppressing effect of the hypercapnic acidosis is relieved. The present rodent model of BA is to our best knowledge the first one where, consistent with the clinical picture of BA, robust behavioral and electrographic seizures are triggered after and not during the asphyxic insult. HIGHLIGHTS Experimental asphyxia induced severe acidemia and abolished most cortical activity. Cortical activity during asphyxia was closely linked with changes in brai...

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“…Elevated carbon dioxide (CO 2 ) blood levels have a depressant effect on the central nervous system and electroencephalography (EEG) activity 1 2. In adults, hypercapnia can lead to an altered mental state, encephalopathy and coma 3.…”

Section: Introductionmentioning

confidence: 99%

Severe hypercapnia causes reversible depression of aEEG background activity in neonates: an observational study

Weeke

Dix

Groenendaal

et al. 2017

Arch Dis Child Fetal Neonatal Ed

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Seizure susceptibility during recovery from hypercapnia in neonatal dogs

Cited by 10 publications

References 13 publications

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

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

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

Severe hypercapnia causes reversible depression of aEEG background activity in neonates: an observational study

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