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Updated: Feb 5, 2026
Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury
Published on: November 24, 2017
Changes in Cerebral Oxidative Metabolism during Neonatal Seizures Following Hypoxic-Ischemic Brain Injury
Subhabrata Mitra1, Gemma Bale2, Sean Mathieson1
1Department of Neonatology, Institute for Women's Health, University College London , London , UK.
Insights
Neonatal seizures after hypoxic-ischemic encephalopathy increase brain energy demand, indicated by cerebral cytochrome-c-oxidase oxidation state changes. This suggests impaired mitochondrial function during prolonged seizures in newborns.
Area of Science:
- Neuroscience
- Neonatal Medicine
- Biochemistry
Background:
- Seizures are common after hypoxic-ischemic encephalopathy (HIE) in newborns.
- Prolonged seizures can worsen brain damage, but mechanisms are unclear.
- Cytochrome-c-oxidase (CCO) is crucial for mitochondrial ATP production.
Observation:
- A novel near-infrared spectroscopy system measured cerebral cytochrome-c-oxidase oxidation state (Δ[oxCCO]) and hemodynamics.
- Measurements were taken during recurrent neonatal seizures post-HIE.
- Cerebral oxygenation and blood volume dropped before seizures but recovered during them.
Findings:
- Δ[oxCCO] rapidly increased at seizure onset, correlating with EEG voltage, indicating heightened neuronal activity and energy demand.
- A progressive decline in the Δ[oxCCO] baseline during seizures suggests impaired mitochondrial oxidative metabolism.
- These findings link neonatal seizures to altered brain energy metabolism.
Implications:
- Understanding the bioenergetic impact of seizures in HIE is critical for developing targeted therapies.
- This study highlights the potential of near-infrared spectroscopy for monitoring brain metabolism in neonates.
- Further research can elucidate the precise mechanisms of seizure-induced neuronal damage in HIE.
Abstract:
Seizures are common following hypoxic-ischemic brain injury in newborn infants. Prolonged or recurrent seizures have been shown to exacerbate neuronal damage in the developing brain; however, the precise mechanism is not fully understood. Cytochrome-c-oxidase is responsible for more than 90% of ATP production inside mitochondria. Using a novel broadband near-infrared spectroscopy system, we measured the concentration changes in the oxidation state of cerebral cytochrome-c-oxidase (Δ[oxCCO]) and hemodynamics during recurrent neonatal seizures following hypoxic-ischemic encephalopathy in a newborn infant. A rapid increase in Δ[oxCCO] was noted at the onset of seizures along with a rise in the baseline of amplitude-integrated electroencephalogram. Cerebral oxygenation and cerebral blood volume fell just prior to the seizure onset but recovered rapidly during seizures. Δ[oxCCO] during seizures correlated with changes in mean electroencephalogram voltage indicating an increase in neuronal activation and energy demand. The progressive decline in the Δ[oxCCO] baseline during seizures suggests a progressive decrease of mitochondrial oxidative metabolism.
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