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.
Highlights
Seizures occur in ~75% of infants with hypoxic–ischemic encephalopathy (HIE) [1]
We evaluate the changes in cerebral mitochondrial oxidative metabolism synchronously with changes in cerebral oxygenation, hemodynamics, and electroencephalogram (EEG) during neonatal seizures following hypoxic–ischemic brain injury
Our observed increase in mitochondrial oxidative metabolism during neonatal seizures concurs with these findings and the progressive decrease in [oxCCO] baseline with recurrent seizures in our study indicated a decrease in mitochondrial oxidative metabolism
Summary
Animal studies have indicated that prolonged and frequent seizures in the developing brain result in long-term neurological sequelae [2]. Clinical studies suggest that neonatal seizures are independently associated with further neuronal injury [3] and poor outcome [4, 5]; the mechanisms for these harmful effects are not clear. Mitochondrial metabolism is closely related to neuronal activity. Studies using phosphorus-31 magnetic resonance spectroscopy (31P MRS) have revealed that high-energy phosphates decrease by one-third and mitochondrial oxidative phosphorylation increases by 45% during neonatal seizures [5], indicating a depleted cerebral energy state during seizures. Near-infrared spectroscopy (NIRS) measures concentration changes in oxygenated (Δ[HbO2]) and deoxygenated hemoglobin (Δ[HHb]) which can be used to derive changes in total hemoglobin
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