Abstract
The timing and mechanisms of protection by hyperbaric oxygenation (HBO) in hypoxic-ischemic brain damage (HIBD) have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders) were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI) and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm) occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI.
Highlights
Medical research has long focused on understanding the pathophysiology of hypoxic-ischemic brain damage (HIBD) in newborns, which still has a high incidence in the world, causing negative developmental outcomes in children [1]
The secondary drop in the HIBD and HIBD+ hyperbaric oxygenation (HBO) groups occurred from 12 h to 3 days after HI, and the extent of the secondary drop was more severe in the HIBD+HBO group, indicating that HBO in the early stage after HI might not be a good therapy to improve mitochondrial function in the cerebral cortex
A secondary recovery occurred after 4 days of HBO treatment, elevating DCm of the ipsilateral cortex in the HIBD+HBO group to near normal levels
Summary
Medical research has long focused on understanding the pathophysiology of hypoxic-ischemic brain damage (HIBD) in newborns, which still has a high incidence in the world, causing negative developmental outcomes in children [1]. There is a cascade of brain cell damage after HI insult, from O2 deprivation, followed by N-methyl-D-aspartate (NMDA) receptor activation and intracellular free calcium accumulation, to mitochondrial dysfunction and other biochemical changes of brain cells, resulting in the death of cells via apoptosis or necrosis [4]. Any intervention that effectively reverses each step in the cascade may have a potential treatment effect in HIBD. Under any circumstance of hypoxia/ischemia-inducing cell death, mitochondrial dysfunction caused by energy failure is the earliest pathophysiology process [6,7]. The usual pathway is: energy failure – free calcium accumulation in the cell – mitochondrial dysfunction – cytochrome C released from the mitochondria – other cascade steps of cell damage – cell necrosis/apoptosis
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