New Aspects of Central Nervous System Adaptation to Prenatal Hypoxia

The aim of the investigation was to study the effect of chronic and acute prenatal hypoxia on the parameters of CNS functional activity and to assess the role of mitochondria in the protection of the CNS against experimental hypoxic influence in vivo.

Materials and Methods. The experiments in vivo were performed on C57BL/6 mice. In order to model chronic prenatal hypoxia, pregnant female mice were placed daily into a hypobaric chamber beginning with the fourteenth day of gestation up to delivery. 280–300 mm Hg pressure corresponding to the altitude of 8000 m above sea level was maintained in the chamber for 2 h. Acute prenatal hypoxia was modeled on the eighteenth day of gestation. Pregnant females were placed for 4–5 min (till the first agonal breath) in the hypobaric chamber under 220–240 mm Hg pressure corresponding to the altitude of 10,000 m above sea level.

Oxygen consumption rate by mice brain mitochondria was assessed on the first day of the post-natal period using a high-resolution Oxygraph-2k respirometer (Oroboros Instruments, Austria). To determine a general state of the CNS in the remote post-hypoxic period, a neurological status of the 4-week-old animals was evaluated according to the neurological deficit scale for small laboratory animals and Garcia’s scale. Mnestic and cognitive abilities were also tested in Morris water maze.

Results. Protocols of acute and chronic prenatal hypoxia modeling for mice have been designed. Acute hypoxic damage has been shown to result in the significant decrease of the basal oxygen consumption rate and intensity of oxidative phosphorylation by the brain mitochondria of the newborn mice, and in the activation of the respiratory complex II. After chronic prenatal hypoxia, the basal oxygen consumption rate and oxidative phosphorylation intensity significantly increased relative to the intact group.

Conclusion. The designed protocols of experimental prenatal hypoxia modeling allowed us to reveal a specific pattern of mitochondrial apparatus adaptation to various types of hypoxic damage. Chronic hypoxia leads to adaptation of the mitochondrial apparatus characterized by intensification of oxidative phosphorylation.

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Urazov М.D., Astrakhanova Т.А., Usenko А.V., Mishchenko Т.А., Schelchkova N.А., Kravchenko G.A., Vedunova М.V., Mitroshina Е.V. New Aspects of Central Nervous System Adaptation to Prenatal Hypoxia. Sovremennye tehnologii v medicine 2018; 10(4): 60, https://doi.org/10.17691/stm2018.10.4.07