4.6 Article

Proteasome and Neuroprotective Effect of Hyperbaric Oxygen Preconditioning in Experimental Global Cerebral Ischemia in Rats

Journal

FRONTIERS IN NEUROLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fneur.2022.812581

Keywords

proteasome; MG132; Bim; PUMA; nestin; cerebral ischemia; preconditioning; hyperbaric oxygen

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This study investigated the role of the proteasome in the mechanism of preconditioning with hyperbaric oxygen (HBO-PC). The results showed that HBO-PC can protect the brain against severe ischemic brain insult and this protection may be linked to a depletion of apoptotic proteins and improved regenerative potential.
ObjectivesWe investigated the involvement of the proteasome in the mechanism of preconditioning with hyperbaric oxygen (HBO-PC). MethodsThe experiments were performed on male Wistar rats subjected to a transient global cerebral ischemia of 5 min duration (2-vessel occlusion model) and preconditioned or not with HBO for 5 preceding days (1 h HBO at 2.5 atmosphere absolute [ATA] daily). In subgroups of preconditioned rats, the proteasome inhibitor MG132 was administered 30 min prior to each preconditioning session. Twenty-four hours and 7 days post-ischemia, after neurobehavioral assessment, the brains were collected and evaluated for morphological changes and quantitative immunohistochemistry of cell markers and apoptosis-related proteins. ResultsWe observed reduced damage of CA1 pyramidal cells in the HBO preconditioned group only at 7 days post-ischemia. However, both at early (24 h) and later (7 days) time points, HBO-PC enhanced the tissue expression of 20S core particle of the proteasome and of the nestin, diminished astroglial reactivity, and reduced p53, rabbit anti-p53 upregulated modulator of apoptosis (PUMA), and rabbit anti-B cell lymphoma-2 interacting mediator of cell death (Bim) expressions in the hippocampus and cerebral cortex. HBO-PC also improved T-maze performance at 7 days. Proteasome inhibitor abolished the beneficial effects of HBO-PC on post-ischemic neuronal injury and functional impairment and reduced the ischemic alterations in the expression of investigated proteins. SignificancePreconditioning with hyperbaric oxygen-induced brain protection against severe ischemic brain insult appears to involve the proteasome, which can be linked to a depletion of apoptotic proteins and improved regenerative potential.

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