Effect of Hyperbaric Oxygen Treatment on Lipid Metabolism and Neurovascular Microenvironment in an Apolipoprotein E Knockout Mouse Model

Background: Dyslipidemia during midlife represents a significant risk factor for neuropathological alterations associated with cognitive decline. Given the currently incurable nature of dementia, implementation of preventive strategies and early therapeutic interventions prior to disease progression are paramount. Emerging evidence suggests that hyperbaric oxygen (HBO) therapy exhibits neuroprotective properties in various neurological conditions. However, whether HBO treatment modulates lipid metabolism dysregulation and subsequent neurodegeneration remains unanswered. This investigation aimed to elucidate the therapeutic potential of HBO treatment in ameliorating cerebral dysfunction and metabolic perturbations using apolipoprotein E (ApoE)-deficient (ApoE-/-) mice. Methods: ApoE-/- mice received HBO treatment for 10 consecutive days, and then behavioral assessment tests were performed. Serum and brain tissue were collected to measure oxidative stress levels and inflammatory factors. Results: Compared with ApoE-/- group, cognitive declines was significantly reversed in mice of the ApoE-/-+HBO mice. The blood lipid profiles of ApoE-/- mice were also improved after HBO treatment, accompanied by a reduction in body weight. Moreover, HBO treatment was found to ameliorates neuronal injury and amyloid-β deposition in the hippocampus of ApoE-/- mice. Further studies have revealed that the benefits of HBO treatment occurred through the reduction of inflammatory factors and attenuation of oxidative stress. Conclusions: These findings indicate that HBO treatment effectively improves the intracerebral microenvironment of ApoE-/- mice, providing a novel regulatory mechanism of protection against dyslipidemia-associated brain deficits by HBO treatment.