Ozone (O3) is a component of photochemical smog, which is a major air pollutant and demonstrates properties that are harmful to health because of the toxic properties that are inherent to its powerful oxidizing capabilities. Environmental O3 exposure is associated with many symptoms related to respiratory disorders, which include loss of lung function, exacerbation of asthma, airway damage, and lung inflammation. The effects of O3 are not restricted to the respiratory system or function - adverse effects within the central nervous system (CNS) such as decreased cognitive response, decrease in motor activity, headaches, disturbances in the sleep-wake cycle, neuronal dysfunctions, cell degeneration, and neurochemical alterations have also been described; furthermore, it has also been proposed that O3 could have epigenetic effects. O3 exposure induces the reactive chemical species in the lungs, but the short half-life of these chemical species has led some authors to attribute the injurious mechanisms observed within the lungs to inflammatory processes. However, the damage to the CNS induced by O3 exposure is not well understood. In this review, the basic mechanisms of inflammation and activation of the immune system by O3 exposure are described and the potential mechanisms of damage, which include neuroinflammation and oxidative stress, and the signs and symptoms of disturbances within the CNS caused by environmental O3 exposure are discussed.

The World Health Organization identified urban outdoor air pollution as the eighth highest mortality risk factor in high-income countries. Exposure to ambient pollutants such as ozone (O₃) increases the number of hospital admissions. O₃ is a highly reactive gas that reacts with cells lining the airways, producing the formation of reactive oxygen species and inflammation. Beyond the respiratory system, O₃ exposure also produces fatigue, lethargy, headaches, and significant decrease in rapid-eye-movement sleep related to an increase in slow-wave sleep. Interestingly, these sleep changes can be significantly mitigated by treatment with indomethacin, which suggests that an inflammatory mechanism may be responsible for these neurological symptoms. To characterize the inflammatory mechanisms by which O₃ affects tissues outside the pulmonary system, we evaluated inflammatory factors in both lung and brain. Rats exposed to 1 part per million O₃ for 1, 3 or 6 h, as well as rats exposed daily for 1 or 3 h over five consecutive days, showed increases in TNF-α and IL-6 levels within the lungs as well as increases in TNF-α, IL-6, NF-κB p50 and GFAP levels in the cerebral cortex. These results support the hypothesis that the neuroinflammatory response may be responsible for the central nervous system effects of O₃ exposure.

Background: The ketogenic diet (KD), high in fat and low in carbohydrates, was introduced in the 1920s as a non-pharmacological treatment for refractory epilepsy. Although its mechanism of action is not fully understood, beneficial effects have been observed in neurological diseases such as epilepsy, Alzheimer’s disease, and Parkinson’s disease. Objective: This review examines the impact of the ketogenic diet and its molecular and neuroglial effects as a complementary therapy for neurological diseases. Discussion: KD is associated with neuroprotective and antioxidant effects that improve mitochondrial function, regulate neurotransmitter flow, and reduce neuroinflammation and oxidative stress. Glial cells play an essential role in the utilization of ketone bodies (KBs) within the central nervous system’s metabolism, particularly during ketosis induced by the KD. Thus, the KD represents a broad and promising strategy that involves both neurons and glial cells, with a molecular impact on brain metabolism and neuroinflammatory homeostasis. Conclusion: Multiple molecular mechanisms have been identified to explain the benefits of the KD in neurological diseases; however, further experimental and clinical studies are needed to address various molecular pathways in order to achieve conclusive results.