Review on the Role of Mitochondrial Dysfunction in Septic Encephalopathy.

Abstract

Septic Encephalopathy (SE) is a frequent and severe complication of sepsis, characterized by a range of neurocognitive impairments from mild confusion to deep coma. The underlying pathophysiology of SE involves systemic inflammation, neuroinflammation, blood-brain barrier (BBB) disruption, and mitochondrial dysfunction. Among these factors, mitochondrial dysfunction plays a pivotal role, contributing to impaired ATP production, increased reactive oxygen species (ROS) generation, and activation of apoptotic pathways, all of which exacerbate neuronal damage and cognitive deficits. Diagnosis of SE relies on clinical evaluation, neuroimaging, electroencephalography (EEG), and laboratory tests, though specific diagnostic markers are still lacking. Epidemiological data show SE is prevalent in intensive care unit (ICU) patients, especially those with severe sepsis or septic shock, with incidence rates varying widely depending on the population and diagnostic criteria used. Recent research highlights the importance of mitochondrial dynamics, including biogenesis, fission, and fusion, in the development of SE. Mitophagy, a selective form of autophagy that degrades damaged mitochondria, plays a critical role in maintaining mitochondrial health and protecting against dysfunction. Targeting mitochondrial pathways and enhancing mitophagy offers a promising therapeutic strategy to mitigate the effects of SE, reduce oxidative stress, prevent apoptosis, and support the resolution of neuroinflammation. Further research is essential to elucidate the mechanisms of mitochondrial dysfunction and mitophagy in SE and develop effective interventions to improve patient outcomes.