RESUMO
Neuroinflammation is a complex inflammatory process in the central nervous system, which is sought to play an important defensive role against various pathogens, toxins or factors that induce neurodegeneration. The onset of neurodegenerative diseases and various microbial infections are counted as stimuli that can challenge the host immune system and trigger the development of neuroinflammation. The homeostatic nature of neuroinflammation is essential to maintain the neuroplasticity. Neuroinflammation is regulated by the activity of neuronal, glial, and endothelial cells within the neurovascular unit, which serves as a "platform" for the coordinated action of pro- and anti-inflammatory mechanisms. Production of inflammatory mediators (cytokines, chemokines, reactive oxygen species) by brain resident cells or cells migrating from the peripheral blood, results in the impairment of blood-brain barrier integrity, thereby further affecting the course of local inflammation. In this review, we analyzed the most recent data on the central nervous system inflammation and focused on major mechanisms of neurovascular unit dysfunction caused by neuroinflammation and infections.
Assuntos
Infecções do Sistema Nervoso Central/imunologia , Sistema Nervoso Central/irrigação sanguínea , Sistema Nervoso Central/imunologia , Inflamação/imunologia , Doenças Neurodegenerativas/etiologia , Animais , Barreira Hematoencefálica/imunologia , Encéfalo/imunologia , Movimento Celular , Sistema Nervoso Central/crescimento & desenvolvimento , Sistema Nervoso Central/microbiologia , Infecções do Sistema Nervoso Central/sangue , Infecções do Sistema Nervoso Central/complicações , Quimiocinas/metabolismo , Citocinas/metabolismo , Humanos , Inflamação/fisiopatologia , Doenças do Sistema Nervoso/imunologia , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/fisiopatologia , Espécies Reativas de Oxigênio , Viroses/complicaçõesRESUMO
Alzheimer's type of neurodegeneration dramatically affects H2S and NO synthesis and interactions in the brain, which results in dysregulated vasomotor function, brain tissue hypoperfusion and hypoxia, development of perivascular inflammation, promotion of Aß deposition, and impairment of neurogenesis/angiogenesis. H2S- and NO-signaling pathways have been described to offer protection against Alzheimer's amyloid vasculopathy and neurodegeneration. This review describes recent developments of the increasing relevance of H2S and NO in Alzheimer's disease (AD). More studies are however needed to fully determine their potential use as therapeutic targets in Alzheimer's and other forms of vascular dementia.