About this Research Topic
Dementia and mild cognitive impairment are widely prevalent progressive neurological disorders, causing a significant global socio-economic impact. Alzheimer disease (AD) and vascular dementia (VD) are the two most common forms of dementia, accounting for 60-70% and 20% of cases, respectively. Although efforts have been made to identify and classify the underlying etiology of dementia, there currently exists no cure, indicating the necessity of further investigation to support the development of successful prevention and treatment measures. There is a growing debate over the infectious etiology of AD. Neurotropic infectious agents, including viruses (e.g. herpes simplex viruses [HSVs] and cytomegalovirus [CMV]), bacteria (e.g. Chlamydia pneumoniae) and parasites (e.g. Toxoplasma gondii), establish infection in the central nervous system (CNS) that may or may not cause neurological dysfunction. Acute CNS infection (e.g. Streptococcus pneumoniae) has been shown to cause enduring cognitive disorders in patients’ later lives, while malaria parasites (Plasmodium spp.) never enter the CNS parenchyma, nonetheless, may cause persistent changes in CNS function. In addition to CNS infection, peripheral infection, such as periodontal infection (e.g. Porphyromonas gingivalis) and viral hepatitis (e.g. Hepatitis C virus [HCV]), may also increase a person’s risk of developing dementia. Furthermore, imbalance in the gut microbiome may be linked to the development and progression of dementia, suggesting that host-microbe interaction, both in the CNS and periphery, might contribute to dementia development.
Interactions between infectious agents and hosts are particularly complex in the CNS, where, compared to peripheral tissues, immune components have relatively limited access. The CNS employs unique mechanisms to protect the brain while maintaining homeostasis. The blood-brain barrier (BBB) restricts the entry of cells and macromolecules into the CNS parenchyma, while microglia and perivascular macrophages eliminate pathogens. In addition, recent findings suggest that the CNS parenchyma is subject to adaptive immune surveillance, which comprises CD8+ and CD4+ tissue-resident memory T cell populations. However, during acute infection, some agents may cause severe disruption of the BBB and initiate a cascade of inflammatory responses in the CNS resulting in permanent brain damage that might be associated with neuropsychological disorders. Furthermore, host immune reactions to infectious agents can be a double-edged sword, and in both acute and chronic infections, dysregulated neuroinflammation may pose a threat to the functionality of the CNS via several mechanisms, including cytokine storm and oxidative stress.
This Research Topic will investigate the complex interplay between host and microbes. A broad overview of the various cellular and molecular mechanisms involved in the interaction between different infectious agents and the CNS cells will allow an in-depth investigation of the diversity and / or similarity of these mechanisms and their neurophysiological impacts. For example, how this interaction can lead to CNS dysfunction and contribute to the development of cognitive dysfunction? Could this interaction be modulated in infected individuals to develop new therapeutic strategies? Original research, Brief Case Reports, Reviews, and hypotheses are welcomed.
Keywords: infection, brain pathology, neuroinflammation, synaptic dysfunction, Dementia
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