Advances in the Study of Mechanisms of Pathogen Invasion into Central Nervous System

Abstract

In post-pandemic period of COVID-19, the increase in the number of sub-healthy population, coupled with factors such as global travel, climate change, and increased contact with wildlife, may lead to a rise in the incidence of central nervous system (Central nervous system, CNS) infections by potential zoonotic pathogens, which has become one of the main reasons for the increase in adjusted life years lost due to human disability. Due to the high case fatality rate of CNS infection and the severe sequelae of the body, it is also one of the most serious global public health challenges at present. To resist pathogen invasion, hosts have constructed a series of barrier structures on their surfaces and within their bodies, including skin barrier, blood-lung barrier, blood-testis barrier and blood-brain barrier (BBB). Among these, the BBB is a complex barrier structure composed of various cellular and non-cellular components. As a biological barrier isolating the CNS from the periphery, BBB can prevent a vast majority of harmful substances from entering the brain, thus ensuring the dynamic equilibrium of the brain's internal environment and the normal functioning of the CNS. However, through long-term evolution, pathogens have developed multiple pathways to cross the BBB and invade the CNS. Currently, five invasion pathways have been confirmed by researchers, including infection or disruption of brain endothelial cells; crossing the BBB through transcellular migration; infiltrating through the BBB as a "Trojan horse" via infected leukocytes; entering the CNS through paracellular spaces; and bypassing the BBB and entering the CNS through axonal transport from the periphery. The severity and complexity of CNS infectious diseases are influenced by the nature of the pathogen itself, the structure and function of the host BBB and the diversity of neural invasion pathways. Furthermore, the molecular mechanisms by which pathogens utilize protein interactions, regulate BBB permeability, and invade the CNS through phagocytosis have been elucidated in detail. This has made CNS delivery of certain drugs possible and also laid a theoretical foundation for the development of entirely new CNS drug delivery systems. Therefore, a comprehensive understanding of the structure of the BBB and the pathways through which pathogens invade the CNS will contribute to the development of strategies to control pathogen invasion, novel brain-targeted drugs, and new delivery systems to mitigate established infections in the host CNS.

Keywords

• central nervous system
• blood-brain barrier
• pathogenic microorganism
• infection
• invasion mechanism