[Transmission routes of neuropathogenic pathogens-Possible mechanisms of neuroinvasion]

Despite natural protective barriers, many human pathogens can penetrate the nervous system. The pathogens have developed sophisticated mechanisms to overturn the privileged immune status of the nervous system. The central nervous system (CNS) has natural barriers and immunological protective mechanisms, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), that prevent the invasion of pathogens. Bacteria enter the CNS, for example, through transcellular penetration, paracellular entry or via infected leucocytes from the peripheral circulation. Viruses can enter the CNS by hematogenous routes, by direct infection of endothelial cells or by paracellular passage between disrupted endothelial cells (cribriform plate). Also, a few "enhanced barriers", such as the cribriform plate and circumventricular organs (CVO) can serve as entry points for viruses. Viruses can also gain access to the CNS by infection of peripheral nerves. Importantly, most successful neurotropic pathogens are not necessarily restricted to a CNS entry portal. The majority of viral pathogens are of animal origin. Through sometimes sophisticated immune mechanisms for example in bats, highly pathogenic pathogens arose through cross-species transmission. In the last 50 years, various viruses, such as West Nile, Ebola, Marburg, Zika, Nipah and Hendra viruses have also been transmitted from animals to humans. Knowledge of these biological strategies is crucial to hinder, contain or prevent CNS infections.