Fig.2.

Schematic to show oral pathogen/endotoxin entry direct and/or indirect into the brain following bacteraemias. A) Attenuated P. gingivalis/LPS within the systemic circulation can gain access to the brain via transport across the blood-brain barrier (BBB). Once organisms are present in the ventricular cerebrospinal fluid (CSF), they can potentially invade the subarachnoid space. From the CSF, bacteria cross the ependymal epithelial cell layer lining the ventricle wall for entry into the brain parenchyma. A1 represents an infection encountered in advanced age and A2 in younger age. Bacteria within the systemic circulation can gain access to the perivascular spaces, which in turn connect with the subarachnoid space. The CSF connects to and communicates with the lateral and third ventricles providing access for pathogens to all parts of the CNS. B) Endotoxin transfer directly into the brain via circumventricular organs and indirectly via antigen presentation: The meninges have a well-developed population of dendritic cells and meningeal cells that communicate through lymphatic vessels with the adaptive immune system located in the systemic lymph nodes. Dendritic cells in blood vessels of the choroid plexus and the meninges/leptomeninges house cells expressing the mannose receptor, lipopolysaccharide (LPS) receptor (CD14), and the highly conserved toll like receptors 2 and 4 (TLR 2 and 4).