Immunological defense of CNS barriers against infections

What SARS-CoV-2 does to our brains

“…Instead, interstitial fluid drains-in addition to the route of CSF-from the parenchyma into the intramural perivascular spaces between endothelial cells and astrocytic endfeet (Virchow-Robin space) around arterioles and venules of the white matter and basal ganglia toward cervical lymph nodes (Cserr et al, 1981;Lam et al, 2017;Szentistvanyi et al, 1984;Zhang et al, 1990). This ''glymphatic pathway'' is separated from the CSF by the pia mater (Iliff et al, 2012) and is considered a second route of the afferent arm of the immune system, carrying antigens (but not APCs) from the CNS parenchyma to regional lymph nodes (recommended reviews: Engelhardt et al,2016, Ampie andMcGavern, 2022). In the cerebral cortex, the perivascular space is only virtual, in contrast to what was first assumed from erroneous interpretations of sample preparation artefacts (Morris et al, 2016) but instead possess highly permeable fenestrated capillaries that are lined by tanycytes, specialized ependymal and/or glial cells, allowing the passage of peptides and hormones from the CNS to circulating blood (Kaur and Ling, 2017;Wislogki and King, 1936).…”

Streptococcus pneumoniae meningitis and the CNS barriers

“…The BCSFB is structurally distinct from the BBB: the vascular endothelium here lacks tight junctions and is fenestrated so may pose less of a mechanical challenge to bacterial translocation. However, extravasating bacteria enter the subependymal space which contains resident macrophages and patrolling T cells and subsequently have to cross the epithelial layer, where the cells are joined by tight junctions, in order to access the CSF ( Ampie and McGavern, 2022 ).…”

“…The CNS is also contained within an anatomically closed compartment and is therefore vulnerable to oedema induced by the inflammatory response, which raises the intracerebral pressure leading to tissue ischaemia ( Tuomanen et al., 1995 ; Nayak et al., 2012 ). Due to the vulnerability of the CNS to homeostatic disruption and inflammation, the cerebral environment is closely controlled with the movement of ions, molecules and cells tightly regulated by barriers at the interface of the brain with the blood and CSF ( Abbott et al., 2006 ; Engelhardt and Coisne, 2011 ; Ampie and McGavern, 2022 ).…”

“…The basement membrane at this site is also structurally distinct, being composed of two layers separated by a perivascular space containing perivascular macrophages ( Sorokin, 2010 ). External to the basement membrane are astrocyte endfeet, forming an additional barrier to entry of bacteria and leukocytes into the cerebral parenchyma from the circulation ( Ampie and McGavern, 2022 ).…”

“…External to this are the epithelial cells of the ventricular cavity which possess tight junctions, limiting the movement of cells and molecules between the subependymal space and the CSF. ( Ampie and McGavern, 2022 ). At its periphery, the brain is bounded by astrocytes forming the glia limitans superficialis, and external to this the meninges and further CSF spaces: the pia mater, the subarachnoid space, arachnoid mater, and then the dura mater.…”