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Coles, J. A.

Publications and source records attributed to Coles, J. A..

2 recordsLinked to original sources

Exercise and the brain: a mechanical model for pulsation on flow of cerebrospinal fluid

Exchange of molecules between cerebrospinal fluid (CSF) and brain cells contributes to brain function and protection from dementia. Despite widespread acceptance of the glymphatic theory, the route by which CSF is brought close enough to the neural tissue for solutes to be exchanged by extracellular diffusion is not entirely clear. Exogenous molecules injected into CSF are observed to reach the basement lamina that surrounds the dense capillary network. Transport of solutes by diffusion along the basement lamina, a gel of macromolcules about 100 nm thick, would be too slow; bulk flow in a static geometry would require unphysiologically high pressures. However, it is known that the pulsation of blood aids transport of CSF, and we hypothesized that this is because the pulsation intermittently squeezes the pericapillary lamina. In a primitive mimicry, we have tested whether intermittent squeezing increases flow through an agar gel. In all but one of 216 tests, pulsation caused a reversible increase, sometimes by a factor of 100 or more. The enhancement was greatest for frequencies 5-11 Hz and, over the tested range of pressure heads (20 - 50 cmH2O), was greatest for the lowest pressure. The results suggest a reason why exercise slows the aging of the brain.

physiology↗

Streptococcus pneumoniae rapidly translocates from the nasopharynx through the cribriform plate to invade and inflame the dura

The entry routes and translocation mechanisms of bacterial pathogens into the central nervous system remain obscure. We report here that Streptococcus pneumoniae (Sp) or polystyrene microspheres, applied to the nose of a mouse, appeared in the meninges of the dorsal cortex within minutes. Recovery of viable bacteria from dissected tissue and fluorescence microscopy showed that up to at least 72h, Sp and microspheres were predominantly in the outer of the two meninges, the pachymeninx. No Sp were found in blood or cerebrospinal fluid. Evidence that this was not an artifact of the method of administration is that in mice infected by horizontal transmission, Sp were also predominantly in the meninges and absent from blood. Intravital imaging through the skull, and flow cytometry showed recruitment and activation of LysM+ cells in the dorsal pachymeninx at 5h and 10h following intranasal infection. Imaging of the cribriform plate suggested that both Sp and microspheres entered through its foramina via an inward flow of fluid connecting the nose to the pachymeninx. Our findings bring further insight into the invasion mechanisms of bacterial pathogens such as Sp into the central nervous system, but are also pertinent to the delivery of drugs to the brain, and the entry of air-borne particles into the cranium.

microbiology↗