Enhanced distribution of molecules in the brain due to oscillations of interstitial flow

Background The movement of molecules in the grey matter interstitial spaces is most often viewed as being governed primarily by passive Brownian diffusion with a slow advective component. MRI measurements from a decade old study of the physical properties of brain tissue observed a dynamic pulsating fluid flow attributed to the cardiac cycle. The effects of this cyclic flow pattern on distribution of molecules in the brain needs to be determined. Methods The MRI measurements of water flow in and out of the brain tissue with the cardiac pulsation have been used in a simplified model to quantitate the distance a molecule would move carried by this flow. We estimate that the interstitial fluid flow in two scenarios: Scenario 1 without transmantle pressure differences and Scenario 2 with transmantle pressure differences. The results are then used to calculate the effects of this flow on a “morphological” dispersion of molecules which we define in the paper. In Scenario 3, respiration effects are also calculated and added to the cardiac induced flow. Results Based on modeling we suggest that the cardiac induced flow in the interstitial space is enough to reach the threshold of morphological dispersion and respiratory effects would make this well above that threshold. This would help explain the high effective diffusion found in MRI measurements of a marker infused into the CSF in human subjects that is well above what would be expected. Conclusion The interstitial space should be viewed as a region of dynamic oscillatory flow being driven by cardiac and respiratory cycles. This oscillatory flow could produce significant dispersion of molecules and explain the higher than expected effective diffusion suggested in human studies. It also may be possible to augment or slow this flow by applied external forces.