Biology subjects

Kedarasetti, R.

Publications and source records attributed to Kedarasetti, R..

4 recordsLinked to original sources

bioRxiv2025

Gut-Brain Hydraulics: Brain motion and CSF circulation is driven by mechanical coupling with the abdomen

The brain moves within the skull, but the drivers and function of this motion are not understood. We visualized brain motion relative to the skull in awake head-fixed mice using high-speed, multi-plane two-photon microscopy. Brain motion was primarily rostrally and laterally directed, and was tightly correlated with locomotion, but not with respiration or the cardiac cycle. Electromyography recordings in abdominal muscles and microCT reconstructions of the trunk and spinal vasculature showed that brain motion was driven by abdominal muscle contractions that activate a hydraulic-like vascular connection between the nervous system and the abdominal cavity. Externally-applied abdominal pressure generated brain motion similar to those seen during abdominal muscle contractions. Simulations showed that brain motion drives substantial volumes of interstitial fluid through and out of the brain (at volumetric rates several times higher than production) into the subarachnoid space, in the opposite direction of fluid flow seen during sleep. The brain is hydraulically linked to the abdominal compartment, and fluid flow in the brain is coupled to body movements, providing a mechanism by which the mechanics of the viscera directly impact brain health.

neuroscience↗

bioRxiv2021

Arterial vasodilation drives convective fluid flow in the brain: a poroelastic model

The movement of fluid into, through, and out of the brain plays an important role in clearing metabolic waste. However, there is controversy regarding the mechanisms driving fluid movement, and whether the movement metabolic waste is primarily driven by diffusion or convection. The dilation of penetrating arterioles in the brain in response to increases in neural activity (neurovascular coupling) is an attractive candidate for driving fluid circulation, as it drives deformation of the brain tissue and of the paravascular space around arteries, resulting in fluid movement. We simulated the effects of vasodilation on fluid movement into and out of the brain using a novel poroelastic model of brain tissue. We found that arteriolar dilations could drive convective flow through the brain radially outward from the arteriole, and that this flow is sensitive to the dynamics of the dilation. Simulations of sleep-like conditions, with larger vasodilations and increased extracellular volume in the brain showed enhanced movement of fluid from the paravascular space into the brain. Our simulations suggest that both sensory-evoked and sleep-related arteriolar dilations can drive convective flow of cerebrospinal fluid from the paravascular space into the brain tissue around arterioles.

neuroscience↗

bioRxiv2020

Arterial pulsations drive oscillatory flow of CSF but not directional pumping

The brain lacks a traditional lymphatic system for metabolite clearance. The existence a "glymphatic system" where metabolites are removed from the brains extracellular space by convective exchange between interstitial fluid (ISF) and cerebrospinal fluid (CSF) along the paravascular spaces (PVS) around cerebral blood vessels has been controversial for nearly a decade. While recent work has shown clear evidence of directional flow of CSF in the PVS in anesthetized mice, the driving force for the observed fluid flow remains elusive. The heartbeat-driven peristaltic pulsation of arteries has been proposed as a probable driver of directed CSF flow. In this study, we use rigorous fluid dynamic simulations to provide a physical interpretation for peristaltic pumping of fluids. Our simulations match the experimental results and show that arterial pulsations only drive oscillatory motion of CSF in the PVS. The observed directional CSF flow can be explained by naturally occurring and/or experimenter-generated pressure differences.

neuroscience↗

bioRxiv2019

Functional hyperemia drives fluid exchange in the paravascular space

Maintaining the ionic and chemical composition of the extracellular spaces in the brain is extremely important for its health and function. However, the brain lacks a conventional lymphatic system to remove metabolic waste. It has been proposed that the fluid movement through the paravascular space (PVS) surrounding penetrating arteries can help remove metabolites from the brain. The dynamics of fluid movement in the PVS and its interaction with arterial dilation and brain mechanics are not well understood. Here, we performed simulations to understand how arterial pulsations and dilations interact with brain deformability to drive fluid flow in the PVS. In simulations with compliant brain tissue, arterial pulsations did not drive appreciable flows in the PVS. In contrast, when the artery dilated with dynamics like those seen during functional hyperemia, there was a marked movement of fluid through the PVS. Our simulations suggest that in addition to its other purposes, functional hyperemia may serve to increase fluid exchange between the PVS and the subarachnoid space, improving the clearance of metabolic waste. We measured displacement of the blood vessels and the brain tissue simultaneously in awake, head-fixed mice using two-photon microscopy. Our measurements show that brain tissue can deform in response to fluid movement in the PVS, as predicted by simulations. The results from our simulations and experiments show that the deformability of the soft brain tissue needs to be accounted for when studying fluid flow and metabolite transport in the brain.

neuroscience↗