Flow of cerebrospinal fluid (CSF) through perivascular spaces (PVSs) in the brain is important for clearance of metabolic waste. Arterial pulsations are thought to drive flow, but this has never been quantitatively shown. We used particle tracking to quantify CSF flow velocities in PVSs of live mice. CSF flow is pulsatile and driven primarily by the cardiac cycle. The speed of the arterial wall matches that of the CSF, suggesting arterial wall motion is the principal driving mechanism, via a process known as perivascular pumping. Increasing blood pressure leaves the artery diameter unchanged but changes the pulsations of the arterial wall, increasing backflow and thereby reducing net flow in the PVS. Perfusion-fixation alters the normal flow direction and causes a 10-fold reduction in PVS size. We conclude that particle tracking velocimetry enables the study of CSF flow in unprecedented detail and that studying the PVS in vivo avoids fixation artifacts.
Stroke affects millions each year. Poststroke brain edema predicts the severity of eventual stroke damage, yet our concept of how edema develops is incomplete and treatment options remain limited. In early stages, fluid accumulation occurs owing to a net gain of ions, widely thought to enter from the vascular compartment. Here, we used magnetic resonance imaging, radiolabeled tracers, and multiphoton imaging in rodents to show instead that cerebrospinal fluid surrounding the brain enters the tissue within minutes of an ischemic insult along perivascular flow channels. This process was initiated by ischemic spreading depolarizations along with subsequent vasoconstriction, which in turn enlarged the perivascular spaces and doubled glymphatic inflow speeds. Thus, our understanding of poststroke edema needs to be revised, and these findings could provide a conceptual basis for development of alternative treatment strategies.
Collective animal behaviour occurs at nearly every biological size scale, from single-celled organisms to the largest animals on earth. It has long been known that models with simple interaction rules can reproduce qualitative features of this complex behaviour. But determining whether these models accurately capture the biology requires data from real animals, which has historically been difficult to obtain. Here, we report three-dimensional, time-resolved measurements of the positions, velocities, and accelerations of individual insects in laboratory swarms of the midge Chironomus riparius. Even though the swarms do not show an overall polarisation, we find statistical evidence for local clusters of correlated motion. We also show that the swarms display an effective large-scale potential that keeps individuals bound together, and we characterize the shape of this potential. Our results provide quantitative data against which the emergent characteristics of animal aggregation models can be benchmarked.
Collective animal behaviour is often modeled by systems of agents that interact via effective social forces, including short-range repulsion and long-range attraction. We search for evidence of such effective forces by studying laboratory swarms of the flying midge Chironomus riparius. Using multi-camera stereoimaging and particle-tracking techniques, we record three-dimensional trajectories for all the individuals in the swarm. Acceleration measurements show a clear short-range repulsion, which we confirm by considering the spatial statistics of the midges, but no conclusive long-range interactions. Measurements of the mean free path of the insects also suggest that individuals are on average very weakly coupled, but that they are also tightly bound to the swarm itself. Our results therefore suggest that some attractive interaction maintains cohesion of the swarms, but that this interaction is not as simple as an attraction to nearest neighbours.
Background Periarterial spaces (PASs) are annular channels that surround arteries in the brain and contain cerebrospinal fluid (CSF): a flow of CSF in these channels is thought to be an important part of the brain’s system for clearing metabolic wastes. In vivo observations reveal that they are not concentric, circular annuli, however: the outer boundaries are often oblate, and the arteries that form the inner boundaries are often offset from the central axis. Methods We model PAS cross-sections as circles surrounded by ellipses and vary the radii of the circles, major and minor axes of the ellipses, and two-dimensional eccentricities of the circles with respect to the ellipses. For each shape, we solve the governing Navier–Stokes equation to determine the velocity profile for steady laminar flow and then compute the corresponding hydraulic resistance. Results We find that the observed shapes of PASs have lower hydraulic resistance than concentric, circular annuli of the same size, and therefore allow faster, more efficient flow of cerebrospinal fluid. We find that the minimum hydraulic resistance (and therefore maximum flow rate) for a given PAS cross-sectional area occurs when the ellipse is elongated and intersects the circle, dividing the PAS into two lobes, as is common around pial arteries. We also find that if both the inner and outer boundaries are nearly circular, the minimum hydraulic resistance occurs when the eccentricity is large, as is common around penetrating arteries. Conclusions The concentric circular annulus assumed in recent studies is not a good model of the shape of actual PASs observed in vivo, and it greatly overestimates the hydraulic resistance of the PAS. Our parameterization can be used to incorporate more realistic resistances into hydraulic network models of flow of cerebrospinal fluid in the brain. Our results demonstrate that actual shapes observed in vivo are nearly optimal, in the sense of offering the least hydraulic resistance. This optimization may well represent an evolutionary adaptation that maximizes clearance of metabolic waste from the brain.
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