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Cerebrospinal fluid (CSF) flowing through periarterial spaces is integral to the brain’s mechanism for clearing metabolic waste products. Experiments that track tracer particles injected into the cisterna magna (CM) of mouse brains have shown evidence of pulsatile CSF flow in perivascular spaces surrounding pial arteries, with a bulk flow in the same direction as blood flow. However, the driving mechanism remains elusive. Several studies have suggested that the bulk flow might be an artifact, driven by the injection itself. Here, we address this hypothesis with new in vivo experiments where tracer particles are injected into the CM using a dual-syringe system, with simultaneous injection and withdrawal of equal amounts of fluid. This method produces no net increase in CSF volume and no significant increase in intracranial pressure. Yet, particle-tracking reveals flows that are consistent in all respects with the flows observed in earlier experiments with single-syringe injection.

The flow of cerebrospinal fluid (CSF) through perivascular spaces surrounding the vasculature is thought to be an important part of the brain9s mechanism for clearing metabolic waste products, including those associated with disorders such as Alzheimer9s disease. Experiments that track tracer particles injected into the cisterna magna of mouse brains have shown evidence of pulsatile CSF flow in perivascular spaces around pial (surface) arteries, with a bulk (average) flow in the same direction as the blood flow. Although measurements are consistent with the idea that this flow is driven primarily by arterial pulsations, the driving mechanism is still not completely understood, and several published articles have suggested that the bulk flow might be an artifact, driven by the injection itself. Here we address this hypothesis with new in vivo experiments in which the injection of suspended tracer particles into the cisterna magna is done with a dual-syringe system, with simultaneous injection and withdrawal of equal amounts of fluid. This method produces no net increase in CSF volume and no significant increase in intracranial pressure, and yet particle-tracking reveals flows in the pial periarterial spaces that are completely consistent with the flows observed in earlier experiments with single-syringe injection.