Induction of hemodynamic traveling waves by glial-driven vasomotion in a rat model of neuroinflammation: implications for functional neuroimaging

Cerebral hemodynamics are crucial for brain homeostasis and serve as a key proxy for brain activity. Although this process involves coordinated interaction between vessels, neurons and glial cells, its dysregulation in neuroinflammation is not well understood. We used in vivo mesoscopic functional ultrasound imaging to monitor cerebral blood volume changes during neuroinflammation in rats injected with lipopolysaccharide (LPS) in the visual cortex, under resting-state or visual stimulation, combined to advanced ex vivo techniques for glial cell reactivity analysis. Cortical neuroinflammation induced large oscillatory hemodynamic traveling waves in the frequency band of vasomotion (~0.1 Hz) in both anesthetized and awake rats. Vasomotor waves traveled through large distances between adjacent penetrating vessels, spanning the entire cortex thickness, and even extending to subcortical areas. Moreover, vasomotion amplitude correlated with microglial morphology changes and was significantly reduced by astrocytic toxins, suggesting that both microglia and astrocytes are involved in the enhancement of vasomotion during neuroinflammation. Notably, functional connectivity was increased under this oscillatory state and functional hyperemia was preserved or even exacerbated. These findings reveal new spatiotemporal properties and cellular mechanisms of cerebral vasomotion, and suggest that this is an important component of brain hemodynamics in pathological states. Moreover, reactive microglia and astrocytes are participating to increased vasomotion during neuroinflammation. These results call for a reassessment of vasomotion and traveling waves as major phenomena when imaging brain hemodynamic activity, particularly in conditions associated with neuroinflammation. Overall design: Nuclei of rat visual cortex were isolated and then selected using Fluorescence-activated nuclei sorting (FANS) based on high DAPI intensity for analysis using snRNA-seq. Nuclei were individually barcoded trough split-seq technology used in the Evercode WT technology by PARSE Biosciences without equipment and libraries were prepared according to PARSE Biosciences protocol.