Induction of haemodynamic travelling waves by glial-related vasomotion in a rat model of neuroinflammation: implications for functional neuroimaging.

Abstract

BACKGROUND: Cerebral haemodynamics are crucial for brain homoeostasis 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. METHODS: We used in vivo mesoscopic functional ultrasound imaging to monitor cerebral blood volume changes during neuroinflammation in male 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. FINDINGS: Cortical neuroinflammation induced large oscillatory haemodynamic travelling waves in the frequency band of vasomotion (∼0.1 Hz) in both anaesthetized and awake rats. Vasomotor waves travelled 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 hyperaemia was exacerbated. INTERPRETATION: These findings further reveal the spatiotemporal properties of cerebral vasomotion and suggest this is a major component of brain haemodynamics in pathological states. Moreover, reactive microglia and astrocytes are participating to increase vasomotion during neuroinflammation. For the field of functional neuroimaging, our results advocate for considering 0.1 Hz haemodynamic oscillations as an important complement to traditional measurements, particularly in neuroinflammatory conditions. Indeed, brain haemodynamics may provide insights not only into neuronal activity but also glial reactivity. FUNDING: Supported by ANR ("LabCom-NI2D", "Labex Cortex") and Auvergne-Rhône-Alpes Region ("BI2D").