Astrocyte Ca2+ Waves and Subsequent Non-Synchronized Ca2+ Oscillations Coincide with Arteriole Diameter Changes in Response to Spreading Depolarization.

Réka Tóth,Eszter Farkas,Péter Makra,Ferenc Bari,Ákos Menyhárt,István A Krizbai,Attila E Farkas

doi:10.3390/ijms22073442

Abstract

Spreading depolarization (SD) is a wave of mass depolarization that causes profound perfusion changes in acute cerebrovascular diseases. Although the astrocyte response is secondary to the neuronal depolarization with SD, it remains to be explored how glial activity is altered after the passage of SD. Here, we describe post-SD high frequency astrocyte Ca2+ oscillations in the mouse somatosensory cortex. The intracellular Ca2+ changes of SR101 labeled astrocytes and the SD-related arteriole diameter variations were simultaneously visualized by multiphoton microscopy in anesthetized mice. Post-SD astrocyte Ca2+ oscillations were identified as Ca2+ events non-synchronized among astrocytes in the field of view. Ca2+ oscillations occurred minutes after the Ca2+ wave of SD. Furthermore, fewer astrocytes were involved in Ca2+ oscillations at a given time, compared to Ca2+ waves, engaging all astrocytes in the field of view simultaneously. Finally, our data confirm that astrocyte Ca2+ waves coincide with arteriolar constriction, while post-SD Ca2+ oscillations occur with the peak of the SD-related vasodilation. This is the first in vivo study to present the post-SD astrocyte Ca2+ oscillations. Our results provide novel insight into the spatio-temporal correlation between glial reactivity and cerebral arteriole diameter changes behind the SD wavefront.

Highlights

The outcome of acute brain injury worsens with the occurrence of secondary pathophysiological events that compromise cerebral perfusion in the subacute and chronic phase of injury
Fewer astrocytes were involved in Ca2+ oscillations at a given time point, in contrast with Ca2+ waves, which engaged all astrocytes in the field of view virtually simultaneously (Figure 1D)
In the present study, we visualized astrocyte Ca2+ changes and vascular responses associated with Spreading depolarization (SD) in the anesthetized mouse somatosensory cortex

Summary

Introduction

The outcome of acute brain injury worsens with the occurrence of secondary pathophysiological events that compromise cerebral perfusion in the subacute and chronic phase of injury. As in physiological neurovascular coupling [20,21], astrocytes are thought to release vasoactive substances (e.g., arachidonic acid and its prostanoid derivatives) during SD, which cause the contraction or relaxation of cerebrovascular smooth muscle cells [4,22,23,24,25] In accordance with these results, SD was found to trigger fast astrocyte Ca2+ waves that temporally coincided with arteriolar constrictions in mice [26,27,28,29]. We have previously reported that the SD-related arteriole constriction is driven by perivascular K+ release through large-conductance Ca2+-activated potassium channels (BK channels) on astrocyte endfeet [24]

Methods

Results

Conclusion