Astrocytic endfoot Ca²⁺ correlates with parenchymal vessel responses during 4-AP induced epilepsy: An in vivo two-photon lifetime microscopy study

Abstract

Neurovascular coupling (NVC) underlying the local increase in blood flow during neural activity forms the basis of functional brain imaging and is altered in epilepsy. Because astrocytic calcium (Ca) signaling is involved in NVC, this study investigates the role of this pathway in epilepsy. Here, we exploit 4-AP induced epileptic events to show that absolute Ca concentration in cortical astrocyte endfeet in vivo correlates with the diameter of precapillary arterioles during neural activity. We simultaneously monitored free Ca concentration in astrocytic endfeet with the Ca-sensitive indicator OGB-1 and diameter of adjacent arterioles in the somatosensory cortex of adult mice by two-photon fluorescence lifetime measurements following 4-AP injection. Our results reveal that, regardless of the mechanism by which astrocytic endfoot Ca was elevated during epileptic events, increases in Ca associated with vasodilation for each individual ictal event in the focus. In the remote area, increases in Ca correlated with vasoconstriction at the onset of seizure and vasodilation during the later part of the seizure. Furthermore, a slow increase in absolute Ca with time following multiple seizures was observed, which in turn, correlated with a trend of arteriolar constriction both at the epileptic focus and remote areas.

A Pilot Study Investigating Changes in Capillary Hemodynamics and Its Modulation by Exercise in the APP-PS1 Alzheimer Mouse Model

“…In this study, we aimed to quantify the hemodynamic properties of and modulatory role of exercise on cerebral capillaries in AD due to the important role of microcirculation in cognitive health (Østergaard et al, 2016;Erdener et al, 2017;Zhang et al, 2017;Hernández et al, 2019). Exploiting awake microscopic vascular imaging and a transgenic mouse model of AD, we found that in this model (APP-PS1), AD is associated with hemodynamic disruption in capillaries.…”

Neuron-Glia Interactions in Neurodevelopmental Disorders

“…Astrocytes are located close to blood vessels. The endfeet of astrocytes surround the vessels and contribute to neurovascular coupling (NVC) [ 20 ]. Astrocytic calcium levels are increased in the activated form.…”

The yin and yang of KV channels in cerebral small vessel pathologies

“…NVC is the process that links localized neuronal activity in the brain to vasodilation of proximate PAs so as to ensure adequate delivering of oxygen and nutrients to metabolically active regions of the central nervous system. A key component of NVC is the K IR ‐dependent SMC hyperpolarization and vasodilation that results from modest increases in [K + ] o within the perivascular space . In isolated PAs, raising [K + ] o from 3 mM to 8 mM hyperpolarizes the SM V m to near the new E K of −76 mV, causing near maximum vasodilation by decreasing Ca 2+ influx .…”