Cooperation between astrocytes and neurons is a unique interaction between two highly specialized cell types of the brain. Therefore, lack of nutrient supply during
ischemia requires tight coordination of metabolism between astrocytes and neurons to keep the brain functions intact. To understand the impact of energy limitation on astrocytes, the functions of astrocytes have to be considered: (i) supplementation of neuronal cells, (ii) modulation of the extracellular milieu, mainly of the
glutamate level, and (iii) elimination of
reactive oxygen species (ROS). In cultured astrocytes and neurons inhibition of oxidative phosphorylation, using
rotenone, was tested. Interestingly, this had only a negligible effect on Ca2+ homeostasis in astrocytes, even in combination with a severe
glutamate stress. In contrast, in neurons
glutamate in the presence of
rotenone induced Ca2+ deregulation. Ca2+ homeostasis is very critical for cell survival. A massive and prolonged Ca2+ rise will lead to deregulation of many processes in such a way that the cells affected can hardly survive. Ca2+ homeostasis depends on the energy-consuming processes, which maintain the steep gradient between intracellular and extracellular Ca2+ concentration. Deprivation of
oxygen and
glucose during
ischemia leads to a depletion of
ATP in the brain, due to inhibited glycolytic and mitochondrial activity, whereas energy-consuming processes like
ion pumps drain the
ATP pools. On the other hand, specific mechanisms can protect brain structures against the massive insult of
ischemia.
Glycogen, stored in astrocytes, can maintain both neurons and astrocytes alive during short limitation of
oxygen and
glucose. Moreover, astrocytes can fuel
ATP generation by providing
lactate for neurons.