The astrocytic contribution to neurovascular coupling--still more questions than answers?

Cerebral blood flow adequate for brain activity and metabolic demand is maintained through the processes of autoregulation and neurovascular coupling. Astrocytes undoubtedly make an important contribution to these processes. The critical factors that determine the polarity of astrocytic response include: metabolites (e.g., arachidonic acid and its derivatives, lactate and oxygen concentrations), ions (H(+), Ca(2+) and K(+)), gliotransmitters (glutamate, Glu; gamma-aminobutyric acid, GABA; d-serine; adenosine 5'-triphosphate, ATP and brain derived neurotrophic factor, BDNF), neuronal activity and vascular tone. Although the astrocytic contribution to neurovascular coupling has been intensively studied, a few important questions still remain, such as: (1) the modulatory function of astrocytes in tripartite synapses, including effects related to the strength of synaptic stimulation and the particular signaling pathway (astrocytic or neuronal) that becomes activated, (2) the significance of the vasoconstrictive reaction evoked by arachidonic acid metabolites (e.g., 20-hydroxyeicosatetraenoic acid, 20-HETE) under both physiological and pathological conditions, (3) the relationship between brain activity level and metabolic processes occurring in astrocytes, which is studied using neuroradiological techniques and (4) the astrocytic contribution to the neurovascular response under pathological conditions. Hence, the function of astrocytes in neurovascular coupling remains ambiguous. The function of astrocytes is beneficial and integrative in physiological conditions, but under definitive pathological conditions may become detrimental and involved in the development of diseases like ischemic stroke, arterial hypertension and Alzheimer's disease.