Induction of reactive gliosis by purinoceptor activation: a critical appraisal

In recent years various authors brought forward the interesting hypothesis that extracellular ATP is released by damaged neurones and acts on astrocytes and microglia to cause the reactive gliotic response of damaged tissue. This review analyses the facts presented in favour of this hypothesis. All these facts are based on studies involving cultured astrocytes and microglia. The available studies on freshly isolated astrocytes, brain slices or in vivo preparations fail to verify this hypothesis: 1. No evidence was found for release of ATP by damaged neurones. This concept is indeed based on measurements in cardiac tissue and conformation in CNS tissue is lacking. 2. Freshly isolated astrocytes and astrocytes in situ lack the ATP-evoked increases in the intracellular Ca2+ concentration and show no change in the membrane current pattern. 3. No studies have been undertaken with non-cultured microglia to verify purinergic responses. 4. No convincing evidence is yet available to show that reactive gliosis involves purinergic receptors in an in vivo preparation. Thus, there is an urgent need for studies involving glial cells in situ or freshly isolated cells. Without any additional studies involving noncultured cells the hypothesis for an ATP mediated induction of reactive gliosis lacks credibility.