Role of astrocytes in the spreading depression signal between ischemic core and penumbra

The evidence for spreading depression waves between the ischemic core and penumbra and its role in extending the core into the penumbra is reviewed. Experiments from the author's laboratory using primary cultures of astrocytes and intracellular pH and K(+)-sensitive microelectrodes are described. The results suggest a passive involvement of astrocytes during an ischemic process. Neurones react by equilibrating their K+ and Na+ gradients very quickly. The resulting glial depolarization leads to passive Donnan-mediated KCl and water fluxes into astrocytes. Such a mechanism could explain the depolarizing phase of spreading depression. The repolarization phase must involve energy-consuming processes which are probably located in neurones. These processes are still unknown.