Mechanisms involved in spreading depression

Abstract

SUMMARYApplication of unlabelled glutamate t o the isolated chicken retina caused an increase in the tissue transparency and a reIease of labelled glutamate with which the retina had previously been charged. The threshold for both responses was about 0.2 mM. Stimulation with KC1 and direct current elicited transparency changes a t a threshold of 8 mM and 4-6 V, respectively, and a release of the label a t higher KC1 concentrations (75 mM) and potentials (15 V). The transparency change caused by glutamate stimulation was severely depressed by MgC1, (10-15 mM) in contrast to the changes elicited by KC1 and direct current which were little affected by Mg ions. It was postulated that glutamate causes transparency changes by acting on neuronal elements. KC1 would act on glia and would only in high concentrations affect neurons. It was furthermore suggested that the propagation of spreading depression is dependent both on the release of glutamate from the intracellular compartment and on the depolarization of neuronal elements resulting from this release.

Repeated Negative DC Deflections in Rat Cortex following Middle Cerebral Artery Occlusion are Abolished by MK-801: Effect on Volume of Ischemic Injury

“…The cortical DC deflections are presumably generated in the periphery of the ischemic territory in response to pathological events occurring at the center of the infarct. The most likely cause is the rise of extracellular potassium (Hansen and Neder gaard, 1988) and glutamate, which are released from the intracellular compartment at flow values below 20 mlllOO g/min (Astrup et aI., 1977;Shimada et aI., 1990) and are known to evoke spreading cortical depression (Van Harreveld and Fifkova, 1973). Ob viously, the flow rate of brain regions into which cortical depolarization spreads must be above the threshold for membrane failure because the tissue spontaneously repolarizes.…”

Multiparametric Imaging of Blood Flow and Metabolism after Middle Cerebral Artery Occlusion in Cats

“…Re cently, it has been pointed out that spreading depression results in a dissociation between flow and metabolic activity (Gjedde et aI., 1981;Lau ritzen et aI., 1982;Mies and Paschen, 1984). Spreading depression can be evoked by a variety of lesions that cause the sudden increase of extracel lular potassium and/or glutamate (van Harreveld and Fifkova, 1973). It is therefore conceivable that the release of potassium or glutamate from ischemic foci into the extracellular compartment causes spreading depression of still normally perfused re gions in the vicinity of this lesion (Schuier and Hossmann, 1980).…”

Experimental brain infarcts in cats. II. Ischemic brain edema.

“…One factor which may lead to electrolyte disturbances in the presence of energy-rich compounds could be a selective change in membrane permeability for sodium, such as during spreading depression or in the presence of high glutamate levels. 41 Another factor might be a shutdown of cortical activity, leading to a saving of the energy demands of the tissue. **-** A decrease in EEG amplitude has been observed at substantially higher flow values than those causing a breakdown of energy metabolism.…”