Submerged hippocampal slices were exposed to 30 minutes of moderate or mild hypoxia at 29°C and then reoxygenated. Synaptic transmission was lost at the same rate in response to either grade of hypoxia, but recovery was faster following mild hypoxia. Hyperexcitability of synaptic transmission was a lasting feature following moderate hypoxia, but it was transient following mild hypoxia; after mild hypoxia the strength of synaptic transmission eventually returned to normal. Extracellular calcium did not change during moderate hypoxia. The extracellular pH of slices was always more acid than the bath; pH decreased further in response to both moderate and mild hypoxia. Extracellular potassium increased more during moderate than during mild hypoxia, and a period of rapid potassium uptake was also more pronounced following moderate hypoxia. Extracellular DC potential demonstrated a small positive shift during hypoxia, more so during mild hypoxia. These experiments suggest that synaptic function can be reversibly suppressed in mildly hypoxic brain tissue without severe depolarization of neurons; in addition, the degree and duration of posthypoxic hyperexcitability are correlated with the degree of hypoxia and the magnitude of the release of K+ from cells into their environment. (Stroke 1987;18:30-37) A GROWING body of evidence suggests that / \ neuronal activity is suppressed by ischemia A. A . before the structural integrity of neurons is lost. How long neurons can exist in such an inactive state before irreversible damage occurs depends on the degree and duration of blood flow reduction 1 and the specific vulnerability to ischemia of individual neurons.
2Following complete occlusion of a cerebral vessel, a gradient of flow exists: from near or total cessation of flow in the central area of a vessel's territory of distribution to normal or increased flow at the periphery of the territory.3 It has been postulated that there exists a region where blood flow is reduced to levels where cerebral functions (electroencephalogram and evoked potentials) are suppressed but ion homeostasis is mostly preserved -the "ischemic penumbra."4 That areas of reduced flow consistent with an ischemic penumbra exist in human stroke patients is known, 3 but whether such tissue is capable of regaining full function on resumption of normal oxygen delivery cannot be determined from available information. Indeed, whether an ischemic penumbra exists as originally conceived has aroused considerable controversy.
3Ischemia is a complex insult consisting of impaired oxygen and glucose delivery and impaired metabolic waste removal. It is difficult to investigate how graded changes in one variable of ischemia, such as hypoxia, affect the brain in situ because of accompanying vascular and other systemic responses. The thin in vitro Received November 27, 1985; accepted July 2, 1986. brain slice therefore provides a practical method to study the effect of hypoxia on the physiology of functioning neural tissue. We have previously shown that synaptic tra...