Journal of Neuroscience, Vol 14, 5635-5643, Copyright © 1994 by Society for Neuroscience
Mild acidosis delays hypoxic spreading depression and improves neuronal recovery in hippocampal slices
GC Tombaugh
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710.
Severe tissue acidosis has been viewed traditionally as a damaging
component of cerebral hypoxia. However, a neuroprotective action of low pH
during hypoxia has been described in primary neuronal cultures. To identify
and characterize this effect in mature brain tissue, adult rat hippocampal
slices were made hypoxic after adjusting pHo with HCl or NaOH.
Ion-selective microelectrodes were positioned in CA1 to record evoked field
potentials, extracellular DC voltage (Vo), pHo, and [Ca2+]o. Orthodromic
population spike amplitude was used as a measure of slice recovery 2 hr
after reoxygenation. All slices became markedly acidotic during hypoxia
(delta pHo approximately 0.4 pH unit). Following restoration of O2 and bath
pH to 7.4, slice pHo returned to its pretreatment level regardless of
experimental treatment, hypoxic duration, or the degree of
electrophysiological recovery. When either the period of hypoxia or the
duration of HSD was held constant, acid- treated slices exhibited a
significant improvement in recovery. However, in neither paradigm did the
recovery of alkaline-treated slices differ from controls. Mild acidosis
(bath pH = 6.9-7.3) caused a reversible depression of the orthodromic
population spike, an increase in the latency of hypoxic spreading
depression-like depolarization (HSD), and a decrease in the magnitude of
the associated negative Vo shift. For each of these parameters, mild
alkalinity (bath pH = 7.7) had the opposite effect. Acid treatment did not
affect the decrease in [Ca2+]o during HSD but accelerated its recovery
after reoxygenation. These results suggest that mild acidosis may limit
hypoxic neuronal injury in vitro by delaying HSD onset and by additional
mechanisms unrelated to the degree of calcium influx during neuronal
depolarization.
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