Synaptic depression and neuronal loss in transiently acidic hippocampal slice cultures

Acidosis is a rapid and inevitable event accompanying cerebral ischemia or trauma. We used hippocampal slice cultures to examine an immediate effect o f acidosis, synaptic depression; and a delayed effect, neuronal loss. Expos ure to low bicarbonate artificial cerebral spinal fluid (aCSF), pH 6.70 for 30 min at 32 degreesC, acidified intracellular pH from 7.31+/-0.12 to 6.53 +/-0.08. Accompanying intracellular acidosis was a depression of synaptic r esponses. Both effects rapidly reversed after treatment with normal aCSF pH 7.35. Death analysis after acidosis treatment revealed no delayed neuronal loss. Increasing the duration of the acidosis to 60 min, however, induced irreversible synaptic depression and delayed neuronal loss. Increasing acid osis temperature to 37 degreesC acidified intracellular pH and depressed sy naptic responses. Delayed neuronal loss was also observed. Acidosis using l actate aCSF, pH 6.70 for 30 min at 32 degreesC acidified intracellular pH f rom 7.19+/-0.13 to 6.43+/-0.07 and depressed synaptic responses. After repe rfusion with lactate containing aCSF pH 7.35, intracellular pH recovered ye t synaptic responses remained depressed and delayed neuronal loss was obser ved. This suggested that, for a 30-min treatment at 32 degreesC, lactate ac idosis was neurotoxic while low bicarbonate acidosis was not. Increasing th e duration or temperature of low bicarbonate acidosis induced neuronal loss . These data provide additional evidence that acidosis contributes to the n eurotoxicity during stroke and trauma. (C) 2000 Elsevier Science B.V. All r ights reserved.