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 of acidosis, synaptic depression; and a delayed effect, neuronal loss. Exposure to low bicarbonate artificial cerebral spinal fluid (aCSF), pH 6.70 for 30 min at 32 degrees C, acidified intracellular pH from 7.31+/-0.12 to 6.53+/-0.08. Accompanying intracellular acidosis was a depression of synaptic responses. 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 acidosis temperature to 37 degrees C acidified intracellular pH and depressed synaptic responses. Delayed neuronal loss was also observed. Acidosis using lactate aCSF, pH 6. 70 for 30 min at 32 degrees C acidified intracellular pH from 7. 19+/-0.13 to 6.43+/-0.07 and depressed synaptic responses. After reperfusion with lactate containing aCSF pH 7.35, intracellular pH recovered yet synaptic responses remained depressed and delayed neuronal loss was observed. This suggested that, for a 30-min treatment at 32 degrees C, lactate acidosis was neurotoxic while low bicarbonate acidosis was not. Increasing the duration or temperature of low bicarbonate acidosis induced neuronal loss. These data provide additional evidence that acidosis contributes to the neurotoxicity during stroke and trauma.
Xiang
Z
Z
Department of Physiology and Pharmacology, State University of New York-Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
Bergold
P J
PJ
D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002021:Buffers; D002452:Cell Count; D046508:Culture Techniques; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D019344:Lactic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001639:Bicarbonates; D002021:Buffers; D019344:Lactic Acid