The Influence of Acidosis on Hypoglycemic Brain Damage

Abstract

The objective of the study was to explore whether hypoglycemic brain damage is affected by superimposed acidosis. To that end, animals with insulin-induced hypoglycemic coma, defined in terms of a negative DC potential shift, massive release of K+, or cellular uptake of Ca2+, were exposed to excessive hypercapnia (Paco2 ∼200 or ∼300 mm Hg) during the last 25 min of the 30-min coma period. Animals were allowed to survive for 7 days before their brains were fixed by perfusion, and the cell damage was assessed by light microscopy. Other animals were analyzed with respect to changes in extracellular pH (pHe) or extracellular K+ or Ca2+ concentrations (K+e and Ca2+e, respectively). The total CO2 content (Tco2) was also measured to allow derivation of intracellular pH (pHi). The increase in Paco2 to 190 ± 15 and 312 ± 23 mm Hg (means ± SD) reduced the pHe from a predepolarization value of ∼7.4 and a postdepolarization value (after the first 5 min of coma) of ∼7.3 to 6.8 and 6.7, respectively. The corresponding mean pHi values were 6.7 and 6.5. The hypercapnia did not alter the K+e, which rose to 50–60 m M at the onset of hypoglycemic coma, but it increased the Ca2+e from −0.05 to 0.10–0.16 m M. Normocapnic animals with induced hypoglycemic coma of 30-min duration showed the expected neuronal lesions in the neocortex, hippocampus, and caudoputamen. Hypercapnia clearly aggravated this damage, particularly in the caudoputamen, subiculum, and CA1 region of the hippocampus, and caused additional damage to cells in the CA3 region and piriform cortex. A rise in CO2 tension from −200 to 300 mm Hg did not further aggravate the damage. The results thus demonstrate that relative moderate acidosis aggravates damage that is believed to be mostly neuronal, sparing glia cells and vascular tissue.