The Influence of Acidosis on Hypoglycemic Brain Damage

J Cereb Blood Flow Metab. 1995 Jan;15(1):78-87. doi: 10.1038/jcbfm.1995.9.


The objective of the study was to explore whether hypoglycemic brain damage is affected by super-imposed 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 approximately 200 or approximately 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 approximately 7.4 and a postdepolarization value (after the first 5 min of coma) of approximately 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 mM at the onset of hypoglycemic coma, but it increased the Ca2+e from approximately 0.05 to 0.10-0.16 mM. 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 approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acidosis / complications*
  • Animals
  • Brain Diseases / etiology*
  • Brain Diseases / pathology
  • Calcium / blood
  • Caudate Nucleus / pathology
  • Coma / complications
  • Hippocampus / pathology
  • Hydrogen-Ion Concentration
  • Hypercapnia / complications
  • Hypoglycemia / complications*
  • Hypoglycemia / pathology
  • Insulin
  • Kinetics
  • Male
  • Neurons / pathology
  • Potassium / blood
  • Putamen / pathology
  • Rats
  • Rats, Wistar


  • Insulin
  • Potassium
  • Calcium