Brain lactic acidosis and ischemic cell damage: 2. Histopathology

J Cereb Blood Flow Metab. 1981;1(3):313-27. doi: 10.1038/jcbfm.1981.35.


The influence of severe tissue lactic acidosis during incomplete brain ischemia (30 min) on cortex morphology was studied in fasted rats. Production of lactate in the ischemic tissue was varied by preischemic infusions (i.v.) of either a saline or a glucose solution. The brains were fixed by perfusion with glutaraldehyde at 0, 5, or 90 min of recirculation. In saline-infused animals (tissue lactate about 15 mumol g-1), changes observed at 0 and 5 min of recirculation were strikingly discrete: slight condensation of nuclear chromatin, mild to moderate mitochondrial swelling, and only slight astrocyte edema. These changes had virtually disappeared after 90 min recirculation and, at this time, only discrete ribosomal changes were observed. In contrast, glucose-infused rats (tissue lactate about 35 mumol g-1) showed severe changes: marked clumping of nuclear chromatin and cell sap in all cells was already evident at 0 and 5 min recirculation, while mitochondrial swelling was mild to moderate. Although tissue fixation was inadequate at 90 min, the ultrastructural appearance indicated extensive damage. It is concluded that excessive tissue lactic acidosis during brain ischemia exaggerates structural alterations and leads to irreversible cellular damage. A tentative explanation is offered for the paucity (less than 0.2%) of condensed neurons with grossly swollen mitochondria, previously considered a hallmark of ischemic cell injury.

Publication types

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

MeSH terms

  • Acidosis / complications
  • Acidosis / metabolism
  • Acidosis / pathology*
  • Animals
  • Brain Ischemia / complications
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology*
  • Electroencephalography
  • Energy Metabolism
  • Glucose / pharmacology
  • Lactates / metabolism*
  • Male
  • Neurons / pathology
  • Neurons / ultrastructure
  • Rats
  • Sodium Chloride / pharmacology


  • Lactates
  • Sodium Chloride
  • Glucose