Relation of impaired energy metabolism to apoptosis and necrosis following transient cerebral hypoxia-ischaemia.

Abstract

This study investigated whether both mild and severe hypoxia-ischaemia (HI) caused significant numbers of cells to die by apoptosis in the developing brain in vivo. Newborn piglets were subjected to transient global HI and the fraction of all cells in the cingulate gyrus that were apoptotic or necrotic counted 48 h after resuscitation. The mean (S.D.) proportion of apoptotic cells was 11.9% (6.7%) (sham operated controls 4.1% (2.7%)), while 11.4% (8.4%) were necrotic (controls 0.7% (1.3%)) (P<0.05). Apoptotic and necrotic cell counts were both linearly related to the severity of impaired cerebral energy metabolism measured by magnetic resonance spectroscopy (P<0.05), as shown by: (1) the decline in the ratio of nucleotide triphosphates to the exchangeable phosphate pool during HI; (2) the fall in the ratio of phosphocreatine to inorganic phosphate 8 - 48 h after HI; and (3) an increased ratio of lactate to total creatine at both these times. Thus both apoptosis and necrosis occurred in the cingulate gyrus after both severe and mild HI in vivo in proportion to the severity of the insult.