Brain lactic acidosis and ischemic cell damage: a topographic study with high-resolution light microscopy of early recovery in a rat model of severe incomplete ischemia.

Transient severe incomplete ischemia was induced in rats by a combination of bilateral carotid artery clamping and hypovolemic hypotension. Production of lactic acid in the ischemic brain was modified by preischemic administration of glucose or saline. After 30 min of ischemia and 5 or 90 min of recirculation, the animals were fixed by perfusion. High-resolution light microscopy based on whole hemisphere plastic sections revealed that the model produces a highly predictable ischemia in the telencephalon, with a more inconstant injury in the diencephalon, rostral brain stem, and cerebellum. The extent of injury correlates well with studies of local cerebral blood flow in the same model. The present study largely confirmed the opinion, based on the earlier study of the frontoparietal cortex, that the neuronal injury is predominantly of the 'pale' type, although fair amounts of 'dark' injury also appeared with predilection to the pyriform cortex, hippocampus, and occasionally the cerebellum. Excessive tissue lactic acidosis due to glucose pretreatment aggravated both types of neuronal injury. It was also accompanied by marked astrocytic edema as well as capillary obstruction in the group with long recirculation. A novel type of ischemic tissue change emerged, consisting of osmiophilic granules and whorls probably derived from damaged cell membranes.