The Ischemic Penumbra: Usefulness of PET

Abstract

Studies in experimental animals have provided a detailed description of the changes in cerebral blood flow (CBF) and metabolism that occur during and after transient focal cerebral ischemia [2, 8, 9, 13, 15]. When a vessel is occluded, a central core of severe ischemia is produced that is surrounded by zone with less reduction in blood flow where perfusion is maintained by collateral circulation. No changes in brain metabolism or function occur as long as CBF is above approximately 20 ml 100 g^-1 min^-1. Below this level, brain electrical activity fails and neurological deficits appear. Normal cellular biochemistry is disrupted as energy supply becomes insufficient due to inadequate supply of oxygen. Depletion of high energy phosphate stores (ATP, phosphocreatine [PCr]) occurs. Anaerobic metabolism of the small amount of residual glucose from intracellular stores and remaining blood flow results in lactic acidosis. With more severe reduction in CBF to approximately 10–12 ml 100 g^-1 min^-1, integrity of cell membranes is lost with leakage of intracellular K⁺ into extracellular spaces and influx of extracellular Ca⁺⁺ into cells. Cell death will follow if reperfusion does not occur. Following reperfusion, biochemical and ionic perturbations resolve to variable degrees depending on the severity of the ischemic insult. However, further cell damage may occur due to generation of free radicals and prostanoids and to the influx of blood-borne leukocytes.

Supported by Grants NS06833, NS 28700, and NS 28947 of the National Institutes of Health, the Lillian Strauss Institute for Neuroscience and the Jewish Hospital of St. Louis.