The acute ischemic penumbra: topography, life span, and therapeutic response

Recent advances in computerized image-averaging, used in conjunction with refined techniques for engendering highly reproducible rodent models of focal ischemia, now make it possible to derive topographically precise, quantitative descriptors of the ischemic penumbra--its localization, lifespan, metabolic and hemodynamic features, and responses to therapy. Physiologically monitored normothermic rats received 2-h middle cerebral artery occlusion (MCAo) by means of a poly-L-lysine-coated intraluminal suture. In matched groups, local cerebral blood flow (LCBF) or glucose utilization (LCMRglc) were measured autoradiographically at either 2-h MCAo or at 1-h recirculation and were correlated on a pixel-by-pixel basis with histopathological infarction after 3-day survival. A large, consistent ischemic penumbra (defined as LCBF 20-40% of control) surrounded the core (0-20% of control). Penumbral LCMRglc at 2-h MCAo was near-normal, and its metabolism/flow ratio was elevated 4-fold above normal. By 1-h recirculation, however, LCMRglc throughout the prior zone of ischemia was depressed. Infarctive histopathology was precisely determined by the antecedent LCBF decrement during ischemia: 70% and 89% of infarcted pixels had antecedent LCBF values below the upper-core and upper-penumbral ranges, respectively, at 2-h MCAo. High-dose albumin therapy at the onset of recirculation dramatically attenuated cortical infarction and brain edema and appeared, by LCBF analysis at 1-h recirculation, to increase postischemic LCBF primarily in the former penumbra.