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.
Ginsberg
M D
MD
Department of Neurology, University of Miami School of Medicine, Florida, USA.
Belayev
L
L
Zhao
W
W
Huh
P W
PW
Busto
R
R
D000208:Acute Disease; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy; D002560:Cerebrovascular Circulation; D005947:Glucose / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology; D012709:Serum Albumin / Q000627:therapeutic use; D013997:Time Factors
D018696:Neuroprotective Agents; D012709:Serum Albumin; D005947:Glucose