Which targets are relevant for therapy of acute ischemic stroke?
BACKGROUND
The efficiency of various strategies of neuroprotection is well documented in animal experiments but is thus far disappointing in ischemic stroke, for which only early reperfusion induced by thrombolysis has improved clinical outcome. This discrepancy between expectation from experimental research and clinical reality may be related to differences in the pathogenetic factors contributing to infarction.


RESULTS
Positron emission tomography cerebral blood flow studies within 3 hours of onset were used to identify the various compartments of the infarct outlined on MRI 2 to 3 weeks after a hemispheric stroke in 10 patients. Critical hypoperfusion below the viability threshold accounted for the largest proportion (mean, 70%) of the final infarct, whereas penumbral tissue (18%) and initially sufficiently perfused tissue (12%) were responsible for considerably smaller portions of the final infarct.


CONCLUSIONS
These results indicate that early critical flow disturbance leading to rapid cell damage is the predominant cause of infarction, while secondary and delayed pathobiochemical processes in borderline or initially sufficiently perfused regions contribute only little to the final infarct. Therefore, emerging therapeutic strategies should be targeted to the initially critically perfused tissue subcompartments. Clinical drug trials might benefit from stratification of patients for target tissue compartments applying functional imaging.
Heiss
W D
WD
Max Planck Institut für neurologische Forschung and Neurologische Universitätsklinik Köln, Köln, Germany.
Thiel
A
A
Grond
M
M
Graf
R
R
D000208:Acute Disease; D000368:Aged; D002545:Brain Ischemia / Q000150:complications*; D002544:Cerebral Infarction / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology* / Q000628:therapy*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use; D015424:Reperfusion; D014055:Tomography, Emission-Computed
D018696:Neuroprotective Agents