Pathogenic mechanisms in ischemic damage: a computational study.
The pathogenesis of penumbral tissue infarction during acute ischemic stroke is controversial. This peri-infarct tissue may subsequently die, or survive and recuperate, and its preservation has been a prime goal of recent therapeutic trials in acute stroke. Two major hypotheses currently under consideration are that penumbral tissue is recruited into an infarct by cortical spreading depression (CSD) waves, or by a non-wave self-propagating process such as glutamate excitotoxicity (GE). Careful experimental attempts to discriminate between these two hypotheses have so far been quite ambiguous. Using a computational metabolic model of acute focal stroke we show here that the spatial patterns of tissue damage arising from artificially induced foci of infarction having specific geometric shapes are inherently different. This is due to the distinct propagation characteristics underlying self-regenerating waves and non-wave diffusional processes. The experimental testing of these predicted spatial patterns of damage may help determine the relative contributions of the two pathological mechanisms hypothesized for ischemic tissue damage.
Ruppin
E
E
Department of Physiology, Tel-Aviv University, Israel. ruppin@math.tau.ac.il
Ofer
E
E
Reggia
J A
JA
Revett
K
K
Goodall
S
S
D000208:Acute Disease; D000465:Algorithms; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000473:pathology / Q000503:physiopathology; D003198:Computer Simulation; D013181:Cortical Spreading Depression / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D011188:Potassium / Q000378:metabolism / Q000502:physiology; D014022:Tissue Survival
D018698:Glutamic Acid; D011188:Potassium