Pathogenic mechanisms in ischemic damage: a computational study

The pathogenesis of penumbral tissue infarction during acute ischemic strok e is controversial. This peri-infarct tissue may subsequently die, or survi ve and recuperate, and its preservation has been a prime goal of recent the rapeutic trials in acute stroke. Two major hypotheses currently under consi deration are that penumbral tissue is recruited into an infarct by cortical spreading depression (CSD) waves, or by a non-wave self-propagating proces s such as glutamate excitotoxicity (GE). Careful experimental attempts to d iscriminate between these two hypotheses have so far been quite ambiguous. Using a computational metabolic model of acute focal stroke we show here th at the spatial patterns of tissue damage arising from artificially induced foci of infarction having specific geometric shapes are inherently differen t. This is due to the distinct propagation characteristics underlying self- regenerating waves and non-wave diffusional processes. The experimental tes ting of these predicted spatial patterns of damage may help determine the r elative contributions of the two pathological mechanisms hypothesized for i schemic tissue damage. (C) 1999 Elsevier Science Ltd. All rights reserved.