IMR Press / FBL / Volume 13 / Issue 4 / DOI: 10.2741/2776

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Flow-dependent versus spreading-like impairment of brain tissue integrity during focal cerebral ischemia and its consequences for neuroprotective strategies
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1 Department of Neurosurgery, Charite, Universitaetsmedizin Berlin, Berlin
2 Department of Neurology, Saechsisches Krankenhaus Arnsdorf, Arnsdorf
3 Department of Neurosurgery, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Front. Biosci. (Landmark Ed) 2008, 13(4), 1500–1506;
Published: 1 January 2008

Focal cerebral ischemic lesions demonstrate a gradual reduction of blood flow from the rim to the core. Flow reduction induces irreversible damage in the core region, whereas more peripheral tissue, i.e. penumbral tissue, is applicable to therapeutic interventions. Secondary mechanisms for lesion growth involve excitotoxicity, extracellular ion shifts, lactate generation, tissue acidosis, inflammation, spreading depolarization and many other processes. These toxic mediators accumulate in the ischemic core and endanger the still viable rim by diffusion or other spreading-like mechanisms, probably in part largely independent from blood flow. A substantial proportion of hemodynamic penumbral tissue could be demonstrated both in experimental settings and in clinical practice, whereas the precise spatial and temporary contribution of secondary mechanisms is much more difficult to investigate in our patients. Diffusion or spreading-mediated neurotoxicity will affect a small rim around the necrotic lesion. Due to the third power of volumetric analysis this would contribute to a large amount in small experimental lesions, but to a negligible amount of tissue in large clinical lesions and could therefore explain the difference in efficacy of neuroprotective strategies between experimental and clinical setups. Therefore, we discuss the likelihood of direct flow-dependent versus diffusion- or spreading-mediated impairment of endangered tissue in focal cerebral ischemia.

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