title: Modeling molecular pathways of neuronal ischemia.
abstract: Neuronal ischemia, the consequence of a stroke (cerebrovascular accident), is a condition of reduced delivery of nutrients to brain neurons. The brain consumes more energy per gram of tissue than any other organ, making continuous blood flow critical. Loss of nutrients, most critically glucose and O2, triggers a large number of interacting molecular pathways in neurons and astrocytes. The dynamics of these pathways take place over multiple temporal scales and occur in multiple interacting cytosolic and organelle compartments: in mitochondria, endoplasmic reticulum, and nucleus. The complexity of these relationships suggests the use of computer simulation to understand the interplay between pathways leading to reversible or irreversible damage, the forms of damage, and interventions that could reduce damage at different stages of stroke. We describe a number of models and simulation methods that can be used to further our understanding of ischemia.
authors.affiliation: Department of Physiology & Pharmacology, SUNY Downstate, New York, USA.
authors.forename: Zachary H
authors.initials: ZH
authors.lastname: Taxin
authors.affiliation: Department of Physiology & Pharmacology, SUNY Downstate, New York, USA.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Neymotin
authors.affiliation: Department of Physiology & Pharmacology, SUNY Downstate, New York, USA.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Mohan
authors.affiliation: Department of Neuroscience, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Lipton
authors.affiliation: Department of Physiology & Pharmacology, SUNY Downstate, New York, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Lytton
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000235:genetics*; D053263:Gene Regulatory Networks; D006801:Humans; D008959:Models, Neurological; D009474:Neurons / Q000473:pathology*; D015398:Signal Transduction
keywords: Astrocytic metabolism; Boolean networks; Calcium dynamics; Computer simulation; Infarct; Ischemia; Ischemic penumbra; Mitochondria; Reaction–diffusion; Stroke