Modelling of the physiological response of the brain to ischaemic stroke

Identification of salvageable brain tissue is a major challenge when planning the treatment of ischaemic stroke. As the standard technique used in this context, the perfusion–diffusion mismatch, has not shown total accuracy, there is an ongoing search for new imaging protocols that could better identify the region of the brain at risk and for new physiological models that could, on the one hand, incorporate the imaged parameters and predict the evolution of the condition for the individual, and, on the other hand, identify future biomarkers and thus suggest new directions for the design of imaging protocols. Recently, models of cellular metabolism after stroke and blood–brain barrier transport at tissue level have been introduced. We now extend these results by developing a model of the propagation of key metabolites in the brain's extracellular space owing to stroke-related oedema and chemical concentration gradients between the ischaemic and normal brain. We also couple the resulting chemical changes in the extracellular space with cellular metabolism. Our work enables the first patient-specific simulations of stroke progression with finite volume models to be made.

[1]  S. Payne A model of the interaction between autoregulation and neural activation in the brain. , 2006, Mathematical biosciences.

[2]  D. Mozaffarian,et al.  Heart disease and stroke statistics--2010 update: a report from the American Heart Association. , 2010, Circulation.

[3]  L. Caplan,et al.  Thrombolytic therapy in acute ischemic stroke , 2003, Current treatment options in cardiovascular medicine.

[4]  Stephen J. Payne,et al.  A generalized mathematical framework for estimating the residue function for arbitrary vascular networks , 2013, Interface Focus.

[5]  Stephen Payne,et al.  The Influence of Network Structure on the Transport of Blood in the Human Cerebral Microvasculature , 2012, Microcirculation.

[6]  B. Jähne,et al.  Measurement of the diffusion coefficients of sparingly soluble gases in water , 1987 .

[7]  Serdar Kuyucak,et al.  Temperature dependence of the transport coefficients of ions from molecular dynamics simulations , 2005 .

[8]  R J Seitz,et al.  Diffusion- and perfusion-weighted MRI. The DWI/PWI mismatch region in acute stroke. , 1999, Stroke.

[9]  Charles Nicholson,et al.  Diffusion and related transport mechanisms in brain tissue , 2001 .

[10]  C. Nicholson,et al.  The Migration of Substances in the Neuronal Microenvironment a , 1986, Annals of the New York Academy of Sciences.

[11]  Scott Hamilton,et al.  Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials , 2004, The Lancet.

[12]  Computational modeling of cerebral diffusion-application to stroke imaging. , 2003, Magnetic resonance imaging.

[13]  B. Siesjö,et al.  Thresholds in cerebral ischemia - the ischemic penumbra. , 1981, Stroke.

[14]  C. Nicholson,et al.  Changes in brain cell shape create residual extracellular space volume and explain tortuosity behavior during osmotic challenge. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Simard,et al.  Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications , 2007, The Lancet Neurology.

[16]  A. Chvátal,et al.  Extracellular Volume Fraction and Diffusion Characteristics during Progressive Ischemia and Terminal Anoxia in the Spinal Cord of the Rat , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[17]  V. Feigin,et al.  Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review , 2009, The Lancet Neurology.

[18]  L. G. Longsworth,et al.  Diffusion Measurements, at 25°, of Aqueous Solutions of Amino Acids, Peptides and Sugars , 1952 .

[19]  M. Moskowitz,et al.  Pathobiology of ischaemic stroke: an integrated view , 1999, Trends in Neurosciences.

[20]  H. Lutsep,et al.  Safety and Efficacy of Mechanical Embolectomy in Acute Ischemic Stroke: Results of the MERCI Trial , 2005, Stroke.

[21]  Brett J Tully,et al.  Cerebral water transport using multiple-network poroelastic theory: application to normal pressure hydrocephalus , 2010, Journal of Fluid Mechanics.

[22]  M. Biddle,et al.  A report from the American Heart Association Council on Cardiovascular and Stroke Nursing. , 2015, The Journal of cardiovascular nursing.

[23]  R Gruetter,et al.  Extracellular–Intracellular Distribution of Glucose and Lactate in the Rat Brain Assessed Noninvasively by Diffusion-Weighted 1H Nuclear Magnetic Resonance Spectroscopy In Vivo , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[24]  Michael D Hill,et al.  Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. , 2004, The New England journal of medicine.

[25]  J. Broderick,et al.  Pilot randomized trial of tissue plasminogen activator in acute ischemic stroke. The TPA Bridging Study Group. , 1993, Stroke.

[26]  John P. Lowry,et al.  An integrative dynamic model of brain energy metabolism using in vivo neurochemical measurements , 2009, Journal of Computational Neuroscience.

[27]  W. Heiss,et al.  Does the Mismatch Match the Penumbra?: Magnetic Resonance Imaging and Positron Emission Tomography in Early Ischemic Stroke , 2005, Stroke.

[28]  J. Alger,et al.  Beyond Mismatch: Evolving Paradigms in Imaging the Ischemic Penumbra With Multimodal Magnetic Resonance Imaging , 2003, Stroke.

[29]  C. St-Denis,et al.  Diffusivity of oxygen in water , 1971 .

[30]  Gaute T. Einevoll,et al.  Dependence of spontaneous neuronal firing and depolarisation block on astroglial membrane transport mechanisms , 2011, Journal of Computational Neuroscience.

[31]  A. Hansen,et al.  Brain interstitial volume fraction and tortuosity in anoxia. Evaluation of the ion-selective micro-electrode method. , 1992, Acta physiologica Scandinavica.

[32]  V. Grau,et al.  Modelling of pH dynamics in brain cells after stroke , 2011, Interface Focus.

[33]  Jean-Pierre Boissel,et al.  Mathematical Modelling of an Ischemic Stroke: An Integrative Approach , 2004, Acta biotheoretica.

[34]  M. Shimizu [Electrolyte solutions]. , 2019, [Kango] Japanese journal of nursing.