Neural dynamics in the energy deprived brain

Identifying Circulating Tumor Cells by Image Analysis


Koen Dijkstra

PhD defence: 24 March 2017

Koen Dijkstra


Organization:

Funded by:

Twente Graduate School

PhD:

Koen Dijkstra

Supervisor:

Stephan van Gils / Michel van Putten

Collaboration:

Medisch Spectrum Twente


Description:

Cerebral function is critically dependent on a sufficient supply of energy and if this supply drops below a critical level, neuronal function is rapidly compromised. 

Biophysically realistic, mathematical models are formulated in order to investigate neural dynamics after cortical stroke or traumatic brain injury; conditions that are both associated with a period of low energy supply to the brain. A multiscale-modeling approach is employed which relates the (sub)cellular processes to brain network dynamics: Starting with conductance-based models at the level of individual neurons, a firing rate reduction is formulated, which is not only based on input to the cell due to network activity, but also includes the intra- and extracellular ionic concentrations as a novel aspect. Taking into account the roles of the extracellular space, glial buffering and ion pumps allows a characterization of neural activity under both physiological and pathological conditions. Thereafter, at the macroscopic level, the collective action of many such neurons is studied, taking into account the synaptic connectivity between neurons as well as the transmission delays involved.

This model can then in turn be analyzed mathematically and numerically and results of this analysis yield direct physiological interpretations. Hence we might attain novel insights into processes occurring after energy depletion, as well as the dynamical phenomena that result in an increased ATP demand, i.e. seizures and spreading depressions. This will further our understanding of the microscopic mechanisms of secondary damage and ultimately may result in improved treatment strategies limiting the extent of the cerebral injury. If this can be reliably detected or predicted in patients at risk, potential strategies to limit the secondary damage include treatment with hypothermia or medication, e.g. anti-epileptic drugs.

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