Mathematical modeling of reactive gliosis using in silico Bayesian method

AUZMENDI, A.; ROSCIZEWSKI, G.; L. MOFFATT; RAMOS, A.J.

Mar del Plata

Congreso; XXX SAN annual meeting; 2015

Sociedad Argentina de Investigaciones en Neurociencias

Reactive astrogliosis (RA) is a general, graded,glial response to brain injury. Reactive astrocytes are characterized by an increase of the cellular volume and secretion ofpro-inflammatory molecules. Until now it is unknown which are the signals thatinitiate/propagate RA, but it is proposed that diffusion of damage associatedmolecules pattern (DAMP) from the necrotic core;  calcium waves propagated by glial gapjunctions or dramatic changes in extracellular milieu (i.e. ATP levels) arelikely to be involved.  We here evaluatedtwo main paradigms to understand the progression of RA using mathematicalmodeling. Model I is a simple mechanism that contemplates the diffusion of DAMPfrom the necrotic core as the main responsible for the RA. Model II is morecomplex mechanism involves a subsequent signal carried out by soluble mediatorssecreted by the proximal astrocytes acting as amplifiers of the signal. Startingwith GFAP-stained brain sections of animals subjected to corticaldevascularization analyzed by Sholl analysis and confocal 3D reconstruction, westudied the morphology of the cortical astrocytes at 3 and 7 days post ischemicinjury. Then, we applied a Bayesian Computational Modeling approach by buildinga parametric mathematical model using partial differential equation for diffusionof DAMP and soluble mediators coupled with a Markovian Model for thesignal-triggered RA. Finally, we tested both models and found strong evidencefor model II with soluble mediators.