Sepsis Associated Encephalopathy lists among the frequent complications of sepsis and yet remains largely unexplored. Both a predictor of early mortality and a gateway to long term cognitive decline, the complexity of CNS associated with a still evolving understanding of sepsis hasn’t as of yet allowed for a therapeutic to be proposed.
Current philosophy in sepsis management is drifting towards reactivating surviving “dysfunctional/hibernating” cells, including immune system’s own, rather than preventing the non-reachable acute destructive wave of immune activation. In parallel to this line of thought, growing awareness on the control immune cells can exert on brain physiology and repair further interrogates on the impact long term immune dysfunctions seen after sepsis could induce on cognitive or emotional features.
In sepsis, the amount of accumulated cellular dysfunctions makes pharmacological’s usual “one target” approach a challenge, to which the multiplicity of molecules expressed at any one time by a healthy cell could conceptually answer.
The aim of this work is to evaluate the effect of non-permanent replacement cell therapy in treating SAE at clinically relevant time-points. We will try to understand how to influence cells prior to their injection to shorten their in vivo time-to-efficiency, and will see how immune effectors (lymphocytes, monocytes) compare with mesenchymal stromal cells in terms of tissular (neuro-inflammation, apotosis) and cognitive function modulation after sepsis.