Acute Brain Injury, whether of traumatic or vascular aetiology, is frequently associated with non-neurological organ dysfunction, the aetiology of which is unclear. The development of Acute Respiratory Distress Syndrome (ARDS) after Acute Brain Injury is associated with low oxygen levels in brain tissue and worse neurologic outcomes. Most potential donor lungs are considered unsuitable because of ARDS that occurs coincident with brain injury. Despite the clinical importance of ARDS after brain injury, little is known about the factors driving this association or how to predict its onset. There are no treatments for ARDS.
Ex Vivo Lung Perfusion (EVLP) is an established technique that facilitates assessment of marginal donor lungs for transplantation. We have established the first EVLP research facilities in Ireland at Beaumont Hospital and Royal College of Surgeons in Ireland (RCSI). EVLP provides unlimited potential to investigate intact human lungs and to recondition injured donor lungs for transplantation.
The overall objective of the research project is to develop strategies to treat ARDS after brain injury and to expand the donor lung pool for transplantation. Our strategic approach is to study innate immune dysfunction after brain injury and in the ex vivo perfused human lung. Our hypothesis is that modulating innate immune dysfunction after brain injury, using mesenchymal stromal cells and specialized pro-resolving mediators, will allow us to effectively enhance lung repair.
Three aims will test the hypothesis by molecular and physiologic investigations, in patients with Acute Brain Injury and in the human EVLP model:
(1) Does the innate immune response, including activated neutrophils, monocytes and lipid mediator class switching, contribute to ARDS in patients with brain injury?
(2) Can mesenchymal stromal cells or cell products be used to repair injured donor lungs during EVLP?
(3) Can specialized pro-resolving mediators be used to repair injured donor lungs during EVLP
