The use of a murine model of brain death for mechanistic studies on treatment for donor lung injury

Introduction: Only 15-25% of brain death (BD) donors match the ideal donor criteria for lung transplantation. The mechanisms of BD-related lung injury are not fully understood justifying further research. Materials and methods: Brain death in mice was induced by rapid inflation of a subdural balloon catheter.Animals were randomly divided into 4 groups ( n =3 each): 2h sham [S2], 2h BD [BD2], 4h sham [S4], 4h BD [BD4]. Heart rate (HR), mean arterial pressure (MAP) and cortical activity (EEG) were continuously monitored.At the end of the experiment,bronchoalveolar lavage (BAL) was performed and biopsies were collected for histological analysis. Results: In both BD groups,the Cushing reflex was characterized by a rapid increase in MAP from induction (85.0mmHg±26.0) to hypertensive peak (121.6mmHg±16.8), with normalization of MAP 10 min after BD confirmation (88.6mmHg±17.0).After BD,HR increased significantly (from 322.8bpm±75.3 to 405.0bpm±75.0) and remained high during the rest of the experiment. In the sham groups,HR and MAP remained constant after balloon insertion. A higher number in BAL neutrophils were seen in [BD4](28.6%±12) compared to [BD2](3.0%±3.0),[S2](1.4%±1.2),and [S4](1.8%±1.6).More neutrophilic infiltration, interstitial oedema and congestion were seen on histology in [BD4](2.7,2.7,and 2.3;respectively) compared to [BD2](1,2,and 2;respectively) and sham (0,0,and 0;respectively). Conclusion: The creation of a BD model in mice to study lung injury was successful facilitating further mechanistic studies to attenuate lung injury at immunological level using knock-out animals. A 4-hour period after BD is needed to observe significant inflammatory changes in BAL and lung histology.