Distinct Responses in the Brain Compared to Lung in a Rat Model of Fat Embolism Syndrome

Abstract

Fat embolism syndrome (FES) caused by release of emboli into the bloodstream after surgery or injury, can lead to severe neurological complications. We have previously shown that FES induced in rats by intravenous injection of triolein (T) causes pulmonary pathology after 48 hours that persists up to 10 weeks. Elevated expression of markers in the Renin Angiotensin System (RAS) are associated with pulmonary damage, and RAS inhibitors reduce pulmonary damage 1‐4. All components of the system (renin/ACE/AngII/AT1R) have been reported in the Central Nervous System and shown to be involved in neuroinflammation and eventual neurodegeneration5. To investigate the role of the brain RAS in response to FES, brains of T treated, and control rat models were examined for markers of RAS and neural pathology.Methodology24 rats received intravenous 200ul of T or Saline (S). Organs were processed at 48 hours or 10 weeks, sectioned, and immunostained with antibodies to Renin and Prorenin receptors in RAS; Glial Fibrillar Acidic Protein and Ib1a to identify makers of inflammation; Parp1 and Phospohistone S10 to identify cell death and proliferation respectively. Images were coded, blinded and quantified and statistically compared using GraphPad software.ResultsAs previously reported, lungs exhibited inflammation, vasculitis, and fibrosis at 48 hours and 10 weeks1,2. A significant increase in fat emboli was observed in the brain at 48 hours with persistence of micro‐emboli up to 10 weeks (S, N=6, relative emboli proportion (REP) = 7.2; FES N=5, REP = 11.0, p<0.001). Contrary to the lung, vasculitis was not observed in the brain after 48 hours or 10 weeks (S, vs FES, 48 hours, p<0.25; 10 weeks p<0.35). Regional differences (hippocampus, cerebellum, cerebral cortex, hypothalamus) in expression of markers of RAS and markers of inflammation were observed in T versus S samples at 48 hours and 10 weeks.ConclusionThis study highlights differences in organ responses to FES and identifies distinct regions in the brain that may be susceptible to FES. Adaptations of components of brain RAS have been linked to increased oxidative stress through activation of NADPH oxidase and production of reactive oxygen species in the brain5. Release of reactive oxygen species and activation of inflammatory mediators is shown to be associated with progression of neurodegeneration and cognitive dysfunction5. Understanding the acute and long‐term impacts of FES on localized brain RAS, could provide further insight into the susceptibility and resistance of other organs RAS response.