Altered brain perfusion and structure accompany experimental sepsis-associated encephalopathy: A combined magnetic resonance imaging and histology study

Abstract

Sepsis-associated encephalopathy (SAE) refers to brain dysfunction during systemic inflammation, which can range from mild delirium to coma. Despite its clinical relevance and poor outcome, SAE remains poorly understood even though magnetic resonance imaging (MRI) in septic patients has provided indications of cerebral vasospasms and diffuse edema. In the present work, we combined advanced MRI modalities and post mortem histology to study the brains of the same animals 24 h after induction of sepsis by cecal ligature and puncture (CLP) in an attempt to better understand the pathophysiology of SAE. Sepsis was accompanied by the classical signs of sickness behavior, but also by reduced reflexes indicating nervous system dysfunction. Assessment of cerebral perfusion with Arterial Spin Labeling (ASL) revealed that the cortex of animals that underwent CLP received less blood relative to the whole brain compared to sham surgery. T2 MRI indicated the presence of more water in the cerebral cortex after CLP than after sham surgery. Diffusion Tensor Imaging (DTI) showed increased water diffusion parallel to the fibers of the corpus callosum after CLP as compared to sham surgery. These imaging findings indicating both functional and structural CNS changes during experimental sepsis. We are currently studying to what extent these changes are linked to perivascular prostaglandin and NO production, blood-brain barrier breakdown and glial responses affecting water diffusion on brain sections of the same animals.