Liver inflammation before spinal cord injury worsens neuropathology, hepatic injury, metabolic syndrome and locomotor deficits

Abstract

ABSTRACTLiver inflammation can enhance acute leukocyte recruitment to sites of central nervous system (CNS) injury. The consequences of hepatic inflammation on recovery after injury, however, are unknown. Here, we hypothesize that liver inflammation at the time of spinal cord injury (SCI) will exacerbate spinal cord pathology and impair recovery. Rats receiving SCI with concomitant liver inflammation had worse intraspinal pathology and greater locomotor deficits than rats with baseline liver inflammation. Hepatic inflammation also potentiated SCI-induced non-alcoholic steatohepatitis (NASH), endotoxemia, insulin resistance and adiposity. Circulating and cerebrospinal levels of Fetuin-A were higher in SCI rats with liver inflammation. When microinjected into intact spinal cords, Fetuin-A caused robust macrophage activation, iron accumulation and neuron loss. These studies verify that outcomes from CNS injury are worse if the liver is concomitantly inflamed and implicate Fetuin-A as a potential neuropathological mediator. These novel data suggest hepatic inflammation is a potential clinical target for improving recovery from SCI.