Examining Pathological Effects of Hepatic Inflammation after Traumatic Spinal Cord Injury

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Date

2016-05

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The Ohio State University

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Abstract

Sensory and motor functions of the body are regulated by the spinal cord, and traumatic spinal cord injury (SCI) permanently impairs these basic functions. The long term consequences of SCI include chronic medical conditions altering each patient’s health and quality of life. In addition to the loss of proper sensory and motor function, injury to the spinal cord disrupts homeostasis of directly innervated peripheral organs such as the liver. Previously our lab showed that chronic pathological changes in the liver following SCI include enhanced lipid deposition and activation of resident liver macrophages called Kupffer cells (KCs) leading to chronic hepatic inflammation. Interestingly, after SCI the hepatic inflammatory response precedes intraspinal inflammation, and some reports suggest hepatic inflammation leads to exacerbated spinal cord lesion pathology. However, the ability of hepatic inflammation to alter chronic SCI outcomes has never been tested. Therefore, the current study examines the effects of exacerbated or attenuated liver inflammation after SCI. Liver inflammation was induced using a total bile duct ligation (BDL) model in a “gain of function” experiment to upregulate KC-mediated inflammation in the liver prior and subsequent to a mid-thoracic SCI. Liver tissue showed an upregulation of cytokine mRNA expression, KC activation, fibrosis, and lipid deposition at 28 days post-SCI when BDL preceded SCI compared to naïve and BDL Sham-operated animals. This reveals that injury to the spinal cord exacerbated the effects of BDL on liver pathology. However, no significant changes in spinal cord lesion size or immune activation were observed between the groups. A “loss of function” experiment showed depletion of KCs using gadolinium chloride (GdCl3) occurs within 48 hours after injection. This model will be used to test if KC depletion improves outcomes after SCI. These studies support the link between hepatic and CNS inflammation and open the door for new therapeutic targets to improve quality of patient health and recovery in a clinical SCI setting.

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2016 Denman Undergraduate Research Forum Winner

Keywords

Spinal Cord Injury, Acute Phase Response, Kupffer Cells, Inflammation, Metabolic Syndrome

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