Poster abstracts
Poster number 70 submitted by Anthony Alfredo
Hepatic sympathetic denervation improves intraspinal tissue sparing after spinal cord injury
Anthony N. Alfredo (Neuroscience Graduate Program), Dana M. McTigue (Department of Neuroscience, The Ohio State University)
Abstract:
Spinal cord injury (SCI) is a devastating neurological impairment affecting locomotor function and physiological homeostasis. There are approximately 250 – 375,000 individuals living with SCI in the US, and average life expectancy post-injury has not improved in nearly 40 years. Because the spinal cord innervates all the organs of the body, SCI causes detrimental impairments of visceral organs and their regulation. Recent studies from our group reveal that the liver plays a role in the inflammatory response after SCI and that liver inflammation at the time of SCI exacerbates spinal cord pathology. Additionally, we determined lipid accumulation and liver inflammation persist chronically and lead to a novel form of neurogenic non-alcoholic steatohepatitis (nNASH). However, the mechanism of post-SCI nNASH is currently not known. Reports in the literature suggest that the sympathetic nervous system (SNS) activates Kupffer cells (KCs), the resident macrophages of the liver, increasing liver inflammation and facilitating the development of NASH. Therefore, we hypothesize that removing sympathetic input to the liver following SCI will reduce liver and spinal cord pathology. Thus, rats received a moderate contusion injury at T8. At 14 days post-injury (dpi), injured rats received a hepatic sympathectomy (hSymX) or sham surgery to remove SNS innervation specifically to the liver. Animals survived for 14d post-hSymX and were sacrificed at 28 dpi by intracardiac perfusion. In contrast to our hypothesis, liver histology revealed a surprising significant increase in KCs in animals receiving hSymX + SCI compared to hSymX Sham + SCI. However, hSymX + SCI animals had significantly more spared white matter and decreased macrophages in the spinal cord compared to hSymX Sham + SCI. Thus, SNS innervation to the liver plays a complicated role in SCI recovery. Future studies will investigate the mechanism of action for increased spinal tissue sparing with concomitant increased KC activation after post-SCI removal of liver SNS innervation to determine if the neuroprotective effects can be preserved without enhancing hepatic KC activation.
Keywords: Spinal Cord Injury, Inflammation, Kupffer Cells