Effect of endogenous and exogenous ketosis in acute spinal cord injury in Wistar rats

Abstract Acute spinal cord injury is a condition with a poor prognosis, leading to reduced quality of life and high economic costs for both patients and health systems, and only a minority of patients with this injury can achieve a meaningful recovery. Given the high frequency of traumatic events such as vehicle collisions and falls, research aimed at limiting injury extension, promoting neuronal recovery, and improving prognosis is essential. It has been shown that ketone bodies have anti-inflammatory properties and also mediate the Nrf2 pathway, exerting antioxidant effects. The aim was to identify any alternative to mitigate the extension and progression of secondary injury by using 1,3 butanediol as a β-hydroxybutyrate source. An experimental model (n= 60) of clinically healthy male Wistar rats were used, divided into five groups (n=12) as a control group, while the remaining rats were subjected to extradural spinal cord clipping according to the following groups (n=12): Spinal Cord Injury (SCI); endogenous ketosis + methylprednisolone (Endo-K+MP); exogenous ketosis + methylprednisolone (Exo-K+MP), and methylprednisolone (MP). After 8 hours of spinal cord injury, tissue was collected, immunohistochemistry and PCR analyses were carried out. Nrf2 and 3NT for the antioxidant pathway, and HIF-1, NFkB, NLRP3, TNF-ɑ and IL-1β for inflammation were analyzed. Results demonstrated that the groups thrown into a ketosis state had better outcomes, and, according to the Exo-k+MP and Endo-k+MP groups, increased Nrf2 and decreased 3NT (p < 0.05), which resulted in an upregulation of antioxidant pathways. According to HIF-1α and NFκB, Endo-K+MP showed better outcomes p