id_956. THE IMPACT OF KETOGENIC DIET ON GLIAL SCAR FORMATION AND NEUROINFLAMMATION AFTER TRAUMATIC BRAIN INJURY
Zuzanna Rauk1,2, Zuzanna Setkowicz1
1 Jagiellonian University, Institute of Zoology and Biomedical Research, Laboratory of Experimental Neuropathology, Kraków, Poland
2 Jagiellonian University, Doctoral School of Exact and Natural Sciences, Kraków, Poland
INTRODUCTION: Traumatic brain injury (TBI) is a disorder of complex pathophysiology including neuroinflammatory processes and related reactive gliosis. Ketogenic diet (KD) is considered a solution in TBI due to its neuroprotective and anti-inflammatory properties.
AIM(S): The aim of this project was to evaluate the effects of KD on astrogliosis and microgliosis, and the levels of inflammatory markers after TBI.
METHOD(S): Ketogenic or standard diet (SD) were introduced on postnatal day 27 (P27) in male and female rats. Penetrating cortical brain injury was induced on P30. Animals were perfused 2, 8, 16, and 30 days post-injury (DPI). Brains were stained against glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba1). GFAP-positive and Iba1-positive area fractions were quantified in perilesional cortex of injured animals and controls. The fractal and Sholl analysis of astrocytes and microglia in perilesional cortex was performed in FIJI. The other cohort of animals undergoing KD or SD was sacrificed 6h, 2 days or 30 days after brain injury, the cortical tissue was collected and homogenized and the levels of inflammatory markers were analysed using membrane-based antibody arrays.
RESULTS: KD did not alter GFAP-positive area fraction in perilesional cortex, but modified astrocyte morphology, reducing cell area, convex hull area, sum of intersections and ramifications index in both males and females after TBI. Iba1-positive area fraction was reduced in KD-fed injured females at 30DPI compared with SD-fed injured females. KD reduced the expression of LIX (LPS-induced CXC chemokine) in KD-fed females 6h after TBI compared to SD-fed injured females, with similar trend for MCP-1 (Monocyte chemoattractant protein 1).
CONCLUSIONS: Overall, ketogenic diet attenuated astrocyte hypertrophy in both sexes, modulated microgliosis and limited the expression of inflammatory factors in females following TBI.
FINANCIAL SUPPORT: National Science Centre Preludium 21 Grant (2022/45/N/NZ4/03028)