KETOGENIC DIET LIMITS NEURONAL LOSS AND MODIFIES ASTROCYTE MORPHOLOGY AFTER TRAUMATIC BRAIN INJURY

Traumatic brain injury (TBI) is a disorder of complex pathophysiology including reactive gliosis and neuronal loss. Ketogenic diet (KD) is considered a solution in TBI due to its neuroprotective properties. The aim of this project was to evaluate the effects of KD on astrogliosis and microgliosis, and neuronal degeneration after TBI. 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), ionized calcium-binding adapter molecule 1 (Iba1) and neuropeptide Y (NPY). GFAP-positive and Iba1-positive area fractions and NPY-positive cells were quantified in perilesional cortex of injured animals and controls. Fractal and Sholl analyses of glia in perilesional cortex were performed in FIJI. 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 and microglial cells convex hull area was reduced in KD-fed injured females at 30DPI compared with SD-fed injured females. Massive loss of NPY-positive neurons was observed in SD-fed injured animals compared with controls. KD increased the number of NPY-positive neurons in perilesional cortex of injured females relative to SD-fed injured females. Overall, KD attenuated astrocyte hypertrophy in both sexes, modulated microgliosis and limited NPY-positive neurons loss in females following TBI.
Research was funded by NSC, Poland (2022/45/N/NZ4/03028).