Oral Supplementation of n-3 Polyunsaturated Fatty Acids (n-3-PUFA) Can Prevent TBI-Induced Visual, Motor, and Emotional Deficits in Mice.

Abstract

Traumatic brain injury (TBI) causes neuroinflammation and can generate long-term pathological consequences, including motor and visual impairments, cognitive deficits, and depression. In our previous study, we found that Fat1⁺-transgenic mice with higher endogenous n-3 polyunsaturated fatty acids (n-3 PUFA) were protected from post-TBI behavioral deficits and exhibited reduced levels of TBI-induced microglial activation, inflammatory factors, and sphingolipid ceramide, a lipid mediator of inflammation and cell death. This study's objective was to evaluate if feeding n-3 PUFA (EPA and docosahexaenoic acid, DHA 2:1) could restrict the elevation of ceramide in brain tissue and prevent TBI-mediated sensory-motor and behavioral deficits. Wildtype C57/BL6 mice were gavage pre-fed with PUFA (EPA: DHA = 2:1) at 500 mg/kg body weight/week for 2 weeks before and 4 weeks after exposure to left side focal cranial air-blast (50 psi) TBI or sham-blast (0-psi). Saline-gavaged mice served as controls. Following blast injury, various motor, visual, and behavioral tests were conducted, and brain tissues were collected for histological and biochemical assays. Lipidomics analysis confirmed a significant elevation of EPA in the plasma and brain tissue of PUFA-fed mice. TBI-Blast brain tissues were found to have elevated ceramide levels in control mice but not in PUFA-fed mice. Moreover, PUFA-fed mice demonstrated protection against motor impairment, photoreceptor dysfunction, depression, oculomotor nerve degeneration, and microglia activation in the optic tract. Our results demonstrate that EPA-mediated suppression of ceramide biosynthesis and neuroinflammatory factors in PUFA-fed mice is associated with significant protection against the visual, motor, and emotional deficits caused by TBI.