engleski

Repetitive mild traumatic brain injury in mice causes increases in the iNOS and TLR2 expressions and microglial activation and polarization in the frontal cortex

Repetitive mild traumatic brain injury (rmTBI) is an important health issue, which mostly occurs in young people involved in sport activities, domestic violence or military service. Previous clinical and animal studies have shown that rmTBI causes lifelong behavioral, emotional, physical and memory impairments, but the exact pathological processes involved in their development are still unclear. The aim of our study was to investigate some inflammatory changes and microglial activation in the mouse frontal cortex in the first week after rmTBI, using the weight drop model described by Kane et al. (2012). Briefly, 9-11-weeks-old lightly anesthetized mice were subjected to head injury twice per day, in interval of 6 hours, 5 days in a row. Sham-injured animals, used as the control group, underwent equal procedures as rmTBI group, but did not receive the head impacts. Animals were sacrificed 1, 3 or 7 days after the last trauma/sham procedure and their frontal cortices were collected for the Western blot analyses. Brains from a separate cohort of mice were collected for the immunohistological studies. In the cortices of the injured mice, significant increase in the protein levels of inducible nitric oxide synthase (iNOS) was detected on the first day, while the toll like receptor 2 (TLR2) was upregulated on the third day after trauma. Significant microglial activation, i.e. increase in the number of ionized calcium binding adaptor molecule 1 (Iba1) positive cells, was detected on the third day after rmTBI. Double immunofluorescence labeling of Iba1 with CD86 or CD206 revealed microglia phenotype polarization to pro-inflammatory (M1) or anti- inflammatory (M2) state, respectively. In conclusion, these results showed increases in some parameters of inflammation as well as microglial activation and polarization in the frontal cortex of mice within the first week after rmTBI. This research was supported by the Croatian Science Foundation grant IP-2016-06- 4602 to G.Ž.

Repetitive traumatic brain injury, inflammation, microglia, mouse

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