Endogenous Interleukin-17a Contributes to Normal Spatial Memory Retention but Does Not Affect Early Behavioral or Neuropathological Outcomes after Experimental Traumatic Brain Injury

Abstract

Interleukin-17 (IL-17) is a proinflammatory cytokine primarily secreted in the brain by inflammatory T lymphocytes and glial cells. IL-17+ T-helper (Th17) cells are increased in the ipsilateral hemisphere after experimental traumatic brain injury (TBI), and IL-17 levels are increased in serum and brain tissue. We hypothesized that il17a and related gene expression would be increased in brain tissue after TBI in mice and il17a?/? mice would demonstrate neuroprotection versus wild type. The controlled cortical impact (CCI) model of TBI in adult male C57BL6/J mice was used for all experiments. Data were analyzed by analysis of variance (ANOVA) or repeated-measures two-way ANOVA with the Bonferroni correction. A value of p?<?0.05 determined significance. Expression of il17a was significantly reduced in the ipsilateral cortex and hippocampus by day 3 after TBI, and expression remained low at 28 days. There were no differences between il17a?/? and il17a+/+ mice in beam balance, Morris water maze performance, or lesion volume after CCI. Surprisingly, na?ve il17a?/? mice performed significantly (p?=?0.02) worse than na?ve il17a+/+ mice on the probe trial. In conclusion, sustained depression of il17a gene expression was observed in brains after TBI in adult mice. Genetic knockout of IL-17 was not neuroprotective after TBI. IL-17a may be important for memory retention in na?ve mice.

Keywords

• head trauma
• interleukin
• lymphocyte
• neuroinflammation