Interleukin-10 deficiency aggravates traumatic brain injury in male but not female mice

Abstract

The goal of this study was to determine whether deficiency of anti-inflammatory cytokine interleukin-10 (IL-10) affects traumatic brain injury (TBI) outcomes in a sex-dependent manner. Moderate TBI was induced by controlled cortical impact in 8-10 week-old wild-type and IL-10-deficient mice. In wild-type mice, serum IL-10 was significantly increased after TBI in males but not in females. At 4-5 weeks after TBI, sensorimotor function, cognitive function (Y-maze and novel object recognition tests), anxiety-related behavior (light-dark box and open field test), and depression-like behavior (forced swim test) were assessed. IL-10-deficient male mice had larger lesion volumes than did wild-type mice in the early recovery phase and worse performance on sensorimotor tasks, cognitive tests, and anxiety- and depression-related tests in the late recovery phase, whereas female IL-10-deficient mice had lesion volume equivalent to that of wild-type females and worse performance only on sensorimotor tasks. At 3 days after TBI, the number of GFAP- and Iba1-positive cells were augmented in areas in proximity to the injury (cerebral cortex and hippocampus) and in remote functional regions (striatum and amygdala) of IL-10-deficient male, but not female, mice. Moreover, on day 35, significantly fewer NeuN-positive cells were present in cortex, striatum, and amygdala of IL-10-deficient male mice than in wild-type males. This difference was not evident in females. We conclude that IL-10 deficiency aggravates cognitive and emotional recovery from TBI in association with enhanced gliosis and neuronal loss selectively in males, suggesting that recruitment of this cytokine limits damage in a sex-dependent manner.

Keywords: Controlled cortical impact; interleukin-10; neurobehavior; neuroinflammation; traumatic brain injury.