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. 2022 Sep:355:114125.
doi: 10.1016/j.expneurol.2022.114125. Epub 2022 May 26.

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

Yanting Gu  1 , Yinfeng Dong  1 , Jieru Wan  1 , Honglei Ren  1 , Raymond C Koehler  2 , Jian Wang  1
Affiliations

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

Yanting Gu et al. Exp Neurol. 2022 Sep.

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.

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