75 - Repeated rotational acceleration injury reveals sex differences in acute cytokine expression but not in motor impairments or astrocytic/microglial activation
Abstract Text: The biomechanical force of rotational acceleration on the brain contributes significantly to neuropathology and functional impairment following traumatic brain injury (TBI). The Closed Head Impact Model of Engineered Rotational Acceleration (CHIMERA) is a translationally relevant model in which biomechanical forces that are experienced by athletes in contact sports can be scaled to a preclinical model. Most research using the CHIMERA model has been conducted using male rodents, but there is a need to better understand sex differences following TBI given the rates of concussion in women in sports and in the military. Male (n = 70) and female (n = 70) mice were separated into two groups: repetitive injury by CHIMERA (n = 40) or sham (n = 30). Using an energy equivalent of 0.7 Joules, injury was induced on four consecutive days, 24 hours apart. Multiplex immunoassays for 10 cytokines/chemokines were conducted at 6-hour and 24-hour time-points following injury and tissue was collected for histology on day 5 after injury. Rotarod and beam walk tasks showed significant impairment in motor function of injured mice following each injury and up to 5 days later compared to sham mice that sustained no injuries. Six hours after repeated injury, the hippocampus of females showed increased levels of the cytokines KC/GRO and TNF-α, but by 24 hours after injury, cytokines IL-1β, TNF-α, and KC/GRO were elevated only in the cerebellum of females. No change in cytokines of five brain regions surveyed were observed in males at either time point. Subtle changes in gait were seen in injured but not sham treated mice. Histology showed increased glial activation in the corpus callosum and optic tracts, but not the hippocampus at 5 days following injury in both sexes. Although no sex differences were seen in motor function or glial activation after injury, cytokine expression differed between male and female mice at acute time points. These results indicate a need for further research using females as well as males to better characterize mechanisms of the immune response to injury and to inform development of treatments for TBI.
Disclaimer: The opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army, Department of Defense, the U.S. Government or the Uniformed Services University of the Health Sciences. The use of trade names does not constitute an official endorsement or approval of the use of reagents or commercial hardware or software. This work was supported by The Defense Health Agency [65642-3.00-310288] to JM.
