mTBI-Induced Systemic Vascular Dysfunction in a Mouse mTBI Model

Abstract

Mild traumatic brain injury (mTBI) without skull fracturing is the most common occurrence of all TBIs and is considered as a serious public health concern. Animal models of mTBI are essential to investigation of TBI and its effects. In the current study, we developed and characterized a reproducible mouse model of mild TBI, meanwhile, the effects of this mTBI model, as well as repetitive mTBIs (rmTBIs), on the endothelial function of mouse aortas were also studied. In variety of closed-head models of mTBI, impact velocity, weight, and dwell time are the main parameters that affect the severities of injury. Here, we used a device, converting parameters of velocity, tip weight, and dwell time into impact force, to develop a mouse model of close-head mTBI. Mice were subjected to a mild TBI induced by the impact forces of 500, 600, 700 and 800 kdyn, respectively. Later, brain injuries were assessed histologically and molecularly. Systemic and brain inflammation were measured by plasma cytokine assay and glial fibrillary acidic protein (GFAP) staining. The composite neurobehavioral test revealed significant acute functional deficits in mice after mTBI, corresponding to the degree of injury. Mice brain undergoing mTBI had significant elevated GFAP staining. Plasma cytokines interleukin-1β (IL-1β) and superoxide dismutase (SOD) were significantly increased within 2 h after mTBI. Taken together, these data suggest that the mTBI mouse model introduce within our study exhibits good repeatability and comparable pathological characters. Moreover, we used this mTBI mouse model to determine the effect of single or rmTBIs on systemic vasoconstriction and relaxation. The isometric-tension results indicate that rmTBIs induce a pronounced and long-lasting endothelial dysfunction in mouse aorta.