Brain-specific TRAF7 deletion ameliorates traumatic brain injury by suppressing MEKK3-regulated glial inflammation and neuronal death.

Neuronal death and neuroinflammation play critical roles in regulating the progression of traumatic brain injury (TBI). However, associated pathogenesis has not been fully understood. Tumor necrosis factor receptor-associated factor 7 (TRAF7), as the unique noncanonical member of the TRAF family, mediates various essential biological processes. Nevertheless, the effects of TRAF7 on TBI are still unclear. In this study, we showed that TRAF7 expression was markedly up-regulated in cortex and hippocampus of mice after TBI. Brain-specific TRAF7 deletion markedly ameliorated neuronal death in cortical and hippocampal samples of TBI mice, accompanied with cognitive impairments and motor dysfunction. Moreover, the aberrant activation of astrocyte and microglia in cortex and hippocampus of TBI mice was significantly restrained by TRAF7 conditional knockout in brain, as indicated by the increased expression of GFAP and Iba1. In addition, the releases of pro-inflammatory factors caused by TBI were also considerably diminished by brain-specific TRAF7 knockout, which were largely through the blockage of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways. Importantly, mitogen-activated protein kinase kinase kinase 3 (MEKK3) expression levels were greatly enhanced in cortex and hippocampus of mice with TBI, while being dramatically ameliorated by TRAF7 knockout in brain. Mechanistically, we showed that TRAF7 directly interacted with MEKK3. Of note, MEKK3 over-expression almost abrogated the capacity of TRAF7 knockout to mitigate neuronal death and neuroinflammation in the isolated primary cortical neurons and glial cells upon oxygen-glucose-deprivation/reperfusion (OGD/R) stimulation. Collectively, TRAF7 may be an important molecular switch that leads to TBI in a MEKK3-dependent manner, and can be served as a therapeutic target for TBI treatment.

Correlation Between Serum TSH Levels Within Normal Range and Serum Lipid Profile.

The aim of the work was to investigate the correlation between serum TSH (thyrotropin) levels within normal range and serum lipids. A total of 1962 subjects with normal thyroid function were enrolled. The subjects were divided into four groups according to the quartiles of serum normal TSH levels, [Q1 (0.27-1.68) mIU/l, Q2 (1.69-2.35) mIU/l, Q3 (2.36-3.07) mIU/l, and Q4 (3.08-4.20) mIU/l]. The effect of serum normal TSH levels on serum lipid profiles of different age or gender was analyzed. The total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels of the Q3 group and TG levels of the Q4 group were higher than those of the Q1 group in youth (p <0.05). The TC levels of the Q3 group were higher than those of the Q2 group in middle age (p <0.05). The LDL-C levels of middle age or elderly were higher than those of youth at the same TSH levels (p <0.05), while the TC levels of middle age were higher than those of youth in Q1, Q3, or Q4 group (p <0.05), and the TC and HDL-C levels of elderly were higher than those of youth in the Q2 group (p <0.05). The TG levels of the Q3 group were higher than those of Q1 group in males (p <0.05). The LDL-C levels of the Q3 group were higher than those of the Q1 group in females (p <0.05). In conclusion, the normal serum TSH levels were found to be closely related to serum lipid profiles, and with increasing TSH levels, serum lipids levels increased gradually.