Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

Alzheimer Disease/drug therapy* ; Humans

Objective To investigate G protein-coupled estrogen receptor(GPER)mediated neuroprotective effect and mechanism in an ischemic stroke model. Methods Bilateral ovariectomy (OVX)was used to establish a castrated model of adult SPF grade female SD rats. Enzyme-linked immunosorbent assay was used to detect serum estrogen level at 4 weeks after procedure.Middle cerebral artery occlusion(MCAO)was use to prepare a stroke model.The rats were randomly divided into sham operation(n=6),MCAO(n=7),MCAO+estrogen(MCAO+E2,n=8),MCAO+agonist(MCAO+G1,n=8)and MCAO +antagonist G15(MCAO +G15,n =7)groups. The neurological severity score (NSS),2,3,5-triphenyltetrazolium chloride(TTC)staining were used to measure the volume of cerebral infarction in order to assess the effects of different interventions.Western blot was used to detect the protein expression of hypoxia inducible factor-1α(HIF-1α),c-Jun N-terminal kinase(JNK),and Caspase-3 in the ischemic penumbra. Results (1)Estrogen level:after OVX,The level of serum estrogen in rats was significantly lower than that before castration(20 ± 9 ng/L vs. 73 ± 21 ng/L,P <0. 01).(2)NSS score:the NSS score of MCAO in each group was significant higher than that in the sham operation group (P<0.01);The NSS score of the MCAO+G1 group was significantly lower than that of the MCAO group and the MCAO+G15 group(6.0 ±1.8 vs.11.9 ±2.0 and 10.0 ±2.1).The difference was statistically significant (all P<0.05).(3)Cerebral infarct volume:there was significant difference in infarcted volume between the sham operation group and all other groups(all P<0.01);Compared with the MCAO group and the MCAO+G15 group,the infarct volume of the MCAO+E2 group and MCAO+G1 group was significantly reduced(19.8 ± 4.0%,14.0 ± 2.9%)vs.29.7 ± 5.8% and 27.6 ± 3.6%).The difference was statistically significant (all P<0.05).(4)Results of Western blot:the relative optical density values of HIF-1α,JNK,and Caspase-3 of the MCAO group were higher than those of the MCAO + G1 group(all P <0.01). Conclusions GPER mediates the neuroprotective effect of estrogen in the ischemic stroke model.This protective effect is associated with the regulation of the expression levels of HIF-1α,JNK,and Caspase-3.

Objective To investigate the effect of intravenous tranexamic acid (TXA) on perioperative hidden blood loss in percutaneous pedicle screw fixation for thoracolumbar fractures.Methods A prospective study was conducted in the 113 patients who would be subjected to percutaneous pedicle screw fixation for thoracolumbar fracture from January 2017 to December 2017.They were randomly assigned into an observation group (n =58) receiving intravenous drip of 15 mg/kg TXA 30 minutes preoperation or a control group (n =55) receiving intravenous drip of normal saline solution 30 minutes preoperation.The total blood loss and hidden blood loss 24 hours postoperation,D-dimer volume,incidences of deep vein thrombosis and other complications were recorded and compared between the 2 groups.Results There were 54 patients in the observation group and 50 patients in the control group for statistic analysis.The observation group had significantly less total blood loss (319.0 ± 140.5 mL) and hidden blood loss (242.0 ± 143.4 mL) 24 hours postoperation than the control group (418.7 ± 188.1 mL and 354.7 ± 181.9 mL,respectively) (P ＜ 0.05).There were no significant differences between the 2 groups in operation time or intraoperative blood loss (P ＞ 0.05).The volume of postoperative D-dimer was significantly higher than the preoperative value in both groups (P ＜ 0.05).No thromboembolic events occurred in either group.Conclusion Intravenous TXA may significantly reduce intraoperative hidden blood loss with no increased rik of thromboembolic events in percutaneous pedicle screw fixation for thoracolumbar fractures.

Objective To compare minimally invasive percutaneous pedicle screw fixation and open pedicle screw fixation for neurologically intact thoracolumbar fractures.Methods A retrospective study was conducted in the 180 patients who had been treated for thoracolumbar fractures without neurological deficits from January 2016 to December 2016.Of them,93 were treated by minimally invasive percutaneous pedicle screw fixation and 87 by open pedicle screw fixation.The 2 groups were compared in terms of blood loss,radiological parameters,visual analogue scale (VAS) and Oswestry disability index (ODI).Results Compared with the open surgery group,the minimally invasive surgery group had significantly shorter operating time (95.8 ±33.4 min versus 106.3 ±30.9 min),significantly less intraoperative blood loss (65.8 ±40.3 mL versus 183.1 ± 77.5 mL),significantly less total blood loss in theory 24 hours after surgery (374.7 ± 160.6 mL versus 614.8 ± 242.6 mL) and significantly shorter hospital stay (5.2 ± 2.0 d versus 6.7 ± 2.7 d),but significantly longer C-arm exposure time (23.6 ±4.2 min versus 12.4 ±4.1 min) and significantly more hidden blood loss 24 hours after surgery (308.9 ± 159.0 mL versus 243.5 ± 195.5 mL) (P ＜ 0.05).Compared with preoperation,significant improvements were observed at one week postoperation and the last follow-up in the 2 groups regarding the percentage of anterior height of the fractured vertebral body and cobb angle (P ＜ 0.05),but there were no significant differences in the percentage of anterior height of the fractured vertebral body or cobb angle between the 2 groups at one week postoperation or at the last follow-up (P ＞ 0.05).At 3 days postoperation,significant better pain relief was observed in the minimally invasive surgery group than in the open surgery group (P ＜ 0.01),but at the last follow-up no obvious pain was reported in either group.At the last follow-up,there was no significant difference between the 2 groups in ODI (6.2 ± 1.1 versus 6.0 ± 1.4) (P =0.320).Conclusions In the treatment of neurologically intact thoracolumbar fractures,minimally invasive percutaneous pedicle screw fixation may lead to shorter operating time,less blood loss and shorter hospital stay but no poorer radiological outcomes or long-term patient-reported outcomes than the open pedicle screw fixation.However,it should be noted that the former may lead to a higher volume of hidden blood loss.