Objectives To investigate the neuroprotective mechanism of vagus nerve stimulation ( VNS) by stimulating the vagus nerve in ischemic cerebral tissue in a rat model of transient focal cerebral ischemia. Methods Twenty-six adult male Sprague-Dawley ( SD ) rats were randomly divided into sham operation group (n=6),model group (n=10),and VNS-treated group (n=10) . The model of rat transient focal cerebral ischemia was induced by the intraluminal suture method. At 30 min after modeling,the right side neck VNS in the VNS-treated group was stimulated ( stimulus intensity 0. 5 mA, interval 0. 5 ms, frequency 20 Hz),once every 5 min within 1 h,and once for 30 s. The model group repeated the steps of the VNS-treated group,but did not stimulate. The sham operation group repeated the experimental steps,but it neither embolized the vessels nor stimulated nerves. The changes of cerebral blood flow were monitored with a laser Doppler flowmeter. The rats were sacrificed after 24 h. The expressions of interleukin 6(IL-6) and caspase-3 in brain tissue were determined by immunohistochemistry staining. The neuronal apoptosis was observed by the in situ end-labelling technique. Results ( 1 ) Compared with the sham operation group, the number of positive cells of IL-6,caspase-3,and the numbers of neuronal apoptosis in the model group were significantly increased (20. 7 ± 5. 0 cells/HP vs. 2. 3 ± 1. 0 cells/HP,44. 5 ± 9. 5 cells/HP vs. 0,30. 9 ± 9. 0 cells/HP vs.0).Thereweresignificantdifferences(P<0.05).(2)Comparedwiththemodelgroup,thenumber of positive cells of IL-6(10. 9 ± 3. 7 cells/HP),the caspase-3 (18. 9 ± 6. 7 cells/HP),and the numbers of neuronal apoptosis (14. 0 ± 5. 2 cells/HP) in the VNS-treated group decreased significantly. There were significant differences (P<0. 01). (3) Before and after modeling,there were no significant differences in cerebral blood flow in various periods between the model group and the VNS-treated group (P>0. 05). Conclusion The neuroprotective mechanism of VNS for cerebral ischemia may be associated with the inhibition of neuronal apoptosis and decreasing inflammatory response. It may not be associated with the changes of cortical cerebral blood flow.

Objective To investigate the neuroprotective effect of vagus nerve stimulation ( VNS) on a model rat of focal cerebral ischemia. Methods A total of 42 adult male Sprague-Dawle ( SD) rats were randomly divided into a sham operation group (n=10),a model group (n=16),and a VNS-treated group ( n = 16 ) . Each group was randomly redivided into 2 subgroups:left VNS subgroup and right VNS subgroup. A model of focal cerebral ischemia (2 h) in rats was induced by the intraluminal suture method. At 30 minutes after modeling, the VNS-treated group received cervical VNS, the stimulation intensity was 0. 5 mA,the interval was 0. 5 ms,and the frequency was 20 Hz. Stimulation was once every 5 min within 1 h and each lasted for 30 s. The model group did not give any stimulation. Neither blood vessels were embolized nor were the nerves stimulated in the sham operation group. The changes of somatosensory evoked potentials ( SEP) on the lesion sides during operation were monitored. At 24 h after modeling,the neurobehavioral scores were performed. The rats were sacrificed,and their brain infarct volume was measured. Results (1) During the stimulation of left VNS in rats,the neurobehavioral scores of the sham operation group,model group and VNS-treated group were 0. 4 ± 0. 2,9. 5 ± 0. 4,6. 4 ± 0. 3,respectively;during the stimulation of right VNS in rats,the neurobehavioral scores of the 3 groups were 0. 6 ± 0. 2,9. 3 ± 0. 4,and 6. 9 ± 0. 4,respectively. There were significant differences between the scores of the model group and those of the other 2 groups (P<0. 05). (2) Compared with the model group,the brain infarct volume of the VNS-treated group was reduced ( stimulating the left VNS of the 2 groups was 120 ± 7 and 56 ± 7 mm3 respectively;stimulating the right VNS was 115 ± 10 and 54 ± 8 mm3 respectively ) . There were significant differences ( P <0. 05). (3) Compared with the sham operation group and the VNS-treated group,the SEP N1 amplitude of the model group was decreased significantly and the P1 latency was prolonged significantly. There was significant difference (P<0. 05). (4) There were no significant differences in the stimulation of the left or right VNS in the VNS-treated group among the infarct volume, neurobehavioral scores, SEP amplitude,and latency (P>0. 05). Conclusion No matter whether to stimulate the left or right vagus nerves, they both have neuroprotective effects on ischemic brain injury, and there was no significant difference on the action effects.

Objective: : EID3 (EP300-interacting inhibitor of differentiation) was identified as a novel member of EID family and plays a pivotal role in colorectal cancer development. However, its role in glioma remained elusive. In current study, we identified EID3 as a novel oncogenic molecule in human glioma and is critical for glioma cell survival, proliferation and invasion. Methods: : A total of five patients with glioma were recruited in present study and fresh glioma samples were removed from patients. Four weeks old male non-obese diabetic severe combined immune deficiency (NOD/SCID) mice were used as transplant recipient models. The subcutaneous tumor size was calculated and recorded every week with vernier caliper. EID3 and AMP-activated protein kinase α1 (AMPKα1) expression levels were confirmed by real-time polymerase chain reaction and Western blot assays. Colony formation assays were performed to evaluate cell proliferation. Methyl thiazolyl tetrazolium (MTT) assays were performed for cell viability assessment. Trypan blue staining approach was applied for cell death assessment. Cell Apoptosis DNA ELISA Detection Kit was used for apoptosis assessment. Results: : EID3 was preferentially expressed in glioma tissues/cells, while undetectable in astrocytes, neuronal cells, or normal brain tissues. EID3 knocking down significantly hindered glioma cell proliferation and invasion, as well as induced reduction of cell viability, apoptosis and cell death. EID3 knocking down also greatly inhibited tumor growth in SCID mice. Knocking down of AMPKα1 could effectively rescue glioma cells from apoptosis and cell death caused by EID3 absence, indicating that AMPKα1 acted as a key downstream regulator of EID3 and mediated suppression effects caused by EID3 knocking down inhibition. These findings were confirmed in glioma cells generated patient-derived xenograft models. AMPKα1 protein levels were affected by MG132 treatment in glioma, which suggested EID3 might down regulate AMPKα1 through protein degradation. Conclusion : Collectively, our study demonstrated that EID3 promoted glioma cell proliferation and survival by inhibiting AMPKα1 expression. Targeting EID3 might represent a promising strategy for treating glioma.