1.Expression and role of bone morphogenetic protein receptor Ⅱ in focal cortical dysplasia
Wei GUO ; Chunqing ZHANG ; Sixun YU ; Haifeng SHU ; Shiyong LIU ; Ning AN ; Hui YANG
Chinese Journal of Trauma 2011;27(5):472-476
Objective To detect the expression of bone morphogenetic protein receptor Ⅱ ( BMPR Ⅱ ) in human focal cortical dysplasia ( FCD Ⅱ b). Methods Fourteen specimens of FCD Ⅱ b surgically removed and pathologically verified were collected from June 2008 to June 2010 and the expression of BMPR Ⅱ in the normal brain tissues and the pathological specimens was detected by means of immunohistochemistry and western blot. Results In the normal brain tissues, BMPR Ⅱ was widely expressed in the cortical neurons of the grey matter, with no positive immunostaining in the white matter. In the cortical lesion of FCD Ⅱ b, BMPR Ⅱ was strongly expressed in the misshapen cells including balloon cells (BCs) , dysmorphic neurons (DNs) and giant neurons (GNs). Positive BMPR Ⅱ expression was also observed in the reactive astroeytes and low level expression of BMPR Ⅱ was found in the normal-appearing (NA) neurons. Western-blot analysis showed that BMPR Ⅱ expression tended to be lowered in the FCD Ⅱ b specimens compared with the normal brain tissues ( P < 0. 05 ). Conclusion The expression of BMPR Ⅱ is altered and reduced in the FCD Ⅱ b, suggesting that BMP signal pathway may participate in the pathogenesis of FCD.
2.In vivo biocompatibility of nano-hydroxyapatite/polyphenylene sulfide composites
Kexia FAN ; Yuan MA ; Weizhong YANG ; Sixun YU ; Zhiyong SUN ; Xun XIA ; Libin YANG ; Heng GUO ; Yongqin KUANG ; Jianwen GU
Chinese Journal of Tissue Engineering Research 2017;21(22):3547-3554
BACKGROUND:There is a lack of the research concerning the biocompatibility of nano-hydroxyapatite/polyphenylene sulfide (nHA/PPS) composites.OBJECTIVE:To evaluate the in vivo biocompatibility of nHA/PPS composites based on the completed research in vitro.METHODS:Systemic toxicity test:Sprague-Dawley rats were given the intraperitoneal injection of nHA/PPS extract or normal saline.The general situation,body mass and the histological changes of the liver and kidney were observed at 72 hours after injection.Delayed type hypersensitivity test:nHA/PPS extract or normal saline was injected subcutaneously into the back of the rats.Afterwards,skin irritation symptoms were observed at 72 hours.Local reaction experiment:nHA/PPS composites and polyethylene were respectively implanted into the back of the rats.The pathological changes of the implanted materials and their surrounding tissues were observed at 15 and 30 days after implantation.RESULTS AND CONCLUSION:(1) The rats were in good situation after nHA/PPS injection;the body mass increased steadily,which showed no significant difference from the control group (P < 0.05);the morphology and color of the liver and kidney were normal,and the systemic toxicity of the composite materials was normal according to the degree of toxicity classification.(2) There were no obvious skin irritation symptoms after the subcutaneous injection of nHA/PPS composites,and the primary irritation index was less than 0.4,suggesting a low hypersensitivity.After implantation of nHA/PPS composites,there was no obvious degradation,absorption and rejection,and both the degree of inflammatory reaction (15 days ≤ level Ⅲ,30 days ≤ level Ⅱ) and the thickness of fibrous capsule (15 days ≤ level Ⅲ,30 days ≤ level Ⅱ) revealed the good biocompatibility of the composites.These results suggest that the nHA/PPS composites hold an excellent biocompatibility in vivo.
3.Protective role of inhibition of adenosine monophosphate activated protein kinase activity in cerebral ischemia-induced blood brain barrier injury and its mechanism
Rui LI ; Li ZHANG ; Yanbing YU ; Sixun ZHANG ; Yue YUAN ; Jia YOU ; Qing FANG
Chinese Journal of Neuromedicine 2015;14(9):910-917
Objective To investigate the protective effect of inhibition of adenosine monophosphate activated protein kinase (AMPK) on blood brain barrier (BBB) and its mechanism in hypoxic/ischemic models.Methods Two hundred healthy male SD rats were randomly divided into sham-operated group,model group (ischemia 2 h-reperfusion 0,24 and 72 h [I/R]),and Compound C treated group (giving intraperitoneal injection of 20 mg/kg AMPK specific inhibitor Compound C).Focal cerebral ischemia rat models were established by occluding the middle cerebral artery (MCAO).Neurological deficit was determined by Zea Longa test,infarct size and brain water content were measured by TTC staining,leakage of BBB was determined by Evans blue (EB) staining.Expressions of matrix metalloproteinase (MMP)-2/MMP-9 and nuclear factor (NF)-κB,and release of inflammatory factors were detected by Western blotting.Results As compared with those in the model group,significantly reduced neurological deficit scores in Compound C treated group were noted at I/R 0,24 and 72 h (P<0.05).After I/R 72 h,Compound C treated group had significantly reduced brain infarct size,brain water content and EB leakage as compared with model group (P<0.05).The expressions of MMP2/MMP9 in model group (52.58±8.12 and 33.15±6.45) were significantly higher than those in the Compound C treated group (21.20±3.39 and 15.46±4.71,P<0.05).What is more,as compared with the model group,Compound C treated group had significantly reduced expressions of NF-κB and inflammatory factors (P<0.05).Conclusions Inhibition of AMPK shows a protective role in BBB after ischemic injury,mainly by inhibiting NF-κB signaling pathway,inhibiting the expression of MMP-2/MMP-9 to reduce the degradation of the base metal film,and maintain the integrity of BBB,thus,improving the ischemic symptoms,reducing the brain water content and reducing infarct size.
4.Changes of electroencephalogram of patients with drug resistant epilepsy after vagus nerve stimulation
Shihua DANG ; Lingli JIANG ; Haifeng SHU ; Tao YANG ; Zhi ZHANG ; Zhichuang QU ; Sixun YU ; Xin CHEN ; Yuan MA ; Yufang ZHAO ; Hongmei WANG
Chinese Journal of Neuromedicine 2022;21(9):912-915
Objective:To investigate the characteristics and change trends of electroencephalogram (EEG) in patients with drug resistant epilepsy (DRE) after vagus nerve stimulation (VNS).Methods:Twenty-five patients with DRE, admitted to our hospital from July 2016 to May 2019, were chosen; all patients accepted VNS and followed up for 12 months. Long range video EEG (VEEG) monitoring was performed before VNS, and 3, 6 and 12 months after VNS, and the tracing time of each monitoring was longer than 12 h. The EEG characteristics of these patients before and different times after VNS were analyzed.Results:In the VEEG monitoring before VNS, 25 patients showed sharp wave, spike wave, sharp slow wave, and compound spike slow wave in the interictal period; 3 patients (12%) could locate the brain region. The interictal EEG of 11 patients 3 months after VNS showed different degrees of improvement as compared with the preoperative one, which manifested as mixed rhythms: mono-spiking as sharp wave, sharp slow wave or spike wave; 8 patients had McHugh grading I-II. The interictal EEG of 18 patients 6 months after VNS showed different degrees of improvement as compared with the preoperative one; 11 patients had McHugh grading I-II. The interictal EEG of 21 patients 12 months after VNS showed different degrees of improvement as compared with the preoperative one; 15 patients had McHugh grading I-II.Conclusion:The EEG improvement effect of DRE patients after VNS is gradually improved with time; in some patients, the EEG improvement is earlier than improvement of clinical symptoms.
5.Changes of electroencephalogram of patients with drug resistant epilepsy after vagus nerve stimulation
Shihua DANG ; Lingli JIANG ; Haifeng SHU ; Tao YANG ; Zhi ZHANG ; Zhichuang QU ; Sixun YU ; Xin CHEN ; Yuan MA ; Yufang ZHAO ; Hongmei WANG
Chinese Journal of Neuromedicine 2022;21(9):912-915
Objective:To investigate the characteristics and change trends of electroencephalogram (EEG) in patients with drug resistant epilepsy (DRE) after vagus nerve stimulation (VNS).Methods:Twenty-five patients with DRE, admitted to our hospital from July 2016 to May 2019, were chosen; all patients accepted VNS and followed up for 12 months. Long range video EEG (VEEG) monitoring was performed before VNS, and 3, 6 and 12 months after VNS, and the tracing time of each monitoring was longer than 12 h. The EEG characteristics of these patients before and different times after VNS were analyzed.Results:In the VEEG monitoring before VNS, 25 patients showed sharp wave, spike wave, sharp slow wave, and compound spike slow wave in the interictal period; 3 patients (12%) could locate the brain region. The interictal EEG of 11 patients 3 months after VNS showed different degrees of improvement as compared with the preoperative one, which manifested as mixed rhythms: mono-spiking as sharp wave, sharp slow wave or spike wave; 8 patients had McHugh grading I-II. The interictal EEG of 18 patients 6 months after VNS showed different degrees of improvement as compared with the preoperative one; 11 patients had McHugh grading I-II. The interictal EEG of 21 patients 12 months after VNS showed different degrees of improvement as compared with the preoperative one; 15 patients had McHugh grading I-II.Conclusion:The EEG improvement effect of DRE patients after VNS is gradually improved with time; in some patients, the EEG improvement is earlier than improvement of clinical symptoms.
6.High-frequency oscillations analysis in stereotactic electroencephalogram guided radiofrequency thermocoagulation in treating refractory epilepsy
Zhichuang QU ; Xin CHEN ; Juan LUO ; Yuanyuan ZHANG ; Sixun YU ; Haifeng SHU
Chinese Journal of Neuromedicine 2023;22(6):585-591
Objective:To explore the clinical application values of radiofrequency thermocoagulation (RF-TC) based on stereotactic electroencephalogram (SEEG) high-frequency oscillations (HFOs) analysis in patients with refractory epilepsy.Methods:Fourteen patients with refractory epilepsy treated with SEEG-guided RF-TC were selected from Department of Neurosurgery, PLA Western Theater Command General Hospital from August 2019 to December 2021. Automatic detection algorithm of Matlab was used to calculate the HFOs incidence in each montage, and the fitting curves of HFOs incidences were used to formulate the threshold of HFOs and delimit the HFOs regions (ripples and fast ripples). These patients were divided into non-seizure group and seizure group according to the prognoses 3 and 6 months after RF-TC. At the last follow-up, these patients were divided into good prognosis group and poor prognosis group according to Engel grading; the differences of ripple thermocoagulation rate and fast ripple thermocoagulation rate between the 2 groups were compared.Results:A total of 7,332 ripples and 1,144 fast ripples were detected in SEEG data from 14 patients. Six months after surgery, neurological dysfunction incidence was 14.3%, without permanent neurological dysfunction, intracranial infection, intracranial hemorrhage, or electrode equipment failure. Within 3 months of RF-TC, seizure-free rate was 71.4% (10/14), and fast ripple thermocoagulation rate in non-seizure group was significantly higher than that in seizure group ( P<0.05); within 6 months of RF-TC, seizure-free rate was 57.1% (8/14), and ripple thermocoagulation rate in non-seizure group was significantly higher than that in seizure group ( P<0.05). At last follow-up, 6 patients had good prognosis and 8 patients had poor prognosis; the ripple thermocoagulation rate in good prognosis group was significantly higher than that in poor prognosis ( P<0.05). Conclusions:HFOs can assist in designating epileptogenic regions. Patients with wider range of thermocoagulation ripples or fast ripples will have better short-term efficacy; patients with wider range ofthermocoagulation ripples will have better prognosis.
7.Recent advance in mechanism of Hevin/SPARC in central nervous system synaptogenesis/reorganization
Yao WANG ; Xingyue HAN ; Jing XU ; Xin CHEN ; Sixun YU ; Haifeng SHU
Chinese Journal of Neuromedicine 2023;22(9):937-941
Hevin is one of the extracellular matrix proteins secreted by astrocytes. Under physiological conditions, Hevin plays an important role in synaptogenesis in the central nervous system (CNS); secreted protein, acidic and rich in cysteine (SPARC) is its homologue and antagonizes the synaptogenic effects of Hevin. In pathological conditions, the expressions of Hevin and SPARC are altered, suggesting their possible roles at synaptic reorganization in various disease process, such as brain injury, Alzheimer's disease, epilepsy and brain tumors; however, the specific mechanism is not totally understood yet. So this paper reviews the mechanism of Hevin/SPARC in CNS synaptogenesis, reorganization and diseases to provide ideas for further research.
8. Advances of Nogo-A protein in the mechanism of epilepsy
Jinwei ZHANG ; Tao CHEN ; Sixun YU ; Haifeng SHU ; Yongqin KUANG
Chinese Journal of Neurology 2019;52(11):967-973
The myelin-associated protein Nogo-A was considered to be the axon growth inhibitory factor, which participates in a variety of pathophysiological regulation of nervous system. In recent years, a growing number of studies have shown that Nogo-A protein is closely related to epilepsy by regulating dendritic plasticity, mediating abnormal nerve migration and regulating glial cell activation, etc. This article will review the research progress of Nogo-A in epilepsy in recent years.