Duraplasty with autologous nuchal ligament fascia to reduce postoperative complications in pediatric patients undergoing neoplasia resection with a suboccipital midline approach.

OBJECTIVE: The authors sought to explore the safety and efficacy of an autologous nuchal ligament for dural repair in pediatric patients undergoing tumor resection through a suboccipital midline approach. METHODS: Pediatric patients diagnosed with posterior fossa neoplasia who underwent surgery through a suboccipital midline approach were retrospectively reviewed. The patients were divided into artificial graft and autograft groups according to whether artificial duraplasty material or autologous nuchal ligament was used to repair the dura. Postoperative complications were reviewed and analyzed, including CSF leak, pseudomeningocele, and meningitis, during hospitalization and follow-up. Univariate and multivariate logistic regression analyses were used to investigate the relationship between duraplasty material and postoperative complications, as well as other risk factors for postoperative complications. Furthermore, multinomial logistic regression analysis was used to clarify which postoperative complications the autologous nuchal ligament tended to reduce. RESULTS: This retrospective study included 66 pediatric patients who underwent tumor resection through a suboccipital midline approach. The clinical baseline characteristics were comparable between the two groups. The results showed that the autograft group had significantly fewer postoperative complications, especially pseudomeningocele, compared with the artificial graft group. Moreover, the time required to repair the dura in the autograft group was significantly less than that in the artificial graft group. Further results revealed that the duraplasty material, ependymoma, preoperative severe hydrocephalus requiring an external ventricular drain (EVD), and postoperative hydrocephalus exacerbation were independent risk factors for postoperative complications. In particular, the autologous fascia of the nuchal ligament tended to reduce pseudomeningocele more than CSF leak and meningitis. However, compared with pseudomeningocele and CSF leak, both ependymoma and postoperative hydrocephalus exacerbation were more likely to increase the occurrence of meningitis. In contrast, preoperative severe hydrocephalus requiring EVD led to increased rates of postoperative complications. CONCLUSIONS: For pediatric patients with intracranial tumors who need to undergo resection through a suboccipital midline approach, dural repair using the nuchal ligament is safe, cost-effective, and time saving and significantly reduces postoperative complications.

Preoperative antiepileptic drug prophylaxis for early postoperative seizures in supratentorial meningioma: a single-center experience.

OBJECTIVE: Perioperative antiepileptic drug (AED) prophylaxis for early postoperative seizures (EPSs) in patients with supratentorial meningiomas without preoperative seizures is controversial. This paper discusses the incidence, risk factors, control rate and AED withdrawal indications of EPS in patients undergoing supratentorial convexity and parasagittal/falx meningioma resection without preoperative seizures. METHODS: Patients treated for a histologically confirmed supratentorial convexity and parasagittal/falx meningioma at the authors' institution between 2015 and 2021 were retrospectively examined. Clinical and imaging data were assessed. Variates were analyzed using univariate and multivariate regression analyses. A PubMed review of the literature published between 2011 and 2021 was performed. RESULTS: In total, 517 patients met the selection criteria. EPS (within the first postoperative week) was observed in 30/517 cases (5.8%). Multivariate analysis revealed that surgical/medical complications (OR 16.33, 95% CI 7.07-37.7, P < 0.001) were the only independent predictors of EPS. The dose of valproic was increased and levetiracetam was added based on the frequency of seizures (≤ 2, > 2 times and status epilepticus). EPS control rates were 94.1% (16/17) and 92.3% (12/13), respectively. AEDs were discontinued at 2 weeks and 4-6 weeks, respectively. The authors identified 10 relevant studies in the literature. Based on their review of the literature, the incidence of EPS was 3.7% (47/1282) with AED use and 6.2% (95/1525) without AED use patients in supratentorial meningiomas without preoperative seizures. The incidence of EPS was 9.0% (19/209) in patients without AED use with convexity and parasagittal/falx meningiomas without preoperative seizures. CONCLUSIONS: AED prophylaxis can reduce the incidence of EPS in patients with convexity and parasagittal/falx meningiomas without preoperative seizures. Avoiding postoperative complications is an important means to prevent EPS. Combined medication has a significant effect on controlling repeated EPS. The timing of AED withdrawal was evaluated according to the clinical symptoms and imaging findings.

Prognostic and predictive factors of secondary gliosarcoma: A single-institution series of 18 cases combined with 89 cases from literature.

Introduction: Secondary gliosarcomas (SGS) are rare malignancies that are diagnosed subsequent to pre-existing glioma. Clinical features and optimal treatment strategies for SGS have not been conclusively established. This study aimed to assess the clinicopathological features and outcomes of SGS. Methods: We assessed the clinicopathological features and outcomes of SGS via retrospective analysis of data for SGS patients at Tangdu Hospital. Data from SGS patients in prior publications were also analyzed in accordance with PRISMA guidelines. Results: Eighteen SGS patients who had been treated at Tangdu Hospital between 2013 and 2020 were enrolled in this study. Additional 89 eligible SGS patients were identified from 39 studies. The median age for the patients was 53 years old, and the most common location was the temporal lobe. The most common initial diagnosis was glioblastoma (GBM) (72.0%). Radiology revealed enhanced masses in 94.8% (73/77) of patients. Ten patients (10/107, 9.35%) had extracranial metastases at or after SGS diagnosis. Patients with initial diagnosis of non-GBM and who were younger than 60 years of age were significantly associated with a long duration of disease progression to SGS. After SGS diagnosis, patients with initial non-GBM diagnosis, gross total resection and chemoradiotherapy exhibited prolonged survival outcomes. Patients who had been initially diagnosed with GBM and received both chemoradiotherapy and active therapy after disease progression to SGS, had a significantly longer overall survival than patients who did not. Conclusion: Initial diagnosis of GBM was a poor prognostic factor for SGS. Patients who underwent gross total resection and chemoradiation had better overall survival outcomes than those who did not. However, during treatment, clinicians should be cognizant of possible extracranial metastases.

MYC/NBS1-Mediated DNA Damage Response is Involved in the Inhibitory Effect of Hydroxysafflor Yellow A on Glioma Cells.

BACKGROUND: The role of Hydroxysafflor Yellow A (HSYA) in glioma is less studied, this research determined the effect of HSYA on glioma cells. METHODS: The expressions of MYC and NBS1 in glioma tissues were detected by bioinformatics analysis and verified by RT-qPCR. The target relationship between MYC and NBS1 was predicted by bioinformatics. After treating the cells with HSYA, silenced MYC, or overexpressed NBS1, the viability, apoptosis, proliferation, invasion, migration, and DNA damage of the glioma cells were detected by MTT, flow cytometry, colony formation, transwell, wound healing, and γH2AX immunofluorescence assays, respectively. IC50 of HSYA in glioma cells was analyzed by Probit regression analysis. The expressions of MYC, NBS1, factors related to migration, invasion, apoptosis, and DNA damage of the glioma cells were determined by Western blot or RT-qPCR. RESULTS: MYC and NBS1 were high-expressed in glioma, and NBS1 was targeted by MYC. HSYA and siRNA targeting MYC inhibited the cell viability, proliferation, invasion, migration, and induced the cell apoptosis of glioma cells. HSYA upregulated the expressions of MYC, γH2AX, E-Cadherin, Bax, and Cleaved-PARP1, stimulated the activation of NBS1, MRE11, RAD50, and ATM, and downregulated the expressions of N-Cadherin and Bcl2 in glioma cells. SiMYC decreased the IC50 of HSYA in the glioma cells, enhanced the sensitivity of glioma cells to HSYA, and inhibited the activation of NBS1 and ATM. NBS1 overexpression reversed the effect of siRNA targeting MYC on glioma cells. CONCLUSION: MYC silencing inhibited the DNA damage response via regulation of NBS1, leading to DNA repair deficiency, and subsequently enhanced the sensitivity of glioma cells to HSYA.

Classification of Peritumoral Veins in Convexity and Parasagittal Meningiomas and Its Significance in Preventing Cerebral Venous Infarction.

OBJECTIVE: The medium (2-4 cm) convexity located closer to the sinus and parasagittal meningiomas (Sindou type I-Ⅲ) without obvious invasion of the superior sagittal sinus are considered simple to operate on. However, the tumors are often accompanied by the cortical bridging vein. Because of lack of collateral vein circulation in cortical areas, the damage of peritumoral veins will subsequently lead to venous infarction. To avoid the serious complications caused by intraoperative injury of peritumoral veins, it is necessary to define the classification of the progression of peritumoral veins and tumors to guide surgical safety. METHODS: The clinical information of 57 patients with convexity and parasagittal meningiomas was collected and retrospectively analyzed. All patients underwent preoperative magnetic resonance imaging and magnetic resonance venography scanning to observe the imaging characteristics of peritumoral veins and preoperative evaluation. The actual relationship between the tumor and peritumoral vein was observed intraoperatively. Postoperative computed tomography and magnetic resonance imaging were used to determine tumor resection and the presence of venous infarction. RESULTS: According to preoperative magnetic resonance venography and intraoperative findings, we divided the peritumoral veins into 3 types: type A (n = 33, 57.9%), the vein surrounds the tumor; type B (n = 15, 26.3%), the vein is located on the ventral side of the tumor; and type C (n = 9, 15.8%), the vein is located on the dorsal side of the tumor. Peritumoral vein injury occurred in 6 cases followed by serious complications. Treatments were as follows: 4 cases underwent decompression and 2 cases were treated conservatively. The prognosis Glasgow Outcome Scale (GOS) scores were as follows: 3 cases were score 5 for injury of posterior frontal vein or middle frontal vein, 2 cases were score 3 for injury of the central vein, 1 case was score 1 for death due to injury of the central vein. All cases were followed up for 6 months. CONCLUSIONS: Attention should be paid to the peritumoral vein of special meningiomas. Injured vein in the medial third of superior sagittal sinus carries a high rate of postoperative morbidity. Understanding the type of peritumoral veins preoperatively can be used as a guide in determining the corresponding protective strategy during surgery, which can significantly decrease postoperative disability and improve quality of life.

Correction: Opposing Effects of PI3K/Akt and Smad-Dependent Signaling Pathways in NAG-1-Induced Glioblastoma Cell Apoptosis.

[This corrects the article DOI: 10.1371/journal.pone.0096283.].

Naringin suppresses the development of glioblastoma by inhibiting FAK activity.

As the most common and lethal primary malignant brain cancer, glioblastoma is hard to timely diagnose and sensitive therapeutic monitoring. It is essential to develop new and effective drugs for glioblastoma multiform. Naringin belongs to citrus flavonoids and was found to display strong anti-inflammatory, antioxidant and antitumor activities. In this report, we found that naringin can specifically inhibit the kinase activity of FAK and suppress the FAKp-Try397and its downstream pathway in glioblastoma cells. Our study showed out that naringin can inhibit cell proliferation by inhibiting FAK/cyclin D1 pathway, promote cell apoptosis through influencing FAK/bads pathway, at the same time, it can also inhibit cell invasion and metastasis by inhibiting the FAK/mmps pathway. All these showed that naringin exerts the anti-tumor effects in U87 MG by inhibiting the kinase activity of FAK.

Epigenetic Suppression of GADs Expression is Involved in Temporal Lobe Epilepsy and Pilocarpine-Induced Mice Epilepsy.

Recent studies have shown that histone acetylation is involved with the regulation of enzyme glutamate decarboxylases (GADs), including GAD67 and GAD65. Here, we investigated the histone acetylation modifications of GADs in the pathogenesis of epilepsy and explored the therapeutic effect of a novel second-generation histone deacetylase inhibitor (HDACi) JNJ-26481585 in epilepsy animals. We revealed the suppression of GADs protein and mRNA level, and histone hypoacetylation in patients with temporal lobe epilepsy and pilocarpine-induced epilepsy mice model. Double-immunofluorescence also indicated that the hypoacetyl-H3 was located in hippocampal GAD67/GAD65 positive neurons in epilepsy mice. JNJ-26481585 significantly reversed the decrease of the GAD67/GAD65 both protein and mRNA levels, and the histone hypoacetylation of GABAergic neurons in epilepsy mice. Meanwhile, single-cell real-time PCR performed in GFP-GAD67/GAD65 transgenic mice demonstrated that JNJ-26481585 induced increase of GAD67/GAD65 mRNA level in GABAergic neurons. Furthermore, JNJ-26481585 significantly alleviated the epileptic seizures in mice model. Together, our findings demonstrate inhibition of GADs gene via histone acetylation plays an important role in the pathgenesis of epilepsy, and suggest JNJ-26481585 as a promising therapeutic strategy for epilepsy.

D2 dopamine receptors modulate neuronal resonance in subthalamic nucleus and cortical high-voltage spindles through HCN channels.

The high-voltage spindles (HVSs), one of the characteristic oscillations that include theta frequencies in the basal ganglia (BG)-cortical system, are involved in immobile behavior and show increasing power in Parkinson's disease (PD). Our previous results suggested that the D2 dopamine receptor might be involved in HVSs modulations in a rat model of PD. Membrane resonance is one of the cellular mechanisms of network oscillation; therefore, we investigated how dopamine modulates the theta frequency membrane resonance of neurons in the subthalamic nucleus (STN), a central pacemaker of BG, and whether such changes in STN neurons subsequently alter HVSs in the BG-cortical system. In particular, we tested whether dopamine modulates HVSs through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels-dependent membrane resonance in STN neurons. We found that an antagonist of D2 receptors, but not of D1 receptors, inhibited membrane resonance and HCN currents of STN neurons through a G-protein activity in acute brain slices. Our further in vivo experiments using local injection of a D2 receptor antagonist or an HCN blocker in STNs of free-moving rats showed an increase in HVSs power and correlation in the BG-cortical system. Local injection of lamotrigine, an HCN agonist, counteracted the effect induced by the D2 antagonist. Taken together, our results revealed a potential cellular mechanism underlying HVSs activity modulation in the BG-cortical system, i.e. tuning HCN activities in STN neurons through dopamine D2 receptors. Our findings might lead to a new direction in PD treatment by providing promising new drug targets for HVSs activity modulation.

Decreased HCN2 expression in STN contributes to abnormal high-voltage spindles in the cortex and globus pallidus of freely moving rats.

Abnormal oscillation in the cortical-basal ganglia loop is involved in the pathophysiology of parkinsonism. High-voltage spindles (HVSs), one of the main type abnormal oscillations in Parkinson's disease, are regulated by dopamine D2-like receptors but not D1-like receptors. However, little is known about how dopamine D2-like receptors regulate HVSs and the role of hyperpolarization-activated cyclic nucleotide-gated2 (HCN2) in HVSs regulation. We simultaneously recorded the local field potential (LFP) in globus pallidus (GP) and electrocorticogram (ECoG) in primary motor cortex (M1) in freely moving 6-hydroxydopamine (6-OHDA) lesioned or control rats. The expression of HCN2 and dopamine D2 receptor in the subthalamic nucleus (STN) was examined by immunochemical staining and Western blotting. We also tested the role of HCN2 in HVSs regulation by using pharmacological and shRNA methodology. We found that dopamine D2-like receptor agonists suppressed the increased HVSs in 6-OHDA lesioned rats. HCN2 was co-expressed with dopamine D2 receptor in the STN, and dopamine depletion decreased the expression of HCN2 as well as dopamine D2 receptor which contribute to the regulation of HVSs. HCN2 was down regulated by HCN2 shRNA, which thereby led to an increase in the HVSs in naïve rats while HCN2 agonist reduced the HVSs in 6-OHDA lesioned rats. These results suggest that HCN2 in the STN is involved in abnormal oscillation regulation between M1 cortex and GP.

Establishment and characterization of a cisplatin­resistant human osteosarcoma cell line.

The aim of the present study was to establish a new cisplatin-resistant human osteosarcoma cell line and investigate its biological characteristics. The human osteosarcoma cell line SOSP-9607 was exposed to cisplatin by stepwisely increasing the concentrations in the medium to select for the drug-resistant subline, SOSP-9607/CDDP cells. The morphological features were observed using inverted microscopy. The growth curves of SOSP-9607 and SOSP-9607/CDDP cells were drawn to calculate the doubling time. FCM was also used to determine the distribution of the cell cycle. The MTT assay was performed to test the drug resistance of SOSP-9607 and SOSP-9607/CDDP cells. Transwell assay was used to examine the invasive capability of the SOSP-9607/CDDP and SOSP-9607 cells. RT-PCR was performed to determine the mRNA expression levels of drug resistance-related and apoptosis-related genes, MDR1, MRP1, MRP2, LRP, ABCG2, GST-π, Bcl-2 and Bax, in both cell lines. SOSP-9607/CDDP cells exhibited changes in morphology, proliferation rate, doubling time, cell cycle distribution and invasive capability as compared with the SOSP-9607 cells. SOSP-9607/CDDP cells were 6.24-fold resistant to cisplatin in comparison with the SOSP­9607 cells and also exhibited cross-resistance to methotrexate and adriamycin. SOSP-9607/CDDP cells overexpressed MRP1, MRP2 and GST-π. In conclusion, SOSP-9607/CDDP cells are invaluable tools with which to study the resistance of anticancer drugs and to identify the methods to overcome resistance.

Opposing effects of PI3K/Akt and Smad-dependent signaling pathways in NAG-1-induced glioblastoma cell apoptosis.

Nonsteroidal anti-inflammatory drug (NSAID) activated gene-1 (NAG-1) is a divergent member of the transforming growth factor-beta (TGF-ß) superfamily. NAG-1 plays remarkable multifunctional roles in controlling diverse physiological and pathological processes including cancer. Like other TGF-ß family members, NAG-1 can play dual roles during cancer development and progression by negatively or positively modulating cancer cell behaviors. In glioblastoma brain tumors, NAG-1 appears to act as a tumor suppressor gene; however, the precise underlying mechanisms have not been well elucidated. In the present study, we discovered that overexpression of NAG-1 induced apoptosis in U87 MG, U118 MG, U251 MG, and T98G cell lines via the intrinsic mitochondrial pathway, but not in A172 and LN-229 cell lines. NAG-1 could induce the phosphorylation of PI3K/Akt and Smad2/3 in all six tested glioblastoma cell lines, except Smad3 phosphorylation in A172 and LN-229 cell lines. In fact, Smad3 expression and its phosphorylation were almost undetectable in A172 and LN-229 cells. The PI3K inhibitors promoted NAG-1-induced glioblastoma cell apoptosis, while siRNAs to Smad2 and Smad3 decreased the apoptosis rate. NAG-1 also stimulated the direct interaction between Akt and Smad3 in glioblastoma cells. Elevating the level of Smad3 restored the sensitivity to NAG-1-induced apoptosis in A172 and LN-229 cells. In conclusion, our results suggest that PI3K/Akt and Smad-dependent signaling pathways display opposing effects in NAG-1-induced glioblastoma cell apoptosis.

Protective effect of quercetin against oxidative stress and brain edema in an experimental rat model of subarachnoid hemorrhage.

Quercetin has been demonstrated to play an important role in altering the progression of ischemic brain injuries and neurodegenerative diseases by protecting against oxidative stress. The effects of quercetin on brain damage after subarachnoid hemorrhage (SAH), however, have not been investigated. This study was designed to explore the effects of quercetin on oxidative stress and brain edema after experimental SAH using four equal groups (n = 16) of adult male Sprague-Dawley (SD) rats, including a sham group, an SAH + vehicle group, an SAH + quercetin10 group, and an SAH + quercetin50 group. The rat SAH model was induced by injection of 0.3 ml of non-heparinised arterial blood into the prechiasmatic cistern. In the SAH + quercetin10 and SAH + quercetin50 groups, doses of 10 mg/kg and 50 mg/kg quercetin, respectively, were directly administered by intraperitoneal injection at 30 min, 12 h, and 24 h after SAH induction. Cerebral tissue samples were extracted for enzymatic antioxidant determination, lipid peroxidation assay, caspase-3 activity and water content testing 48 h after SAH. Treatment with a high dose (50 mg/kg) of quercetin markedly enhanced the activities of copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px), and treatment with this dose significantly reduced the level of malondialdehyde (MDA). Caspase-3 and brain edema was ameliorated and neurobehavioral deficits improved in rats that received the high dose of quercetin. The findings suggest that the early administration of optimal dose of quercetin may ameliorate brain damage and provide neuroprotection in the SAH model, potentially by enhancing the activity of endogenous antioxidant enzymes and inhibiting free radical generation.

Protective effect of HIF-1α against hippocampal apoptosis and cognitive dysfunction in an experimental rat model of subarachnoid hemorrhage.

Hypoxia-inducible factor 1α (HIF-1α) is a master regulator of cellular adaptation to hypoxia and has been proposed as a potent therapeutic target for cerebral ischemia. However, research on the expression and effects of HIF-1α in subarachnoid hemorrhage (SAH) is limited. The aim of the present study was to investigate the expression of HIF-1α in the hippocampus and its possible protective effect against hippocampal apoptosis and cognitive dysfunction in a rat model of SAH. Seventy-two Sprague-Dawley (SD) rats were randomly divided into the sham group, the SAH+vehicle group, and the SAH+YC-1 group. Immunohistochemical staining and western blotting analyses revealed that the expression of HIF-1α and its downstream effectors, vascular endothelial growth factor (VEGF), erythropoietin (EPO), and glucose transporter 1 (GLUT1), increased in the hippocampus 48h after the induction of SAH. YC-1 blocked this upregulation. The number of active caspase-3-positive cells and the expression of active caspase-3 in the hippocampus significantly increased in the YC-1 group relative to the vehicle group. A cell death assay further revealed that DNA fragmentation was significantly increased at 48h in the YC-1 group compared with the vehicle group. In Morris water maze (MWM) tests, the YC-1 group showed increased escape latency times and distances as well as reduced time spent and distance traveled in the target quadrant. These results indicate that hippocampal apoptosis increased and cognitive function deteriorated when HIF-1α was inhibited, suggesting that HIF-1α has a neuroprotective effect in SAH and may represent an effective therapeutic target.

Differential expression of estradiol and estrogen receptor α in severe preeclamptic pregnancies compared with normal pregnancies.

The purpose of this study was to investigate the expression of estradiol and estrogen receptor α (ESRα) in severe preeclamptic (sPE) pregnancies compared with normal pregnancies. Sera and placentas were obtained from i) patients with sPE (n=25) and ii) a normal control group (n=25) who underwent elective Cesarean deliveries. Estradiol expression was assessed by enzyme-linked immunosorbent assays (ELISAs). ESRα expression was assessed by reverse transcription polymerase chain reaction (RT-PCR) analysis and western blot analysis. In preeclamptic pregnancies, estradiol was underexpressed (P<0.05), however, ESRα mRNA and protein levels were increased significantly in comparison with normal pregnancies (P<0.05). These results show that estradiol and ESRα are deregulated in preeclamptic pregnancies, which in turn suggests the involvement of these molecules in the pathogenesis of preeclampsia.

Astragaloside IV prevents MPP⁺-induced SH-SY5Y cell death via the inhibition of Bax-mediated pathways and ROS production.

Parkinson's disease (PD) is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra. Oxidative stress and neural degeneration are suggested to be involved in the pathogenesis of PD. Previous studies have revealed that Astragaloside IV (AS-IV) can reduce inflammation and oxidation, making it a potential therapeutic agent for neurodegenerative disease. In this study, we investigated whether AS-IV protect against 1-methyl-4-phenylpyridnium ion (MPP(+))-induced dopaminergic neurotoxicity in SH-SY5Y cells and determined the mechanism of AS-IV neuroprotection. We found that pretreatment with AS-IV significantly reversed the loss of cell viability, nuclear condensation, the generation of intracellular reactive oxygen species (ROS), and the increase in Bax/Bcl-2 ratio and the activity of caspase-3 induced by MPP(+). Our study suggests that the neuroprotective effect of AS-IV is related to mechanisms including ROS production and the inhibition of Bax-mediated pathway. The present study supports the notion that AS-IV may be a promising neuroprotective agent for the treatment of neurodegenerative disorders such as PD.

Function and phenotype of microglia are determined by toll-like receptor 2/toll-like receptor 4 activation sequence.

Toll-like receptors (TLRs) initiate and maintain host defenses. These receptors play important roles in innate immunity and in various diseases. Different TLRs bind to diverse ligands that trigger distinct protein expression patterns. Few studies have focused on the interaction between different TLRs. We found that TLR2 priming downregulates TLR4 transcription, and expression of TLR4 activation induced major histocompatibility complex II (MHC II), adhesion molecule intercellular adhesion molecule-1 (ICAM-1), phagocytosis marker CD11b/CD18, and Fcgamma receptor (FcgammaR) expression. In contrast, TLR4 priming increases TLR2 transcription and expression. In addition, TLR4 priming increases secretion of certain proinflammatory mediators. Expression of costimulatory molecules CD80/CD86 increases with TLR2 or TLR4 activation sequences. Our results reveal that TLR2/TLR4 activation may determine disease pathogenesis and prognosis.

Long-term effects of bilateral deep brain stimulation of the subthalamic nucleus on depression in patients with Parkinson's disease.

OBJECTIVE: To study the long-term effects of deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) on depression in patients with Parkinson's disease (PD) and to discuss the mechanism. METHODS: A STN-DBS group (n = 27) and anti-Parkinson's medication control group with paired designing were set up. The evaluation of the depression and motor function was performed a total of six times. Depression was evaluated by the Self-Rating Depression Scale (SDS) and Hamilton Rating Scale for Depression (HAMD). Motor function was evaluated by the third part of the Unified Parkinson's Disease Rating Scale (UPDRS-III). RESULTS: Compared with the preoperative and the medication control group, the UPDRS-III scores of the STN-DBS group decreased remarkably within 18 months postoperatively (P < or = 0.001), and the SDS scores decreased notably within 6 months postoperatively (P < or = 0.05), and the HAMD scores decreased notably within 3 months postoperatively (P < or = 0.05). The UPDRS-III scores were strongly correlated with their SDS scores within 6 months postoperatively (P < or = 0.05), especially at 5 weeks postoperation (P < or = 0.001). UPDRS-III scores were also strongly correlated with HAMD scores at 5 weeks postoperation (P < or = 0.05). The mean value of the bilateral voltages was obviously correlated with SDS and HAMD scores (P < or = 0.05) within 18 months postoperatively. CONCLUSION: The improvement in motor symptoms resulting from STN-DBS can improve depression in PD patients, but its long-term effects were unremarkable. Within the treatment range, the higher the mean value of bilateral voltages then the more severe was the depression in PD patients.