Bridge-layered decompression technique for vertebral artery-involved hemifacial spasm: technical note.

BACKGROUND: Hemifacial spasm (HFS) is most effectively treated with microvascular decompression (MVD). However, there are certain challenges in performing MVD for HFS when the vertebral artery (VA) is involved in compressing the facial nerve (VA-involved). This study aimed to introduce a "bridge-layered" decompression technique for treating patients with VA-involved HFS and to evaluate its efficacy and safety to treat patients with HFS. METHODS: A single-center retrospective analysis was conducted on the clinical data of 62 patients with VA-involved HFS. The tortuous trunk of VA was lifted by a multi-point "bridge" decompression technique to avoid excessive traction of the cerebellum and reduce the risk of damage to the facial-acoustic nerve complex. To fully decompress all the responsible vessels, the branch vessels of VA were then isolated using the "layered" decompression technique. RESULTS: Among the 62 patients, 59 patients were cured immediately after the surgery, two patients were delayed cured after two months, and one had occasional facial muscle twitching after the surgery. Patients were followed up for an average of 19.5 months. The long-term follow-up results showed that all patients had no recurrence of HFS during the follow-up period, and no patients developed hearing loss, facial paralysis, or other permanent neurological damage complications. Only two patients developed tinnitus after the surgery. CONCLUSION: The "bridge-layered" decompression technique could effectively treat VA-involved HFS with satisfactory safety and a low risk of hearing loss. The technique could be used as a reference for decompression surgery for VA-involved HFS.

Mechanistic insight into glioma through spatially multidimensional proteomics.

Characterizing the tumor microenvironment at the molecular level is essential for understanding the mechanisms of tumorigenesis and evolution. However, the specificity of the blood proteome in localized region of the tumor and its linkages with other systems is difficult to investigate. Here, we propose a spatially multidimensional comparative proteomics strategy using glioma as an example. The blood proteome signature of tumor microenvironment was specifically identified by in situ collection of arterial and venous blood from the glioma region of the brain for comparison with peripheral blood. Also, by integrating with different dimensions of tissue and peripheral blood proteomics, the information on the genesis, migration, and exchange of glioma-associated proteins was revealed, which provided a powerful method for tumor mechanism research and biomarker discovery. The study recruited multidimensional clinical cohorts, allowing the proteomic results to corroborate each other, reliably revealing biological processes specific to gliomas, and identifying highly accurate biomarkers.

NEDD4 Like E3 Ubiquitin Protein Ligase Represses Astrocyte Activation and Aggravates Neuroinflammation in Mice with Depression via Paired Box 6 Ubiquitination.

Astrocytes are implicated in stress-induced neuroinflammatory responses in depression. This paper was to explore the molecular mechanism of the E3 ubiquitin ligase NEDD4L (NEDD4 like E3 ubiquitin protein ligase) in depressed mice by regulating astrocyte activation, and to find a new target for depression. A mouse model of depression was established by CUMS (chronic mild unpredictable stress) in 48 6-week male C57BL/6 mice and injected with sh-NEDD4L vector for testing behavioral and cognitive abilities, histopathological changes, and the number of GFAP-positive cells. The mRNA and protein levels of NEDD4L, PAX6 (paired box 6) and P2X7R (purinergic ligand-gated ion channel 7 receptor) were measured. Inflammation model was established by lipopolysaccharide treatment of mouse astrocyte line C8-D1A and infected with sh-NEDD4L. After CUMS induction, mice showed depression-like symptoms, increased inflammatory infiltration, decreased glial fibrillary acidic protein (GFAP)-positive cells in brain tissue, and increased NEDD4L protein levels. NEDD4L inhibition increased GFAP-positive cells, increased PAX6 protein levels and decreased P2X7R mRNA and protein levels, and decreased inflammatory factor secretion in brain tissue and in vitro cells. PAX6 knockdown or P2X7R overexpression partially reversed the effects of NEDD4L inhibition on astrocyte activation and neuroinflammation. To conclude, highly-expressed NEDD4L in depression-like mouse brain inhibits astrocyte activation and exacerbates neuroinflammation by ubiquitinating PAX6 and promoting P2X7R level.

Study on the relationship between obesity and complications of Pediatric Epilepsy surgery.

OBJECTIVE: Studies have shown that obesity has a significant impact on poor surgical outcomes. However, the relationship between obesity and pediatric epilepsy surgery has not been reported. This study aimed to explore the relationship between obesity and complications of pediatric epilepsy surgery and the effect of obesity on the outcome of pediatric epilepsy surgery, and to provide a reference for weight management of children with epilepsy. METHODS: A single-center retrospective analysis of complications in children undergoing epilepsy surgery was conducted. Body mass index (BMI) percentiles were adjusted by age and used as a criterion for assessing obesity in children. According to the adjusted BMI value, the children were divided into the obese group (n = 16) and nonobese group (n = 20). The intraoperative blood loss, operation time, and postoperative fever were compared between the two groups. RESULTS: A total of 36 children were included in the study, including 20 girls and 16 boys. The mean age of the children was 8.0 years old, ranging from 0.8 to 16.9 years old. The mean BMI was 18.1 kg/m2, ranging from 12.4 kg/m2 to 28.3 kg/m2. Sixteen of them were overweight or obese (44.4%). Obesity was associated with higher intraoperative blood loss in children with epilepsy (p = 0.04), and there was no correlation between obesity and operation time (p = 0.21). Obese children had a greater risk of postoperative fever (56.3%) than nonobese children (55.0%), but this was statistically nonsignificant (p = 0.61). The long-term follow-up outcomes showed that 23 patients (63.9%) were seizure-free (Engel grade I), 6 patients (16.7%) had Engel grade II, and 7 patients (19.4%) had Engel grade III. There was no difference in long-term seizure control outcomes between obese and nonobese groups (p = 0.682). There were no permanent neurological complications after surgery. CONCLUSION: Compared with nonobese children with epilepsy, obese children with epilepsy had a higher intraoperative blood loss. It is necessary to conduct early weight management of children with epilepsy as long as possible.

Hybrid surgery for coexistence of cerebral arteriovenous malformation and primitive trigeminal artery: A case report and literature review.

The primitive trigeminal artery (PTA), an abnormal carotid-basilar anastomosis, forms the vascular anomaly connection between the internal carotid artery and vertebrobasilar system. Rarely, PTA can be complicated by several other cerebrovascular disease, including arteriovenous malformations (AVMs), intracranial aneurysms, moyamoya disease, and carotid-cavernous malformations. Herein, we reported a rare case of PTA combined with an AVM in a male patient. The patient was a 28-year-old male with epileptic seizures at the onset of symptoms. Magnetic resonance imaging showed abnormal signal foci and localized softening foci formation with gliosis in the right parietal temporal lobe. Furthermore, using a digital subtraction angiogram (DSA), it was found that an abnormal carotid-basilar anastomosis had developed through a PTA originating from the cavernous portion of the right internal carotid artery (ICA) and a large AVM on the surface of the right carotid artery. The lesion of AVM tightly developed and draining into superior sagittal sinus. A hybrid operating room was used for the surgery. The main feeding arteries of the AVM originating from three major arteries, including the right middle cerebral artery, the right anterior cerebral artery, and the right posterior cerebral artery, were clipped and subsequently, then the AVM was thoroughly removed. The intraoperative DSA showed that the AVM had been resected completely. Postoperative pathological examination of the resected specimen indicated the presence of an AVM. The patient recovered well after surgery and has been symptom-free for more than 3 months. In summary, the pathogenesis of the coexistence of PTA and AVM remains unknown. As highlighted in this case report, hybrid surgery can be used to remove AVMs and can improve the patients' prognosis. To our best knowledge, this is the first case in the literature of successful AVM treatment using hybrid surgery.

Intraoperative Findings of Inferior Petrosal Vein During Microvascular Decompression for Hemifacial Spasm: A Single-Surgeon Experience.

Objective: This study aims to evaluate the impact of the inferior petrosal veins (IPVs) on operational exploration and to analyze related anatomic features. Methods: A total of 317 patients were retrospectively studied. Surgical outcomes and postoperative complications were analyzed, and patients were divided into two groups according to whether the IPV was sacrificed or preserved. The diameter of the IPV was also recorded during operation. Furthermore, the position where the IPV drained into the jugular bulb was recorded in each patient, and the influence of different injection points on the operation was analyzed. Results: IPVs were conclusively identified in 242/317 (76.3%) of patients, with 110/242 (45.5%) of patients categorized as "IPV sacrifice" versus 132/242 (54.5%) categorized as "IPV preservation." IPV diameter was observed to be <0.5 mm in 58 cases (23.9%), 0.5 mm-1.0 mm (≥0.5 mm and ≤1.0 mm) in 145 cases (59.9%), and >1 mm in 39 cases (16.2%). The position of IPV drainage into the jugular bulb was at the level of the accessory nerve in 163 cases (67.3%), the level of the vagus nerve in 42 cases (17.4%), and the level of the glossopharyngeal nerve or above in 37 cases (15.3%). The diameters of IPV in the sacrifice group were mainly less than 1 mm (94.5% vs. 75%, P < 0.01), and the cases with draining points near the glossopharyngeal nerve were more than that in the preservation group (27.3% vs. 5.3%, P < 0.01). Conclusion: IPV is an obstructive structure in MVD for HFS, with considerable variations in diameters and draining points. IPV near the glossopharyngeal nerve significantly impacts surgical exposure and is often sacrificed for a better view of the operation field. Meanwhile, it is feasible to maintain IPVs with a diameter >1 mm.

Flurbiprofen axetil protects against cerebral ischemia/reperfusion injury via regulating miR-30c-5p and SOX9.

The modulatory mechanism of flurbiprofen axetil (FPA) by which it relieves cerebral ischemia/reperfusion (I/R) injury (CIRI) is still obscure. In the present work, adult male Sprague-Dawley (SD) rats were pre-treated with FPA before the construction of a rat model of CIRI. Longa's scoring method and dry-wet method were employed to examine the neurological function and brain water content of the rats. MiR-30c-5p, SOX9, AQP4, SOX9, NF-κB, and p-NF-κB expression levels in the brain tissues of the rats were examined by qRT-PCR or Western blot. ELISA was executed to evaluate the IL-10, IL-6, and TNF-α levels in the serum of rat. SOD and MDA levels in rat brain homogenates were also examined to indicate the oxidative stress. Hematoxylin-eosin (HE) staining was used to examine the pathological changes of the brain tissues. Dual-luciferase reporter gene experiment was implemented to validate the binding relationship between miR-30c-5p and SOX9. In the present work, compared with the rats with CIRI, FPA pre-treatment attenuated neurological injury, cerebral edema, oxidative stress, inflammatory response, and cerebral pathological changes in the rat model with CIRI. FPA up-modulated miR-30c-5p expression. SOX9 was a downstream target of miR-30c-5p. In conclusion, FPA ameliorates CIRI through up-modulating miR-30c-5p expression and reducing SOX9 expression.

Bruceine D ameliorates the balance of Th1/Th2 in a mouse model of ovalbumin-induced allergic asthma via inhibiting the NOTCH pathway.

Allergic asthma is a heterogeneous inflammatory disorder triggered by inhaled allergens, leading to airflow obstruction, bronchial inflammation, and airway hyperresponsiveness (AHR). T helper (Th) 2 cell-mediated immune response and airway inflammation are the key features of allergic asthma. Bruceine D (BD) is a bioactive compound extracted from the seeds of Brucea javanica. The present study aimed to investigate the effects of increased doses of BD on AHR, secretion of Th1-/Th2-associated cytokines, and inflammatory cell infiltration in ovalbumin (OVA)-induced allergic asthma mice. The results showed that BD reduced OVA-induced inflammatory cell infiltration and bronchial hyperresponsiveness into the peribronchial tissues and perivascular areas. Mice treated with BD also showed significantly decreased expressions of Th2-associated cytokines (i.e., interleukin (IL)-4, IL-5, and IL-13) and elevated production of Th1-associated cytokines (i.e., interferon gamma and IL-2) following OVA stimulation. BD treatment dose-dependently inhibited OVA-induced accumulation of inflammatory cells in asthmatic mice. Further analysis revealed that OVA exposure upregulated pulmonary expressions of NOTCH signaling receptors, a group of transmembrane proteins that communicate signals upon binding to transmembrane ligands expressed on adjacent cells, while BD treatment significantly abolished OVA-induced activation of the NOTCH pathway. In conclusion, BD protected mice against OVA-induced allergic asthma by reducing AHR and restoring the Th1/Th2 balance through the NOTCH signaling pathway. Our findings highlighted the potential of BD as a therapeutic agent for allergic asthma.

proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model.

Brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of post-stroke depression (PSD). However, the precise function and potential mechanism of proBDNF, the precursor form of BDNF, are unknown. In our study, a PSD-like model was established by treating neuronal cells with oxygen-glucose deprivation and corticosterone. We found that the protein proBDNF levels were significantly higher in the cortex and hippocampus in the PSD group than in the control group, suggesting that proBDNF plays a role in the pathophysiology of PSD. Furthermore, we re-established the PSD-like cell model using recombinant p75 neurotrophin receptor (p75NTR) or silencing c-Jun N-terminal kinase (JNK), and found that the PSD-induced upregulation of proBDNF was inhibited by recombinant p75NTR and JNK silencing (siJNK), and increased cellular apoptosis. Moreover, the application of recombinant p75NTR and siJNK in the PSD-like cell model significantly reversed the expression of apoptosis-related and depression-related proteins and decreased cellular apoptosis. Our findings suggest that proBDNF is involved in neural plasticity in PSD in vitro. The RhoA-JNK signaling pathway is activated after proBDNF binds to the p75NTR receptor, followed by the expression of apoptosis-related proteins (PSD95, synaptophysin, and P-cofilin), which contribute to PSD progression. The mechanism might involve the promotion of cellular apoptosis and the inhibition of nerve synapses regeneration by proBDNF.

Bruceine D ameliorates the balance of Th1/Th2 in a mouse model of ovalbumin-induced allergic asthma via inhibiting the NOTCH pathway

Allergic asthma is a heterogeneous inflammatory disorder triggered by inhaled allergens, leading to airflow obstruction, bronchial inflammation, and airway hyperresponsiveness (AHR). T helper (Th) 2 cell-mediated immune response and airway inflammation are the key features of allergic asthma. Bruceine D (BD) is a bioactive compound extracted from the seeds of Brucea javanica. The present study aimed to investigate the effects of increased doses of BD on AHR, secretion of Th1-/Th2-associated cytokines, and inflammatory cell infiltration in ovalbumin (OVA)-induced allergic asthma mice. The results showed that BD reduced OVA-induced inflammatory cell infiltration and bronchial hyperresponsiveness into the peribronchial tissues and perivascular areas. Mice treated with BD also showed significantly decreased expressions of Th2-associated cytokines (i.e., interleukin (IL)-4, IL-5, and IL-13) and elevated production of Th1-associated cytokines (i.e., interferon gamma and IL-2) following OVA stimulation. BD treatment dose-dependently inhibited OVA-induced accumulation of inflammatory cells in asthmatic mice. Further analysis revealed that OVA exposure upregulated pulmonary expressions of NOTCH signaling receptors, a group of transmembrane proteins that communicate signals upon binding to transmembrane ligands expressed on adjacent cells, while BD treatment significantly abolished OVA-induced activation of the NOTCH pathway. In conclusion, BD protected mice against OVA-induced allergic asthma by reducing AHR and restoring the Th1/Th2 balance through the NOTCH signaling pathway. Our findings highlighted the potential of BD as a therapeutic agent for allergic asthma (AU)

Aberrant Expression of Circulating MicroRNA Leads to the Dysregulation of Alpha-Synuclein and Other Pathogenic Genes in Parkinson's Disease.

A group of circulating microRNAs (miRNAs) have been implicated in the pathogenesis of Parkinson's disease. However, a comprehensive study of the interactions between pathogenic miRNAs and their downstream Parkinson's disease (PD)-related target genes has not been performed. Here, we identified the miRNA expression profiles in the plasma and circulating exosomes of Parkinson's disease patients using next-generation RNA sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses showed that the miRNA target genes were enriched in axon guidance, neurotrophin signaling, cellular senescence, and the Transforming growth factor-ß (TGF-ß), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) and mechanistic target of rapamycin (mTOR) signaling pathways. Furthermore, a group of aberrantly expressed miRNAs were selected and further validated in individual patient plasma, human neural stem cells (NSCs) and a rat model of PD. More importantly, the full scope of the regulatory network between these miRNAs and their PD-related gene targets in human neural stem cells was examined, and the findings revealed a similar but still varied downstream regulatory cascade involving many known PD-associated genes. Additionally, miR-23b-3p was identified as a novel direct regulator of alpha-synuclein, which is possibly the key component in PD. Our current study, for the first time, provides a glimpse into the regulatory network of pathogenic miRNAs and their PD-related gene targets in PD. Moreover, these PD-associated miRNAs may serve as biomarkers and novel therapeutic targets for PD.

Sustained antidepressant action of the N-methyl-D-aspartate receptor antagonist MK-801 in a chronic unpredictable mild stress model.

(5S,10R)-5-methyl-10,11-dihydro-5H-dibenzo(A,D)cyclohepten-5,10-imine hydrogen maleate (MK-801) is an N-methyl-D-aspartate non-competitive antagonist that possesses useful biological properties, including anticonvulsant and anesthetic activities. Studies have indicated the rapid antidepressant effects of MK-801 in animal models. However, there are no reports concerning a sustained antidepressant effect in the chronic unpredictable mild stress (CUMS) model. Furthermore, the antidepressant mechanism remains unclear. The aim of the present study was to examine the effects of MK-801 (0.1 mg/kg) and rapastinel (10 mg/kg) on depression-like behavior in CUMS mice and measure the protein expression of brain-derived neurotrophic factor (BDNF), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (GluA1) and phosphorylated mammalian target of rapamycin (p-mTOR). In the tail suspension and forced swim tests, MK-801 significantly attenuated the increased immobility time in CUMS mice compared with the vehicle group. In the sucrose preference test, a single-dose injection of MK-801 significantly ameliorated the decreased sucrose preference in CUMS mice compared with the vehicle group. Western blot analyses indicated that MK-801 significantly attenuated the decreased BDNF, GluA1 and p-mTOR protein levels in the medial prefrontal cortex (mPFC), dentate gyrus (DG) and CA3 of the hippocampi of CUMS mice. Conversely, this compound had no effect on increased BDNF, GluA1 and p-mTOR protein levels in the nucleus accumbens of CUMS mice. Therefore, the present study revealed the sustained antidepressant effects of MK-801 in the CUMS model. Furthermore, synaptogenesis and neuronal regeneration in the prelimbic regions of mPFC, DG and CA3 of the hippocampus may be implicated as mechanisms that promote a sustained antidepressant response.

Treatment of giant cavernous aneurysm in an elderly patient via extracranial-intracranial saphenous vein bypass graft in a hybrid operating room: A case report.

RATIONALE: Extracranial-intracranial saphenous vein bypass (EC-IC SVB) remains indispensable for treating giant cavernous aneurysms. We report an unusual case of a giant cavernous aneurysm in an elderly patient treated with EC-IC SVB in a hybrid operating room. Immediately following proximal ligation of the internal carotid artery (ICA), she suffered an acute intraoperative encephalocele. PATIENT CONCERNS: A 71-year-old woman had suffered from severe headache and double vision for 4 months. DIAGNOSES: The woman was diagnosed with a right giant cavernous aneurysm. INTERVENTIONS: She was treated with an EC-IC SVB with therapeutic ICA occlusion in the first biplane hybrid operating room in China. Just after proximal ligation of the ICA, she developed an acute encephalocele, and immediately underwent decompressive craniectomy. During the surgery she underwent 3 angiographic explorations. OUTCOMES: After surgery, the aneurysm disappeared, and the graft was patent. Postoperative computed tomography and computed tomography angiography indicated a cranial defect and graft patency. LESSONS: Although a hybrid operating room could improve the patency of grafts, the timing of ICA ligation for giant cavernous aneurysm via EC-IC bypass deserves further discussion. Second-stage ICA occlusion could offer an alternative for elderly patients requiring such treatment. In addition, cranial flap removal could prevent further neurologic deficits in a case of acute intraoperative encephalocele.

Brain-derived neurotrophic factor propeptide inhibits proliferation and induces apoptosis in C6 glioma cells.

There are several forms of brain-derived neurotrophic factor (BDNF), the precursor of BDNF, mature BDNF, and BDNF propeptide. They exert different effects through different transmembrane receptor signaling systems. Precursor of BDNF is enzymatically cleaved, either by intracellular or by extracellular proteases, to generate mature BDNF and its propeptide (BDNF propeptide). The aim of this study was to evaluate the potential molecular mechanisms that underlie the inhibition of glioma cell growth by the BDNF propeptide. To achieve this, we examined the expression of BDNF propeptide in C6 glioma cells. The 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay and the apoptosis assay were used to assess the effects of the BDNF propeptide on the growth and apoptosis of glioma cells. We found that the BDNF propeptide promoted C6 glioma cell apoptosis and decreased in-vitro cell growth. We also found using western blot that cleaved caspase3 and B cell lymphoma 2 (Bcl2)-associated X protein abundances increased, whereas Bcl2 abundance decreased. Our data suggest that the BDNF propeptide may have an inhibitory effect on glioma through activation of the caspase3 pathway.

Antidepressant Effects of (+)-MK-801 and (-)-MK-801 in the Social Defeat Stress Model.

BACKGROUND: Current data on antidepressant action of the N-methyl-D-aspartate receptor antagonist, (+)-MK-801, is inconsistent. This study was conducted to examine the effects of (+)-MK-801 and its less potent stereoisomer, (-)-MK-801, in the social defeat stress model of depression. METHODS: The antidepressant effects of (+)-MK-801 (0.1mg/kg) and (-)-MK-801 (0.1mg/kg) in the social defeat stress model were examined. RESULTS: In the tail suspension and forced swimming tests, both stereoisomers significantly attenuated increased immobility time in susceptible mice. In the sucrose preference test, (+)-MK-801, but not (-)-MK-801, significantly enhanced reduced sucrose consumption 2 or 4 days after a single dose. However, no antianhedonia effects were detected 7 days after a single dose of either stereoisomer. CONCLUSIONS: Both stereoisomers of MK-801 induced rapid antidepressant effects in the social defeat stress model, although neither produced a long-lasting effect (7 days).

Comparison of R-ketamine and rapastinel antidepressant effects in the social defeat stress model of depression.

RATIONALE: The N-methyl-D-aspartate (NMDA) receptor antagonists, including R-ketamine and rapastinel (formerly GLYX-13), show rapid antidepressant effects in animal models of depression. OBJECTIVE: We compared the rapid and sustained antidepressant effects of R-ketamine and rapastinel in the social defeat stress model. RESULTS: In the tail suspension and forced swimming tests, R-ketamine (10 mg/kg, intraperitoneal (i.p.)) or rapastinel (10 mg/kg, i.p.) significantly attenuated the increased immobility time in the susceptible mice, compared with the vehicle-treated group. In the sucrose preference test, both compounds significantly enhanced the reduced preference in susceptible mice 2, 4, or 7 days after a single injection. All mice were sacrificed 8 days after a single injection. Western blot analyses showed that R-ketamine, but not rapastinel, significantly attenuated the reduced brain-derived neurotrophic factor (BDNF)-TrkB signaling, postsynaptic density protein 95 (PSD-95), and GluA1 (a subtype of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor) in the prefrontal cortex, dentate gyrus, and CA3 of the hippocampus in the susceptible mice. In contrast, both compounds had no effect against the increased BDNF-TrkB signaling, PSD-95, and GluA1 seen in the nucleus accumbens of susceptible mice. Moreover, sustained antidepressant effect of R-ketamine (3 mg/kg, intravenous (i.v.)), but not rapastinel (3 mg/kg, i.v.), was detected 7 days after a single dose. CONCLUSIONS: These results highlight R-ketamine as a longer lasting antidepressant compared with rapastinel in social defeat stress model. It is likely that synaptogenesis including BDNF-TrkB signaling in the prefrontal cortex (PFC) and hippocampus may be required for the mechanisms promoting this sustained antidepressant effect.

Regional differences in the expression of brain-derived neurotrophic factor (BDNF) pro-peptide, proBDNF and preproBDNF in the brain confer stress resilience.

Using learned helplessness (LH) model of depression, we measured protein expression of brain-derived neurotrophic factor (BDNF) pro-peptide, BDNF precursors (proBDNF and preproBDNF) in the brain regions of LH (susceptible) and non-LH rats (resilience). Expression of preproBDNF, proBDNF and BDNF pro-peptide in the medial prefrontal cortex of LH rats, but not non-LH rats, was significantly higher than control rats, although expression of these proteins in the nucleus accumbens of LH rats was significantly lower than control rats. This study suggests that regional differences in conversion of BDNF precursors into BDNF and BDNF pro-peptide by proteolytic cleavage may contribute to stress resilience.

Ellagic acid inhibits proliferation and induces apoptosis in human glioblastoma cells.

PURPOSE: To investigate the anticancer activity of ellagic acid (EA) in U251 human glioblastoma cells and its possible molecular mechanism. METHODS: The cells were treated with EA at various concentrations for different time periods. Cell viability and cell proliferation were detected by cell counting kit-8(CCK-8) assay and live/dead assay respectively. Cell apoptosis were measured with Annexin V-FITC/PI double staining method by flow cytometry and Mitochondrial membrane potential assay separately. Cell cycle was measured with PI staining method by flow cytometry. The expressions of Bcl-2, Survivin, XIAP, Caspase-3, Bax, JNK, p-JNK, ERK1/2, p-ERK1/2, p38, p-p38, DR4, DR5, CHOP and GRP78-related proteins were detected by western blot after EA treatment. RESULTS: Cell viability and proliferation of glioblastoma cells treated with EA were significantly lower than the control group. EA caused robust apoptosis of the glioblastoma cells compared to the control group. EA significantly decreased the proportion at G0/G1 phases of cell cycling accompanied by increased populations at S phase in U251 cell lines. And the expressions of anti-apoptotic proteins were dramatically down-regulated. CONCLUSION: Ellagic acid potentially up-regulated DR4, DR5 and MAP kinases (JNK, ERK1/2 and p38). EA also caused significant increase in the expressions of CHOP and GRP78. Our findings suggest that EA would be beneficial for the treatment of glioblastoma.