Radiation-induced brachial plexus injury after radiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: Radiation-induced brachial plexus injury is a devastating complication that occurs after radiotherapy in the vicinity of the brachial plexus. Nasopharyngeal carcinoma, the most common type of cancer in Guangdong Province, is primarily treated with radiotherapy with subsequent side effects. However, radiation-induced brachial plexus injury is rarely reported in nasopharyngeal carcinoma. To draw attention to this correlation, we analyzed the clinical characteristics including the imaging findings of 10 patients suffering from radiation-induced brachial plexus injury for nasopharyngeal carcinoma. METHODS: We considered the patients' medical histories, analyzed their clinical characteristics, and monitored the long-term efficacy of treatment. RESULTS: The total irradiation dose of the nasopharynx ranged from 66.6 to 74 Gy, and that of the supraclavicular fossa ranged from 60 to 70 Gy. The mean latency was 8.2 ± 5.5 years. Seven patients initially complained of bilateral weakness, and three patients complained of isolated pain. The injuries of eight patients reached Grade 3 or worse. Magnetic resonance imaging showed a low signal on T1-weighted images and a high signal on short tau inversion recovery sequences in all cases. Swollen nerve fibers were clearly displayed in magnetic resonance diffusion tensor imaging. Electromyography showed myokymia in three patients. With conservative therapy, only one patient was temporarily relieved of pain, while the conditions of others were not ameliorated. CONCLUSIONS: Radiation-induced brachial plexus injury is a late but catastrophic complication in patients with nasopharyngeal carcinoma. Clinicians should be aware of radiation-induced brachial plexus injury when deciding on treatment and should give them regular follow-up post radiotherapy.

Evaluating team-based, lecture-based, and hybrid learning methods for neurology clerkship in China: a method-comparison study.

BACKGROUND: Neurology is complex, abstract, and difficult for students to learn. However, a good learning method for neurology clerkship training is required to help students quickly develop strong clinical thinking as well as problem-solving skills. Both the traditional lecture-based learning (LBL) and the relatively new team-based learning (TBL) methods have inherent strengths and weaknesses when applied to neurology clerkship education. However, the strengths of each method may complement the weaknesses of the other. Combining TBL with LBL may produce better learning outcomes than TBL or LBL alone. We propose a hybrid method (TBL + LBL) and designed an experiment to compare the learning outcomes with those of pure LBL and pure TBL. METHODS: One hundred twenty-seven fourth-year medical students attended a two-week neurology clerkship program organized by the Department of Neurology, Sun Yat-Sen Memorial Hospital. All of the students were from Grade 2007, Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University. These students were assigned to one of three groups randomly: Group A (TBL + LBL, with 41 students), Group B (LBL, with 43 students), and Group C (TBL, with 43 students). The learning outcomes were evaluated by a questionnaire and two tests covering basic knowledge of neurology and clinical practice. RESULTS: The practice test scores of Group A were similar to those of Group B, but significantly higher than those of Group C. The theoretical test scores and the total scores of Group A were significantly higher than those of Groups B and C. In addition, 100% of the students in Group A were satisfied with the combination of TBL + LBL. CONCLUSIONS: Our results support our proposal that the combination of TBL + LBL is acceptable to students and produces better learning outcomes than either method alone in neurology clerkships. In addition, the proposed hybrid method may also be suited for other medical clerkships that require students to absorb a large amount of abstract and complex course materials in a short period, such as pediatrics and internal medicine clerkships.

Beneficial effects of ulinastatin on gut barrier function in sepsis.

BACKGROUND & OBJECTIVES: The gut contains some endogenous and exogenous microorganisms that can become potential pathogens of sepsis under certain circumstances. Therefore, the integrity and normal function of gut barrier is important for preventing the development of sepsis. The present study was designed to assess the effects of ulinastatin, a urinary trypsin inhibitor on gut barrier function and mortality in experimental sepsis. METHODS: Male Sprague-Dawley rats were subjected to ceacal ligation and puncture (CLP) or sham procedure. Rats were then treated with ulinastatin 50,000 U/kg/day or saline. The mortality rate was determined. Histology, apoptosis assays, and PCR were performed using ileum specimens at 3, 6, and 12 h following CLP. Serum levels of tumour necrosis factor α (TNF-α) and interleukin-6 (IL-6) were also measured at 0, 3, 6, and 12 h following CLP. RESULTS: Compared with the saline-treated CLP rats, the ulinastatin CLP rats had significantly increased survival time (P<0.05), lower histopathological scores of intestinal injury (P<0.05), reduced apoptosis detected by terminal deoxynucleotidyl transferase dUTP nick end labelling assay and caspase 3 activity (P<0.01). Moreover, RD-5 mRNA expression was significantly higher in ulinastatin-treated CLP animals than saline controls (P<0.05). These results suggested a preserved integrity and function of the gut barrier. Significantly lower plasma TNFα and IL-6 levels were detected in CLP rats with ulinastatin treatment, which contributed to increased survival time. INTERPRETATION & CONCLUSIONS: Our results suggest that ulinastatin has a therapeutic potential to prevent gut barrier dysfunction in the early stage of sepsis, thereby improving the outcome of sepsis. Further studies need to be done to understand the mechanism of action of ulinastatin.

Serum concentration of high-mobility group box 1, Toll-like receptor 4 as biomarker in epileptic patients.

Epilepsy is one of the most common neurological diseases with severe outcome. High-mobility Group Box 1/Toll-like Receptor 4 axis is proposed to participate in the epileptogenesis and correlate with seizure severity in animal models. To explore whether HMGB1 and TLR4 could serve as clinical biomarkers in epileptic patients, we recruited a total of 72 epilepsy patients and measured the serum level of HMGB1 and TLR4 by flow fluorescence technology and ELISA respectively. We found that the serum levels of HMGB1 and TLR4 were elevated in epileptic patients. The serum levels of HMGB1 and TLR4 were also significantly higher in drug-resistant group compared with drug-effective group. There was a positive linear correlation between HMGB1 and TLR4 in the study group (R2 = 0.479). The HMGB1 level was found to be related to seizures frequency (F = 6.71, P = 0.012), the duration of disease (F = 6.55, P = 0.013) and drug reactivity (F = 3.96, P = 0.024) in epileptic patients, while TLR4 level was related to seizures frequency (F = 4.68, P = 0.034) and drug reactivity (F = 3.80, P = 0.027). Our result provides experimental evidences that the expression of HMGB1 and TLR4 was correlated with clinical symptom in epileptic patients, which could be used as clinical biomarkers to monitor therapeutic effect.

Atypical antipsychotics for Parkinson's disease psychosis: a systematic review and meta-analysis.

PURPOSE: To assess the present evidence regarding the efficiency, safety, and potential risks of pharmacotherapy used for Parkinson's disease psychosis (PDPsy) treatment. PATIENTS AND METHODS: We searched the following databases: PubMed, the Cochrane Library, ISI Web of Science, and Embase using the following terms: atypical antipsychotics, pimavanserin, olanzapine, quetiapine, clozapine, Parkinson's disease and psychosis. We systematically reviewed all randomized placebo-controlled trials comparing an atypical antipsychotic with a placebo. RESULTS: A total of 13 randomized placebo-controlled trials for a total 1142 cases were identified involving pimavanserin (n=4), clozapine (n=2), olanzapine (n=3), and quetiapine (n=4). For each atypical antipsychotic, a descriptive synthesis and meta-analyses was presented. Pimavanserin was associated with a significant improvement in psychotic symptoms compared to a placebo without worsening motor function. Clozapine was efficacious in alleviating psychotic symptoms and did not exacerbate motor function either. Quetiapine and Olanzapine did not demonstrate significant differences in reducing psychotic symptoms but may aggravate motor function. CONCLUSIONS: There is strong evidence that pimavanserin is effective for the treatment of PDPsy. Clozapine is also recommended but should be used with caution due to its side effects. In the future, more well-designed randomized controlled trials (RCTs) are needed to confirm and update the findings reported in this meta-analysis.

Carotid stenosis prevalence after radiotherapy in nasopharyngeal carcinoma: A meta-analysis.

PURPOSE: Radiotherapy (RT) is the most effective treatment for nasopharyngeal carcinoma (NPC) but may cause stenosis of the carotid arteries. This meta-analysis evaluates the prevalence of carotid stenosis after radiation therapy. MATERIALS AND METHODS: Online search for studies reporting carotid stenosis in patients with NPC who received radiation therapy (RT) compared to NPC patients who did not receive RT and compared to healthy controls. RESULTS: Twelve studies were included for a total analysis of 1928 patients (837 received RT and 1091 were controls). RT patients showed a statistically significant higher incidence of overall stenosis (pooled risk ratio = 4.17 [2.44, 7.10], p < 0.00001) and an even greater incidence of significant stenosis (50% or more) (pooled risk ratio = 8.72 [3.53, 21.55], p < 0.00001). Analyzing by individual blood vessels showed that the RT patients had significantly higher incidence of stenosis in common carotid artery (CCA), external carotid artery (ECA), carotid bulb, CCA and internal carotid artery (ICA), and CCA/ICA/carotid bulb. CONCLUSIONS: NPC patients who receive RT have increased risk of developing carotid stenosis, and should be screened after treatment.

Pathophysiological Responses in Rat and Mouse Models of Radiation-Induced Brain Injury.

The brain is the major dose-limiting organ in patients undergoing radiotherapy for assorted conditions. Radiation-induced brain injury is common and mainly occurs in patients receiving radiotherapy for malignant head and neck tumors, arteriovenous malformations, or lung cancer-derived brain metastases. Nevertheless, the underlying mechanisms of radiation-induced brain injury are largely unknown. Although many treatment strategies are employed for affected individuals, the effects remain suboptimal. Accordingly, animal models are extremely important for elucidating pathogenic radiation-associated mechanisms and for developing more efficacious therapies. So far, models employing various animal species with different radiation dosages and fractions have been introduced to investigate the prevention, mechanisms, early detection, and management of radiation-induced brain injury. However, these models all have limitations, and none are widely accepted. This review summarizes the animal models currently set forth for studies of radiation-induced brain injury, especially rat and mouse, as well as radiation dosages, dose fractionation, and secondary pathophysiological responses.

Photoluminescence Study of the Photoinduced Phase Separation in Mixed-Halide Hybrid Perovskite CH3NH3Pb(BrxI1-x)3 Crystals Synthesized via a Solvothermal Method.

We systematically synthesized mixed-halide hybrid perovskite CH3NH3Pb(BrxI1-x)3 (0 ≤ x ≤ 1) crystals in the full composition range by a solvothermal method. The as-synthesized crystals retained cuboid shapes, and the crystalline structure transitioned from the tetragonal phase to the cubic phase with an increasing Br-ion content. The photoluminescence (PL) of CH3NH3Pb(BrxI1-x)3 crystals exhibited a continuous variation from red (768 nm) to green (549 nm) with increasing the volume ratio of HBr (VHBr%), corresponding to a variation in the bandgap from 1.61 eV to 2.26 eV. Moreover, the bandgap of the crystals changed nonlinearly as a quadratic function of x with a bowing parameter of 0.53 eV. Notably, the CH3NH3Pb(BrxI1-x)3 (0.4 ≤ x ≤ 0.6) crystals exhibited obvious phase separation by prolonged illumination. The cause for the phase separation was attributed to the formation of small clusters enriched in lower-band-gap, iodide-rich and higher-band-gap, bromide-rich domains, which induced localized strain to promote halide phase separation. We also clarified the relationship between the PL features and the band structures of the crystals.

Rifampicin inhibits rotenone-induced microglial inflammation via enhancement of autophagy.

Mitochondrial and autophagic dysfunction, as well as neuroinflammation, are associated with the pathophysiology of Parkinson's disease (PD). Rotenone, an inhibitor of mitochondrial complex I, has been associated as an environmental neurotoxin related to PD. Our previous studies reported that rifampicin inhibited microglia activation and production of proinflammatory mediators induced by rotenone, but the precise mechanism has not been completely elucidated. BV2 cells were pretreated for 2h with rifampicin followed by 0.1µM rotenone, alone or in combination with chloroquine. Here, we demonstrate that rifampicin pretreatment alleviated rotenone induced release of IL-1ß and IL-6, and its effects were suppressed when autophagy was inhibited by chloroquine. Moreover, preconditioning with 50µM rifampicin significantly increased viability of SH-SY5Y cells cocultured with rotenone-treated BV2 cells in the transwell coculture system. Chloroquine partially abolished the neuroprotective effects of rifampicin pretreatment. Rifampicin pretreatment significantly reversed rotenone-induced mitochondrial membrane potential reduction and reactive oxygen species accumulation. We suggest that the mechanism for rifampicin-mediated anti-inflammatory and antioxidant effects is the enhancement of autophagy. Indeed, the ratio of LC3-II/LC3-I in rifampicin-pretreated BV2 cells was significantly higher than that in cells without pretreatment. Fluorescence and electron microscopy analyses indicate an increase of lysosomes colocalized with mitochondria in cells pretreated with rifampicin, which confirms that the damaged mitochondria were cleared through autophagy (mitophagy). Taken together, the data provide further evidence that rifampicin exerts neuroprotection against rotenone-induced microglia inflammation, partially through the autophagy pathway. Modulation of autophagy by rifampicin is a novel therapeutic strategy for PD.

[Effect of ulinastatin on apoptosis in ileal mucosa of rats with hemorrhagic shock].

OBJECTIVE: To investigate the effect of ulinastatin on apoptosis in ileal mucosa of rats with hemorrhagic shock. METHODS: A prospective, controlled animal study was performed. The rat model of hemorrhagic shock was replicated according to method described by Chaudry. After 60 minutes period of bleeding, rats were resuscitated by transfusion of shed blood and normal saline. A part of the animals were additionally treated with ulinastatin. The expression of tumor necrosis factor-alpha (TNF-alpha), malondialdehyde (MDA) content in serum, and expression of Bax, Bcl-2, caspase 3 protein in ileal mucosa were determined at different time points after reperfusion. RESULTS: Compared with the normal saline group, the expression levels of TNF-alpha, MDA content in serum, Bax and caspase 3 protein in ileal mucosa during hemorrhagic shock after resuscitation were significantly increased, while Bcl-2 protein was markedly decreased. After fluid resuscitation, obvious increase in MDA, Bcl-2 protein, significant decrease in the level of TNF-alpha, the expression of Bax and caspase 3 protein in ileal mucosa were observed in the ulinastatin group compared with normal saline group. CONCLUSION: Ulinastatin has protective effect on rats with hemorrhagic shock by suppressing the apoptosis in ileal mucosa.

High-Quality Crystal Growth and Characteristics of AlGaN-Based Solar-Blind Distributed Bragg Reflectors with a Tri-layer Period Structure.

To realize AlGaN-based solar-blind ultraviolet distributed Bragg reflectors (DBRs), a novel tri-layer AlGaN/AlInN/AlInGaN periodical structure that differs from the traditional periodically alternating layers of high- and low-refractive-index materials was proposed and grown on an Al0.5Ga0.5N template via metal-organic chemical vapour deposition. Because of the intentional design of the AlInGaN strain transition layer, a state-of-the-art DBR structure with atomic-level-flatness interfaces was achieved using an AlGaN template. The fabricated DBR exhibits a peak reflectivity of 86% at the centre wavelength of 274 nm and a stopband with a full-width at half-maximum of 16 nm.

Graphene quantum dots conjugated neuroprotective peptide improve learning and memory capability.

Alzheimer disease (AD) is a neurodegenerative disorder and the most common form of dementia. Histopathologically is characterized by the presence extracellular neuritic plaques and with a large number of neurons lost. In this paper, we design a new nanomaterial, graphene quantum dots (GQDs) conjugated neuroprotective peptide glycine-proline-glutamate (GQDG) and administer it to APP/PS1 transgenic mice. The in vitro assays including ThT and CD proved that GQDs and GQDG could inhibit the aggregation of Aß1-42 fibrils. Morris water maze was performed to exanimate learning and memory capacity of APP/PS1 transgenic mice. The surface area of Aß plaque deposits reduced in the GQDG group compared to the Tg Ctrl groups. Furthermore, newly generated neuronal precursor cell and neuron were test by immunohistochemical. Besides, neurons were impregnated by DiI using gene gun to show dendritic spine. Results indicated enhancement of learning and memory capacity and increased amounts of dendritic spine were observed. Inflammation factors and amyloid-ß (Aß) were tested with suspension array and ELISA, respectively. Several pro-inflammatory cytokines (IL-1α, IL-1ß, IL-6, IL-33, IL-17α, MIP-1ß and TNF-α) had decreased in GQDG group compared with Control group. Reversely, anti-inflammatory cytokines (IL-4, IL-10) had increased in GQDG group compared with Control group. Thus, we demonstrate that the GQDG is a promising drug in treatment of neurodegenerative diseases such as AD.

Rifampicin attenuates rotenone-induced inflammation via suppressing NLRP3 inflammasome activation in microglia.

A growing body of evidence has supported that environmental factors, such as exposure to heavy metal and pesticides, play an important role in the pathogenesis of Parkinson׳s disease (PD). Rotenone, the active ingredient in various pesticides, has been identified as an inducer of PD. It has been revealed that rotenone induces activation of microglia and generation of pro-inflammatory factors in PD. Our previous studies demonstrated that rifampicin possessed neural protective effect in PD. In this study, we aimed to study the effect of rifampicin on the inflammation induced by rotenone in microglia and the underlying mechanisms. Results demonstrated that rifampicin pretreatment significantly reduced rotenone-induced cytotoxicity and gene expression of IL-1ß in BV2 microglia. Moreover, western blot analysis verified that rifampicin pretreatment suppressed NLRP3 inflammasome activation via inhibiting caspase-1 cleavage and protein expression of NLRP3. As it is indicated that reactive oxidative stress (ROS) is one of the activators for NLRP3 inflammasome, we further employed 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining and Rhodamine123 staining to detect intracellular ROS and mitochondrial membrane potential (MMP), respectively. Results confirmed that rifampicin obviously reduced intracellular ROS and reversed loss of MMP in BV2 cells treated by rotenone. Taken together, our data indicate that rifampicin pretreatment inhibits maturation of IL-1ß and neuroinflammation induced by rotenone via attenuating NLRP3 inflammasome activation. Rifampicin might emerge as a promising candidate for modulating neuroinflammation in PD.

Inhibitory effects of edaravone in ß-amyloid-induced neurotoxicity in rats.

Amyloid protein can damage nerve cells through a variety of biological mechanisms including oxidative stress, alterations in calcium homeostasis, and proapoptosis. Edaravone, a potent free radical scavenger possessing antioxidant effects, has been proved neuroprotective effect in stroke patients. The current study aimed to investigate the effects of EDA in an Aß-induced rat model of AD, by studying Aß 1-40-induced voltage-gated calcium channel currents in hippocampal CA1 pyramidal neurons, learning and memory behavioral tests, the number of surviving cholinergic neurons in the basal forebrain, and the acetylcholine level in the hippocampus in this rat model of AD. The results showed that the Aß 1-40-induced increase of I Ca can be inhibited by EDA in a dose-dependent manner. Treatment with EDA significantly improved Aß 1-40-induced learning and memory performance. Choline acetyltransferase positive cells in basal forebrain and acetylcholine content in the hippocampus were increased by the administration of EDA as compared with the non-EDA treated Aß 1-40 group. These results demonstrate that EDA can inhibit the neurotoxic effect of Aß toxicity. Collectively, these findings suggest that EDA may serve as a potential complemental treatment strategy for AD.

Rifampicin protects PC12 cells from rotenone-induced cytotoxicity by activating GRP78 via PERK-eIF2α-ATF4 pathway.

Rifampicin has been proposed as a therapeutic candidate for Parkinson's disease (PD). We previously showed that rifampicin was neuroprotective in PD models in vivo and in vitro. However, the molecular mechanisms underlying are not fully elucidated. In this study, using the comprehensive proteomic analysis, we identified that the 78 kDa glucose-regulated protein (GRP78), a hallmark of the unfolded protein response (UPR), was upregulated in rifampicin-treated PC12 cells. Western blot analysis confirmed GRP78 activation. GRP78 functions cytoprotectively in stressed cells, therefore, we hypothesized that GRP78 mediated rifampicin-induced neuroprotection. Using RNA interference, we found that GRP78 gene knockdown significantly attenuated the neuroprotective effects of rifampicin. Next, we examined three UPR transducers, namely, protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol requiring kinase α (IREα) and activating transcription factor 6 (ATF 6), and how they regulated rifampicin-stimulated GRP78 expression. Our results showed that PERK, eukaryotic initiation factor 2α (eIF2α), and activating transcription factor 4 (ATF4) were activated in rifampicin-treated PC12 cells. Silencing the ATF4 gene using RNAi inhibited GRP78 stimulation. Interestingly, we did not detect significant IREα activation, X-box binding protein 1 mRNA splicing, or ATF6 cleavage up to 24 h after rifampicin treatment. Taken together, our data suggested that rifampicin induced GRP78 via the PERK-eIF2α-ATF4 pathway to protect neurons against rotenone-induced cell damage. Targeting molecules in this pathway could be a novel therapeutic approach for PD treatment.

Rifampicin improves neuronal apoptosis in LPS-stimulated co­cultured BV2 cells through inhibition of the TLR-4 pathway.

Agents inhibiting microglial activation are attracting attention as candidate drugs for neuroprotection in neurodegenerative diseases. Recently, researchers have focused on the immunosuppression induced by rifampicin. Our previous study showed that rifampicin inhibits the production of lipopolysaccharide (LPS)-induced pro-inflammatory mediators and improves neuron survival in inflammation; however, the mechanism through which rifampicin inhibits microglial inflammation and its neuroprotective effects are not completely understood. In this study, we examined the effects of rifampicin on morphological changes induced by LPS in murine microglial BV2 cells. Then we investigated, in BV2 microglia, the effects of rifampicin on two signaling pathway componentss stimulated by LPS, the Toll­like receptor-4 (TLR-4) and the nuclear factor-κB (NF-κB). In addition, we co-cultured BV2 microglia and neurons to observe the indirect neuroprotective effects of rifampicin. Rifampicin inhibited LPS-stimulated expression of the TLR-4 gene. When neurons were co-cultured with LPS-stimulated BV2 microglia, pre-treatment with rifampicin increased neuronal viability and reduced the number of apoptotic cells. Taken together, these findings suggest that rifampicin, with its anti-inflammatory properties, may be a promising agent for the treatment of neurodegenerative diseases.

Correlation between the changes in ambulatory electroencephalography findings and epilepsy recurrence after medication withdrawal among the population in southern China.

Patients suffering from epilepsy need long-term medication. However, after the epilepsy is completely under control, the recurrence rate is high once the drug dose is reduced gradually. The present study investigated the possible correlation between the changes shown by ambulatory electroencephalography (EEG) and epilepsy recurrence after medication withdrawal, and assessed the value of ambulatory EEG findings in predicting the recurrence of epilepsy after medication withdrawal, in 265 patients from Southern China followed up for 5 years. Anticonvulsants were withdrawn until onset had been controlled thoroughly for over 3 years and ambulatory EEG detected no abnormalities. Ambulatory EEG was performed at least once per year, and findings at the first visit, during treatment, and before and after medication withdrawal were compared and analyzed. There were 47 patients with recurrent epilepsy in this study. Patients with normal ambulatory EEG findings at the first visit and during treatment had lower recurrence rate (about 8.1%) compared to patients with epileptic waves (25.0%), and patients with focal epileptic waves in the temporal, occipital, frontal, and parietal lobes, or in multiple areas was even higher. Patients with epileptic waves also showed higher clinical recurrence rate during the follow-up period. Abnormal ambulatory EEG findings are an important indicator of epileptic recurrence, and is of great value in predicting the recurrence of epilepsy after medication withdrawal.

Inhibition of 26S protease regulatory subunit 7 (MSS1) suppresses neuroinflammation.

Recently, researchers have focused on immunosuppression induced by rifampicin. Our previous investigation found that rifampicin was neuroprotective by inhibiting the production of pro-inflammatory mediators, thereby suppressing microglial activation. In this study, using 2-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS), we discovered that 26S protease regulatory subunit 7 (MSS1) was decreased in rifampicin-treated microglia. Western blot analysis verified the downregulation of MSS1 expression by rifampicin. As it is indicated that the modulation of the ubiquitin-26S proteasome system (UPS) with proteasome inhibitors is efficacious for the treatment of neuro-inflammatory disorders, we next hypothesized that silencing MSS1 gene expression might inhibit microglial inflammation. Using RNA interference (RNAi), we showed significant reduction of IkBα degradation and NF-kB activation. The production of lipopolysaccharides-induced pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide, cyclooxygenase-2, and prostaglandin E(2) were also reduced by MSS1 gene knockdown. Taken together, our findings suggested that rifampicin inhibited microglial inflammation by suppressing MSS1 protein production. Silencing MSS1 gene expression decreased neuroinflammation. We concluded that MSS1 inhibition, in addition to anti-inflammatory rifampicin, might represent a novel mechanism for the treatment of neuroinflammatory disorders.

Basic fibroblast growth factor protects C17.2 cells from radiation-induced injury through ERK1/2.

AIMS: To establish a radiation-induced neural injury model using C17.2 neural stem cells (NSCs) and to investigate whether basic fibroblast growth factor (bFGF) can protect the radiation-induced injury of C17.2 NSCs. Furthermore, we aim to identify the possible mechanisms involved in this model. METHODS: C17.2 NSCs received a single exposure (3, 6, and 9 Gy, respectively) at a dose rate of 300 cGy/min with a control group receiving 0 Gy. Different concentrations of bFGF were added for 24 h, 5 min postirradiation. The MTS assay and flow cytometry were used to detect cytotoxicity and apoptosis. Expression of FGFR1, ERK1/2, and p-ERK1/2 proteins was detected with or without U0126 was pretreated prior to C17.2 NSCs receiving irradiation. RESULTS: C17.2 NSCs showed a dose-dependent cell death as the dose of radiation was increased. Additionally, the rate of apoptosis in the C17.2 NSCs reached 31.2 ± 1.23% in the 6 Gy irradiation group, which was the most significant when compared to the other irradiation treated groups. bFGF showed protective effect on cell apoptosis in a dose-dependent manner. The mean percentage of apoptotic cells decreased to 7.83 ± 1.75% when 100 ng/mL bFGF was given. Furthermore, U0126 could block the protective effect of bFGF by inhibiting the phosphorylation of ERK1/2. CONCLUSIONS: An in vitro cellular model of radiation-induced apoptosis of NSCs, in C17.2 NSCs, was developed successfully. Additionally, bFGF can protect neurons from radiation injury in vitro via the ERK1/2 signal transduction pathway.

Differentiation of HT22 neurons induces expression of NMDA receptor that mediates homocysteine cytotoxicity.

INTRODUCTION: Neurotoxic homocysteine (Hcy) is thought to be an independent risk factor for neurodegenerative diseases, including Alzheimer's disease. This study is to determine whether HT22 cells, a murine hippocampal neuronal model, can be used as an in vitro model, besides the primary neuronal cultures, to investigate the effects of Hcy. MATERIALS AND METHODS: MTS assay and Hoechst 33342/propidium iodide discrimination were used to assess the cell viability and cell death on undifferentiated and differentiated HT22 cells. Semi-quantitative reverse transcription polymerase chain reaction and western blot were used to determine the expression of N-methyl D-aspartate (NMDA) receptor. RESULTS: We found that undifferentiated and differentiated HT22 cells responded to Hcy toxicity differentially, with the undifferentiated cells resistant while the differentiated cells sensitive. The underlying mechanism appeared to be the differential expression levels of NMDA glutamate receptor between the undifferentiated and differentiated cells. Similar to what have been observed in primary neuronal cultures, the Hcy toxicity in the differentiated HT22 cells was largely attenuated by NMDA receptor antagonists, MK-801 and memantine. CONCLUSION: These results suggest for the first time that the differentiation of HT22 cells could induce the expression of NMDA receptors, which lead to Hcy mediate concentration-dependent apoptosis-necrotic continuum of HT22 cell death. The differentiation status of the HT22 cells is important for modeling neurons in vitro, with the differentiated HT22 neurons resembling more characteristics of primary hippocampal neurons while the undifferentiated HT22 cells being proliferating neuronal precursor cells. The differentiated HT22 neurons can be used as a platform to study Hcy toxicity.