Morphometric and volumetric analysis of the posterior cranial fossa in adult Chiari malformation type I with and without group B basilar invagination.

BACKGROUND: The frequent association of basilar invagination (BI) makes the understanding of the pathogenesis of Chiari malformation type I (CMI) difficult. The influence of group B type of BI (the BI without obvious atlantoaxial instability) on the skeletal morphology has not been thoroughly studied. The objective of this study is to evaluate the skeletal alterations in the posterior cranial fossa (PCF) of adult CMI cases with and without group B BI. METHODS: Fifty-four adult CMI without BI cases (CMI-only group) and 30 adult CMI with group B BI cases (CMI-BI group) were retrospectively studied. Fifty-six adult patients with unruptured intracranial aneurysms were included as the controls. Several linear and angular variables, and the bony volume of the PCF were analyzed based on thin-slice computed tomography data. RESULTS: Morphological analysis revealed a significant difference in several variables from controls compared to CMI-only, and CMI-BI patients. The clivus and occipital bone, shortened and elevated in CMI-only patients, were further flattened in BI-associated CMI patients. Furthermore, although out of the scope for the diagnostic threshold of BI, the CMI-only cases also had a tendency to form BI. The association of BI modified several variables, without further reducing the bony PCF volume. CONCLUSIONS: These findings indicate that the variables associated with group B BI tend to be a continuum of the same pathological abnormalities that originate from the same pathological alterations in CMI patients.

Disrupting nNOS-PSD95 Interaction Improves Neurological and Cognitive Recoveries after Traumatic Brain Injury.

Excessive activation of N-methyl-D-aspartate receptors (NMDARs) and the resulting neuronal nitric oxide synthase (nNOS) activation plays a crucial role in the pathogenesis of traumatic brain injury (TBI). However, directly inhibiting NMDARs or nNOS produces adverse side effects because they play key physiological roles in the normal brain. Since interaction of nNOS-PSD95 is a key step in NMDAR-mediated excitotoxicity, we investigated whether disrupting nNOS-PSD95 interaction with ZL006, an inhibitor of nNOS-PSD95 interaction, attenuates NMDAR-mediated excitotoxicity. In cortical neuronal cultures, ZL006 treatment significantly reduced glutamate-induced neuronal death. In a mouse model of controlled cortical impact (CCI), administration of ZL006 (10 mg/kg, i.p.) at 30 min postinjury significantly inhibited nNOS-PSD95 interaction, reduced TUNEL- and phospho-p38-positive neurons in the motor cortex. ZL006 treatment also significantly reduced CCI-induced cortical expression of apoptotic markers active caspase-3, PARP-1, ratio of Bcl-2/Bax, and phosphorylated p38 MAPK (p-p38). Functionally, ZL006 treatment significantly improved neuroscores and sensorimotor performance, reduced somatosensory and motor deficits, reversed CCI-induced memory deficits, and attenuated cognitive impairment. Histologically, ZL006 treatment significantly reduced the brain lesion volume. These findings collectively suggest that blocking nNOS-PSD95 interaction represents an attractive strategy for ameliorating consequences of TBI and that its action is mediated via inhibiting neuronal apoptosis and p38 MAPK signaling.

Sodium houttuyfonate exerts its neuroprotection effect by inhibiting the M1 microglia polarization in a TLR4/NF-κB signal pathway.

Neuroinflammation plays an important role in secondary injury after spinal cord injury (SCI) and may aggravate neurological dysfunction. Several studies have indicated that sodium houttuyfonate (SH) can significantly inhibit macrophage- mediated inflammation; however, its effects on SCI still needs to be elucidated. We found that SH improved Basso, Beattie, and Bresnahan scores and performance in the inclined plane test of SCI model rats. The injured spinal cord exhibited less neuronal loss, cell apoptosis, and M1 microglial polarization after SH treatment. In vitro, SH reduced TLR4/NF-κB expression in cultured primary microglia and decreased M1 microglial polarization and cell apoptosis in a lipopolysaccharide (LPS)-pretreated microglia and neuron coculture system. These results indicated that SH may exert a neuroprotective effect by inhibiting M1 microglial polarization after SCI via the TLR4/NF-κB signalling pathway.

C1-2 Fusion in Atlantoaxial Dislocation and Basilar Invagination with and without Chiari Malformation: Clinical/Radiological and Craniometric Results.

OBJECTIVE: Patients with Chiari malformation (CM) associated with atlantoaxial dislocation (AAD) and basilar invagination (BI) may present with a small posterior cranial fossa, but data on the volumetric analysis are lacking. Additionally, whether additional foramen magnum decompression (FMD) is needed together with atlantoaxial fusion remains controversial. This study evaluated the volumetric alterations of the posterior cranial fossa in these patients and analyzed the radiological and clinical outcomes after posterior C1-C2 reduction and fixation plus C1 posterior arch resection. METHODS: Thirty-two adult CM patients with AAD and BI (CM-AAD/BI group) and 21 AAD and BI patients without CM (AAD/BI-only group) who received posterior atlantoaxial fusion plus C1 posterior arch resection were retrospectively studied. The clinical and radiological outcomes and volumetric measurements of the posterior cranial fossa were evaluated. RESULTS: The majority of CM-AAD/BI patients (94%) improved clinically and radiologically at 12 mo postoperatively, and none required additional FMD. Morphological analysis revealed a significant reduction in the bony posterior cranial fossa volumes of the CM-AAD/BI group (P < 0.01) and the AAD/BI-only group (P < 0.01) relative to those of the CM group. No significant differences were observed between the CM-AAD/BI and AAD/BI groups. CONCLUSIONS: Compared with patients with simple CM, patients with AAD/BI with or without CM demonstrated a considerably and equally reduced bony posterior cranial fossa volume. No additional FMD is needed in the treatment of CM-AAD/BI patients after posterior reduction and fusion plus C1 posterior arch resection.

Dynamic Measurements of Cerebral Blood Flow Responses to Cortical Spreading Depolarization in the Murine Endovascular Perforation Subarachnoid Hemorrhage Model.

Delayed cerebral ischemia (DCI) is the most severe complication after subarachnoid hemorrhage (SAH), and cortical spreading depolarization (CSD) is believed to play a vital role in it. However, the dynamic changes in cerebral blood flow (CBF) in response to CSD in typical SAH models have not been well investigated. Here, SAH was established in mice with endovascular perforation. Subsequently, the spontaneous CBF dropped instantly and then returned to baseline rapidly. After KCl application to the cortex, subsequent hypoperfusion waves occurred across the groups, while a lower average perfusion level was found in the SAH groups (days 1-7). Moreover, in the SAH groups, the number of CSD decreased within day 7, and the duration and spreading velocity of the CSD increased within day 3 and day 14, respectively. Next, we continuously monitored the local field potential (LFP) in the prefrontal cortex. The results showed that the decrease in the percentage of gamma oscillations lasted throughout the whole process in the SAH group. In the chronic phase after SAH, we found that the mice still had cognitive deficits but experienced no obvious tissue damage. In summary, SAH negatively affects the CBF responses to CSD and the spontaneous LFP activity and causes long-term cognitive deficits in mice. Based on these findings, in the specific phase after SAH, DCI is induced or exacerbated more easily by potential causers of CSD in clinical practice (edema, erythrocytolysis, inflammation), which may lead to neurological deterioration.

A survival nomogram model constructed with common clinical characteristics to assist clinical decisions for diffuse low-grade gliomas: A population analysis based on SEER database.

Background: The prognosis of diffuse low-grade gliomas (DLGGs, WHO grade 2) is highly variable, making it difficult to evaluate individual patient outcomes. In this study, we used common clinical characteristics to construct a predictive model with multiple indicators. Methods: We identified 2459 patients diagnosed with astrocytoma and oligodendroglioma from 2000 to 2018 in the SEER database. After removing invalid information, we randomly divided the cleaned patient data into training and validation groups. We performed univariate and multivariate Cox regression analyses and constructed a nomogram. Receiver operating characteristic (ROC) curve, c-index, calibration curve, and subgroup analyses were used to assess the accuracy of the nomogram by internal and external validation. Results: After univariate and multivariate Cox regression analyses, we identified seven independent prognostic factors, namely, age (P<0.001), sex (P<0.05), histological type (P<0.001), surgery (P<0.01), radiotherapy (P<0.001), chemotherapy (P<0.05) and tumor size (P<0.001). The ROC curve, c-index, calibration curve, and subgroup analyses of the training group and the validation group showed that the model had good predictive value. The nomogram for DLGGs predicted patients' 3-, 5- and 10-year survival rates based on these seven variables. Conclusions: The nomogram constructed with common clinical characteristics has good prognostic value for patients with DLGGs and can help physicians make clinical decisions.

The lncRNA-AK046375 Upregulates Metallothionein-2 by Sequestering miR-491-5p to Relieve the Brain Oxidative Stress Burden after Traumatic Brain Injury.

We previously discovered that traumatic brain injury (TBI) induces significant perturbations in long noncoding RNA (lncRNA) levels in the mouse cerebral cortex, and lncRNA-AK046375 is one of the most significantly changed lncRNAs after TBI. lncRNA-AK046375 overexpression and knockdown models were successfully constructed both in vitro and in vivo. In cultured primary cortical neurons and astrocytes, lncRNA-AK046375 sequestered miR-491-5p, thereby enhancing the expression of metallothionein-2 (MT2), which ameliorated oxidative-induced cell injury. In addition, upregulated lncRNA-AK046375 promoted the recovery of motor, learning, and memory functions after TBI in C57BL/6 mice, and the underlying mechanism may be related to ameliorated apoptosis, inhibited oxidative stress, reduced brain edema, and relieved loss of tight junction proteins at the blood-brain barrier in the mouse brain. Therefore, we conclude that lncRNA-AK046375 enhances MT2 expression by sequestering miR-491-5p, ultimately strengthening antioxidant activity, which ameliorates neurological deficits post-TBI.

Computational identification of immune-related lncRNA signature for predicting the prognosis and immune landscape of human glioblastoma multiforme.

Emerging evidence shows immune-related long noncoding RNAs (ir-lncRNAs) perform critical roles in tumor progression and prognosis assessment. However, the identification of ir-lncRNAs and their clinical significance in human glioblastoma multiforme (GBM) remain largely unexplored. Here, a designed computational frame based on immune score was used to identify differentially expressed ir-lncRNAs (DEir-lncRNAs) from The Cancer Genome Atlas (TCGA) GBM program. The immune-related lncRNA signature (IRLncSig) composed of prognosis-related DEir-lncRNAs selected by Cox regression analysis and its clinical predictive values were verified, which was further validated by another dataset from the Gene Expression Omnibus database (GEO). Subsequently, the association between IRLncSig and immune cell infiltration, immune checkpoint inhibitor (ICI) biomarkers, O6-methylguanine-DNA methyltransferase (MGMT) gene expression, and biological function were also analyzed. After calculation, five prognosis-related ir-lncRNAs were included in the establishment of IRLncSig. The risk assessment based on IRLncSig indicated that the high-IRLncSig-score group was significantly associated with poor prognosis (p < 0.001), significant aggregation of macrophages (p < 0.05), higher ICI biomarker expression, and MGMT gene expression (p < 0.05). Signature-related lncRNAs may be involved in immune activities in the tumorigenesis and progression of GBM. In summary, the novel IRLncSig shows a promising clinical value in predicting the prognosis and immune landscape of GBM.

Restoring mitochondrial cardiolipin homeostasis reduces cell death and promotes recovery after spinal cord injury.

Alterations in phospholipids have long been associated with spinal cord injury (SCI). However, their specific roles and signaling cascades in mediating cell death and tissue repair remain unclear. Here we investigated whether alterations of cardiolipin (CL), a family of mitochondrion-specific phospholipids, play a crucial role in mitochondrial dysfunction and neuronal death following SCI. Lipidomic analysis was used to determine the profile of CL alteration in the adult rat spinal cord following a moderate contusive SCI at the 10th thoracic (T10) level. Cellular, molecular, and genetic assessments were performed to determine whether CL alterations mediate mitochondrial dysfunction and neuronal death after SCI, and, if so, whether reversing CL alteration leads to neuroprotection after SCI. Using lipidomic analysis, we uncovered CL alterations at an early stage of SCI. Over 50 distinct CL species were identified, of which 50% showed significantly decreased abundance after SCI. The decreased CL species contained mainly polyunsaturated fatty acids that are highly susceptible to peroxidation. In parallel, 4-HNE, a lipid peroxidation marker, significantly increased after SCI. We found that mitochondrial oxidative stress not only induced CL oxidation, but also resulted in CL loss by activating cPLA2 to hydrolyze CL. CL alterations induced mitochondrial dysfunction and neuronal death. Remarkably, pharmacologic inhibition of CL alterations with XJB-5-131, a novel mitochondria-targeted electron and reactive oxygen species scavenger, reduced cell death, tissue damage and ameliorated motor deficits after SCI in adult rats. These findings suggest that CL alteration could be a novel mechanism that mediates injury-induced neuronal death, and a potential therapeutic target for ameliorating secondary SCI.

Chromobox Homolog 8 (CBX8) in Human Tumor Carcinogenesis and Prognosis: A Pancancer Analysis Using Multiple Databases.

Some emerging studies have suggested that chromobox homolog 8 (CBX8) may play a critical role in carcinogenesis and prognosis in human cancer. Based on The Cancer Genome Atlas (TCGA)'s available data and the Gene Expression Omnibus (GEO) database, we conducted a systematic analysis of the carcinogenic effects of the CBX8 gene. We used TIMER2, GEPIA2, UALCAN, cBioPortal, Kaplan-Meier plotter, OncoLnc, STRING, HPA, and Oncomine data analysis websites and R data analysis software to analyze available data. The results show that the level of expression of CBX8 was significantly different among 27 different types of tumors and adjacent normal tissues. Moreover, we found that CBX8 expression had a close relationship with prognosis in some kinds of cancers. The phosphorylation level of some protein sites (such as S256) was significantly increased in tumors. CD8 + T-cell, B-cell and cancer-associated fibroblast infiltration levels were associated with CBX8 expression. The results of enrichment analysis indicated that the main biological activities of CBX8 are connected to gene transcription and repair of DNA damage. In conclusion, the level of expression of CBX8 was closely related to carcinogenesis and prognosis of some kinds of tumors, which needs further experimental verification.

Diabetes increases the risk of meningioma: A systematic review and meta-analysis of observational studies.

BACKGROUND: Increasing epidemiological evidence suggests that diabetes may be associated with meningioma risk, but the evidence supporting this association is still inconclusive. Therefore, we performed a meta-analysis of all eligible observational studies to evaluate the potential association of diabetes with meningioma risk. METHODS: A comprehensive literature search was performed in the PubMed, Web of Science and Cochrane Library databases up to November 30, 2020. A random-effects model was applied to calculate the pooled effect size (ES) and its 95 % confidence interval (CI). RESULTS: Eight studies were included in this study. In a random-effects pooled analysis, the results showed that DM (diabetes mellitus) increased the risk of meningioma (ES 1.17, 95 % CI: 1.02-1.35, P = 0.027). In subgroup analyses, DM increased the risk of meningioma in women (ES: 1.19, 95 % CI: 1.02-1.40, P = 0.027) and men (ES: 1.53, 95 % CI: 1.25-1.88, P = 0.000). This effect was not observed in the postmenopausal group (ES: 1.18, 95 % CI: 0.64-2.18, P = 0.597). CONCLUSION: Our meta-analysis showed that DM increases the risk of meningioma, but the association was only present in some subgroups. This conclusion should be further confirmed.

Suppression of Akt1 phosphorylation by adenoviral transfer of the PTEN gene inhibits hypoxia-induced proliferation of rat pulmonary arterial smooth muscle cells.

Recent findings identify the role of proliferation of pulmonary artery smooth muscle cells (PASMCs) in pulmonary vascular remodeling. Phosphoinositide 3 kinase (PI3K) and serine/threonine kinase (Akt) proteins are expressed in vascular smooth muscle cells. In addition, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has been identified as a negative regulator of cytokine signaling that inhibits the PI3K-Akt pathway. However, little is known about the role of PTEN/Akt signaling in hypoxia-associated vascular remodeling. In this study, we found that hypoxia-induced the expression of Akt1 mRNA and phosphorylated protein by at least twofold in rat PASMCs. Phospho-PTEN significantly decreased in the nuclei of PASMCs after hypoxic stimulation. After forcing over-expression of PTEN by adenovirus-mediated PTEN (Ad-PTEN) transfection, the expression of phospho-Akt1 was significantly suppressed in PASMCs at all time-points measured. Additionally, we showed here that hypoxia increased proliferation of PASMCs by nearly twofold and over-expression of PTEN significantly inhibited hypoxia-induced PASMCs proliferation. These findings suggest that phospho-PTEN loss in the nuclei of PASMCs under hypoxic conditions may be the major cause of aberrant activation of Akt1 and may, therefore, play an important role in hypoxia-associated pulmonary arterial remodeling. Finally, the fact that transfection with Ad-PTEN inhibits the phosphorylation of Akt1 in PASMCs suggests a potential therapeutic effect on hypoxia-associated pulmonary arterial remodeling.

Functional recovery in acute traumatic spinal cord injury after transplantation of human umbilical cord mesenchymal stem cells.

OBJECTIVE: Spinal cord injury results in loss of neurons, degeneration of axons, formation of glial scar, and severe functional impairment. Human umbilical cord mesenchymal stem cells can be induced to form neural cells in vitro. Thus, these cells have a potential therapeutic role for treating spinal cord injury. DESIGN AND SETTING: Rats were randomly divided into three groups: sham operation group, control group, and human umbilical cord mesenchymal stem cell group. All groups were subjected to spinal cord injury by weight drop device except for sham group. SUBJECTS: Thirty-six female Sprague-Dawley rats. INTERVENTIONS: The control group received Dulbecco's modified essential media/nutrient mixture F-12 injections, whereas the human umbilical cord mesenchymal stem cell group undertook cells transplantation at the dorsal spinal cord 2 mm rostrally and 2 mm caudally to the injury site at 24 hrs after spinal cord injury. MEASUREMENTS: Rats from each group were examined for neurologic function and contents of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and neurotrophin-3. Survival, migration, and differentiation of human umbilical cord mesenchymal stem cells, regeneration of axons, and formation of glial scar were also explored by using immunohistochemistry and immunofluorescence. MAIN RESULTS: Recovery of hindlimb locomotor function was significantly enhanced in the human umbilical cord mesenchymal stem cells grafted animals at 5 wks after transplantation. This recovery was accompanied by increased length of neurofilament-positive fibers and increased numbers of growth cone-like structures around the lesion site. Transplanted human umbilical cord-mesenchymal stem cells survived, migrated over short distances, and produced large amounts of glial cell line-derived neurotrophic factor and neurotrophin-3 in the host spinal cord. There were fewer reactive astrocytes in both the rostral and caudal stumps of the spinal cord in the human umbilical cord-mesenchymal stem cell group than in the control group. CONCLUSIONS: Treatment with human umbilical cord mesenchymal stem cells can facilitate functional recovery after traumatic spinal cord injury and may prove to be a useful therapeutic strategy to repair the injured spinal cord.

Chiari Malformations Type I without Basilar Invagination in Adults: Morphometric and Volumetric Analysis.

BACKGROUND: Chiari malformation type I (CMI) cases are frequently associated with basilar invagination (BI), which complicates the understanding of the pathology of CMI. We specifically evaluated the morphometric and volumetric alterations in the bony structures of CMI patients without BI. METHODS: Fifty adult CMI patients without BI treated at our institution from January 2015 to December 2019 were retrospectively studied. The morphometric and volumetric characteristics of the posterior cranial fossa (PCF) were analyzed using thin-slice computed tomography images. RESULTS: Compared with the controls, the clivus length (P < 0.001), supraoccipital length (P < 0.001), Klaus height index (P < 0.001), axial length (P < 0.001), clivo-axial angle (P < 0.001), tentorial angle (P < 0.05), and bony PCF volume (P < 0.001) of the CMI-only group were significantly smaller, and the distance between the Chamberlain line and the dens axis (P < 0.001), clivus angle (P < 0.001), and basal angle (P < 0.001) of the CMI-only group were significantly larger, while the distance between the McRae line and the dens axis, McRae line, anteroposterior diameter of the PCF, occipital angle, occipital canal angle, and tentorial Twining line angle showed no significant difference between the 2 groups. CONCLUSIONS: Hypoplasia of the clivus and occipital bone were confirmed in CMI patients without BI, thus providing further evidence for the notion that CMI is secondary to the underdevelopment of the PCF.

Microbleeds after Stent-assisted Coil Embolization of Unruptured Intracranial Aneurysms: Incidence, Risk Factors and the Role of Thromboelastography.

OBJECTIVE: To analyze the incidence and risk factors of microbleeds lesions and to use thromboelastography (TEG) to evaluate the relationship between perioperative platelet function and microbleed events in patients with unruptured intracranial aneurysms (UIAs) undergoing Stent-Assisted Coil (SAC) embolization. METHODS: We retrospectively enrolled 261 patients with UIAs undergoing SAC embolization between November 2017 and October 2019. All patients received unanimous antiplatelet protocol (aspirin 300 mg and clopidogrel 300 mg). Platelet function was evaluated by TEG, and magnetic resonance susceptibility-weighted imaging (SWI) was performed for microbleeds detection before and after surgery. Univariate and multivariate logistic regression analyses were used to identify potential risk factors for microbleeds following embolization. RESULTS: Microbleed lesions were identified in 122 of 261 patients (46.7%). Most of the microbleeds were asymptomatic, except for 22 patients complaining slight headaches, and 3 patients who developed cerebral hemorrhage after discharge. Among the clinical characters, female, previous intracerebral hemorrhage (ICH) history and TEG parameters variation (higher reaction time (R) and lower maximum amplitude of adenosine diphosphate (MAADP)) were associated with microbleeds occurrence. Subsequent multivariate analysis indicated that gender, hemorrhage history, R, and MAADP were still independent risk factors of microbleeds. The R-value (>7.6 min) and MAADP (<29.2 mm) were predictive values, yielding areas under the receiver operating curve (ROC) of 0.76 (95% CI 0.70 to 0.82) and 0.89 (95% CI 0.86 to 0.93), respectively. CONCLUSION: The incidence of microbleeds may be high in UIA patients treated with SAC and dual antiplatelet therapy. Lesions occurred more frequently in female patients and patients with ICH history. Among the TEG parameters, the R-value and MAADP were predictors for microbleed events.

Sporadic Solid/Cystic Hemangioblastomas in the Cerebellum: Retrospective Study of More Than Ten Years of Experience in a Single Center.

BACKGROUND: Solid/cystic hemangioblastomas are rare, and they lack a systematic description. We clarify the epidemiology, clinical features, imaging characteristics, and surgical outcomes of sporadic solid/cystic hemangioblastomas in the cerebellum. METHODS: A total of 75 patients with sporadic hemangioblastomas from 2006 to 2018 were enrolled in this retrospective study and divided into solid (26/75), cystic (40/75), and solid/cystic (9/75) groups according to the imaging findings. All patients underwent microsurgical resection and had a definite 31 pathologic diagnosis. RESULTS: The age at diagnosis in the solid/cystic group was the highest among the 3 groups (P < 0.05). The solid/cystic group showed the shortest symptom duration (P < 0.05), which was related to obvious peritumoral brain edema (P < 0.05). The combination of computed tomography angiography and magnetic resonance imaging helped with the differential diagnosis. The solid/cystic group showed the lowest rate of gross total resection (P < 0.05) as a result of the obscure brain-tumor interface, and the guidance of intraoperative ultrasonography helped with the microsurgical procedures to a certain extent. Patients in the solid/cystic group showed greater intraoperative blood loss (P < 0.05), a lower ratio of symptom improvement (P < 0.05), and a longer mean hospital stay (P < 0.05) than did patients in the cystic group. CONCLUSIONS: Cerebellar sporadic solid/cystic hemangioblastomas are rare and usually affect elderly people. The combination of computed tomography angiography and magnetic resonance imaging may improve the preoperative diagnosis. Solid/cystic hemangioblastomas showed the lowest rate of gross total resection as a result of the obscure brain-tumor interface.

ASK1 phosphorylation regulates astrocytic reactive gliosis in vitro and in vivo.

Apoptosis signal-regulating kinase 1 (ASK1) may play a pivotal role in reactive gliosis. To assess the role of ASK1 in trauma-induced reactive gliosis, we examined the phosphorylation of ASK1 and the expression of glial fibrillary acidic protein (GFAP) and vimentin after scratch injury in cultured astrocytes and spinal cord injury (SCI) in rats. Enhanced phosphorylation of ASK1 was detected during reactive gliosis both in vitro and in vivo, and P38 MAPK relayed the signal from phosphorylated ASK1 to the activation of astrocytes. Immunoprecipitation analyses suggested that 14-3-3 was dissociated from ASK1 during astrocyte activation. Finally, treatment with thioredoxin reduced ASK1 phosphorylation and reactive gliosis and promoted hindlimb locomotion recovery in SCI rats. These results indicated that ASK1 may play an important role in mechanical-injury-induced reactive gliosis.

In vitro labeling of human umbilical cord mesenchymal stem cells with superparamagnetic iron oxide nanoparticles.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) transplantation has been shown to promote regeneration and neuroprotection in central nervous system (CNS) injuries and neurodegenerative diseases. To develop this approach into a clinical setting it is important to be able to follow the fates of transplanted cells by noninvasive imaging. Neural precursor cells and hematopoietic stem cells can be efficiently labeled by superparamagnetic iron oxide (SPIO) nanoparticle. The purpose of our study was to prospectively evaluate the influence of SPIO on hUC-MSCs and the feasibility of tracking for hUC-MSCs by noninvasive imaging. In vitro studies demonstrated that magnetic resonance imaging (MRI) can efficiently detect low numbers of SPIO-labeled hUC-MSCs and that the intensity of the signal was proportional to the number of labeled cells. After transplantation into focal areas in adult rat spinal cord transplanted SPIO-labeled hUC-MSCs produced a hypointense signal using T2-weighted MRI in rats that persisted for up to 2 weeks. This study demonstrated the feasibility of noninvasive imaging of transplanted hUC-MSCs.

Bovine serum albumin promotes IL-1beta and TNF-alpha secretion by N9 microglial cells.

Bovine serum albumin (BSA) is generally used in biomedical experiments. In the solution of some reagents, BSA is necessary to maintain the stability and concentration of the effective component. Therefore, the potential impact of BSA on experimental results should not be neglected when BSA is used. In this study, we observed that BSA induced significant upregulation of mRNA expression and release of pro-inflammatory cytokines, IL-1beta, and TNF-alpha, by N9 microglial cells. Our results suggest that the effects of BSA should be taken into account in experiments on microglia or the central nervous system when BSA is used. In light of the high similarity and homology among mammalian albumins, our findings also indicate that serum albumin may be a potent trigger of cytokine release by microglia.

Protease-activated receptor-2 regulates glial scar formation via JNK signaling.

The study aimed to determine the effects of protease-activated receptor-2 (PAR-2) on glial scar formation after spinal cord injury (SCI) in Sprague-Dawley (SD) rats and the underlying mechanisms. Rivlin and Tator's acute extradural clip compression injury (CCI) model of severe SCI was established in this study. Animals were divided into four groups: 1) sham group (laminectomy only); 2) model group, treated with normal saline; 3) PAR-2 inhibitor group; 4) PAR-2 activator group. Enhanced GFAP and vimentin expression were the markers of glial scar formation. To determine whether JNK was involved in the effects of PAR-2 on GFAP and vimentin expression, we administered anisomycin (a JNK activator) in the presence of PAR-2 inhibitor and SP600125 (a JNK inhibitor) in the presence of PAR-2 activator. At 1, 7, 14 and 28 day after SCI, Basso, Beattie, and Bresnahan (BBB) locomotor score test was used to assess the locomotor functional recovery; immunofluorescence and western blot analysis were used to assess the expression level of GFAP, vimentin and p-JNK. Double immunofluorescence staining with GFAP and tubulin beta was used to assess the glial scar formation and the remaining neurons. Results suggested that PAR-2 is involved in glial scar formation and reduces neurons residues which can cause a further worsening in the functional outcomes after SCI via JNK signaling. Therefore, it may be effective to target PAR-2 in the treatment of SCI.