Hippocampal Lnx1-NMDAR multiprotein complex mediates initial social memory.

Social interaction and communication are evolutionary conserved behaviours that are developed in mammals to establish partner cognition. Deficit in sociability has been represented in human patients and animal models of neurodevelopmental disorders, which are connected with genetic variants of synaptic glutamate receptors and associated PDZ-binding proteins. However, it remains elusive how these key proteins are specialized in the cellular level for the initial social behaviour during postnatal developmental stage. Here we identify a hippocampal CA3 specifically expressed PDZ scaffold protein Lnx1 required for initial social behaviour. Through gene targeting we find that Lnx1 deficiency led to a hippocampal subregional disorder in neuronal activity and social memory impairments for partner discrimination observed in juvenile mice which also show cognitive defects in adult stage. We further demonstrate that Lnx1 deletion causes NMDA receptor (NMDAR) hypofunction and this is attributable to decreased GluN2B expression in PSD compartment and disruption of the Lnx1-NMDAR-EphB2 complex. Specific restoration of Lnx1 or EphB2 protein in the CA3 area of Lnx1-/- mice rescues the defective synaptic function and social memory. These findings thus reveal crucial roles of postsynaptic NMDAR multiprotein complex that regulates the formation of initial social memory during the adolescent period.

Prognostic Value of Different Computed Tomography Scoring Systems in Patients With Severe Traumatic Brain Injury Undergoing Decompressive Craniectomy.

OBJECTIVE: In this study, we investigate the preoperative and postoperative computed tomography (CT) scores in severe traumatic brain injury (TBI) patients undergoing decompressive craniectomy (DC) and compare their predictive accuracy. METHODS: Univariate and multivariate logistic regression analyses were used to determine the relationship between CT score (preoperative and postoperative) and mortality at 30 days after injury. The discriminatory power of preoperative and postoperative CT score was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: Multivariate logistic regression analysis adjusted for the established predictors of TBI outcomes showed that preoperative Rotterdam CT score (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.13-11.50; P = 0.030), postoperative Rotterdam CT score (OR, 4.17; 95% CI, 1.63-10.66; P = 0.003), preoperative Stockholm CT score (OR, 3.41; 95% CI, 1.42-8.18; P = 0.006), postoperative Stockholm CT score (OR, 4.50; 95% CI, 1.60-12.64; P = 0.004), preoperative Helsinki CT score (OR, 1.44; 95% CI, 1.03-2.02; P = 0.031), and postoperative Helsinki CT score (OR, 2.55; 95% CI, 1.32-4.95; P = 0.005) were significantly associated with mortality. The performance of the postoperative Rotterdam CT score was superior to the preoperative Rotterdam CT score (AUC, 0.82-0.97 vs 0.71-0.91). The postoperative Stockholm CT score was superior to the preoperative Stockholm CT score (AUC, 0.76-0.94 vs 0.72-0.92). The postoperative Helsinki CT score was superior to the preoperative Helsinki CT score (AUC, 0.88-0.99 vs 0.65-0.87). CONCLUSIONS: In conclusion, assessing the CT score before and after DC may be more precise and efficient for predicting early mortality in severe TBI patients who undergo DC.

Effect of α7nAChR on learning and memory dysfunction in a rat model of diffuse axonal injury.

Diffuse axonal injury (DAI) is the predominant effect of severe traumatic brain injury and significantly contributes to cognitive deficits. The mechanisms that underlie these cognitive deficits are often associated with complex molecular alterations. α7nAChR, one of the abundant and widespread nicotinic acetylcholine receptors (nAChRs) in the brain, plays important physiological functions in the central nervous system. However, the relationship between temporospatial alterations in the α7nAChR and DAI-related learning and memory dysfunction are not completely understood. Our study detected temporospatial alterations of α7nAChR in vulnerable areas (hippocampus, internal capsule, corpus callosum and brain stem) of DAI rats and evaluated the development and progression of learning and memory dysfunction via the Morris water maze (MWM). We determined that α7nAChR expression in vulnerable areas was mainly reduced at the recovery of DAI in rats. Moreover, the escape latency of the injured group increased significantly and the percentages of the distance travelled and time spent in the target quadrant were significantly decreased after DAI. Furthermore, α7nAChR expression in the vulnerable area was significantly positively correlated with MWM performance after DAI according to regression analysis. In addition, we determined that a selective α7nAChR agonist significantly improved learning and memory dysfunction. Rats in the α7nAChR agonist group showed better learning and memory performance than those in the antagonist group. These results demonstrate that microstructural injury-induced alterations of α7nAChR in the vulnerable area are significantly correlated with learning and memory dysfunctions after DAI and that augmentation of the α7nAChR level by its agonist contributes to the improvement of learning and memory function.

Inhibition of miRNA-21 promotes retinal ganglion cell survival and visual function by modulating Müller cell gliosis after optic nerve crush.

BACKGROUND: Müller cell gliosis not only plays an important physiological role by maintaining retinal neuronal homeostasis but is also associated with multiple pathological events in the retina, including optic nerve crush (ONC) injury. Modulating Müller cell gliosis contributes to the creation of a permissive environment for neuronal survival. However, the underlying mechanism of Müller cell gliosis has remained elusive. OBJECTIVE: To investigate the underlying mechanism of Müller cell gliosis after ONC. METHODS: Rats with ONC injury were transfected with miRNA-21 (miR-21) agomir (overexpressing miR-21) or antagomir (inhibiting miR-21) via intravitreous injection. Immunofluorescence and western blotting were performed to confirm the effects of miR-21 on Müller cell gliosis. The retinal nerve fiber layer (RNFL) thickness was measured using optical coherence tomography and the positive scotopic threshold response (pSTR) was recorded using electroretinogram. RESULTS: In the acute phase (14 days) after ONC, compared with the crushed group, inhibiting miR-21 promoted Müller cell gliosis, exhibiting thicker processes and increased GFAP expression. In the chronic phase (35 days), inhibiting miR-21 ameliorated Müller cell gliosis, which exhibited thicker and denser processes and increased GFAP expression. Retinal ganglion cell (RGC) counts in retinas showed that the number of surviving RGCs increased significantly in the antagomir group. The thickness of the RNFL increased significantly, and pSTR showed significant preservation of the amplitudes in the antagomir group. CONCLUSIONS: Inhibition of miR-21 promotes RGC survival, RNFL thickness and the recovery of RGC function by modulating Müller cell gliosis after ONC.

Take it seriously or not: postoperative pneumocephalus in CSDH patients?

Background: Pneumocephalus is a common finding after burr-hole drainage of chronic subdural hematoma (CSDH). Its effects have not been specifically studied.Methods: A retrospective analysis was performed in 140 patients with CSDH with single burr-hole drainage. The pre- and postoperative volumes of intracranial hematoma and the postoperative volume of pneumocephalus were calculated and analyzed with their relationships with Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS) scores.Results: The preoperative hematoma volume and the patient ages are positively correlated with the 1-day postoperative pneumocephalus volume (p < 0.001, p < 0.01). There is no correlation between postoperative pneumocephalus volume and GCS/GOS scores (p > 0.05) and there is no difference of GCS/GOS scores or CSDH recurrence rate between patients with and without pneumocephalus (p > 0.05). The age and the volume of 1-day postoperative pneumocephalus are positively correlated with the absorbing rate of pneumocephalus (p < 0.01, p < 0.001).Conclusions: The pneumocephalus at a certain range has no effect on the prognosis of patients with CSDH and requires no specific intervention due to its self-absorbing capacity in the normal progress after surgery.HighlightsNo correlation between postoperative pneumocephalus volume and GCS/GOS scores.No difference of GCS/GOS or recurrence between patients with pneumocephalus or not.Pneumocephalus at certain range has no effect on the prognosis of patients.

Neuronal GAP-Porf-2 transduces EphB1 signaling to brake axon growth.

Axonal outgrowth and guidance require numerous extracellular cues and intracellular mediators that transduce signals in the growth cone to regulate cytoskeletal dynamics. However, the way in which cytoskeletal effectors respond to these signals remains elusive. Here, we demonstrate that Porf-2, a neuron-expressed RhoGTPase-activating protein, plays an essential role in the inhibition of initial axon growth by restricting the expansion of the growth cone in a cell-autonomous manner. Furthermore, the EphB1 receptor is identified as an upstream controller that binds and regulates Porf-2 specifically upon extracellular ephrin-B stimulation. The activated EphB forward signal deactivates Rac1 through the GAP domain of Porf-2, which inhibits growth cone formation and brakes axon growth. Our results therefore provide a novel GAP that regulates axon growth and braking sequentially through Eph receptor-independent and Eph receptor-dependent pathways.

Transforming growth factor beta induced (TGFBI) is a potential signature gene for mesenchymal subtype high-grade glioma.

Previous study revealed that higher expression of transforming growth factor beta induced (TGFBI) is correlated to poorer cancer-specific survival and higher proportion of tumor necrosis and Fuhrman grades III and IV in clear cell renal cell carcinomas. However, the relationships between TGFBI expression and malignant phenotypes of gliomas remain unclear. We downloaded and analyzed data from seven GEO datasets (GSE68848, GSE4290, GSE13041, GSE4271, GSE83300, GSE34824 and GSE84010), the TCGA database and the REMBRANDT database to investigate whether TGFBI could be a biomarker of glioma. From microarray data (GSE68848, GSE4290) and RNA-seq data (TCGA), TGFBI expression levels were observed to correlate positively with pathological grade, and TGFBI expression levels were significantly higher in gliomas than in normal brain tissues. Furthermore, in GSE13041, GSE4271 and the TCGA cohort, TGFBI expression in the mesenchymal (Mes) subtype high-grade glioma (HGG) was significantly higher than that in the proneural subtype. Kaplan-Meier survival analysis of GBM patients in the GSE83300 dataset, REMBRANDT and TCGA cohort revealed that patients in the top 50% TGFBI expression group survived for markedly shorter periods than those in the bottom 50%. Analysis of grade III gliomas showed that the median survival time was significantly shorter in the TGFBI high expression group than in the TGFBI low expression group. In addition, we found that TGFBI expression levels might relate to several classical molecular characterizations of glioma, such as, IDH mutation, TP53 mutation, EGFR amplification, etc. These results suggest that TGFBI expression positively correlates with glioma pathological grades and that TGFBI is a potential signature gene for Mes subtype HGG and a potential prognostic molecule.

Rho GTPase-activating proteins: Regulators of Rho GTPase activity in neuronal development and CNS diseases.

The Rho family of small GTPases was considered as molecular switches in regulating multiple cellular events, including cytoskeleton reorganization. The Rho GTPase-activating proteins (RhoGAPs) are one of the major families of Rho GTPase regulators. RhoGAPs were initially considered negative mediators of Rho signaling pathways via their GAP domain. Recent studies have demonstrated that RhoGAPs also regulate numerous aspects of neuronal development and are related to various neurodegenerative diseases in GAP-dependent and GAP-independent manners. Moreover, RhoGAPs are regulated through various mechanisms, such as phosphorylation. To date, approximately 70 RhoGAPs have been identified; however, only a small portion has been thoroughly investigated. Thus, the characterization of important RhoGAPs in the central nervous system is crucial to understand their spatiotemporal role during different stages of neuronal development. In this review, we summarize the current knowledge of RhoGAPs in the brain with an emphasis on their molecular function, regulation mechanism and disease implications in the central nervous system.

Ommaya reservoir implantation for the treatment of contralateral progressive traumatic subdural effusion secondary to decompressive craniectomy: a case report.

This report describes a new method for the treatment of traumatic subdural effusion (TSE). Following Ommaya reservoir implantation, a patient with contralateral progressive TSE secondary to decompressive craniectomy after traumatic brain injury made a good postoperative recovery.

Insight into astrocyte activation after optic nerve injury.

In response to optic nerve damage, astrocytes become reactive. This reactivity can be identified by the presence of morphological and molecular changes throughout the retina and optic nerve as well as the formation of a glial scar. The process of astrocyte activation exhibits spatial and temporal characteristics, and it is finely regulated by complex signaling mechanisms. Excessive astrocyte activation plays a crucial role in progressive optic nerve injury. This review focuses on the spatial and temporal characteristics and mechanisms of astrocyte activation and discusses the modulation of astrocyte activation. Further insight into astrocyte activation might provide targets for future therapeutic interventions.

Overexpression of Wnt3a facilitates the proliferation and neural differentiation of neural stem cells in vitro and after transplantation into an injured rat retina.

Neural stem cell-based therapy is a promising option for repair after injury. However, poor stem cell proliferation and insufficient differentiation of the stem cells into neurons are still difficult problems. The present study investigated whether transplantation of neural stem cells (NSCs) genetically modified to express Wnt3a is a promising approach to overcome these difficulties. We explored the possibility that Wnt3a might contribute to the therapeutic effect of NSC transplantation in retinal repair. The relative promotion of proliferation and neural differentiation by modified NSCs was investigated in a rat model of optic nerve crush. A recombinant lentivirus (Lenti-Wnt3a) was engineered to express Wnt3a. NSCs infected with control lentivirus (Lenti-GFP) or Lenti-Wnt3a were transplanted into the subretinal space immediately after the optic nerve crush. The proliferation and neural differentiation activity of the NSCs were assessed in vitro and in vivo. Overexpression of Wnt3a in NSCs induced activation of Wnt signaling, promoted proliferation, and directed the differentiation of the NSCs into neurons both in vitro and in vivo. Our study suggests that Wnt3a can potentiate the therapeutic benefits of NSC-based therapy in the injured retina.

Biomarkers of cognitive dysfunction in traumatic brain injury.

Acetylcholine, glutamate, dopamine, serotonin (5-HT), gamma-aminobutyric acid, substance P (SP), amyloid-ß (Aß) and neurotrophic protein S100B are arguably the most important cognition-related biomarkers in the brain. Among this list are five neurotransmitters that signal through postsynaptic receptors. Our knowledge of cognition-related biomarkers has been advanced through translational experiments and clinical case-study data. Although these biomarkers are widespread in the brain and pronounced individual variations exist, these biomarkers can be used to identify both acute and chronic abnormalities following traumatic brain injury. Changes in these biomarkers likely indicate damage to brain networks or to key brain cell types that support cognitive functions. Identification of such biomarker abnormalities could result in earlier diagnoses, improved prognoses and therapies that enable neurotransmitters to return to normal levels.

Inhibition of human glioma U251 cells growth in vitro and in vivo by hydroxyapatite nanoparticle-assisted delivery of short hairpin RNAs against SATB1.

Special AT-rich sequence-binding protein-1 (SATB1) has been reported to be over-expressed in many human tumors and knockdown of SATB1 can inhibit tumor growth. The present study was designed to determine the role of SATB1 in the growth of human glioma U251 cells using the plasmid-based SATB1 short hairpin RNA (shRNA) delivered by hydroxyapatite nanoparticles in vitro and in vivo. The in vitro growth, invasion and angiogenesis assays of human glioma U251 cells were done. U251 cells tumor blocks were transplanted into the nude mice. CaCl2-modified hydroxyapatite nanoparticles carrying shRNA-SATB1 plasmids were injected into the tumors. The apoptosis of the tumor U251 cells was examined with TUNEL assay and flow cytometer (FCM). The tumor growth and immunohistochemistry were measured. The expression level of SATB1 mRNA was investigated by RT-PCR. The expression levels of SATB1, Cyclin D1, MMP-2, VEGF, Bax and Caspase-9 protein were determined by western blot analysis. The results showed that hydroxyapatite nanoparticles-delivered shRNA-SATB1 could significantly inhibit the growth, invasion and angiogenesis of U251 cells in vitro and the growth of U251 cells in vivo. FCM results showed that Nano HAP-shRNA-SATB1-induced apoptosis (up to 67.8 %). SATB1 expression was strongly down-regulated in the tumor U251 cells. Cyclin D1, MMP-2 and VEGF were also down-regulated in the tumor tissues that also displayed significant increased in Bax expression and Caspase-9 activity. These results show that Nano HAP-shRNA-SATB1 can inhibit the growth of human glioma U251 cells in vitro and in vivo, and hydroxyapatite nanoparticles can be used for the in vitro and in vivo delivery of plasmid-based shRNAs into U251 cells.

Predictive value of the SLC22A18 protein expression in glioblastoma patients receiving temozolomide therapy.

BACKGROUND: Our previous study showed that SLC22A18 downregulation and promoter methylation were associated with the development and progression of glioma and the elevated expression of SLC22A18 was found to increase the sensitivity of glioma U251 cells to the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). In this study, we investigated the predictive value of SLC22A18 promoter methylation and protein expression in glioblastoma multiforme (GBM) patients receiving temozolomide (TMZ) therapy. PATIENTS AND METHODS: SLC22A18 promoter methylation and protein expression were examined by methylation-specific polymerase chain reaction (MSP) and Western blotting respectively, then we compared SLC22A18 promoter methylation and protein expression in tumor cell explants in regard to prediction of TMZ response and survival time of 86 GBM patients. RESULTS: SLC22A18 promoter methylation was detected in 61 of 86 (71%) samples, whereas 36 of 86 (42%) cases were scored positive for SLC22A18 protein expression. Overall SLC22A18 promoter methylation was significantly related to SLC22A18 protein expression, but a subgroup of cases did not follow this association. Multivariate Cox regression analysis indicated that SLC22A18 protein expression, but not promoter methylation, was significantly correlated with TMZ therapy. SLC22A18 protein expression predicted a significantly shorter overall survival in 51 patients receiving TMZ therapy, whereas no differences in overall survival were observed in 35 patients without TMZ therapy. CONCLUSIONS: These results show that lack of SLC22A18 protein expression is superior to promoter methylation as a predictive tumor biomarker in GBM patients receiving temozolomide therapy.

Glial cells activation potentially contributes to the upregulation of stromal cell-derived factor-1α after optic nerve crush in rats.

Stromal cell-derived factor-1α (SDF-1α) plays an important role after injury. However, little is known regarding its temporal and spatial expression patterns or how it interacts with glial cells after optic nerve crush injury. We characterized the temporal and spatial expression pattern of SDF-1α in the retina and optic nerve following optic nerve crush and demonstrated that SDF-1α is localized to the glial cells that are distributed in the retina and optic nerve. CXCR4, the receptor for SDF-1α, is expressed along the ganglion cell layer (GCL). The relative expression levels of Sdf-1α mRNA and SDF-1α protein in the retina and optic nerve 1, 2, 3, 5, 7, 10 and 14 days after injury were determined using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay, respectively, and the Cxcr4 mRNA expression was determined using real-time PCR. Immunofluorescence and immunohistochemical approaches were used to detect the localization of SDF-1α and CXCR4 after injury. The upregulation of Sdf-1α and Cxcr4 mRNA was detected as early as day one after injury in the retina and day two in the optic nerve, the expression peaks 5-7 days after injury. The expression of Sdf-1α and Cxcr4 mRNA was maintained for at least 14 days after the optic nerve crush injury. Furthermore, SDF-1α-positive zones were distributed locally in the reactive glial cells, which suggested potential autocrine stimulation. CXCR4 was mainly expressed in the GCL, which was also adjacent to the the glial cells. These findings suggest that following optic nerve crush, the levels of endogenous SDF-1α and CXCR4 increase in the retina and optic nerve, where activated glial cells may act as a source of increased SDF-1α protein.

Default mode network overshadow executive control network in coma emergence and awakening prediction of patients with sTBI.

OBJECTIVE: We aimed to explore the pathogenesis of traumatic coma related to functional connectivity (FC) within the default mode network (DMN), within the executive control network (ECN) and between the DMN and ECN and to investigate its capacity for predicting awakening. METHODS: We carried out resting-state functional magnetic resonance imaging (fMRI) examinations on 28 traumatic coma patients and 28 age-matched healthy controls. DMN and ECN nodes were split into regions of interest (ROIs), and node-to-node FC analysis was conducted on individual participants. To identify coma pathogenesis, we compared the pairwise FC differences between coma patients and healthy controls. Meanwhile, we divided the traumatic coma patients into different subgroups based on their clinical outcome scores at 6 months postinjury. Considering the awakening prediction, we calculated the area under the curve (AUC) to evaluate the predictive ability of changed FC pairs. RESULTS: We found a massive pairwise FC alteration in the patients with traumatic coma compared to the healthy controls [45% (33/74) pairwise FC located in the DMN, 27% (20/74) pairwise FC located in the ECN, and 28% (21/74) pairwise FC located between the DMN and ECN]. Moreover, in the awake and coma groups, there were 67% (12/18) pairwise FC alterations located in the DMN and 33% (6/18) pairwise FC alterations located between the DMN and ECN. We also indicated that pairwise FC that showed a predictive value of 6-month awakening was mainly located in the DMN rather than in the ECN. Specifically, decreased FC between the right superior frontal gyrus and right parahippocampal gyrus (in the DMN) showed the highest predictive ability (AUC = 0.827). CONCLUSION: In the acute phase of severe traumatic brain injury (sTBI), the DMN plays a more prominent role than the ECN and the DMN-ECN interaction in the emergence of traumatic coma and the prediction of 6-month awakening.

Intravitreal injection of Huperzine A promotes retinal ganglion cells survival and axonal regeneration after optic nerve crush.

Traumatic optic neuropathy (TON) is a condition that causes massive loss of retinal ganglion cells (RGCs) and their axonal fibers, leading to visual insufficiency. Several intrinsic and external factors can limit the regenerative ability of RGC after TON, subsequently resulting in RGC death. Hence, it is important to investigate a potential drug that can protect RGC after TON and enhance its regenerative capacity. Herein, we investigated whether Huperzine A (HupA), extracted from a Chinese herb, has neuroprotective effects and may enhance neuronal regeneration following the optic nerve crush (ONC) model. We compared the three modes of drug delivery and found that intravitreal injection of HupA could promote RGC survival and axonal regeneration after ONC. Mechanistically, HupA exerted its neuroprotective and axonal regenerative effects through the mTOR pathway; these effects could be blocked by rapamycin. To sum up, our findings suggest a promising application of HupA in the clinical treatment of traumatic optic nerve.

Knockdown of Porf-2 restores visual function after optic nerve crush injury.

Retinal ganglion cells (RGCs), the sole output neurons in the eyes, are vulnerable to diverse insults in many pathological conditions, which can lead to permanent vision dysfunction. However, the molecular and cellular mechanisms that contribute to protecting RGCs and their axons from injuries are not completely known. Here, we identify that Porf-2, a member of the Rho GTPase activating protein gene group, is upregulated in RGCs after optic nerve crush. Knockdown of Porf-2 protects RGCs from apoptosis and promotes long-distance optic nerve regeneration after crush injury in both young and aged mice in vivo. In vitro, we find that inhibition of Porf-2 induces axon growth and growth cone formation in retinal explants. Inhibition of Porf-2 provides long-term and post-injury protection to RGCs and eventually promotes the recovery of visual function after crush injury in mice. These findings reveal a neuroprotective impact of the inhibition of Porf-2 on RGC survival and axon regeneration after optic nerve injury, providing a potential therapeutic strategy for vision restoration in patients with traumatic optic neuropathy.

Upregulation of SATB1 is associated with the development and progression of glioma.

BACKGROUND: Special AT-rich sequence-binding protein-1 (SATB1) has been reported to be expressed in several human cancers and may have malignant potential. This study was aimed at investigating the expression and potential role of SATB1 in human glioma. METHOD: The relationship between SATB1 expression, clinicopathological parameters, Ki67 expression and MGMT promoter methylation status was evaluated, and the prognostic value of SATB1 expression in patients with gliomas was analyzed. SATB1-specific shRNA sequences were synthesized, and U251 cells were transfected with SATB1 RNAi plasmids. Expression of SATB1 mRNA and protein was investigated by RT-PCR and immunofluoresence staining and western blotting. The expression of c-Met, SLC22A18, caspase-3 and bcl-2 protein was determined by western blotting. U251 cell growth and adherence was detected by methyl thiazole tetrazolium assay. The apoptosis of U251 cells was examined with a flow cytometer. The adherence, invasion, and in vitro angiogenesis assays of U251 cells were done. The growth and angiogenesis of SATB1 low expressing U251 cells was measured in an in vivo xenograft model. RESULTS: Of 70 tumors, 44 (62.9%) were positive for SATB1 expression. SATB1 expression was significantly associated with a high histological grade and with poor survival in univariate and multivariate analyses. SATB1 expression was also positively correlated with Ki67 expression but negatively with MGMT promoter methylation in glioma tissues. SATB1 shRNA expression vectors could efficiently induce the expression of SLC22A18 protein, increase the caspase-3 protein, inhibit the expression of SATB1, c-Met and bcl-2 protein, the growth, invasion, metastasis and angiogenesis of U251 cells, and induce apoptosis in vitro. Furthermore, the tumor growth of U251 cells expressing SATB1 shRNA were inhibited in vivo, and immunohistochemical analyses of tumor sections revealed a decreased vessel density in the animals where shRNA against SATB1 were expressed. CONCLUSIONS: SATB1 may have an important role as a positive regulator of glioma development and progression, and that SATB1 might be a useful molecular marker for predicting the prognosis of glioma.

Maf1 regulates axonal regeneration of retinal ganglion cells after injury.

Retinal ganglion cells (RGCs) are the sole output neurons that carry visual information from the eye to the brain. Due to various retinal and optic nerve diseases, RGC somas and axons are vulnerable to damage and lose their regenerative capacity. A basic question is whether the manipulation of a key regulator of RGC survival can protect RGCs from retinal and optic nerve diseases. Here, we found that Maf1, a general transcriptional regulator, was upregulated in RGCs from embryonic stage to adulthood. We determined that the knockdown of Maf1 promoted the survival of RGCs and their axon regeneration through altering the activity of the PTEN/mTOR pathway, which could be blocked by rapamycin. We further observed that the inhibition of Maf1 prevented the retinal ganglion cell complex from thinning after optic nerve crush. These findings reveal a neuroprotective effect of knocking down Maf1 on RGC survival after injury and provide a potential therapeutic strategy for traumatic optic neuropathy.