Effects of light perception on visual function recovery in patients with traumatic optic neuropathy.

This study aimed to assess the impact of light perception presence or absence on visual function recovery in patients with traumatic optic neuropathy (TON). A retrospective analysis was conducted on the clinical data of 206 TON patients. Based on the presence or absence of light perception after injury, patients were categorized into a light perception group and a non-light perception group. A comparison was made between the two groups regarding visual acuity recovery before and after treatment. The non-light perception group comprised 63 patients, with a treatment effectiveness rate of 39.68%. The light perception group consisted of 143 patients, with a treatment effectiveness rate of 74.83%. The difference between the two groups was statistically significant (χ2 = 23.464, P < 0.01). Subgroup analysis indicated that surgical treatment appeared to be more effective than steroid hormone therapy for patients with light perception. Conversely, for patients without light perception, there was no significant difference in the effectiveness of the two methods. The total effectiveness rate of the light perception group was significantly higher than that of the non-light perception group, suggesting that patients with light perception before treatment experience better outcomes compared to those without light perception. Treatment choices should be individualized to ensure optimal results.

Acute traumatic coma awakening by right median nerve electrical stimulation: a randomised controlled trial.

PURPOSE: Severe traumatic brain injury (TBI) leads to acute coma and may result in prolonged disorder of consciousness (pDOC). We aimed to determine whether right median nerve electrical stimulation is a safe and effective treatment for accelerating emergence from coma after TBI. METHODS: This randomised controlled trial was performed in 22 centres in China. Participants with acute coma at 7-14 days after TBI were randomly assigned (1:1) to either routine therapy and right median nerve electrical stimulation (RMNS group) or routine treatment (control group). The RMNS group received 20 mA, 300 µs, 40 Hz stimulation pulses, lasting 20 s per minutes, 8 h per day, for 2 weeks. The primary outcome was the proportion of patients who regained consciousness 6 months post-injury. The secondary endpoints were Glasgow Coma Scale (GCS), Full Outline of Unresponsiveness scale (FOUR), Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale (DRS) and Glasgow Outcome Scale Extended (GOSE) scores reported as medians on day 28, 3 months and 6 months after injury, and GCS and FOUR scores on day 1 and day 7 during stimulation. Primary analyses were based on the intention-to-treat set. RESULTS: Between March 26, 2016, and October 18, 2020, 329 participants were recruited, of whom 167 were randomised to the RMNS group and 162 to the control group. At 6 months post-injury, a higher proportion of patients in the RMNS group regained consciousness compared with the control group (72.5%, n = 121, 95% confidence interval (CI) 65.2-78.7% vs. 56.8%, n = 92, 95% CI 49.1-64.2%, p = 0.004). GOSE at 3 months and 6 months (5 [interquartile range (IQR) 3-7] vs. 4 [IQR 2-6], p = 0.002; 6 [IQR 3-7] vs. 4 [IQR 2-7], p = 0.0005) and FOUR at 28 days (15 [IQR 13-16] vs. 13 [interquartile range (IQR) 11-16], p = 0.002) were significantly increased in the RMNS group compared with the control group. Trajectory analysis showed that significantly more patients in the RMNS group had faster GCS, CRS-R and DRS improvement (p = 0.01, 0.004 and 0.04, respectively). Adverse events were similar in both groups. No serious adverse events were associated with the stimulation device. CONCLUSION: Right median nerve electrical stimulation is a possible effective treatment for patients with acute traumatic coma, that will require validation in a confirmatory trial.

Cortical and Subcortical Alterations and Clinical Correlates after Traumatic Brain Injury.

Background: Traumatic brain injury (TBI) often results in persistent cognitive impairment and psychiatric symptoms, while lesion location and severity are not consistent with its clinical complaints. Previous studies found cognitive deficits and psychiatric disorders following TBI are considered to be associated with prefrontal and medial temporal lobe lesions, however, the location and extent of contusions often cannot fully explain the patient's impairments. Thus, we try to find the structural changes of gray matter (GM) and white matter (WM), clarify their correlation with psychiatric symptoms and memory following TBI, and determine the brain regions that primary correlate with clinical measurements. Methods: Overall, 32 TBI individuals and 23 healthy controls were recruited in the study. Cognitive impairment and psychiatric symptoms were examined by Mini-Mental State Examination (MMSE), Hospital Anxiety and Depression Scale (HADS), and Wechsler Memory Scale-Chinese Revision (WMS-CR). All MRI data were scanned using a Siemens Prisma 3.0 Tesla MRI system. T1 MRI data and diffusion tensor imaging (DTI) data were processed to analyze GM volume and WM microstructure separately. Results: In the present study, TBI patients underwent widespread decrease of GM volume in both cortical and subcortical regions. Among these regions, four brain areas including the left inferior temporal gyrus and medial temporal lobe, supplementary motor area, thalamus, and anterior cingulate cortex (ACC) were highly implicated in the post-traumatic cognitive impairment and psychiatric complaints. TBI patients also underwent changes of WM microstructure, involving decreased fractional anisotropy (FA) value in widespread WM tracts and increased mean diffusivity (MD) value in the forceps minor. The changes of WM microstructure were significantly correlated with the decrease of GM volume. Conclusions: TBI causes widespread cortical and subcortical alterations including a reduction in GM volume and change in WM microstructure related to clinical manifestation. Lesions in temporal lobe may lead to more serious cognitive and emotional dysfunction, which should attract our high clinical attention.

[The Mechanism Study on Histone Acetylation Activating Glioblastoma-derived Neurotrophic Factor Transcription].

OBJECTIVE: To study the regulation role and mechanism of protein acetylation on the expression of glioblastoma-derived neurotrophic factor (GDNF) in human glioma. METHODS: Six normal brain tissue samples, six low-grade glioma brain tissue (LG-glioma), and six high-grade glioma brain tissue (HG-glioma) were collected for study. Human glioma U251 cells were treated with histone acetylase inhibitor and histone deacetylase inhibition. The mRNA level of GDNF in glioma and normal controls was detected by Real-time PCR. H3K9 acetylation level of cAMP-response element binding protein (CREB) binding region on GDNF promoter and the ability of CREB combining to GDNF promoter were detected by ChIP-PCR. The effects of histone acetylase and deacetylase inhibitors on transcription factor binding ability and GDNF expression were detected. RESULTS: The mRNA level of GDNF in HG-glioma was significantly higher than those in normal brain tissue and LG-glioma (P < 0.01). The H3K9 acetylation level of GDNF promoter region in the glioma was increased compared to that in the normal brain tissue (P < 0.01), and the acetylation level in CREB-binding region on the GDNF promoter was higher than that in the non-CREB-binding region (P < 0.01). The binding activity of CREB and GDNF promoter in HG-glioma was higher than those in normal brain tissue and LG-glioma (P < 0.05). After treatment of U251 cells with histone acetyltransferase inhibition, the level of acetylation in CREB-binding region on GDNF promoter, the binding activity of CREB and GDNF promoter was decreased, and GDNF transcription and expression were down-regulated, while histone deacetylase inhibitors had the opposite effect (P < 0.01). CONCLUSION: Histone acetylation promotes the transcription expression of GDNF in glioma by promoting the binding of transcription factor CREB to the promoter region of GDNF gene.

Long non­coding RNA DLEU1 promotes cell proliferation of glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most common malignant tumor with high morbidity and mortality. This study investigated the role of long non­coding RNAs (lncRNAs) in glioblastomagenesis progression. Using the GSE2223 and GSE59612 datasets, and RNA sequencing data of GBM from The Cancer Genome Atlas, differentially expressed (DE) genes including DE messenger RNAs (DEmRNAs) and DElncRNAs between GBM and normal controls were identified. Based on the competing endogenous RNA hypothesis, DElncRNA­micro RNA (miRNA)­DEmRNA interactions were obtained by target gene prediction. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes pathway analysis of DEmRNAs in the DElncRNA­miRNA­DEmRNA network was performed. Expression and function analyses of DElncRNAs were performed by reverse transcription­polymerase chain reaction (RT­PCR) and an established viability assay, respectively. In total, 712 DE genes were identified. Significant upregulation of lncRNA deleted in lymphocytic leukemia 1 (DLEU1) was revealed in GBM and a number of other types of cancer. DLEU1 interacted with 315 miRNAs and 105 DEmRNAs. The DEmRNAs were mainly enriched in tumorigenesis­associated GO terms (angiogenesis, positive regulation of cell proliferation, positive regulation of fibroblast apoptotic processes and regulation of neutrophil migration) and pathways (Hippo signaling pathway, cancer pathways, and Wnt signaling pathway). Correlation analysis revealed that mRNA TNF receptor associated factor 4 (TRAF4) was associated with DLEU1 expression. RT­PCR demonstrated that the expression levels of DLEU1 and TRAF4 were increased in GBM tissues. Small interfering RNA demonstrated that silencing DLEU1 downregulated TRAF4. The viability of GBM cells was significantly decreased following RNA interference with DLEU1 and TRAF4 production. The results demonstrate that DLEU1 and TRAF4 is highly expressed in GBM tissues and promotes proliferation of GBM cells. It may act as a competing endogenous RNA and influence tumorigenesis of GBM.

Analysis of the Factors Affecting the Prognosis of Glioma Patients.

This retrospective study was carried out to investigate factors affecting the prognosis of gliomas for better management of treatment. Clinical data from 186 glioma patients treated in our hospital from January 2013 to June 2016 were analyzed. There was slightly more male than female patients in the cohort. The main clinical symptoms included sudden limb twitching, headache and fatigue, vomiting, vision reduction and speaking disorders. The malignancy was high and the prognosis was poor in the patients, with an overall survival rate of 54.84 % by October 2017. Univariate analysis showed that the prognosis was mainly affected by age, tumor grade, preoperative Karnofsky performance status (KPS), surgical method, postoperative radiotherapy and chemotherapy, and postoperative use of temozolomide (TMZ). Multivariate Cox regression analysis showed that the independent risk factors for the prognosis were old age (≥ 60), advanced tumor, partial tumor resection, KPS of < 70, no chemotherapy after operation and < 4 courses of postoperative TMZ. The prognosis is negatively affected by age, tumor grade, KPS, and partial tumor resection. Surgical resection combined with chemotherapy and multi-course use of TMZ prolongs the survival time of patients.

Beam deformation within an acousto-optic lens.

The acousto-optic lens (AOL) is becoming a popular tool in the neuroscience field. Here we analyzed the deformation of the diffraction beam after passage through an AOL consisting of a pair of acousto-optic deflectors using both theoretical and experimental data. The results showed that, because of the high sensitivity of optical spatial frequencies of acousto-optic deflectors, the boundary strength of the diffraction beam of the AOL decreases significantly. When the focal length of AOL diminishes, the deformation of the diffraction beam becomes more serious with a smaller beam size. This deformation of the diffraction beam finally leads to a decreased illuminative numerical aperture, which worsens the image's spatial resolution.

Fluorescence micro-optical sectioning tomography using acousto-optical deflector-based confocal scheme.

Fluorescent labeling has opened up the possibility of clarifying the complex distribution and circuit wiring of specific neural circuits for particular functions. To acquire the brain-wide fluorescently labeled neural wiring, we have previously developed the fluorescence micro-optical sectioning tomography imaging system. This employs simultaneous mechanical sectioning and confocal imaging of the slices, and is capable of acquiring the image dataset of a centimeter-sized whole-mouse brain at a voxel resolution of [Formula: see text]. We analyze the key optical considerations for the use of an acousto-optical deflector (AOD) scanner-based confocal detection scheme in this system. As a result, the influence of confocal detection, the imaging site during sectioning, and AOD fast scan mode on signal-to-background noise ratio are described. It is shown that mechanical sectioning to separate the slice and optical sectioning by confocal detection should be combined to maximize background suppression in simultaneous fast scan imaging while sectioning system setup.

Hyperacetylation of histone H3K9 involved in the promotion of abnormally high transcription of the gdnf gene in glioma cells.

The mechanism underlying abnormally high transcription of the glial cell line-derived neurotrophic factor (GDNF) gene in glioma cells is not clear. In this study, to assess histone H3K9 acetylation levels in promoters I and II of the gdnf gene in normal human brain tissue, low- and high-grade glioma tissues, normal rat astrocytes, and rat C6 glioblastoma cells, we employed chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR), real-time PCR, and a pGL3 dual fluorescence reporter system. We also investigated the influence of treatment with curcumin, a histone acetyltransferase inhibitor, and trichostatin A (TSA), a deacetylase inhibitor, on promoter acetylation and activity and messenger RNA (mRNA) expression level of the gdnf gene in C6 cells. Compared to normal brain tissue, H3K9 acetylation in promoters I and II of the gdnf gene increased significantly in high-grade glioma tissues but not in low-grade glioma tissues. Moreover, H3K9 promoter acetylation level of the gdnf gene in C6 cells was also remarkably higher than in normal astrocytes. In C6 cells, curcumin markedly decreased promoter II acetylation and activity and GDNF mRNA expression. Conversely, all three measurements were significantly increased following TSA treatment. Our results suggest that histone H3K9 hyperacetylation in promoter II of the gdnf gene might be one of the reasons for its abnormal high transcription in glioma cells.

Changes in transcriptional factor binding capacity resulting from promoter region methylation induce aberrantly high GDNF expression in human glioma.

Glial cell line-derived neurotrophic factor (GDNF), which belongs to transforming growth factor ß superfamily, plays important roles in glioma pathogenesis. Gdnf mRNA is aberrantly increased in glioma cells, but the underlying transcription mechanism is unclear. Here, we found that although the base sequence in the promoter region of the gdnf gene was unchanged in glioma cells, there were significant changes in the methylation level of promoter region I (P < 0.05) in both high- and low-grade glioma tissues. However, the methylation degree in promoter region II was notably decreased in low-grade glioma tissue compared to normal brain tissue (P < 0.05), and the demethylation sites were mainly located in the enhancer region. Conversely, methylation was markedly increased in high-grade glioma tissue (P < 0.05), and the sites with decreased methylation level were mainly located in the silencer region. The binding capacities of several transcriptional factors, such as activating protein 2, specificity protein 1, ETS-related gene 2, and cAMP response element binding protein, which specifically bind to regions with altered methylation status decreased along with the pathological grade of glioma, and the differences between high-grade glioma and normal brain tissue were significant (P < 0.05). The results suggest that changes in transcriptional factor binding capacity are due to changes in promoter region methylation and might be the underlying mechanism for aberrantly high gdnf expression in glioma.