Depletion of Microglia Attenuates Dendritic Spine Loss and Neuronal Apoptosis in the Acute Stage of Moderate Traumatic Brain Injury in Mice.

Microglia are the primary immune cells in the central nervous system and undergo significant morphological and transcriptional changes after traumatic brain injury (TBI). However, their exact contribution to the pathogenesis of TBI is still debated and remains to be elucidated. In the present study, thy-1 GFP mice received a colony-stimulating factor 1 receptor inhibitor (PLX3397) for 21 consecutive days, then were subjected to moderate fluid percussion injury (FPI). Brain samples were collected at 1 day and 3 days after FPI for flow cytometry analysis, immunofluorescence, dendrite spine quantification, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and Western blot. We found that PLX3397 treatment significantly attenuated the percentages of resident microglia and infiltrated immune cells. Depletion of microglia promoted neurite outgrowth, preserved dendritic spines and reduced total brain cell and neuronal apoptosis after FPI, which was accompanied by decreased the protein levels of endoplasmic reticulum stress marker proteins, C/EBP-homologous protein and inositol-requiring kinase 1α. Taken together, these findings suggest that microglial depletion may exert beneficial effects in the acute stage of FPI.

Mild hypothermia reduces endoplasmic reticulum stress-induced apoptosis and improves neuronal functions after severe traumatic brain injury.

BACKGROUND: Mild hypothermia is wildly used in clinical treatment of traumatic brain injury (TBI). However, the effect of mild hypothermia on endoplasmic reticulum (ER) stress-induced apoptosis after severe TBI is still unknown. METHODS: In the present study, we used BALB/c mice to investigate the efficacy of posttraumatic mild hypothermia in reducing ER stress. Severe TBI was induced by controlled cortical impact injury. Mild hypothermia treatment was performed immediately after surgery and maintained for 4 hr. The animals were euthanized at 1 and 7 days after severe TBI. The expression levels of ER stress marker proteins were evaluated using Western blot and immunofluorescence. Cell apoptosis rate was analyzed by TUNEL staining. Neuronal functions of the mice were assessed using rotarod test and Morris water maze. RESULTS: Our results revealed that mild hypothermia significantly attenuated ER stress marker proteins, including p-eIF2α/eIF2α, ATF4, CHOP and IRE-1α, and reduced apoptosis rate in the pericontusion region at 1 and 7 days after severe TBI. Interestingly, mild hypothermia also prevented the translocation of CHOP into nucleus. In addition, posttraumatic mild hypothermia significantly improved neuronal functions after severe TBI. CONCLUSIONS: Our findings illustrated that mild hypothermia could reduce ER stress-induced apoptosis and improve neuronal functions after severe traumatic brain injury.

The Surgical Treatment of Posttraumatic Skull Base Defects with Cerebrospinal Fluid Leak.

Objectives The objective was to explore further the surgical treatment of posttraumatic skull base defects with cerebrospinal fluid (CSF) leak and to identify the most common factors affecting the surgical treatment of posttraumatic skull base defect with CSF leak retrospectively. Materials and Methods This study included 144 patients with head trauma having skull base defect with CSF leak who had been surgically treated at Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University from 1998 to June 2016. There were 113 (78.5%) males and 31 (21.5%) females, with age ranging from 1 to 78 years and mean age of 26.58 ± 14.95 years. We explored the surgical approaches for the treatment of the skull base defect and the graft materials used and also measured the association among surgical approaches; location, size, and type of skull base defects; presence or absence of associated intracranial pathologies; postoperative complications; outcome; age; Glasgow outcome score (GOS) at discharge; and days of hospital stay. Results The location, size, and types of skull base defect and the presence of associated intracranial pathologies were the common factors identified not only for choosing the appropriate surgical approach but also for choosing the materials for defect repair, timing of the surgery, and the method used for the defect as well as leak repair. The statistically significant correlation with p < 0.001 was found in this study. Conclusion From this study, we could conclude that size, location, and types of the defect and the presence of associated intracranial injuries were the common factors that affected the surgical treatment of posttraumatic skull base defect with CSF leak. Hence, the importance of careful evaluation of these factors is essential for proper selection of the surgical approach and for avoiding unnecessary hassles.

A simple classification of cranial-nasal-orbital communicating tumors that facilitate choice of surgical approaches: analysis of a series of 32 cases.

Cranial-nasal-orbital communicating tumors involving the anterior and middle skull base are among the most challenging to treat surgically, with high rates of incomplete resection and surgical complications. Currently, there is no recognized classification of tumors with regard to the choice of surgical approaches. From January 2004 to January 2014, we classified 32 cranial-nasal-orbital communicating tumors treated in our center into three types according to the tumor body location, scope of extension and direction of invasion: lateral (type I), central (type II) and extensive (type III). This classification considerably facilitated the choice of surgical routes and significantly influenced the surgical time and amount of hemorrhage during operation. In addition, we emphasized the use of transnasal endoscopy for large and extensive tumors, individualized treatment strategies drafted by a group of multidisciplinary collaborators, and careful reconstruction of the skull base defects. Our treatment strategies achieved good surgical outcomes, with a high ratio of total resection (87.5 %, 28/32, including 16 cases of benign tumors and 12 cases of malignant tumors) and a low percentage of surgical complications (18.8 %, 6/32). Original symptoms were alleviated in 29 patients. The average KPS score improved from 81.25 % preoperatively to 91.25 % at 3 months after surgery. No serious perioperative complications occurred. During the follow-up of 3 years on average, four patients with malignant tumors died, including three who had subtotal resections. The 3-year survival rate of patients with malignant tumors was 78.6 %, and the overall 3-year survival rate was 87.5 %. Our data indicate that the simple classification method has practical significance in guiding the choice of surgical approaches for cranial-nasal-orbital communicating tumors and may be extended to other types of skull base tumors.

Functionalized nano-graphene oxide particles for targeted fluorescence imaging and photothermy of glioma U251 cells.

AIM: This study was to prepare the functionalized nano-graphene oxide (nano-GO) particles, and observe targeted fluorescence imaging and photothermy of U251 glioma cells under near infrared (NIR) exposure. MATERIAL AND METHODS: The functionalized nano-GO-Tf-FITC particles were prepared and then were incubated with U251 glioma cells. Estimation of CCK8 cell activity was adopted for measurement of cytotoxicity. The effect of fluorescein imaging was detected by fluorescence microscope with anti-CD71-FITC as a control. Finally, we detected the killing efficacy with flow cytometry after an 808 nm NIR exposure. RESULTS: Both nano-GO-Tf-FITC group and CD71-FITC group exhibited green-yellow fluorescence, while the control group without the target molecule nano-GO-FITC was negative. The nano-GO-Tf-FITC was incubated with U251 cells at 0.1 mg/ml, 1.0 mg/ml, 3.0 mg/ml and 5.0 mg/ml. After 48 h of incubation, the absorbance was 0.747 ± 0.031, 0.732 ± 0.043, 0.698 ± 0.051 and 0.682 ± 0.039, while the absorbance of control group is 0.759 ± 0.052. There is no significant difference between the nano-GO-FITC groups and control group. In addition, the apoptosis and death index of nano-GO-Tf-FITC group was significantly higher than that of nano-GO-FITC and blank control group (P < 0.05). CONCLUSION: The nano-GO-Tf-FITC particles with good biological compatibility and low cytotoxicity are successfully made, which have an observed effect of target imaging and photothermal therapy on glioma U251 cells.

miR-21 induces cell proliferation and suppresses the chemosensitivity in glioblastoma cells via downregulation of FOXO1.

miR-21 shares a potential oncogenic function. The overexpression of miR-21 was common in glioblastoma, which is the most common lethal primary intracranial tumor. The study aimed at miR-21 effect on Glioblastoma cell line A172 of proliferation, apoptosis, and chemosensitivity and its definite mechanism of target gene FOXO1. Effect and mechanism were evaluated by colony forming cell assay, annexin V-FITC/PI apoptosis assay, TUNEL apoptosis assay, luciferase-reporter activities assay, RNA interference, western-blot and Real-Time PCR. The statistics revealed miR-21 promoted A172 cell proliferation and suppressed the chemosensitivity, and also showed that miR-21 could bind with FOXO1 mRNA and prevent FOXO1 translation via its 3'UTR to regulate the function. These findings suggest that miR-21 plays an important role in cell proliferation and chemosensitivity by inhibiting FOXO1, and show much more significance for exploring miR-21 inhibitor in A172 therapy.