FMOD Alleviates Depression-Like Behaviors by Targeting the PI3K/AKT/mTOR Signaling After Traumatic Brain Injury.

Depression frequently occurs following traumatic brain injury (TBI). However, the role of Fibromodulin (FMOD) in TBI-related depression is not yet clear. Previous studies have suggested FMOD as a potential key factor in TBI, yet its association with depression post-TBI and underlying mechanisms are not well understood. Serum levels of FMOD were measured in patients with traumatic brain injury using qPCR. The severity of depression was assessed using the self-depression scale (SDS). Neurological function, depressive state, and cognitive function in mice were assessed using the modified Neurological Severity Score (mNSS), forced swimming test (FST), tail suspension test (TST), Sucrose Preference Test (SPT), and morris water maze (MWM). The morphological features of mouse hippocampal synapses and neuronal dendritic spines were revealed through immunofluorescence, transmission electron microscopy, and Golgi-Cox staining. The protein expression levels of FMOD, MAP2, SYP, and PSD95, as well as the phosphorylation levels of the PI3K/AKT/mTOR signaling pathway, were detected through Western blotting. FMOD levels were decreased in TBI patients' serum. Overexpression of FMOD preserved neuronal function and alleviated depression-like behaviour, increased synaptic protein expression, and induced ultrastructural changes in hippocampal neurons. The increased phosphorylation of PI3K, AKT, and mTOR suggested the involvement of the PI3K/AKT/mTOR signaling pathway in FMOD's protective effects. FMOD exhibits potential as a therapeutic target for depression related to TBI, with its protective effects potentially mediated through the PI3K/AKT/mTOR signaling pathway.

[Geometric model of reduction in basilar invagination with atlantoaxial dislocation and its clinical application].

Objectives: To establish a geometric model of the atlantoaxial dislocation and basilar invagination reduction,and examine its value for clinical application. Methods: A retrospective analysis of 35 patients with atlantoaxial dislocation and basilar invagination admitted to the Department of Neurosurgery,First Affiliated Hospital of Chongqing Medical University from May 2018 to May 2020 was conducted.There were 5 males and 30 females,aged (48±15) years(range: 19 to 69 years). The geometric model of the atlantoaxial reduction was established based on the mid-sagittal section of the cervical spine. The relevant data were calculated according to the geometric model before operation,and the fusion cage of the corresponding height was placed into C1-2 facet joint of patient for quantitative reduction. The theoretical reset value, actual reset value, postoperative symptoms and complications were collected. The paired t-test was used to compare the difference between theoretical and actual reset value to verify the reliability of the geometric model. Results: The theoretical vertical reduction distance of all patients was (5.79±2.96) mm(range:1.52 to 10.96 mm),and the actual vertical reduction distance was (7.43±2.96)mm(range: 1.40 to 12.77 mm),and there was no statistical difference between them(t=-1.96,P=0.069).The theoretical reduction angle was (10.80±2.24)°(range: 7.09 to 14.86°), the actual reduction angle was (10.64±7.00)°(range: 3.50 to 20.50°),and there was no statistical difference between them (t=0.09, P=0.933). At 6 months follow-up, 35 patients achieved satisfactory atlanto-axial joint fusion, and the symptoms were relieved. No internal fixation system displacement, fracture, wound infection and other complications occurred. Conclusion: This geometric model can estimate the vertical reduction distance and the reduction angle of the axial before operation,and provide a reference for the height of the fusion cage so as to avoid under or over-reduction.

Recombinant human erythropoietin administration protects cortical neurons from traumatic brain injury in rats.

We explored the regulation of erythropoietin and erythropoietin receptor on traumatic brain injury (TBI), as well as the antiapoptotic effects of recombinant human erythropoietin (rhEPO) treatment. Female Wistar rats were randomly divided into three groups: rhEPO-treated TBI, vehicle-treated TBI, and sham-operated. TBI was induced by the Feeney free falling model. Rats were killed 5, 12, 24, 72, 120, or 168 h after TBI. Regulation of EPO, EPOR and Bcl-2 was detected by reverse transcription-polymerase chain reaction (RT-PCR), western blotting and immunofluorescence. Terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling (TUNEL) was used to assess DNA fragmentation after TBI. Induction of EPOR expression persisted for 168 h after TBI, whereas EPO was only slightly elevated for 72 h. In the rhEPO-treated TBI, Bcl-2 mRNA and protein levels were greater than in the vehicle-treated TBI. Bcl-2 mRNA peaked at 24 h and remained stable for 72-120 h. The number of TUNEL-positive cells in the rhEPO-treated TBI was far fewer than in the vehicle-treated TBI. EPOR regulation is enhanced for almost a week after TBI. Administration of rhEPO protects neurons by enhancing Bcl-2 expression, thereby inhibiting TBI-induced neuronal apoptosis.