Protein profiling identified mitochondrial dysfunction and synaptic abnormalities after dexamethasone intervention in rats with traumatic brain injury

Dexamethasone has been widely used after various neurosurgical procedures due to its anti-inflammatory property and the abilities to restore vascular permeability,inhibit free radicals,and reduce cerebrospinal fluid production.According to the latest guidelines for the treatment of traumatic brain injury in the United States,high-dose glucocorticoids cause neurological damage.To investigate the reason why high-dose glucocorticoids after traumatic brain injury exhibit harmful effect,rat controlled cortical impact models of traumatic brain injury were established.At 1 hour and 2 days after surgery,rat models were intraperitoneally administered dexamethasone 10 mg/kg.The results revealed that 31 proteins were significantly upregulated and 12 proteins were significantly downregulated in rat models of traumatic brain injury after dexamethasone treatment.The Ingenuity Pathway Analysis results showed that differentially expressed proteins were enriched in the mitochondrial dysfunction pathway and synaptogenesis signaling pathway.Western blot analysis and immunohistochemistry results showed that Ndufv2,Maob and Gria3 expression and positive cell count in the dexamethasone-treated group were significantly greater than those in the model group.These findings suggest that dexamethasone may promote a compensatory increase in complex I subunits(Ndufs2 and Ndufv2),increase the expression of mitochondrial enzyme Maob,and upregulate synaptic-transmission-related protein Gria3.These changes may be caused by nerve injury after traumatic brain injury treatment by dexamethasone.The study was approved by Institutional Ethics Committee of Beijing Neurosurgical Institute(approval No.201802001)on June 6,2018.

The etiology,clinical features and medical treatment of somatotroph adenomas

Somatotroph adenomas lead to hypersecretion of growth hormones(GH)and may cause mass effects.Patients with somatotroph adenomas may present with acral and soft tissue enlargement,joint pain,heart and respiratory failure,diabetes mellitus and hypertension,resulting in increased morbidity and mortality.Early diagnosis and treatment are therefore important in prolonging life and improving quality of life.Recent studies depicted the landscape of genetic and epigenetic changes in sporadic somatotroph adenomas.New approaches are being developed for genetic testing,diagnosis and surveillance,which are helpful in early diagnosis,treatment and disease control of somatotroph adenomas.Data suggest that patients with somatotroph adenomas are best treated with multidisciplinary teams composed of neuro-endocrinologists,neurosurgeons,radiation oncologists and other specialists.This mini-review summarizes in a concise way the up-to-date discussion on the etiology,new diagnostic techniques and novel treatments of somatotroph adenomas.

Application of robotic-assisted endoscopic third ventriculostomy

Objective:This case series study explored the application of ROSA(robot of stereotactic assistant)robotic-assisted endoscopic third ventriculostomy(ETV)in the treatment of hydrocephalus.Methods:Three patients(January2016-October2017)diagnosed with hydrocephalus based on preoperative computed tomograph(CT)and magnetic resonance imaging(MRI)scans were recruited.Navigation planning scan was performed before operation.ROSA robot localization program was used to simulate and analyze the path planning of hydrocephalus ETV and store it in the system.All the three patients underwent robotic-assisted ETV.The patients'clinical symptoms,imaging manifestations and related complications were evaluated,and a3-month follow-up survey was conducted.Prognostic factors were also analyzed.Results:ETV under the guidance of ROSA robot was successfully performed on the three patients.CT,MRI and cerebrospinal fluid(CSF)cine showed that the ventricles were narrowed,that the velocity and flow of the stoma were normal,and that the CSF flow was smooth.After discharge,the symptoms of hydrocephalus were significantly improved.Localization of the robot and design of the surgical path were key to success of the operation.Conclusions:ROSA robotic-assisted ETV is a feasible procedure.The patients recovered well,and the symptoms relieved.More efforts are needed to optimize artificial intelligence and the application of precision treatment in the nervous system.

Role of EGFL7/EGFR-signaling pathway in migration and invasion of growth hormone-producing pituitary adenomas

Currently, the primary therapeutic strategy for most growth hormone-producing pituitary adenomas(GHPA) is surgery. Due to the invasiveness of GHPA, high recurrence has limited the benefit of complete adenoma removal surgery. Epidermal growth factor-like domain 7(EGFL7) is a secreted factor implicated in tumor angiogenesis, growth, invasiveness and metastasis in GHPA. Herein, we observed that the expression level of EGFL7 and p-EGFR in invasive GHPAwas much higher than that of non-invasive GHPA. The overexpression of EGFL7 was positively correlated with activation of EGFR(p-EGFR). Noticeably, EGFL7 knockdown significantly inhibited activation of EGFR signaling cascades, including p-ERGR, p-AKT and p-ERK. Further studies showed that EGFL7 knockdown or pharmacological inhibition of EGFR-pathway, using EGFR inhibitor Tyrphostin AG-1478, significantly suppressed migration and invasion of GH3 and GT1-1 cells. In summary, our findings suggest that EGFL7 is a key factor for regulation of EGFR signaling pathway and plays an important role in migration and invasion of invasive GHPA.