Short-term outcomes of robot-assisted minimally invasive surgery for brainstem hemorrhage: A case-control study.

Objective: This work focused on investigating if robot-assisted minimally invasive surgery improved middle term vital outcome for primary brainstem hemorrhage (PBSH). Methods: This work obtained clinical data from patients with PBSH admitted from July 2019 to August 2021. All cases were classified as surgical or conservative treatment group. The general information, Glasgow coma scale (GCS) score, Glasgow outcome score (GOS), along with survival time in patients 60 days after robot-assisted surgery were recorded and analyzed. Results: A prospective analysis was performed on 82 cases meeting eligibility criteria, including 36 from surgical group whereas 46 from the conservative group. Sixty days after onset, the death rate was found to be 19.44% and 50.00% of surgical and conservative groups, separately (cases versus controls, P < 0.05). Furthermore, postoperative GOS and GCS scores of surgical group were significantly higher, and hydrocephalus was lower compared with conservative group. Central fever incidence did not exhibit any significant difference between two groups. Conclusion: Robot-assisted PBSH drainage may improve survivorship and reduce the occurrence of hydrocephalus.

Comparison of endoscopic evacuation, craniotomy, and puncture aspiration for the treatment of spontaneous basal ganglia intracerebral hematoma.

OBJECTIVE: To compare the prognosis of patients with spontaneous basal ganglia intracerebral hematoma treated by endoscopic evacuation, craniotomy, or puncture aspiration. METHODS: This retrospective observational study included information from patients with basal ganglia hematoma who received craniotomy, endoscopic evacuation, or puncture aspiration in the Department of Neurosurgery of the First Affiliated Hospital of USTC between January 2016 and May 2021. Patients were grouped according to their treatment method for comparison. RESULTS: From a total of 184 patients, 62 cases (51 males, aged 54.44 ± 9.92 years) received craniotomy, 64 cases (45 males, aged 53.97 ± 11.87 years) received endoscopic evacuation, and 58 cases (43 males, aged 54.25 ± 10.35 years) received puncture aspiration. No significant difference was found in baseline characteristics among three surgical procedures. Patients in the endoscopy group had the shortest hospital stay (15.16 ± 4.89 days vs. 17.88 ± 5.97 and 20.77 ± 6.96 days), lowest infectious meningitis [1(1.6 %) vs. 2(3.4%) and 8(12.9%)] and pulmonary infection [3(4.7%) vs. 5(8.6%) and 13(21.0%)] rates, and highest hematoma removal rate (90.39 ± 5.22% vs. 35.87 ± 6.23 and 84.76 ± 4.91%) and Glasgow outcome scale 6 months after surgery (4.41 ± 0.53 vs. 3.74 ± 1.09 and 3.81 ± 1.03). The occurrence of gastrointestinal bleeding, epilepsy, and mortality were similar (all p > 0.05) among the groups. CONCLUSION: Patients with spontaneous basal ganglia intracerebral hematoma who received endoscopic evacuation might have better prognosis than those treated with craniotomy or puncture aspiration. In future, endoscopic surgery could become the most common method for treating spontaneous basal ganglia hemorrhages.

Shunt-Dependent Post-Traumatic Hydrocephalus: Predictors and Long-Term Functional Outcomes.

INTRODUCTION: As a disorder of the brain in adults and children, traumatic brain injury (TBI) is considered the major cause of mortality and morbidity. As a serious complication of TBI, post-traumatic hydrocephalus (PTH) is commonly identified and significantly associated with neurocognitive impairment, motor dysfunction, and growth impairment. The long-term functional outcomes after shunt dependence are totally not clear. METHODS: This study included 6279 patients between 2012 and 2022. To identify the unfavorable functional outcomes and the PTH-related factors, we carried out univariable logistic regression analyses. To identify the occurrence time of PTH, we conducted the log-rank test and Kaplan-Meier analysis. RESULTS: Mean patient age was 51.03 ± 22.09 years. Of the 6279 patients with TBI, 327 developed PTH (5.2%). Several PTH development-associated factors, such as intracerebral hematoma, diabetes, longer initial hospital stay, craniotomy, low GCS (Glasgow Coma Scale), EVD (external ventricular drain), and DC (decompressive craniectomy) (p < 0.01), were identified. We also analyzed the factors of unfavorable outcomes after TBI including > 80 years, repeated operations, hypertension, EVD, tracheotomy, and epilepsy (p < 0.01). Ventriculoperitoneal shunt (VPS) itself is not an independent factor of the unfavorable outcome but shunt complication is a strong independent factor of unfavorable outcome (p < 0.05). CONCLUSION: We should emphasize the practices that can minimize the risks of shunt complications. Additionally, the rigorous radiographic and clinical surveillance will benefit those patients at high risk of developing PTH. TRIAL REGISTRATION: ClinicalTrials.gov identifier, ChiCTR2300070016.

Visual Working Memory Capacity in Patients with Temporal Lobe Glioma.

INTRODUCTION: Working memory (WM) refers to the temporary storage and manipulation of information. Short-term memory storage can be divided into separate subsystems for verbal information and visual information. We explored the capacity of visual WM in patients with temporal lobe glioma. METHODS: In this study, we assessed 30 patients with temporal lobe glioma and 30 healthy controls (HCs) using a method that combined memory tests with visual WM tasks (digital span task, spatial capacity N-back task, and emotional N-back task). RESULTS: The results revealed that groups did not differ in terms of demographics, estimated intelligence, and level of psyc distress. For visual WM tasks, statistically significant differences were not found on the 1-back tasks and forward versions of simple span tasks between the temporal patient (TP) group and the HC group. Analysis of correct responses of the experimental tasks suggested that the TP group was significantly different from the HC group in the 2-back tasks and backward versions of simple span tasks. For reaction times, spatial capacity 2-back task and emotional 2-back task showed the TP group was significantly different from the HC group. CONCLUSION: These findings revealed that visual WM scores of temporal glioma patients were lower than HCs, and hence, the temporal lobe may be a certain neuroanatomical structure in the WM network.

Multiple Machine Learning Approaches for Morphometric Parameters in Prediction of Hydrocephalus.

BACKGROUND: The diagnosis of hydrocephalus is mainly based on imaging findings. However, the significance of many imaging indicators may change, especially in some degenerative diseases, and even lead to misdiagnosis. METHODS: This study explored the effectiveness of commonly used morphological parameters and typical radiographic findings in hydrocephalus diagnosis. The patients' imaging data were divided into three groups, including the hydrocephalus group, the symptomatic group, and the normal control group. The diagnostic validity and weight of various parameters were compared between groups by multiple machine learning methods. RESULTS: Our results demonstrated that Evans' ratio is the most valuable diagnostic indicator compared to the hydrocephalus group and the normal control group. But frontal horns' ratio is more useful in diagnosing patients with symptoms. Meanwhile, the sign of disproportionately enlarged subarachnoid space and third ventricle enlargement could be effective diagnostic indicators in all situations. CONCLUSION: Both morphometric parameters and radiological features were essential in diagnosing hydrocephalus, but the weights are different in different situations. The machine learning approaches can be applied to optimize the diagnosis of other diseases and consistently update the clinical diagnostic criteria.

α-Lipoic Acid-Plus Ameliorates Endothelial Injury by Inhibiting the Apoptosis Pathway Mediated by Intralysosomal Cathepsins in an In Vivo and In Vitro Endothelial Injury Model.

α-Lipoic acid-plus (LAP), an amine derivative of α-lipoic acid, has been reported to protect cells from oxidative stress damage by reacting with lysosomal iron and is more powerful than desferrioxamine (DFO). However, the role of LAP in experimental carotid artery intimal injury (CAII) has not yet been well investigated. Therefore, we sought to uncover the role and potential endovascular protective mechanisms of LAP in endothelial injury. In vitro, oxyhemoglobin (OxyHb) stimulation of cultured human umbilical vein endothelial cells (HUVECs) simulated intimal injury. In vivo, balloon compression injury of the carotid artery was used to establish a rat CAII model. We found that the protein levels of cathepsin B/D, ferritin, transferrin receptor (TfR), cleaved caspase-3, and Bax increased in the injured endothelium and HUVECs but were rectified by DFO and LAP treatments, as revealed by western blotting and immunofluorescence staining. Additionally, DFO and LAP decreased oxidative stress levels and endothelial cell necrosis of the damaged endothelium. Moreover, DFO and LAP significantly ameliorated the increased oxidative stress, iron level, and lactic dehydrogenase activity of HUVECs and improved the reduced HUVEC viability induced by OxyHb. More importantly, DFO and LAP significantly reduced mitochondrial damage and were beneficial for maintaining lysosomal integrity, as indicated by acridine orange (AO), Lyso-Tracker Red, JC-1, and ATPB staining in HUVECs. Finally, LAP might offer more significant endovascular protective effects than DFO. Our data suggested that LAP exerted endovascular protective effects by inhibiting the apoptosis signaling pathway mediated by intralysosomal cathepsins by reacting with excessive iron in endothelial lysosomes after intimal injury.

Risk Factors for Cerebral Infarction After Moderate or Severe Traumatic Brain Injury.

PURPOSE: Posttraumatic cerebral infarction (PTCI) is a common and relatively serious complication of traumatic brain injury (TBI) without a clear etiology. Evaluating risk factors in advance is particularly important to predict and avoid the occurrence of PTCI. PATIENTS AND METHODS: We retrospectively analyzed 297 patients with moderate to severe TBI admitted to the Department of Neurosurgery in our hospital from January 2019 to September 2020 and evaluated the effects of various factors such as age, sex, admission Glasgow Coma Scale (GCS), skull base fracture, subarachnoid hemorrhage (SAH), brain herniation, hypotensive shock, and decompressive craniectomy on the incidence of PTCI. We also performed a multivariate logistics regression analysis on the relevant factors identified and evaluated the diagnostic value of each risk factor in advance by receiver operating characteristic (ROC) analyses. RESULTS: Among the patients, 32 (10.77%) suffered PTCI. The incidence rates of PTCI in those with GCS scores of 3-8 and 9-12 were 15.87% (30/189) and 1.85% (2/108), respectively, while the rates were 18.84% (13/69), 15.03% (29/193), 18.57% (13/70), and 20.59% (14/68) in those with skull base fractures, traumatic SAH, brain herniation, and hypotensive shock, respectively, and 14.38% (23/160) in those who underwent decompressive craniectomy. These differences in PTCI incidence were statistically significant. However, the differences in PTCI incidence caused by patient age and sex were not statistically significant. CONCLUSION: Low GCS score, skull base fractures, traumatic SAH, brain herniation, hypotensive shock, and decompressive craniectomy are risk factors for the occurrence of PTCI, while age and sex are not significantly correlated with the occurrence of PTCI.

SOCS1/JAK2/STAT3 axis regulates early brain injury induced by subarachnoid hemorrhage via inflammatory responses.

The SOCS1/JAK2/STAT3 axis is strongly associated with tumor growth and progression, and participates in cytokine secretion in many diseases. However, the effects of the SOCS1/JAK2/STAT3 axis in experimental subarachnoid hemorrhage remain to be studied. A subarachnoid hemorrhage model was established in rats by infusing autologous blood into the optic chiasm pool. Some rats were first treated with JAK2/STAT3 small interfering RNA (Si-JAK2/Si-STAT3) or overexpression plasmids of JAK2/STAT3. In the brains of subarachnoid hemorrhage model rats, the expression levels of both JAK2 and STAT3 were upregulated and the expression of SOCS1 was downregulated, reaching a peak at 48 hours after injury. Simultaneously, the interactions between JAK2 and SOCS1 were reduced. In contrast, the interactions between JAK2 and STAT3 were markedly enhanced. Si-JAK2 and Si-STAT3 treatment alleviated cortical neuronal cell apoptosis and necrosis, destruction of the blood-brain barrier, brain edema, and cognitive functional impairment after subarachnoid hemorrhage. This was accompanied by decreased phosphorylation of JAK2 and STAT3 protein, decreased total levels of JAK2 and STAT3 protein, and increased SOCS1 protein expression. However, overexpression of JAK2 and STAT3 exerted opposite effects, aggravating subarachnoid hemorrhage-induced early brain injury. Si-JAK2 and Si-STAT3 inhibited M1-type microglial conversion and the release of pro-inflammatory factors (inducible nitric oxide synthase, interleukin-1ß, and tumor necrosis factor-α) and increased the release of anti-inflammatory factors (arginase-1, interleukin-10, and interleukin-4). Furthermore, primary neurons stimulated with oxyhemoglobin were used to simulate subarachnoid hemorrhage in vitro, and the JAK2 inhibitor AG490 was used as an intervention. The in vitro results also suggested that neuronal protection is mediated by the inhibition of JAK2 and STAT3 expression. Together, our findings indicate that the SOCS1/JAK2/STAT3 axis contributes to early brain injury after subarachnoid hemorrhage both in vitro and in vivo by inducing inflammatory responses. This study was approved by the Animal Ethics Committee of Anhui Medical University and the First Affiliated Hospital of University of Science and Technology of China (approval No. LLSC-20180202) on March 1, 2018.

Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage.

The Wnt/Frizzled signaling pathway participates in many inflammation-linked diseases. However, the inflammatory response mediated by the Wnt/Frizzled signaling pathway in experimental subarachnoid hemorrhage has not been thoroughly investigated. Consequently, in this study, we examined the potential role of the Wnt/Frizzled signaling pathway in early brain injury in rat models of subarachnoid hemorrhage. Simultaneously, possible neuroprotective mechanisms were also investigated. Experimental subarachnoid hemorrhage rat models were induced by injecting autologous blood into the prechiasmatic cistern. Experiment 1 was designed to examine expression of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. In total, 42 adult rats were divided into sham (injection of equivalent volume of saline), 6-, 12-, 24-, 48-, 72-hour, and 1-week subarachnoid hemorrhage groups. Experiment 2 was designed to examine neuroprotective mechanisms of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. Rats were treated with recombinant human Wnt1 (rhwnt1), small interfering Wnt1 (siwnt1) RNA, and monoclonal antibody of Frizzled1 (anti-Frizzled1) at 48 hours after subarachnoid hemorrhage. Expression levels of Wnt1, Frizzled1, ß-catenin, peroxisome proliferator-activated receptor-γ, CD36, and active nuclear factor-κB were examined by western blot assay and immunofluorescence staining. Microglia type conversion and inflammatory cytokine levels in brain tissue were examined by immunofluorescence staining and enzyme-linked immunosorbent assay. Our results show that compared with the sham group, expression levels of Wnt1, Frizzled1, and ß-catenin were low and reduced to a minimum at 48 hours, gradually returning to baseline at 1 week after subarachnoid hemorrhage. rhwnt1 treatment markedly increased Wnt1 expression and alleviated subarachnoid hemorrhage-induced early brain injury (within 72 hours), including cortical cell apoptosis, brain edema, and neurobehavioral deficits, accompanied by increasing protein levels of ß-catenin, CD36, and peroxisome proliferator-activated receptor-γ and decreasing protein levels of nuclear factor-κB. Of note, rhwnt1 promoted M2-type microglia conversion and inhibited release of inflammatory cytokines (interleukin-1ß, interleukin-6, and tumor necrosis factor-α). In contrast, siwnt1 RNA and anti-Frizzled1 treatment both resulted in an opposite effect. In conclusion, the Wnt/Frizzled1 signaling pathway may participate in subarachnoid hemorrhage-induced early brain injury via inhibiting the inflammatory response, including regulating microglia type conversion and decreasing inflammatory cytokine release. The study was approved by the Animal Ethics Committee of Anhui Medical University and First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (approval No. LLSC-20180202) in May 2017.

Effects of lentivirus-mediated CYP17A1 gene silencing on the biological activity of glioma.

Gliomas are the most common malignant primary brain tumors with poor prognosis. We attempted to explore the role of CYP17A1 in glioma progression. We demonstrated that the expression of CYP17A1 was significantly higher in the glioma tissues than the normal brain tissues, especially in malignant glioma. Moreover, the expression of CYP17A1 gene was positively correlative with glioma pathological grades. In vitro, CYP17A1 gene silence inhibited the proliferation and invasion of glioma cells and promoted the apoptosis in glioma cells. Also, the subcutaneously transplanted tumour in BALB/C-nu showed that CYP17A1 gene silence inhibited glioma growth. These results reveal that CYP17A1 plays a major role in the progress of glioma.

G-protein-coupled receptor kinase-5 promotes glioblastoma progression by targeting the nuclear factor kappa B pathway.

G-protein-coupled receptor kinase-5 (GRK5) plays essential roles in multiple celluar events. However, its role in the development and progression of glioma is poorly understood. In this research, we found that GRK5 is significantly upregulated in human gliomas. For the first time, a close relationship was noted between GRK5 expression and blood vessel development in human glioma. Specifically co-expression of GRK5 and the tumor stem cell marker CD133 was observed in the cytoplasm of high grade glioma cells. The depletion of GRK5 suppressed the proliferation, migration and invasion in glioma cells, and promoted apoptosis. We next discovered that GRK5 knockdown inhibits the nuclear factor kappa B (NF-κB) pathway, thus resulting in downregulation of key downstream secretory products CCL2, IL-6 and IL-8 in glioma cell conditioned medium (CM). In addition, treatment of cells with the NF-κB stimulator PMA reversed this effect and increased the GRK5 level. Our results demonstrate an oncogenic role for GRK5 and reveal an activation of the GRK5-NF-κB pathway during the malignant progression of glioma.

MiR-200c Inhibits the Tumor Progression of Glioma via Targeting Moesin.

We attempt to demonstrate the regulatory role of miR-200c in glioma progression and its mechanisms behind. Here, we show that miR-200c expression was significantly reduced in the glioma tissues compared to paratumor tissues, especially in malignant glioma. Exogenous overexpression of miR-200c inhibited the proliferation and invasion of glioma cells. In addition, the in vivo mouse xenograft model showed that miR-200c inhibited glioma growth and liver metastasis, which is mainly regulated by targeting moesin (MSN). We demonstrated that the expression of MSN in glioma specimens were negatively correlated with miR-200c expression, and MSN overexpression rescued the phenotype about cell proliferation and invasion induced by miR-200c. Moreover, knockdown of MSN was able to mimic the effects induced by miR-200c in glioma cells. These results indicate that miR-200c plays an important role in the regulation of glioma through targeting MSN.

Regulation of p53wt glioma cell proliferation by androgen receptor-mediated inhibition of small VCP/p97-interacting protein expression.

The incidence of glioma in men is higher than that in women; however, little is known about the expression and basic function of the androgen receptor (AR) in gliomas. AR inhibited the small VCP/p97-interacting protein (SVIP) on the transcriptional level was previously reported. The present study shows that the protein level of AR is highly expressed in cell lines of the nervous system. Moreover, the AR expression is increased while SVIP expression is decreased in tumor tissue of glioma patients, which is in agreement with the progressing WHO grades. A statistically significant increase in serum testosterone level of glioma patients compared with that of non-cancer patients was also detected. Furthermore, it has been proved that SVIP is down-regulated as well as AR is up-regulated in glioma cell lines with R1881 treatment. Interestingly, the depletion of SVIP using siRNA facilitated cell proliferation and decreased p53 expression. In addition, overexpression of SVIP increased cell death only in p53wt cell lines. Moreover, U87MG cells, p53wt cell line was susceptible to AR antagonists in vitro and in vivo. The current study provides insight into the biological role of AR in suppressing SVIP and p53 and promoting the progression of glioma as well as the clinical treatment of glioma patients.