Celecoxib treatment alleviates cerebral injury in a rat model of post-traumatic epilepsy.

Background: An important factor contributing to the development and occurrence of post-traumatic epilepsy (PTE) is neuroinflammation and oxidative stress. The effects of celecoxib include inhibiting inflammatory reactions and antioxidant stress and reducing seizures, making it a potential epilepsy treatment solution. Objective: To observe the effect of celecoxib on early epilepsy in post-traumatic epilepsy rats. Methods: Twenty-four adult healthy male Sprague-Dawley rats were randomly assigned to three groups: sham-operated, PTE, and celecoxib. A rat model of PTE was established by injecting ferrous chloride into the right frontal cortex. Afterward, the behavior of rats was observed and recorded. 3.0T superconducting magnetic resonance imaging (MRI) was used to describe the changes in ADC values of the brain. HE and Nissl staining were also used to detect the damage to frontal lobe neurons. Furthermore, the expression of COX-2 protein in the right frontal lobe was detected by Western blot. Moreover, the contents of IL-1 and TNF-α in the right frontal lobe were detected by enzyme-linked immunosorbent assay. Results: Compared with the PTE group, the degree of seizures in rats treated with celecoxib declined dramatically (P < 0.05). Celecoxib-treated rats had significant decreases in tissue structural damage and cell death in the brain. The results of the MRI showed that celecoxib reduced the peripheral edema zone and ADC value of the cortex around the damaged area of the right frontal lobe in the celecoxib-treatment group, which was significantly decreased compared with the PTE group (P < 0.05). Furthermore, celecoxib decreased the expression of COX-2, IL-1ß, and TNF-α in brain tissue (P < 0.05). Conclusions: In PTE rats, celecoxib significantly reduced brain damage and effectively reduced seizures. As a result of celecoxib's ability to inhibit inflammation, it can reduce the edema caused by injury in rat brain tissue.

Angiomatoid fibrous histiocytoma in the spinal canal of T3-T4: a case report and literature review.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumour that occurs in the superficial tissue of extremities of children and young adults. A painless mass in the deep dermis and subcutaneous tissue is the main clinical manifestation. AFH also occurs infrequently in the central nervous system and is relatively common in the cranium. However, spinal canal AFH has not been described yet. We report a rare case of AFH in the cervical canal of a 20-year-old male patient. Microsurgical gross total resection of the tumour was performed, and the diagnosis was confirmed by postoperative pathology. To our knowledge, this is the first case of AFH in the spinal canal.

Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model.

BACKGROUND: Until now, the treatment of patients with autism spectrum disorder (ASD) remain a difficult problem. The insula is involved in empathy and sensorimotor integration, which are often impaired in individuals with ASD. Deep brain stimulation, modulating neuronal activity in specific brain circuits, has recently been considered as a promising intervention for neuropsychiatric disorders. Valproic acid (VPA) is a potential teratogenic agent, and prenatal exposure can cause autism-like symptoms including repetitive behaviors and defective sociability. Herein, we investigated the effects of continuous high-frequency deep brain stimulation in the anterior insula of rats exposed to VPA and explored cognitive functions, behavior, and molecular proteins connected to autism spectrum disorder. METHODS: VPA-exposed offspring were bilaterally implanted with electrodes in the anterior insula (Day 0) with a recovery period of 1 week. (Day 0-7). High-frequency deep brain stimulation was applied from days 11 to 29. Three behavioral tests, including three-chamber social interaction test, were performed on days 7, 13, 18, 25 and 36, and several rats were used for analysis of immediate early genes and proteomic after deep brain stimulation intervention. Meanwhile, animals were subjected to a 20 day spatial learning and cognitive rigidity test using IntelliCage on day 11. RESULTS: Deep brain stimulation improved the sociability and social novelty preference at day 18 prior to those at day 13, and the improvement has reached the upper limit compared to day 25. As for repetitive/stereotypic-like behavior, self- grooming time were reduced at day 18 and reached the upper limit, and the numbers of burried marbles were reduced at day 13 prior to those at day 18 and day 25. The improvements of sociability and social novelty preference were persistent after the stimulation had ceased. Spatial learning ability and cognitive rigidity were unaffected. We identified 35 proteins in the anterior insula, some of which were intimately linked to autism, and their expression levels were reversed upon administration of deep brain stimulation. CONCLUSIONS: Autism-like behavior was ameliorated and autism-related proteins were reversed in the insula by deep brain stimulation intervention, these findings reveal that the insula may be a potential target for DBS in the treatment of autism, which provide a theoretical basis for its clinical application., although future studies are still warranted.

Effect of Microvascular Decompression of the Vagus Root Entry/Exit Zone on Blood Pressure in Patients with Hemifacial Spasm Associated with Essential Hypertension: A Retrospective Clinical Analysis.

Background This study aimed to evaluate blood pressure alterations after microvascular decompression (MVD) surgery in patients with hemifacial spasm (HFS) with coexisting hypertension (HTN). Methods A total of 56 patients with HFS with concurrent HTN who underwent MVD surgery in our center between 2015 and 2019 were retrospectively analyzed. Patients were divided into control and experimental groups: patients who received MVD treatment for only the facial nerve and those who received MVD for the affected facial nerve, ipsilateral vagus nerve, and adjacent ventrolateral medulla, respectively. Preoperative (3 days) and postoperative (7 days and 6 months) blood pressure measurements were analyzed. Results No statistically significant differences were observed in gender, age, HFS course, HTN course, HTN grade, and preoperative blood pressure between the two groups. No significant difference was observed between pre- and postoperative blood pressure in the control group. In the experimental group, systolic blood pressure significantly differed between 3 preoperative days and 7 postoperative days ( p < 0.05), as did diastolic blood pressure ( p < 0.05). Measurement at 6 postoperative months also showed significant differences for both systolic blood pressure and diastolic blood pressure compared with that at 3 preoperative days ( p < 0.05). HTN grade according to the World Health Organization classification criteria significantly differed between preoperative and postoperative measurements ( p < 0.05). Conclusion Vascular decompression of the ipsilateral vagus nerve roots may improve blood pressure management in patients with HFS with coexisting HTN who undergo MVD. Laterality of involvement (left vs. right) did not significantly differ.

Prenatal GABAB Receptor Agonist Administration Corrects the Inheritance of Autism-Like Core Behaviors in Offspring of Mice Prenatally Exposed to Valproic Acid.

This study was performed to evaluate the effects of prenatal baclofen (a GABAB receptor agonist) treatment on the inheritance of autism-like behaviors in valproic acid (VPA)-exposed mice. VPA model mice (first generation, F1) that were prenatally exposed to VPA exhibited robust core autism-like behaviors, and we found that oral administration of baclofen to F1 mice corrected their autism-like behavioral phenotypes at an early age. Based on a previous epigenetics study, we mated the F1 male offspring with litter females to produce the second generation (F2). The F2 male mice showed obvious inheritance of autism-like phenotypes from F1 mice, implying the heritability of autism symptoms in patients with prenatal VPA exposure. Furthermore, we found prenatal baclofen administration was associated with beneficial effects on the autism-like phenotype in F2 male mice. This may have involved corrections in the density of total/mature dendritic spines in the hippocampus (HC) and medial prefrontal cortex (mPFC), normalizing synaptic plasticity. In this research, GABAB receptor agonist administration corrected the core autism-like behaviors of F1 mice and protected against the inheritance of neurodevelopmental disorders in the offspring of F1 mice, suggesting the potential of early intervention with GABAB receptor agonists in the treatment of neurodevelopmental disorders.

The GABAB receptor agonist STX209 reverses the autism­like behaviour in an animal model of autism induced by prenatal exposure to valproic acid.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition characterized by impaired social interaction, compromised communication, and restrictive or stereotyped behaviours and interests. Due to the complex pathophysiology of ASD, there are currently no available medical therapies for improving the associated social deficits. Consequently, the present study investigated the effects of STX209, a selective γ­aminobutyric acid type B receptor (GABABR2) agonist, on an environmental rodent model of autism. The mouse model of autism induced by prenatal exposure to valproic acid (VPA) was used to assess the therapeutic potential of STX209 on autism­like behaviour in the present study. This study investigated the effects of STX209 on VPA model mice via behavioral testing and revealed a significant reversal of core/associated autism­like behavior, including sociability and preference for social novelty, novelty recognition, locomotion and exploration activity and marble­burying deficit. This may be associated with STX209 correcting dendritic arborization, spine density and GABABR2 expression in hippocampus of VPA model mice. However, expression of glutamic acid decarboxylase 65/67 in the hippocampus were not altered by STX209. The present results demonstrated that STX209 administration ameliorated autism­like symptoms in mice exposed to VPA prenatally, suggesting that autism­like symptoms in children with a history of prenatal VPA exposure may also benefit from treatment with the GABABR2 agonist STX209.

Development and Validation of an Immune-Related Gene Pairs Signature in Grade II/III Glioma.

BACKGROUND: Gliomas are prevalent primary intracerebral malignant tumors. Increasing evidence indicates an association between the immune signature and Grade II/III glioma prognosis. Thus, we aimed to develop an immune-related gene pair (IRGP) signature that can be used as a prognostic tool in Grade II/III glioma. METHODS: The gene expression levels and clinical information of Grade II/III glioma patients were collected from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. The TCGA data were randomly divided into a training cohort (n = 249) and a validation cohort (n = 162), and a CGGA dataset served as an external validation group (n = 605). IRGPs significantly associated with prognosis were selected by Cox regression. Gene set enrichment analysis and filtration were performed with the IRGPs. RESULTS: Within a set of 1991 immune genes, 8 IRGPs including 15 unique genes that significantly affect survival constituted a gene signature. In the validation datasets, the IRGP signature significantly stratified patients with Grade II/III glioma into low- and high-risk groups (P < 0.001), and the IRGP index was found to be an independent prognostic factor through univariate and multivariate analyses (P < 0.05). Additionally, 26 functional pathways were identified through the intersection of Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) enrichment analysis. CONCLUSION: The IRGP signature demonstrated good prognostic value for Grade II/III gliomas, which may provide new insights into individual treatment for glioma patients. The IRGPs might function through the identified 26 functional pathways.

Is vagal-nerve stimulation safe during pregnancy? A mini review.

BACKGROUND: Vagus-nerve stimulation (VNS) is the most common neuromodulation technique and has been approved by the FDA for treating refractory epilepsy and refractory depression. Although VNS has been used for nearly 32 years, the impact of VNS on the safety of pregnant women and neonate remains to be evaluated. METHODS: We first analyze the relationship between the vagus nerve and the reproductive system (ovary and uterus) and then determine whether harm is inflicted to the reproductive system, thereby affecting the pregnancy. A comprehensive literature search is performed on PubMed/MEDLINE database, Web of Science, and Scopus. Ten articles are included in the study, and 44 pregnancies of 38 patients are analyzed. RESULTS: The vagus nerve is connected with the reproductive system, but VNS may have little effect on pregnancy. We analyze 10 articles (38 patients with 44 pregnancies) about VNS complications during pregnancy. Two of the 44 pregnancies (2/44, 4.5 %) are miscarriages, and two pregnancies have fetuses with congenital malformations (2/42, 4.8 %), which could also be attributed to polytherapy with antiepileptic drugs. The rest of the pregnant women have no postpartum complications, and their fetuses are healthy. CONCLUSIONS: VNS may be relatively safe and effective for the fetus and mother during pregnancy, and turning off VNS during pregnancy is unnecessary. However, owing to the small sample size and short follow-up time in the present study, further research is needed.

Supplementation With Dexmedetomidine for Transsphenoidal Resection of Pituitary Adenoma: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The effect of dexmedetomidine supplementation on hemodynamic stability for transsphenoidal resection of pituitary adenoma remains controversial. We conduct a systematic review and meta-analysis to explore the influence of dexmedetomidine supplementation on hemodynamic stability for transsphenoidal resection of pituitary adenoma. METHODS: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through August 2020 for randomized controlled trials assessing the effect of dexmedetomidine supplementation on transsphenoidal resection of pituitary adenoma. RESULTS: Four randomized controlled trials involving 160 patients were included in the meta-analysis. Overall, compared with the control group for transsphenoidal resection of pituitary adenoma, dexmedetomidine supplementation resulted in significantly reduced mean arterial pressure at 30 minutes [mean difference (MD), -26.62; 95% confidence interval (CI), -36.71 to -16.53; P < 0.00001], heart rate at 30 minutes (MD, -16.50; 95% CI, -32.48 to -0.53; P = 0.04), blood loss (MD, -112.57; 95% CI, -165.12 to -60.01; P < 0.0001), and fentanyl (MD, -154.13; 95% CI, -303.97 to -4.29; P = 0.04), but demonstrated similar incidence of nausea and vomiting (odds ratio, 0.37; 95% CI, 0.13-1.03; P = 0.06), and hypotension (odds ratio, 2.11; 95% CI, 0.49-9.22; P = 0.32). CONCLUSIONS: Dexmedetomidine supplementation was effective in improving hemodynamic stability for transsphenoidal resection of pituitary adenoma.

Glucagon-Like Peptide-1 Agonist Exendin-4 Facilitates the Extinction of Cocaine-Induced Condition Place Preference.

Accumulating studies suggest that the glucagon-like peptide-1 receptor agonist exendin-4 (Ex4) and toll-like receptor 4 (TLR4) play a pivotal role in the maladaptive behavior of cocaine. However, few studies have assessed whether Ex4 can facilitate the extinction of drug-associated behavior and attenuate the reinstatement of cocaine-induced condition place preference (CPP) in mice. The main objective of the present study was to evaluate Ex4's ability to regulate the extinction and reinstatement of cocaine-induced CPP. C57BL/6 mice were conditioned to either cocaine (20 mg/kg) or an equivalent volume of saline to establish a cocaine-mediated CPP paradigm. To investigate the potential effects of Ex4 on extinction, animals received an intraperitoneal injection of Ex4 either immediately or 6 h after each extinction or only on the test day. The persistence of extinction was measured using the reinstatement paradigm evoked by 10 mg/kg of cocaine. To explore the possible impacts of Ex4 and neuroinflammation on cocaine, the expression levels of TLR4 within the hippocampus was detected using western blotting. As a result, we found that systemic administration of Ex4 immediately after each extinction training, instead of 6 h after each extinction and on the day of extinction test, was capable of facilitating extinction in the confined or non-confined CPP extinction paradigms and blocking the cocaine-primed reinstatement of cocaine-induced CPP. Additionally, we also observed that Ex4 was competent to alleviate TLR4 signaling that has been up-regulated by cocaine. Altogether, our findings indicated that the combination of Ex4 with daily extinction training was sufficient to facilitate extinction of the conditioned behavior, attenuate reinstatement of cocaine-induced CPP and inhibit TLR4 signaling. Thus, Ex4 deserves further investigation as a potential intervention for the treatment of cocaine use disorder.

Continuous High Frequency Deep Brain Stimulation of the Rat Anterior Insula Attenuates the Relapse Post Withdrawal and Strengthens the Extinction of Morphine Seeking.

Deep brain stimulation (DBS) modulates the neuronal activity in specific brain circuits and has been recently considered as a promising intervention for refractory addiction. The insula cortex is the hub of interoception and is known to be involved in different aspects of substance use disorder. In the present study, we investigate the effects of continuous high frequency DBS in the anterior insula (AI) on drug-seeking behaviors and examined the molecular mechanisms of DBS action in morphine-addicted rats. Sprague-Dawley rats were trained to the morphine-conditioned place preference (CPP, day 1-8) followed by bilaterally implanted with DBS electrodes in the AI (Day 10) and recovery (Day 10-15). Continuous high-frequency (HF) -DBS (130 Hz, 150 µA, 90 µs) was applied during withdrawal (Day 16-30) or extinction sessions. CPP tests were conducted on days 16, 30, 40 during withdrawal session and several rats were used for proteomic analysis on day 30. Following the complete extinction, morphine-CPP was reinstated by a priming dose of morphine infusion (2 mg/kg). The open field and novel objective recognition tests were also performed to evaluate the DBS side effect on the locomotion and recognition memory. Continuous HF-DBS in the AI attenuated the expression of morphine-CPP post-withdrawal (Day 30), but morphine addictive behavior relapsed 10 days after the cessation of DBS (Day 40). Continuous HF-DBS reduced the period to full extinction of morphine-CPP and blocked morphine priming-induced recurrence of morphine addiction. HF-DBS in the AI had no obvious effect on the locomotor activity and novel objective recognition and did not cause anxiety-like behavior. In addition, our proteomic analysis identified eight morphine-regulated proteins in the AI and their expression levels were reversely changed by HF-DBS. Continuous HF-DBS in the bilateral anterior insula prevents the relapse of morphine place preference after withdrawal, facilitates its extinction, blocks the reinstatement induced by morphine priming and reverses the expression of morphine-regulated proteins. Our findings suggest that manipulation of insular activity by DBS could be a potential intervention to treat substance use disorder, although future research is warranted.

Inpatient Outcomes of Surgical Treatment for Spinal Tuberculosis: 10-Year Results from the US National Inpatient Sample.

AIM: To evaluate the association between in-hospital outcomes of patients with spinal tuberculosis and different surgical approaches. MATERIAL AND METHODS: This population-based, retrospective observational study analyzed data of hospitalized patients undergoing surgical treatment for spinal tuberculosis in the United States who were identified in the US Nationwide Inpatient Sample (NIS) between 2005 and 2014. The study cohort was stratified by posterior-only, anterior-only, and combined surgical approaches. Logistic and linear regression analyses were performed to evaluate associations between surgical approaches and patient outcomes. RESULTS: Significant differences were found in postoperative complications, number of instrumented levels, and comorbidity scores (all p ? 0.033) between patients who received different surgical approaches. A univariate analysis demonstrated the combined approach was associated with significantly increased odds of postoperative complications compared with the posterior-only approach. This association remained significant when following multivariate analysis after adjustments. For patients who received surgery at the lumbosacral level, the anterior-only approach and combined approach were both associated with significantly increased odds of postoperative complications compared with the posterior-only approach. Among patients who received surgery at the lumbosacral level, multivariate analysis showed that anterior-only and combined approaches were associated with significantly longer length of stay. CONCLUSION: Among patients with spinal tuberculosis who are undergoing surgical treatment, a posterior-only approach was associated with fewer complications and shorter length of stay compared with an anterior-only or combination approaches when performed at the lumbo-sacral spinal level.

Predicting Individual Prognosis and Grade of Patients with Glioma Based on Preoperative Eosinophil and Neutrophil-to-Lymphocyte Ratio.

PURPOSE: Eosinophils are proven to play a role in the prognosis of some malignant-tumors. The prognostic value of eosinophils in glioma patients is, however, scarcely reported. The authors of this article have designed a novel prognostic indicator based on eosinophils and the neutrophil-to-lymphocyte ratio (NLR), named ENS, to predict the survival of patients with glioma. METHODS: A retrospective study was conducted on 217 glioma patients. The cut-off values for eosinophil, NLR, and other clinical variables were determined by the receiver operating characteristic (ROC) curve analysis. Patients with both low eosinophil count (<0.08 ×109/L) and high NLR (≥1.70) were given a score of 2. Those with one or neither got a score of 1 or 0, respectively. The nomogram was based on ENS and several other clinical variables, its performance was determined by the concordance index (c-index). RESULTS: Our results showed that ENS is an independent prognostic indicator for overall survival (OS). The three-year OS rates for low-grade glioma patients (LGGs) were 84.0%, 69.0%, and 46.4% for ENS=0, ENS=1, and ENS=2, respectively (P=0.014). The three-year OS incidence for LGGs stratified into eosinophils count ≥0.08×109/L and<0.08×109/L subgroups were 88.1% and 80.0%, respectively (P=0.043). ENS was positively correlated with glioma grade (r=0.311, P<0.001). The c-index for OS prognosis was 0.80 using this nomogram in LGGs. CONCLUSION: Preoperative ENS can predict OS to some extent for LGGs and can increase prognostic accuracy for individual OS in LGGs postoperatively when incorporating other clinical variables compose a nomogram.

The influence of sertraline on depressive disorder after traumatic brain injury: A meta-analysis of randomized controlled studies.

BACKGROUND: Sertraline showed some potential in alleviating depressive disorder after traumatic brain injury. This systematic review and meta-analysis was conducted to investigate the efficacy of sertraline on the treatment of depressive disorder after traumatic brain injury. METHODS: The databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched for collecting the randomized controlled trials (RCTs) regarding the efficacy of sertraline for traumatic brain injury. RESULTS: This meta-analysis included five RCTs. The initial use of sertraline was within 8 weeks after traumatic brain injury. Compared with control group for traumatic brain injury, sertraline treatment showed no significant improvement on Hamilton Depression Rating Scale (HAM-D) (standard mean difference (Std. MD) = -0.08; 95% confidence interval (CI) = -0.45 to 0.28; P = 0.65), anxiety score (Std. MD = 0.08; 95% CI = -0.32 to 0.48; P = 0.69), aggression score (Std. MD = -0.12; 95% CI = -0.56 to 0.32; P = 0.59), or quality of life (QOL) score (Std. MD = -0.06; 95% CI = -0.49 to 0.37; P = 0.78). There was no statistical difference of diarrhea (risk ratio (RR) = 0.85; 95% CI = 0.92 to 3.71; P = 0.08), dizziness (RR = 1.15; 95% CI = 0.57 to 2.31; P = 0.70), dry mouth (RR = 2.44; 95% CI = 0.43 to 13.89; P = 0.32), nausea or vomiting (RR = 1.17; 95% CI = 0.37 to 3.70; P = 0.79) between sertraline group and control group. CONCLUSIONS: Sertraline showed no obvious benefits for the relief of depressive disorder after traumatic brain injury.