Long-term exercise training down-regulates m6A RNA demethylase FTO expression in the hippocampus and hypothalamus: an effective intervention for epigenetic modification.

BACKGROUND: Exercise boosts the health of some brain parts, such as the hippocampus and hypothalamus. Several studies show that long-term exercise improves spatial learning and memory, enhances hypothalamic leptin sensitivity, and regulates energy balance. However, the effect of exercise on the hippocampus and hypothalamus is not fully understood. The study aimed to find epigenetic modifications or changes in gene expression of the hippocampus and hypothalamus due to exercise. METHODS: Male C57BL/6 mice were randomly divided into sedentary and exercise groups. All mice in the exercise group were subjected to treadmill exercise 5 days per week for 1 h each day. After the 12-week exercise intervention, the hippocampus and hypothalamus tissue were used for RNA-sequencing or molecular biology experiments. RESULTS: In both groups, numerous differentially expressed genes of the hippocampus (up-regulated: 53, down-regulated: 49) and hypothalamus (up-regulated: 24, down-regulated: 40) were observed. In the exercise group, increased level of N6-methyladenosine (m6A) was observed in the hippocampus and hypothalamus (p < 0.05). Furthermore, the fat mass and obesity-associated gene (FTO) of the hippocampus and hypothalamus were down-regulated in the exercise group (p < 0.001). In addition, the Fto co-expression genes of the mouse brain were studied and analyzed using database to determine the potential roles of exercise-downregulated FTO in the brain. CONCLUSION: The findings demonstrate that long-term exercise might elevates the levels of m6A-tagged transcripts in the hippocampus and hypothalamus via down-regulation of FTO. Hence, exercise might be an effective intervention for epigenetic modification.

Shifting subdural fluid collection and hydrocephalus after foramen magnum decompression for basilar invagination.

Background: Postoperative hydrocephalus and subdural fluid collection (SFC) have been reported as the rare complications following foramen magnum decompression in patients with Chiari malformation.Case Description: The paper reports the case of a 63-year-old female patient who underwent foramen magnum decompression for basilar invagination. The patient developed a shifting, bilateral SFC and subsequent acute hydrocephalus. A ventriculoperitoneal shunting was performed and the clinical symptom resolved. The dramatic change in CSF distribution supported the diagnosis of external hydrocephalus, which was associated with a postoperative cervical pseudomeningocele.Conclusions: Postoperative SFC in patients underwent foramen magnum decompression may harbor different mechanisms. Subdural drainage for patients having external hydrocephalus may have a higher recurrence rate.

Predictive Factors of Postoperative Peritumoral Brain Edema after Meningioma Resection.

BACKGROUND: Postoperative peritumoral brain edema (PTBE) is the progressively exacerbating cerebral edema following meningiomas resection. OBJECTIVE: The study aims to identify the predictive factors of postoperative PTBE. MATERIALS AND METHODS: A retrospective study was conducted on the 117 cases of patients who underwent meningioma. The histopathological features of the tumors were re-assessed according to WHO 2016 classification. Clinical and pathohistological features were analyzed. RESULTS: Thirteen patients (11.1%) were diagnosed having postoperative PTBE. Preoperative seizure (odds ratio [OR] = 6.125, P = 0.039) and histological prominent nucleoli (OR = 3.943, P = 0.039) were the independent risk factors for postoperative PTBE. Meningiomas with a parietal localization were more likely to develop postoperative PTBE (OR = 3.576, P = 0.054). Brain invasion and large tumor volume did not increase complication rate. Preoperative edema index was significantly higher in brain invasive meningiomas (3.0 ± 2.2 versus 1.8 ± 1.7, P = 0.001). Patients having moderate preoperative PTBE were prone to the complication (21.4% versus 7.9%, P = 0.100). CONCLUSIONS: Preoperative seizure were the predictive factors for postoperative PTBE. Careful venous protection during the operation may be helpful, especially for tumors locating in the parietal lobe. Prominent nucleoli observed in postoperative pathology should warrant surgeons' attention. Comprehensive perioperative management is essential for these patients.

Spinal arachnoiditis followed by intrathecal tigecycline therapy for central nervous system infection by extremely drug-resistant Acinetobacter baumannii.

In prior research, intrathecal tigecycline was successfully used to treat central nervous system infection by extensively drug-resistant Acinetobacter baumannii. However, little is known about its safe dose and adverse reactions. This study reports the case of a 28-year-old male patient who was diagnosed with central nervous system infection by extensively drug-resistant A. baumannii after the removal of a ventriculoperitoneal shunt. Intravenous and intrathecal tigecycline were administrated simultaneously. Spinal arachnoiditis was discovered after nine doses of intrathecal tigecycline. Spinal arachnoiditis was resolved after discontinuation of the antibiotic. This is the first report of an adverse reaction to intrathecal tigecycline. The case was complicated by spinal arachnoiditis, which obstructed the assessment of cerebrospinal fluid. The appropriate dose and administration schedule of intrathecal tigecycline remain to be determined.

Complications in Staged Late Titanium Cranioplasty and Ventriculoperitoneal Shunting for Patients with Traumatic Brain Injury.

BACKGROUND: Hydrocephalus is a common complication following decompressive craniectomy. Ventriculoperitoneal shunt (VPS) is required for some patients before receiving a cranioplasty (CP). The presence of a VPS is regarded as a risk factor for overall CP complications. METHODS: A retrospective survey was conducted on 176 patients with traumatic brain injury who underwent late (>3 months) titanium CP (Ti-CP) in our hospital from April 2014 to July 2018. Thirteen patients (7.4%) had preoperative VPS. Propensity score matching was performed for these 13 patients with a ratio of 1:5. A total of 78 patients were selected. Preoperative clinical parameters and postoperative complications were analyzed. The period of postoperative follow-up ranged from 3 to 63 months (mean 21.3 ± 17.0 months). RESULTS: The overall complication rate was greater in the VPS group (P = 0.010). These patients were more likely to develop a sunken skin flap (P < 0.001). The rate of postoperative cerebral hemorrhage was greater in the VPS group. Logistic analysis showed that preoperative VPS was an independent risk factor for postoperative extradural collection (odds ratio 17.714, P < 0.001). VPS was not related to postoperative infection and seizure. Postoperative drainage duration longer than 2.5 days significantly increased the risk of postoperative infection (odds ratio 7.715, P = 0.023). CONCLUSIONS: The presence of a VPS significantly increased the risk of extradural collection in patients with traumatic brain injury who underwent late Ti-CP. It also was related to postoperative hemorrhage. The sunken skin flap in patients with VPS increased surgical difficulty and the likelihood of extradural accumulation. Preoperative VPS was not related to postoperative infection and seizure in Ti-CP.

Impact of Surgeon Experience on Postoperative Rehemorrhage in Spontaneous Basal Ganglia Intracerebral Hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (SICH) is of high mortality and morbidity. SICH in the basal ganglia is usually attributed to chronic hypertension. Postoperative rehemorrhage is a severe complication, and it is relative to surgical techniques. METHODS: A retrospective survey was conducted on 123 patients with basal ganglia SICH who received surgery from January 2015 to January 2019. Postoperative rehemorrhage within 24 hours was recorded. Preoperative clinical parameters, surgeon experience (<10 and >20 years), operation time, surgical approach, and hemostasis technique were recorded and analyzed. RESULTS: The total postoperative rehemorrhage rate was 12.2% (15/123). The univariable analysis showed general surgeons had a higher postoperative rehemorrhage rate than experienced surgeons (30.4% vs. 8.6%, respectively; P = 0.068). The operation time (minutes) in experienced surgeons was significantly longer (164.9 ± 53.5 vs. 137.7 ± 30.8, P = 0.016), but they had a higher chance to locate the responsible vessel (74.2% vs. 40.0%, P = 0.001), respectively. Logistic analysis indicated that experienced surgeons significantly reduced the risk of rehemorrhage (odds ratio [OR], 0.242; P = 0.021). Transsylvian approach was a protective factor for postoperative rehemorrhage (OR, 0.291; P = 0.045). CONCLUSIONS: Surgeons' experience plays the most important role in postoperative rehemorrhage. Surgeons with rich experience were willing to spend more time to achieve definitive hemostasis in operation. The use of a transsylvian approach can significantly reduce the rehemorrhage rate. Packing hemostasis with gelatin sponge may increase complications.

Excessive Hemostasis on the Scalp Increases Superficial Surgical Site Infection Rate in Cranioplasty.

BACKGROUND: Cranioplasty is a routine procedure, but it carries a significantly higher complication rate over standard clean cranial surgery. Surgical site infection is the most common but severe complication. Risk factors for surgical site infection are still debated. METHODS: A retrospective survey of 155 patients (≥16 years old) who exclusively underwent customized titanium cranioplasty from April 2014 to January 2017 was performed. Preoperative clinical parameters, surgeon's hemostasis technique, temporalis dissection, operative time, intraoperative blood loss, postoperative catheter duration and drainage, postoperative hemorrhage and extradural fluid collection (EDFC), and prophylactic antibiotics were recorded and compared between patients with superficial surgical site infection (sSSI) and patients with non-sSSI. RESULTS: Overall sSSI rate was 10.3%. Binary logistic analysis showed excessive hemostasis on scalp (odds ratio = 10.302, P = 0.000), presence of postoperative EDFC (odds ratio = 12.740, P = 0.003), and postoperative drainage >277 mL (odds ratio = 10.302, P = 0.000) were independent risk factors for sSSI. Patients who received excessive hemostasis had a longer operative time (P = 0.000). A flaccid cranial defect was a protective factor for postoperative EDFC (odds ratio = 0.130, P = 0.044), whereas presence of ventriculoperitoneal shunt could induce EDFC formation (odds ratio = 9.598, P = 0.020). Postoperative subgaleal drainage was correlated to the size of cranial defect (standardized ß = 0.347, P = 0.000). Timing of cranioplasty and use of prophylactic antibiotics were not related to sSSI. CONCLUSIONS: Surgeons should lower the hemostasis standard for cranioplasty, as this would promote wound healing and reduce operative time, which subsequently decreases SSI rate.

Bilateral External Ventricular Drains Increase Ventriculostomy-Associated Cerebrospinal Fluid Infection in Low Modified Graeb Score Intraventricular Hemorrhage.

BACKGROUND: Ventriculostomy-associated cerebrospinal fluid infection (VAI) is a major complication limiting the use of an external ventricular drain (EVD) in treating patients with intraventricular hemorrhage (IVH). Risk factors of VAI are still under wide discussion. METHODS: We performed a retrospective review of 84 patients with IVH who underwent EVD at our center between January 2012 and January 2017. Preoperative clinical parameters, surgeon status, number of catheters and catheter-days, subgaleal tunneling distance, frequency of urokinase flush, and prophylactic antibiotics were compared between the infective and noninfective groups. RESULTS: The overall rate of VAI was 31.0%. Univariate analysis showed a higher modified Graeb Score (mGS), higher proportion of bilateral catheters, and longer hospital stay in patients with VAI. Binary logistic analysis of all clinical factors identified high mGS (≥16) as an independent risk factor for VAI (odds ratio, 3.242; P = 0.026). Among operative and postoperative factors, the use of bilateral catheters significantly contributed to VAI (odds ratio, 4.211; P = 0.031), but a subgroup comparison showed an increased VAI rate only in the low mGS group (mGS <15). No VAI occurred in patients with a single EVD in the low mGS group. Catheter-days and multiple urokinase flushes were not related to VAI. CONCLUSIONS: Patients with a high mGS are vulnerable to VAI. Bilateral EVD may be an appropriate treatment option for patients with a high mGS, but might increase the risk of infection in those with a low mGS.

Long-term moderate exercise enhances specific proteins that constitute neurotrophin signaling pathway: A TMT-based quantitative proteomic analysis of rat plasma.

Physical exercise has been reported to increase neurotrophin in brain tissues as hippocampus as well as increased neurotrophic level peripherally in blood plasma and might have an effect on/or affect molecular processes of energy metabolism (and homeostasis). In this study, using quantitative proteomic analysis, we obtained a plasma protein profile from the rat with long-term moderate exercise. A total of 752 proteins were identified in the plasma. Among them, 54 proteins were significant up-regulated and 47 proteins were down-regulated in the plasma of exercise group compared with the control group. Bioinformatic analyses showed that these altered proteins are widely involved in multiple biological processes, molecular functions and cellular components, which connect with 11 signaling pathways. Interestingly, 5 up-regulated proteins Rap1b, PTPN11, ARHGDIA, Cdc42 and YWHAE, confirmed by Western blots, are involved in the neurotrophin signaling pathway which shows the lowest P value among the identified pathways. Further analyses showed that the 5 neurotrophin-signaling-pathway-related proteins participate in two important protein-protein interaction networks associated to cell survival and apoptosis, axonal development, synapse formation and plasticity. This study provides an exercise-induced plasma protein profile, suggesting that long-term exercise enhances the proteins involved in neurotrophin signaling pathway which may contribute to health benefit. SIGNIFICANCE: Physical activity contributes to myriad benefits on body health across the lifespan. The changes in plasma proteins after chronic moderate exercise may be used as biomarkers for health and may also play important roles in increase of cardiovascular fitness, enhancement of immune competence, prevention of obesity, decrease of risk for neurological disorders, cancer, stroke, diabetes and other metabolic disorders. Using a TMT-based proteomic method, this study identified 101 altered proteins in the plasma of rats after long-term moderate treadmill running, which may provide novel biomarkers for further investigation of the underlying mechanism of physical exercise. We confirmed that exercise enhances 5 proteins of the neurotrophin signaling pathway that may contribute to health benefits.

[Effect of xiaokeling concentration fluid on mRNA expression of insulin-like growth factor-1 in sciatic nerve of Streptozotocin-induced diabetic rats].

OBJECTIVE: To investigate the effect of xiaokeling concentration fluid on insulin-like growth factor-1 (IGF-1) mRNA expression in sciatic nerve of Streptozotocin-induced diabetic rats. METHODS: Thirty diabetic rats were randomly divided into model group, mecobalamin tablets group, and xiaokeling concentration fluid group. The IGF-1 mRNA level in sciatic nerve of each group was determined after 8 weeks by relative quantity RT-PCR. RESULTS: The IGF-1 mRNA level in sciatic nerve of diabetic rats between xiaokeling concentration fluid group, mecobalamin tablets group and normal group showed no significant difference ( P = 0.213, P = 0.822, P = 0.304 ), while was significantly higher than that of the model group ( P < 0.05 ). IGF-1 mRNA level was negatively correlated with the level of blood sugar (P < 0.05). CONCLUSION: IGF-1 mRNA level decreased in sciatic nerve of diabetic rats. Xiaokeling concentration fluid can increase the IGF-1 mRNA level in sciatic nerve of diabetic rats. Xiaokeling concentration fluid is involved in the regulation of IGF-1 expression, and probably prevents diabetic peripheral neuropathy from deteriorating.