Risk factors for wound healing complications after revascularization for MMD with complete Y-shaped incision.

Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease that can be treated with revascularization. Surgery increases the risk of poor wound healing (PWH) due to the impact on the blood supply to the flap. We aimed to analyze risk factors for PWH in MMD with a complete Y-shaped incision. A total of 125 patients with MMD were enrolled in this prospective observational study. The wounds were assessed and measured on the third and seventh days after surgery. The mean age of these patients was 43.3 ± 10.0 years. The ratio of male to female was 1:1.3. 15 (12.0%) patients had incision complications. 5 patients (4.0%) had redness; 2 patients (1.6%) had swelling; 2 patients (1.6%) had fat necrosis; 3 patients (2.4%) had incision infection; and 3 patients (2.4%) had flap necrosis. Student's t test showed significant differences in BMI (P = 0.040) and fever time (P = 0.050). The standard chi-squared test showed significant differences in incision infection (P = 0.010), suture mode (P = 0.047), and cutting off large branch vessels in the flap (P < 0.001). Multivariate logistic regression analysis suggested that incision infection (P = 0.026, OR 12.958), using a skin stapler (P = 0.030, OR 4.335), cutting off large branch vessels in the flap (P = 0.009, OR 5.227), and BMI (P = 0.027, OR 1.204) were risk factors. The area under the curve for risk factors for PWH on a receiver operating characteristic curve was 0.853. Incision infection, using a skin stapler, higher BMI, and cutting off large branch vessels in the flap are risk factors for PWH.

Noninvasive Prediction of Language Lateralization Through Arcuate Fasciculus Tractography in Patients With Low-Grade Gliomas: Correlation With The Wada Test.

Language lateralization is unique to humans, so clarifying dominant side is helpful for removing gliomas involving language areas. This study investigated the arcuate fasciculus (AF) reconstructed by diffusion tensor imaging-based tractography (DTT) in predicting language lateralization in patients with low-grade gliomas. Wada test was performed to determine the language Dominant Hemisphere (DH) and the Contralateral Hemisphere. DTI data [1.5-T magnetic resonance imaging (MRI)] was used to reconstruct AF by two independent operators using a DTT method. Fiber number, volume, and fractional anisotropy (FA) of bilateral reconstructed AF were measured. Lateralization indexes (LIs), including Number Index (NI), Volume Index (VI), and FA Index (FI), were accordingly calculated by mean values. A total of 21 patients with WHO Grade II gliomas in the left hemisphere were included. Every patient received a successful Wada test and reconstruction of bilateral AF. DTT metrics of reconstructed AF, such as fiber number, volume, and FA, showed significantly asymmetric between hemispheres. All the LI (NI, VI, and FI) values were statistically higher in the DH determined by the Wada test. No discrepancy was found between the prediction using the cutoff values of DTT metrics and the results of WADA test. The Kappa values were 0.829, 0.696, and 0.611, indicating NI and VI as more reliable predictor than FI although FI itself may also be feasible. Compared with the Wada test, we consider that DTT of AF is a non-invasive, simple, relatively accurate, and feasible method in predicting language lateralization in patients with low-grade gliomas.

MiR-101a-3p Attenuated Pilocarpine-Induced Epilepsy by Downregulating c-FOS.

This study aimed to explore the effects and function of microRNA-101a-3p (miR-101a-3p) in epilepsy. Rat model of pilocarpine-induced epilepsy was established and the seizure frequency was recorded. Expression of miR-101a-3p and c-Fos in hippocampus tissues of Rat models were detected by qRT-PCR and western blot. Besides, we established a hippocampal neuronal culture model of acquired epilepsy using Mg2+ free medium to evaluate the effects of miR-101a-3p and c-Fos in vitro. Cells were transfected with miR-101a-3p mimic, si-c-FOS, miR-101a-3p + c-FOS and its corresponding controls. MTT assay was used to detect cell viability upon transfection. Flow cytometry was performed to determine the apoptosis rate. Western blot was performed to measure the protein expression of apoptosis-related proteins (Bcl-2, Bax, and cleaved caspase 3), autophagy-related proteins (LC3 and Beclin1) and c-FOS. The targeting relationship between miR-101a-3p and c-FOS was predicted and verified by TargetScan software and dual-luciferase reporter assay. The role of miR-101a-3p was validated using epilepsy rat models in vivo. Another Rat models of pilocarpine-induced epilepsy with miR-NC or miR-101a-3p injection were established to evaluate the effect of miR-101a-3p overexpression on epilepsy in vivo. MiR-101a-3p was downregulated while c-FOS was increased in hippocampus tissues of Rat model of pilocarpine-induced epilepsy. Overexpression of miR-101a-3p or c-FOS depletion promoted cell viability, inhibited cell apoptosis and autophagy. C-FOS was a target of miR-101a-3p and miR-101a-3p negatively regulated c-FOS expression to function in epilepsy. Overexpression of miR-101a-3p attenuated pilocarpine-induced epilepsy in Rats in vivo. This study indicated that miR-101a-3p could attenuate pilocarpine-induced epilepsy by repressing c-Fos expression.

Propofol inhibited apoptosis of hippocampal neurons in status epilepticus through miR-15a-5p/NR2B/ERK1/2 pathway.

Although a previous study reported that propofol had a therapeutic effect in status epilepticus (SE), the mechanisms underlying the effect of propofol in SE remain unclear. The aim of this study was to explore the regulatory mechanisms underlying propofol-induced inhibition of SE.A rat SE model was established using the lithium-pilocarpine injection method. A qRT-PCR and Western blot were utilized to detect the expression of relative molecules. Cell apoptosis was evaluated by a flow cytometry assay. The interaction between miR-15a-5p and NR2B was assessed using a luciferase reporter assay.Propofol inhibited cell apoptosis and increased miR-15a-5p expression both in hippocampal tissues of SE rats and low Mg2+-induced hippocampal neurons. Propofol-induced attenuation of apoptosis of low Mg2+-induced hippocampal neurons was mediated by miR-15a-5p. miR-15a-5p targeted NR2B and negatively regulated its expression. Propofol downregulated NR2B expression, mediated by miR-15a-5p. In terms of the mechanism of action, propofol suppressed the apoptosis of Mg2+-induced hippocampal neurons through the miR-15a-5p/NR2B/ERK1/2 pathway. In vivo experiment suggested that propofol inhibited the apoptosis of hippocampal neurons in SE rats by upregulating miR-15a-5p.In terms of the molecular mechanism of propofol, it appears to inhibit apoptosis of hippocampal neurons in SE through the miR-15a-5p/NR2B/ERK1/2 pathway. The findings provide theoretical support for propofol treatment of SE.

Retracted Article: Upregulation of miR-26b alleviates morphine tolerance by inhibiting BDNF via Wnt/ß-catenin pathway in rats.

Background: Morphine is a commonly used analgesic drug. However, long-term use of morphine will cause tolerance which limits its clinical application in pain treatment. MicroRNAs (miRNAs) have been reported to be involved in the morphine tolerance, but the underlying mechanism is still poorly understood. Methods: Tail flick test was used to measure the maximum possible effect (MPE). Quantitative real-time PCR was employed to detect miR-26b, BDNF, and Wnt5a expression in rat dorsal root ganglia (DRG). Luciferase report assay was introduced to verify the binding relationship between miR-26b and Wnt5a. BDNF, Wnt5a and ß-catenin protein level were tested by western blotting. Results: MiR-26b was down-regulated during the development of morphine tolerance while BDNF was upregulated. Overexpression of miR-26b or BDNF inhibition alleviated morphine tolerance. Wnt5a was directly targeted and inhibited by miR-26b via binding to the 3'-UTR of Wnt5a. The Wnt/ß-catenin pathway was active in morphine tolerant rats. Moreover, overexpression of Wnt5a could partially enhance miR-26 mimic-mediated morphine tolerance, while a Wnt5a inhibitor could attenuate the tolerance. Conclusion: The present study demonstrated that miR-26b overexpression alleviated morphine tolerance by inhibiting BDNF via the Wnt/ß-catenin pathway in rats, highlighting a promising target for the treatment of morphine tolerance.

LncRNA UCA1 inhibits epilepsy and seizure-induced brain injury by regulating miR-495/Nrf2-ARE signal pathway.

BACKGROUND: Both LncRNA UCA1 and miR-495 are crucial gene regulators in various disorders. This study aims to investigate their role in epilepsy and seizure-induced brain injury. METHODS: In this research, rat model of epilepsy was established by pilocarpine induction. The RNA and protein expression in hippocampal tissues and neurons were determined by qRT-PCR and western blot, respectively. The hippocampal neurons were isolated from hippocampal tissues, and treated with magnesium-free (MGF) physiological solution for epileptiform activity induction. The endogenous expression of related genes was modulated by recombinant plasmids and cell transfection. Flow cytometry was used to analyze the cell apoptosis. Dual luciferase reporter assay was performed to determine the interaction between miR-495 and Nrf2 in HEK-293 cells. RESULTS: The lncRNA UCA1 and Nrf2 were down-regulated in epileptiform hippocampal tissues and neurons, while the miR-495 was up-regulated. Over-expression of UCA1 inhibited apoptosis of hippocampal neurons by suppressing miR-495. MiR-495 negatively regulated Nrf2. UCA1 inhibited apoptosis of hippocampal neurons through miR-495/Nrf2-ARE pathway. UCA1 suppressed pilocarpine-induced epilepsy in rat. CONCLUSION: LncRNA UCA1 suppressed pilocarpine-induced epilepsy by inhibiting apoptosis of hippocampal neurons through miR-495/Nrf2-ARE pathway, and thereby inhibiting brain injury induced by seizure.

Intraoperative high-field magnetic resonance imaging combined with functional neuronavigation in resection of low-grade temporal lobe tumors.

BACKGROUND: The aim of this study is to investigate the role of intraoperative MR imaging in temporal lobe low-grade glioma (LGG) surgery and to report the surgical outcome in our series with regard to seizures, neurological defects, and quality of life. METHODS: Patients with temporal lobe contrast-nonenhancing gliomas who presented with seizures in the course of their disease were enrolled in our prospective study. We non-randomly assigned patients to undergo intraoperative magnetic resonance imaging (iMRI)-guided surgery or conventional surgery. Extent of resection (EOR) and surgical outcomes were compared between the two groups. RESULTS: Forty-one patients were allocated in the iMRI group, and 14 were in the conventional group. Comparable EOR was achieved for the two groups (p = 0.634) although preoperative tumor volumes were significantly larger for the iMRI group. Seizure outcome tended to be better for the iMRI group (Engel class I achieved for 89.7% (35/39) vs 75% (9/12)) although this difference was not statistically different. Newly developed neurological deficits were observed in four patients (10.3%) and two patients (16.7%), respectively (p = 0.928). Free of seizures and neurological morbidity led to a return-to-work or return-to-school rate of 84.6% (33/39) vs 75% (9/12), respectively (p = 0.741). CONCLUSIONS: Our study provided evidence that iMRI was a safe and useful tool in temporal lobe LGG surgery. Optimal extent of resection contributed to favorable seizure outcome in our series with low morbidity rate, which led to a high return-to-work rate.

Aqueduct Stent Placement: Indications, Technique, and Clinical Experience.

OBJECTIVE: Complicated hydrocephalus, such as trapped fourth ventricle, is challenging. Aqueduct stent placement is a possible alternative to the conventional multiple shunts approach. This article discusses the indications, techniques, and clinical experiences of aqueduct stent placement. METHODS: We retrospectively analyzed a series of 10 consecutive patients with hydrocephalus and had aqueduct stent placement between February 2009 and May 2014. The clinical and imaging data were collected and the indications, technique, and clinical experience of aqueduct stent placement were analyzed and discussed. RESULTS: Among the 10 patients (mean age, 38 years; range, 5 months-69 years), 8 patients harbored an obstructive hydrocephalus caused by aqueductal obstruction. The underlying pathology consisted of intraventricular tumor in 3 patients, intraventricular cysticercosis in 2, and membranous or inflammatory obstruction in 3 patients. Two patients presented with trapped fourth ventricle, which resulted from Dandy-Walker malformation and shunt placement, respectively. Aqueduct stents were placed endoscopically in 8 patients, whereas the other 2 were placed microscopically. There were no deaths due to aqueduct stent placement. Postoperatively, all of the patients showed improvement or resolution of their symptoms. After an average follow-up period of 27 months (range, 1-51 months), recurrence of aqueductal obstruction has not been observed. In 1 patient, there was a complication of transient oculomotor paralysis after aqueduct stent placement. A stent migration was observed in 1 patient after remaining stable for 4 years. CONCLUSIONS: Aqueduct stent placement is technically feasible and can be useful in selected patients either with endoscopy or open surgery.

[Intraoperative high-field magnetic resonance imaging combined with functional neuronavigation in resection of low-grade temporal lobe tumors involving optic radiation].

OBJECTIVE: To investigate the clinical value of high-field-strength intraoperative magnetic resonance imaging (iMRI) combined with optic radiation neuro-navigation for the resection of temporal lobe low-grade gliomas. METHODS: From April 2009 to September 2013, 65 patients with temporal lobe low-grade gliomas (WHO grade II) involving optic radiation were operated with iMRI and functional neuro-navigation. Diffusion tensor imaging (DTI) based fiber tracking was used to delineate optic radiation. The reconstructed optic radiations were integrated into a navigation system, in order to achieve intraoperative microscopic-based functional neuro-navigation. iMRI was used to update the images for both optic radiations and residual tumors. Volumetric analyses were performed using 3D Slicer for pre- and intra-operative tumor volumes in all cases. All patients were evaluated for visual field deficits preoperatively and postoperatively. The Student t test was used to evaluate the average rate of extent of resection between groups. Spearman rank correlation analysis was used to assess correlations between predictors and epilepsy prognosis. RESULTS: Preoperative tumor volumes were (78±40) cm3. In 29 cases, iMRI scan detected residual tumor that could be further resected, and extent of resection were increased from 76.2% to 92.7% (t=7.314, P<0.01). In 19 cases (29.2%), gross total resection was accomplished, and iMRI contributed directly to 8 of these cases. Postsurgical follow-up period varied from 13 months to 59 months, mean (33±13) months. Tumor progression were observed in 3 patients, newly developed or deteriorated visual field defects occurred in 4 patients (6.2%). For patients with pre-operative seizures, Engel Class I were achieved for 89.7% of them. Spearman rank correlation analysis revealed that seizure outcome (Engel Class) was related to increased excision of ratio (r=-0.452, P=0.004, 95% CI: -0.636--0.261) and larger tumors (r=0.391, P=0.014, 95% CI: 0.178-0.484). CONCLUSIONS: With iMRI and functional neuro-navigation, the optic radiation can be accurately located, while extent of resection can be evaluated intra-operatively. This technique is safe and helpful for preservation of visual field for the resection of temporal lobe low-grade gliomas involving optic radiation.