Case report: Two case reports of cryptogenic brain abscess caused by Fusobacterium nucleatum and literature review.

Brain abscess originates from a localized cerebritis area of brain parenchyma, remaining a refractory infectious disease in the central nervous system. Causative pathogens can be wide-ranging, including bacteria, fungi, or parasites; thus, precise pathogen identification and individualized antimicrobial therapy determine patients' outcomes. Here, we report two cases where both patients only presented with limb dysfunction, but without symptoms, signs, or biological evidence of infection. Samples were obtained through brain stereoscopic surgeries and microbial identifications were performed to confirm the infection of Fusobacterium nucleatum. Further appropriate treatments were given, and the patients recovered well. Patient 1 was a 73-year-old male with a 20-day history of left-sided limbs weakness. A brain MRI showed a space-occupying lesion with a heterogeneously ring-enhancement character in the right frontal lobe. This patient underwent puncture biopsy of the lesion with robot-assisted guidance to confirm a brain abscess. Empirical antibiotic therapy was immediately given until the pathogen was identified as Fusobacterium nucleatum; thus, he received specific antibiotic therapy with metronidazole and recovered well after treatment. Patient 2 was a 22-year-old female with heart disease history who complained of right-sided limb weakness for nine days. A brain MRI showed a circular enhanced lesion with a thin capsule wall and surrounding edema in the left frontal lobe. This patient underwent puncture drainage of the lesion with robot-assisted guidance and a brain abscess was confirmed. Empirical antibiotic therapy was given until the pathogen was identified as Fusobacterium nucleatum and then she also received metronidazole treatment. Her symptoms recovered and the lesion disappeared after 1 month. Hence, we reviewed the diagnosis and treatment of cryptogenic brain abscess caused by Fusobacterium nucleatum and highlight that precise neurosurgical interventions and identification of causative pathogens are crucial for the management of brain abscess.

Risk factors for the progression of unruptured intracranial aneurysms in patients followed by CT/MR angiography.

BACKGROUND: The progression of an unruptured intracranial aneurysm (UIA) is associated with a higher rupture risk. The aim of this study was to identify the risk factors for the progression of UIAs among Chinese adults and compare them with the ELAPSS (Earlier subarachnoid hemorrhage, IA Location, Age, Population, IA Size and Shape) score. METHODS: Four hundred thirty-eight consecutive patients with 491 UIAs were followed and reviewed retrospectively from August 2011 to November 2019. Follow-up images of the UIAs were used to determine changes in IA size and shape. Patients and IAs were divided into non-progression and progression groups. In addition to the clinical characteristics of the patients, the features of the IAs (e.g., size and shape) were evaluated by computed tomography angiography (CTA) or magnetic resonance angiography (MRA). Independent risk factors for UIA progression were studied using multiple Cox proportional hazards regression analysis. In addition, the diagnostic value of the ELAPSS score for the prediction of UIA progression was calculated. RESULTS: Seventy-two IAs in 68 patients progressed during a mean follow-up time of 24.2±19.68 months. IAs located at the bifurcation [odds ratio (OR) 2.600], with an irregular shape (OR 2.981) or having a high aspect ratio (AR, OR 2.430) were correlated with progression. Based on these three factors, the threshold value of our predictive score was 0.5, and the area under the curve (AUC), sensitivity and specificity were 0.756, 93.1% and 40.6%, respectively, while the AUC, sensitivity and specificity of the ELAPSS score were 0.711, 55.6%, and 75.2%, respectively. CONCLUSIONS: IAs located at the bifurcation, with an irregular shape and with an elevated AR are risk factors for UIA progression in the Chinese population. Our predictive score is of great value in predicting the risk of UIA progression.

Risk of Rupture of Small Intracranial Aneurysms (≤5 mm) Among the Chinese Population.

OBJECTIVE: We sought to develop a model to predict the risk of small intracranial aneurysm (SIA; ≤5 mm) rupture among Chinese adults and to compare the score predicted by our model with the PHASES (population, hypertension, age, size, earlier subarachnoid hemorrhage, aneurysm site) score. METHODS: From August 2011 to June 2015, 366 patients with 394 SIAs were retrospectively evaluated and followed up for ≥5 years. The clinical characteristics of the patients were reviewed from their medical records, and the SIA features were evaluated from the imaging studies. The independent risk factors for SIA rupture were studied using multiple Cox proportional hazards regression analysis. The diagnostic value of the PHASES score for the prediction of SIA rupture was also calculated. RESULTS: Six SIAs in 6 different patients had ruptured during a mean follow-up of 6.4 years. An irregular shape (odds ratio [OR], 31.464), a high aspect ratio (OR, 40.573), and a high size ratio (OR, 20.541) increased the risk of rupture. The predictive score incorporated these three factors. The threshold was 1.5, and the area under the curve, sensitivity, and specificity were 0.986, 100%, and 94.6%, respectively. For the PHASES score, the area under the curve, sensitivity, and specificity were 0.702, 83.3%, and 62.1%, respectively. CONCLUSIONS: An irregular shape, a high aspect ratio, and a high size ratio were associated with SIA rupture in the Chinese population. Our predictive score is of great value in predicting the risk of SIA rupture.

Neuroprotective effects of isoflurane against lipopolysaccharide-induced neuroinflammation in BV2 microglial cells by regulating HMGB1/TLRs pathway.

Microglia, as the first line of defence of the central nervous system (CNS), has a major role in inflammatory response. It was reported that isoflurane has a neuroprotective role in the pathological process of CNS by interfering with inflammatory response. While the mechanism and function of isoflurane in microglia-mediated inflammation are still not clearly articulated. In our study, the inflammation model was established by the activation of lipopolysaccharide (LPS) in BV2 cells in vitro. The results demonstrated that isoflurane inhibited the release of nitric oxide (NO) and enhanced the survival of BV2 cells, meanwhile, isoflurane reduced the levels of inflammatory factors and downregulated the expressions of inflammation-related genes and proteins in LPS-mediated BV2 cells. Furthermore, we demonstrated that overexpression of high-mobility group box 1 protein (HMGB1) could reverse the reduction in NO concentration, enhancement of cell BV2 viability and inhibition of inflammatory response, which were mediated by isoflurane in LPS-induced BV2 cells. Therefore, we suggested that isoflurane inhibits the activation of LPS-induced neuro microglia and reduces the release of inflammatory factors by regulating HMGB1, suggesting that isoflurane might play a protective role in LPS-induced neuroinflammation through the HMGB1 pathway.

Wall enhancement ratio determined by vessel wall MRI associated with symptomatic intracranial aneurysms.

PURPOSE: To study the association of the enhancement ratio (ER) of aneurysmal wall enhancement (AWE) with symptomatic intracranial aneurysms (IAs), we hypothesized that the ER of AWE would be stronger in symptomatic IAs than in asymptomatic IAs, as assessed by high-resolution magnetic resonance imaging (HRMRI). MATERIALS AND METHODS: Between February 2016 and February 2018, 80 consecutive patients with 89 unruptured IAs were reviewed. Patients and IAs were divided into symptomatic and asymptomatic groups. In addition to the clinical characteristics, the IA features (e.g., size, shape) were evaluated via computed tomography angiography, while the ER and enhanced patterns were evaluated by HRMRI. Multiple logistic regression analysis was performed to determine the independent risk factors for symptomatic IAs. Receiver operating characteristic curve analysis was used for the final model to obtain the optimal thresholds. RESULTS: Multiple logistic regression analysis indicated that only the ER was associated with symptomatic IAs. The threshold value of the ER was 60.5%. CONCLUSIONS: A higher ER was more frequently identified in symptomatic IAs. More attention should be paid to this factor in the management of IAs.

Relationships between aneurysmal wall enhancement and conventional risk factors in patients with intracranial aneurysm: A high-resolution MRI study.

BACKGROUND AND PURPOSE: Aneurysmal wall enhancement (AWE) is thought to reflect wall inflammation and is a novel imaging biomarker for intracranial aneurysm (IA) risk evaluation. However, the relationship between AWE and other conventional risk factors (e.g., size) remains unclear. The aim of this study was to investigate the relationship between AWE and other risk factors. MATERIAL AND METHODS: Seventy-six consecutive patients from February 2016 to April 2017 with 88 unruptured IAs were reviewed. Patients and IAs were divided into with AWE and without AWE groups according to high-resolution magnetic resonance imaging (HRMRI) images. In addition to the patients' clinical characteristics, the features of the IAs (e.g., size and aspect ratio (AR)) were evaluated via computed tomography angiography. Multiple logistic regression analysis was used to identify the association between AWE and other risk factors. A receiver operating characteristic curve analysis was performed for the final model to obtain optimal thresholds. RESULTS: IAs with an irregular shape (OR 12.544) and a high AR (OR 32.891) were associated with AWE. The threshold value of the AR was 1.05. CONCLUSIONS: AWE on contrast-enhanced HRMRI was correlated with IAs with an irregular shape and a high AR. AWE may be a marker of instability and even risk of rupture.

Predictive Value of Combined LIPS and ANG-2 Level in Critically Ill Patients with ARDS Risk Factors.

To investigate the predictive value of the acute physiology and chronic health evaluation 2 (APACHE2) score and lung injury prediction score (LIPS) for acute respiratory distress syndrome (ARDS) when combined with biomarkers for this condition in patients with ARDS risk factors. In total, 158 Han Chinese patients with ARDS risk factors were recruited from the Respiratory and Emergency Intensive Care Units. The LIPS, APACHE2 score, primary diagnosis at admission, and ARDS risk factors were determined within 6 h of admission, and PaO2/FiO2 was determined on the day of admission. Blood was collected within 24 h of admission for the measurement of angiopoietin-2 (ANG-2), sE-selectin, interleukin-6 (IL-6), and interleukin-8 (IL-8) levels. ARDS was monitored for the next 7 days. Univariate and multivariate analyses and receiver operating characteristic (ROC) analyses were employed to construct a model for ARDS prediction. Forty-eight patients developed ARDS within 7 days of admission. Plasma ANG-2 level, sE-selectin level, LIPS, and APACHE2 score in ARDS patients were significantly higher than those in non-ARDS patients. ANG-2 level, LIPS, and APACHE2 score were correlated with ARDS (P < 0.001, P < 0.006, and P < 0.042, resp.). When the APACHE2 score was used in combination with the LIPS and ANG-2 level to predict ARDS, the area under the ROC curve (AUC) was not significantly increased. Compared to LIPS or ANG-2 alone, LIPS in combination with ANG-2 had significantly increased positive predictive value (PPV) and AUC for the prediction of ARDS. In conclusion, plasma ANG-2 level, LIPS, and APACHE2 score are correlated with ARDS. Combined LIPS and ANG-2 level displays favorable sensitivity, specificity, and AUC for the prediction of ARDS.

Computed Tomography Angiography Evaluation of Risk Factors for Unstable Intracranial Aneurysms.

OBJECTIVE: To evaluate risk factors for instability in intracranial aneurysms (IAs) using computed tomography angiography (CTA). METHODS: A total of 614 consecutive patients diagnosed with 661 IAs between August 2011 and February 2016 were reviewed. Patients and IAs were divided into stable and unstable groups. Along with clinical characteristics, IA characteristics were evaluated by CTA. Multiple logistic regression analysis was used to identify the independent risk factors associated with unstable IAs. Receiver operating characteristic (ROC) curve analysis was performed on the final model, and optimal thresholds were obtained. RESULTS: Patient age (odds ratio [OR], 0.946), cerebral atherosclerosis (CA; OR, 0.525), and IAs located at the middle cerebral artery (OR, 0.473) or internal carotid artery (OR, 0.512) were negatively correlated with instability, whereas IAs with irregular shape (OR, 2.157), deep depth (OR, 1.557), or large flow angle (FA; OR, 1.015) were more likely to be unstable. ROC analysis revealed threshold values of age, depth, and FA of 59.5 years, 4.25 mm, and 87.8°, respectively. CONCLUSIONS: The stability of IAs is significantly affected by several factors, including patient age and the presence of CA. IA shape and location also have an impact on the stability of IAs. Growth into an irregular shape, with a deep depth, and a large FA are risk factors for a change in IAs from stable to unstable.

Risk Factors for the Rupture of Intracranial Aneurysms Using Computed Tomography Angiography.

OBJECTIVE: To study the clinical and morphologic characteristics associated with risk factors for the rupture of intracranial aneurysms (IAs). METHODS: A total of 1115 consecutive patients with 1282 IAs were reviewed from August 2011 to February 2016. The patients and IAs were divided into ruptured and unruptured groups. Based on the clinical and morphologic findings, the risk factors for IA rupture were assessed using statistical methods. RESULTS: Age, hypertension, diabetes mellitus, and cerebral atherosclerosis were associated with ruptured IAs. IAs located in the anterior cerebral artery, the anterior communicating artery, the posterior communicating artery, and the internal carotid artery were associated with ruptured IAs. Ruptures were also associated with arterial bifurcations, irregular aneurysm shapes, and all continuous data, except neck width. Binary logistic regression showed that IAs located at bifurcations (odds ratio [OR], 1.804), with irregular shapes (OR, 4.677), with high aspect ratios (ARs) (OR, 5.037) or with small mean diameters (MDs) (OR, 0.495) are more prone to rupture. Receiver operating characteristic analysis showed that the threshold values of the AR and MD were 1 and 3.70 mm, respectively. CONCLUSIONS: Morphologic characteristics, such as being located at bifurcations, being irregularly shaped, having a high AR (>1), and having a small MD (<3.70 mm), were better predictors of rupture.

Wall enhancement ratio and partial wall enhancement on MRI associated with the rupture of intracranial aneurysms.

OBJECTIVES: To evaluate the risk factors for rupture of intracranial aneurysms (IAs) using high resolution MRI (HRMRI). METHODS: 91 consecutive patients with 106 IAs were reviewed from February 2016 to April 2017. Patients and IAs were divided into ruptured and unruptured groups. In addition to the clinical characteristics of the patients, the features of IAs (eg, shape) were evaluated by CT angiography, whereas wall thickness, enhanced patterns, and enhancement ratio (ER) were evaluated by MRI. Multiple logistic regression analysis was used to identify independent risk factors associated with the rupture of IAs. Receiver operating characteristic curve analysis was performed on the final model, and the optimal thresholds were obtained. RESULTS: ER (OR 6.638) and partial wall enhancement (PWE) (OR 6.710) were not markers of aneurysms more prone to rupture, but simply were more commonly found in the ruptured aneurysm cohort. The threshold value for ER was 61.5%. CONCLUSIONS: ER (≥61.5%) and IAs with PWE are better predictors of rupture. Increased attentions should be paid to these factors during assessment of IA rupture.

Regulatory factor X1 depresses ApoE-dependent Aß uptake by miRNA-124 in microglial response to oxidative stress.

Decreased proteolytic clearance of soluble amyloid ß (Aß) in microglia affects Aß accumulation on Alzheimer's disease progression. However, the potential molecular mechanism by which microglial Aß uptake is regulated remains unclear. In this study, we identified a microRNA, miR-124, that was down-regulated in aging with a function in regulating apolipoprotein E (ApoE)-dependent Aß uptake by targeting regulatory factor X1 (RFX1) transcripts on BV2 microglia cell. Decreased expression of miRNA-124 in BV2 cells exposed to mild hydrogen peroxide increased RFX1 protein level and decreased the expression of ApoE, a gene which has been suggested to enhance cellular Aß uptake in microglia. We also identified a miR-124 binding site in the 3'-UTR of RFX1 mRNA and a RFX1 binding site in the first intron of ApoE gene. Furthermore, interfering this signaling pathway by knocking down RFX1 significantly improved Aß uptake in BV2 cells. These data demonstrate the mechanism through which decreased miR-124 expression under oxidative stress slowed Aß uptake and suggest that RFX1 might be a target for improving Aß clearance during aging.

Preparation of copper-containing bioactive glass/eggshell membrane nanocomposites for improving angiogenesis, antibacterial activity and wound healing.

UNLABELLED: Effectively stimulating angiogenesis and avoiding wound infection are great challenges in wound care management. Designing new healing dressings with requisite angiogenic capacity and antibacterial performance is of particular significance. In order to achieve this aim, we prepared a copper (Cu)-containing bioactive glass nanocoating (40-50nm) with uniform nanostructure on natural eggshell membrane (Cu-BG/ESM) by the pulsed laser deposition (PLD) technique. The surface physicochemical properties including hydrophilicity and hardness of ESM were significantly improved after depositing Cu-BG nanocoatings. Meanwhile, 5Cu-BG/ESM films containing 5mol% Cu stimulated proangiogenesis by improving vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α protein secretion as well as angiogenesis-related gene expression (VEGF, HIF-1α, VEGF receptor 2 (KDR) and endothelial nitric oxide (eNos)) of human umbilical vein endothelial cells (HUVECs). When used to treat full-thickness skin defects in mice, 5Cu-BG/ESM films enhanced the healing quality as confirmed by the significantly improved angiogenesis (as indicated by CD31 expression) and formation of continuous and uniform epidermis layer in vivo. Furthermore, 5Cu-BG/ESM films could maintain a sustained release of Cu(2+) ions and distinctly inhibited the viability of bacteria (Escherichia coli). The results indicate that Cu(2+) ions released from Cu-BG/ESM nanocomposite films play an important role for improving both angiogenesis and antibacterial activity and the prepared nanocomposite films combined Cu-containing BG nanocoatings with ESM are a promising biomaterial for wound healing application. STATEMENT OF SIGNIFICANCE: Designing new healing dressings with requisite angiogenic capacity and antibacterial performance is of particular significance in wound care management. In our study, we successfully prepared copper-containing bioactive glass/eggshell membrane (Cu-BG/ESM) nanocomposites with uniform bioactive glass nanocoatings by using pulsed laser deposition (PLD) technology. Due to the deposited Cu-BG nanocoatings on the surface of ESM, Cu-BG/ESM nanocomposites possessed significantly improved physicochemical and biological properties, including surface hydrophilicity, hardness, antibacterial ability, angiogenesis rate in vitro and wound healing quality in vivo as compared to pure ESM and BG/ESM films. Our study showed that prepared nanocoatings on Cu-BG/ESM nanocomposites offer a beneficial carrier for sustained release of Cu(2+) ions which played a key role for improving both angiogenesis and antibacterial activity. The prepared nanocomposites combined Cu-containing BG nanocoatings with ESM are a promising biomaterial for wound healing application.

Clinical Features and Treatment of Distal Intracranial Aneurysms.

To analyze the clinical characteristics, therapies, and outcomes of distal intracranial aneurysms, the authors retrospectively studied the clinical and imaging data of 18 patients with distal intracranial aneurysms. There were 10 males and 8 females, aged from 11 months to 59 years (mean, 40.4 ±â€Š11.4 years). All patients were diagnosed by digital subtract angiography. Aneurysm locations were as follows: distal anterior cerebral artery (n = 5), distal middle cerebral artery (n = 2), distal posterior cerebral artery (n = 6), distal posterior inferior cerebellar artery (n = 3), distal anterior inferior cerebellar artery (n = 1), and distal superior cerebellar artery (n = 1). Endovascular embolization was performed on 16 patients, including coil embolization on 10 patients and embolization using Glubran 2 surgical glue on 6 patients, and 7 of the 16 patients also underwent parent artery occlusion. Aneurysms were all completely embolized at the first phase for these 16 patients. The other 2 patients underwent craniotomy with hematoma evacuation and complete aneurysm clipping. Postoperatively, 14 patients showed a good recovery, 2 patients had neurological deficits, 1 patient had seizures and was managed with drugs, 1 patient developed hydrocephalus, and a ventriculo-peritoneal shunt was performed. Follow-up angiographies showed no aneurysm recurrence. Clinical manifestations of distal intracranial aneurysms are varied. Their treatment should follow the principle of individual choice. Endovascular embolization is an effective way to treat distal intracranial aneurysms; and for those with intracranial hematoma, craniotomy with hematoma evacuation and aneurysm clipping may be a feasible treatment.

Isoflurane Post-Treatment Improves Outcome after an Embolic Stroke in Rabbits.

Application of commonly used volatile anesthetics after brain ischemia onset (post-treatment) provides neuroprotection in rodents. To further test its translational potential, this study was designed to determine whether isoflurane post-treatment induced neuroprotection in rabbits after embolic stroke. White male New Zealand rabbits received intra-carotid injection of clots when they were awake. Some rabbits were exposed to 2.5% isoflurane for 1 h at 5 min after the injection. Isoflurane post-treatment increased the tolerance of rabbits to the amount of clots. Isoflurane post-treatment also reduced brain infarct volumes and plasma S100B 3 days after the injection of 5 mg clots and improved neurological deficit scores after the stroke. Isoflurane post-treatment improves neurological outcome in rabbits after embolic stroke.

Inhibition of brain ischemia-caused notch activation in microglia may contribute to isoflurane postconditioning-induced neuroprotection in male rats.

Prolonged exposure to volatile anesthetics alone may be detrimental to the brain. However, volatile anesthetics, such as isoflurane, can provide neuroprotection against various damaging insults. Application of isoflurane after focal brain ischemia reduces ischemic brain injury. We determined whether this isoflurane postconditioning-induced neuroprotection requires inhibition of brain ischemia-induced Notch signaling activation. Here, we showed that TUNEL-positive staining cell density and active caspase 3 expression were increased in the ischemic penumbral brain tissues of male rats after a 90-min middle cerebral arterial occlusion (MCAO). This increase was inhibited by isoflurane postconditioning and a Notch inhibitor. Isoflurane postconditioning and the Notch inhibitor also inhibited brain ischemia-induced Notch activation and proinflammatory cytokine production. Most cells expressing active Notch also were positive for CD11b, a microglial and white blood cell marker. Isoflurane postconditioning and the Notch inhibitor inhibited 1 ng/ml lipopolysaccharide- and oxygen-glucose deprivation-induced Notch activation and proinflammatory cytokine production from microglial cultures. The inhibition of cytokine production by isoflurane postconditioning, but not by a high concentration of the Notch inhibitor, disappeared in the presence of 10 ng/ml lipopolysaccharide. Our results suggest that Notch activation in microglia contributes to the cell apoptosis in the ischemic brain tissues. Inhibiting this Notch activation may participate in isoflurane postconditioning-induced neuroprotection against transient focal brain ischemia in male rats.

Regulatory factor X1 is a new tumor suppressive transcription factor that acts via direct downregulation of CD44 in glioblastoma.

BACKGROUND: The biological functions of regulatory factor (RF)X1, a transcription factor, are not known. Since the RFX1 gene is often epigenetically silenced and clusters of differentiation (CD)44 proteins that regulate cancer cell biology are increased in human glioblastomas, we designed this study to determine whether RFX1 could regulate CD44 expression in glioblastoma. METHODS: Regulatory factor X1 was overexpressed in 4 human glioblastoma cell lines. CD44 expression and cell proliferation, apoptosis, and invasion were assayed under in vitro conditions. In vivo growth of human glioblastoma xenografts was determined in mice. The expression of RFX1 and CD44 in human glioblastoma tissues was quantified. RESULTS: A putative RFX1 binding sequence existed in the first exon of the human CD44 gene. The transcription activity of the DNA fragment containing this putative sequence was decreased in cells overexpressing RFX1. Regulatory factor X1 bound to the CD44 gene in glioblastoma cells. It reduced CD44 expression and activated Akt and extracellular signal-regulated kinase, signaling molecules downstream of CD44 to regulate cell proliferation and survival. Overexpression of RFX1 inhibited the survival, proliferation, and transwell invasion of glioblastoma cells and in vivo growth of human glioblastoma xenografts. CD44 overexpression reversed RFX1 effects on cell proliferation. Finally, CD44 protein levels were inversely correlated with RFX1 protein levels in human glioblastoma tissues. CONCLUSIONS: These results suggest that RFX1 directly regulates CD44 expression. This mechanism may contribute to RFX1's effects on proliferation, survival, and invasion of glioblastoma cells. Our results provide initial evidence that RFX1 may be an important target/regulator of the malignancy of glioblastoma.

Association between XRCC3 Thr241Met polymorphism and risk of brain tumors: a meta-analysis.

X-ray repair cross-complementing group 3 (XRCC3) plays an important role in the process of homologous recombination repair for DNA double-strand breaks which further maintains the stability of the genome. XRCC3 Thr241Met polymorphism has been indicated in the development of cancers, but the association of the XRCC3 Thr241Met polymorphism with risk of brain tumors is still unclear owing to the conflicting findings from previous studies. We performed a meta-analysis to provide a better understanding on the association between the XRCC3 Thr241Met polymorphism and risk of brain tumors. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was used to assess the association. Thirteen case-control studies involving a total of 4,984 cases and 7,472 controls were included. Overall, there was no statistically significant association between the XRCC3 Thr241Met polymorphism and risk of brain tumors under all contrast models. Subgroup analysis by race suggested that the XRCC3 Thr241Met polymorphism was associated with increased risk of brain tumors in Asians under all four contrast models (Met vs. Thr: OR = 1.22, 95 % CI 1.09-1.36, P < 0.01; MetMet vs. ThrThr: OR = 1.89, 95 % CI 1.38-2.57, P < 0.01; MetMet vs. ThrThr/ThrMet: OR = 1.78, 95 % CI 1.31-2.40, P < 0.01; and MetMet vs. ThrThr/ThrMet: OR = 1.19, 95 % CI 1.04-1.36, P = 0.01). However, there was no significant association between the XRCC3 Thr241Met polymorphism and risk of brain tumors in Caucasians. Therefore, the XRCC3 Thr241Met polymorphism is associated with increased risk of brain tumors, especially in Asians.

Electroacupuncture preconditioning-induced neuroprotection may be mediated by glutamate transporter type 2.

Electroacupuncture has been shown to induce a preconditioning effect in the brain. The mechanisms for this protection are not fully elucidated. We hypothesize that this protection is mediated by excitatory amino acid transporters (EAATs) that have been shown to be neuroprotective. To test this hypothesis, two-month old male Sprague-Dawley rats and EAAT type 3 (EAAT3) knockout mice received or did not receive 30-min electroacupuncture once a day for five consecutive days. They were subjected to a 120-min middle cerebral arterial occlusion (MCAO) at 24h after the last electroacupuncture. Neurological outcome was assessed 2days after the MCAO. Brain tissues were harvested at 24h after the last electroacupuncture for Western blotting. Rats subjected to electroacupuncture at the Baihui acupoint had smaller brain infarct volumes and better neurological deficit scores than control rats. Electroacupuncture increased EAAT type 2 (EAAT2) in the cerebral cortex, tended to increase EAAT3 in the hippocampus, and had no effect on EAAT type 1 expression. Dihydrokainate, an EAAT2 inhibitor, worsened the neurological outcome of rats with electroacupuncture pretreatment. Electroacupuncture pretreatment at the Baihui acupoint increased EAAT2 in the cerebral cortex and improved the neurological outcome of EAAT3 knockout mice. Together, our results suggest that EAAT2 may mediate the electroacupuncture preconditioning-induced neuroprotection.

Isoflurane postconditioning reduces ischemia-induced nuclear factor-κB activation and interleukin 1ß production to provide neuroprotection in rats and mice.

Application of isoflurane, a volatile anesthetic, after brain ischemia can reduce ischemic brain injury in rodents (isoflurane postconditioning). This study is designed to determine whether isoflurane postconditioning improves long-term neurological outcome after focal brain ischemia and whether this protection is mediated by attenuating neuroinflammation. Adult male Sprague-Dawley rats were subjected to a 90-min middle cerebral arterial occlusion (MCAO). Isoflurane postconditioning was performed by exposing rats to 2% isoflurane for 60min immediately after the MCAO. Isoflurane postconditioning reduced brain infarct volumes, apoptotic cells in the ischemic penumbral brain tissues and neurological deficits of rats at 4weeks after the MCAO. Isoflurane postconditioning reduced brain ischemia/reperfusion-induced nuclear transcription factor (NF)-κB (NF-κB) activation as well as interleukin 1ß (IL-1ß) and interleukin-6 production in the ischemic penumbral brain tissues at 24h after the MCAO. IL-1ß deficient mice had smaller brain infarct volumes and better neurological functions than wild-type mice at 24h after a 90-min focal brain ischemia. Isoflurane posttreatment failed to induce neuroprotection in the IL-1ß deficient mice. Our results suggest that isoflurane postconditioning improved long-term neurological outcome after transient focal brain ischemia. This protection may be mediated by inhibiting NF-κB activation and the production of the proinflammatory cytokine IL-1ß.

Expression and cellular distribution of vascular endothelial growth factor-C system in cortical tubers of the tuberous sclerosis complex.

Cortical tubers are malformations of cortical development in patients with tuberous sclerosis complex (TSC), and highly associated with pediatric intractable epilepsy. Recent evidence has shown that signaling mediated through vascular endothelial growth factor-C (VEGF-C) and its receptors, VEGFR-2 and VEGFR-3, has direct effects on both neurons and glial cells. To understand the potential role of VEGF-C system in the pathogenesis of cortical tubers, we investigated the expression patterns of VEGF-C signaling in cortical tubers compared with age-matched normal control cortex (CTX). We found that VEGF-C, VEGFR-2 and VEGFR-3 were clearly upregulated in tubers at both the mRNA and protein levels, compared with CTX. The in situ hybridization and immunostaining results demonstrated that VEGF-C, VEGFR-2 and VEGFR-3 were highly expressed in dysplastic neurons (DNs), giant cells (GCs) and reactive astrocytes within tubers. Most DNs/GCs expressing VEGF-C and its receptors co-labeled with neuronal rather than astrocytic markers, suggesting a neuronal lineage. In addition, protein levels of Akt-1, p-Bad and ERK1/2, the important downstream factors of the VEGF-C pathway, were significantly increased in cortical tubers, indicating involvement of VEGF-C-dependent prosurvival signaling in cortical tubers. Taken together, our results suggest a putative role for the VEGF-C signaling pathway in the pathogenesis of cortical tubers.