Metastatic large cell neuroendocrine lung cancer to the foramen magnum: A case report.

RATIONABLE: Large cell neuroendocrine carcinoma of the lung is rare, especially in the area of the foramen magnum. No previous studies have reported metastatic large cell neuroendocrine lung cancer to the foramen magnum. This paper will be the first time to report this special case. PATIENT CONCERNS: A case of a 37-year-old woman presented with headache that had developed 20 days previously. Imaging examination revealed a circular abnormal signal at the posterior margin of the foramen magnum. DIAGNOSES: The patient we report was diagnosed with a metastatic intracranial tumor. INTERVENTIONS: The patient underwent occipital craniotomy. Pathological results showed metastatic neuroendocrine carcinoma of the brain. Whole body PET-CT examination showed that fusiform soft tissue shadows could be seen near the hilum of the lower lobe of the left lung. OUTCOMES: The final bronchoscopy pathological results showed the large cell neuroendocrine carcinoma of the lung. The patient underwent further chemotherapy and radiotherapy in the oncology department. LESSONS: Diagnosis and treatment of large cell neuroendocrine carcinoma of the lung are difficult. The prognosis is poorer, and effective treatment is urgently needed.

MiR-154 Functions as a Tumor Suppressor in Glioblastoma by Targeting Wnt5a.

Recently, deregulated microRNA (miRNA) expression contributes to the development and progression of human glioblastoma. The aim of the present study was to evaluate the level of miR-154 and Wnt5a in glioblastoma tissues and cells. We further investigated the molecular mechanisms of miR-154 and Wnt5a in glioblastoma cell lines. In the present study, we found that miR-154 expression was downregulated in glioblastoma tissues and U87, U251, and A172 cells (all p < 0.001). By contrast, Wnt5a was upregulated. Furthermore, we found that overexpression of miR-154 suppressed cell migration and invasion of U87 and U251 cells. Mechanically, overexpression of miR-154 inhibited epithelial-to-mesenchymal transition (EMT) of U87 and U251 cells. Importantly, we identified that the 3' untranslated region (3'-UTR) of Wnt5a was a direct target of miR-154. Luciferase reporter assays confirmed that miR-154 binding to the 3'-UTR regions of Wnt5a inhibited the expression of Wnt5a in U87 and U251 cells. At the same time, overexpressed Wnt5a also reversed EMT inhibited by miR-154. In conclusion, this study suggested that high miR-154 expression suppressed glioblastoma cell migration, invasion, and EMT development through targeting Wnt5a, which may be recommended as a therapeutic target for glioblastoma.

miR-139 Functions as An Antioncomir to Repress Glioma Progression Through Targeting IGF-1 R, AMY-1, and PGC-1ß.

Gliomas are the most common primary malignant brain tumor with poor prognosis, characterized by a highly heterogeneous cell population, extensive proliferation, and migration. A lot of molecular mechanisms regulate gliomas development and invasion, including abnormal expression of oncogenes and variation of epigenetic modification. MicroRNAs could affect cell growth and functions. Several reports have demonstrated that miR-139 plays multifunctions in kinds of solid tumors through different pathways. However, the antitumor mechanisms of this miR-139 are not unveiled in detail. In this study, we not only validated the low expression level of miR-139 in glioma tissues and cell lines but also detected the effect of miR-139 on modulating gliomas proliferation and invasion both in vitro and in vivo. We identified insulin-like growth factor 1 receptor, associate of Myc 1, and peroxisome proliferator-activated receptor γ coactivator 1ß as direct targets of miR-139 and the levels of them were all inversely correlated with miR-139 in gliomas. Insulin like growth factor 1 receptor promoted gliomas invasion through Akt signaling and increased proliferation in the peroxisome proliferator-activated receptor γ coactivator 1ß-dependent way. Associate of Myc 1 also facilitated gliomas progression by activating c-Myc pathway. Overexpression of the target genes could retrieve the antitumor function of miR-139, respectively, in different degrees. The nude mice transplantation tumor experiment displayed that glioma cells stably expressed miR-139 growth much slower in vivo than the negative control cells. Taken together, these findings suggested miR-139 acted as a favorable factor against gliomas progression and uncovered a novel regulatory mechanism, which may provide a new evidenced prognostic marker and therapeutic target for gliomas.

[Alarming effect of intraoperative neuroelectrophysiological monitoring in microvascular decompression for primary trigeminal neuralgia].

OBJECTIVE: To explore the alarming effect of intraoperative neuroelectrophysiological monitoring in microvascular decompression (MVD) for primary trigeminal neuralgia. METHODS: In 2014, a total of 44 patients with an initial diagnosis of primary trigeminal neuralgia were consecutively recruited for surgery. And 41 of them with an intraoperative confirmation of primary trigeminal neuralgia underwent MVD. Intraoperative neuroelectrophysiological monitoring was employed for brainstem auditory evoked potentials (BAEPs), spontaneous electromyogram for obicularis oculi, obicularisoris and masseter muscles. The real-time alarming report was offered to the operator who adjusted operations accordingly. RESULTS: There were abnormal changes in 23 cases (56.10%) with a total of 77 instances (BAEPs 27, trigeminal nerve 32, facial nerve 18). The outcomes were no facial pain (n=26), pain relief (n=15) and facial numbness (n=6, two with concurrent hearing disturbance). And the rates of facial pain disappearance and sequela occurrence were much better than those in controls without monitoring. CONCLUSION: Intraoperative neuroelectrophysiological monitoring helps enhance the MVD effect and decrease operative squela through alarming reporting.

Spinal astrocytic activation contributes to mechanical allodynia in a rat chemotherapy-induced neuropathic pain model.

Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-evoked CNP rat model with obvious mechanical allodynia, we found that spinal astrocyte rather than microglia was dramatically activated. The mechanical allodynia was dose-dependently attenuated by intrathecal administratration of L-α-aminoadipate (astrocytic specific inhibitor); whereas minocycline (microglial specific inhibitor) had no such effect, indicating that spinal astrocytic activation contributes to allodynia in CNP rat. Furthermore, oxidative stress mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1ß expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal neurons to strengthen pain transmission. Taken together, our findings suggest that spinal activated astrocytes may be a crucial component of the pathophysiology of CNP and "Astrocyte-Cytokine-NMDAR-neuron" pathway may be one detailed neural mechanisms underlying CNP. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for treating CNP.

Posterior reduction and instrumentation with rod-screw construct for atlanto-axial dislocation: a single institutional study with 21 consecutive cases.

OBJECTIVE: Atlanto-axial dislocation is one of the leading causes for occipito-cervical instability. This study aimed for investigating the clinical outcome of rod-screw construct rather than traditional posterior wiring for atlanto-axial dislocation. METHODS: Twenty one consecutive atlanto-axial dislocation patients undergoing surgery in our institution from April 2008 to May 2011 were retrospectively reviewed. Posterior reduction and instrumentation between occipital/C1 lateral mass and C2 pedicle, and concomitant occipital-atlanto-axial fusion were achieved with polyaxial-screw and rod construct. Clinical outcomes and complications were analyzed postoperatively at 3, 6, and 12 months. RESULTS: The satisfactory repositioning and internal fixation of the atlanto-axial joint, rigid screw placement and successful atlanto-axial fusion were confirmed in the 20 cases during follow-up. One patient died of a secondary ischemic injury to the brainstem 12 days after operation. The exception was a pediatric patient with loosened screws at 3 months follow-up postoperatively. Importantly, clinical symptoms and neurological function were significantly improved in all 20 cases during each follow-up as compared to preoperative scenarios. In addition, we noted that ischemic injury and screw detachment may be the main surgical risks. CONCLUSIONS: This surgical procedure provided satisfactory reduction of the atlanto-axial joint with significant neurological improvement. Moreover, we successfully avoided complications of posterior wiring.

MiR-483-5p suppresses the proliferation of glioma cells via directly targeting ERK1.

MicroRNAs (miRNAs) exhibit tumor-specific expression signatures and play crucial roles in tumorigenesis by targeting oncogenes. Here, through analyzing the miRNA-array profiles of human glioblastoma tissues and the adjacent normal brain tissues, we found miR-483-5p was significantly down-regulated in gliomas, which was confirmed in both human glioma specimens and cell lines. The overexpression of miR-483-5p suppressed glioma cell proliferation and induced a G0/G1 arrest. In contrast, miR-483-5p inhibition promoted cell proliferation. Furthermore, by a dual-luciferase reporter assay and expression analysis, we identified extracellular signal-regulated kinase 1 (ERK1) as a direct target of miR-483-5p. ERK1 knockdown can block cell proliferation induced by miR-483-5p inhibition. Thus, our findings provide the first evidence that miR-483-5p can serve as a tumor suppressor in gliomas.

Protective effects of hydrogen-rich saline in a rat model of traumatic brain injury via reducing oxidative stress.

BACKGROUND: Hydrogen gas (H(2)) has been considered as a novel antioxidant to selectively reduce the toxic reactive oxygen species (ROS) such as hydroxyl radical (•OH) without affecting the other signal ROS. Our recent study shows that H(2) inhalation is beneficial to traumatic brain injury (TBI) via reducing oxidative stress. In contrast to H(2), hydrogen-rich saline (HS) may be more suitable for clinical application. The present study was designed to investigate whether HS has a protective effect against TBI via reducing oxidative stress in rats. METHODS: TBI model was induced by controlled cortical impact injury. Different dosages of HS were intraperitoneally administered at 5 min after TBI operation. We then measured the brain edema, blood-brain barrier (BBB) breakdown, neurological dysfunction and injury volume in all animals. In addition, the oxidative products and antioxidant enzymes in brain tissues were detected. RESULTS: TBI-challenged rats exhibited significant brain injuries characterized by the increase of BBB permeability, brain edema, and lesion volume as well as neurological dysfunction, which were dose-dependently ameliorated by HS treatment. Moreover, we found that HS treatment increased the endogenous antioxidant enzymatic activities and decreased the oxidative product levels in brain tissues of TBI-challenged rats. CONCLUSION: Hydrogen-rich saline can exert a protective effect against TBI via reducing oxidative stress. Molecular hydrogen may be a more effective therapeutic strategy for TBI patients.

One-stage apertura thoracis superior approach for four-vessel occlusion in rats.

OBJECTIVE: There are a great number of modified models based on the four-vessel occlusion (4VO) model of Pulsinelli and Brierley which has been used worldwide for brain ischemia research. However, up to now the problems of collateral circulations of 4VO and the difficulty in arranging a surgery to occlude the basilar artery in other models are not satisfactorily solved yet. In this study, an improved 4-vessel occlusion (I4VO) rat model which is easy to handle and able to decrease the effect of collateral circulation is reported. METHODS: The common carotid arteries and the beginning of the subclavical arteries of rats were occluded for different time by one-stage apertura thoracis superior approach. Neurological deficit scores defined by the modified Garcia scoring system and histopathological method were used to evaluate the effects of this model up to 7 days after reperfusion. RESULTS: The neurological scores in the 15-min and 25-min groups decreased significantly at 24, 48 and 72 hours after reperfusion (P less than 0.05), and the histopathologic study showed that there were stable, symmetrical changes of lesions in bilateral hippocampus in all the ischemia samples from two ischemia groups compared with sham operated group (P less than 0.05). CONCLUSION: This modified model is safe, easy, reliable, stable, mini-invasive as well as time-saving in making bilateral hemispheric ischemia, which can effectively decrease collateral circulations and meanwhile lead to stable lesions in hippocampus and cortex.

MnSOD expression inhibited by electromagnetic pulse radiation in the rat testis.

Male Sprague Dawley rats were exposed to EMP irradiation of 100 kV/m peak-to-peak e-field intensity and different numbers of pulses. Rat sperm samples were prepared for analysis of sperm qualities; Testes were assessed by transmission electron microscopy and serum hormone concentrations were examined by radioimmunoassay; Enzymatic activities of Total-superoxide dismutase(T-SOD) and manganese-superoxide dismutase (MnSOD), the mRNA levels of MnSOD and cuprozinc-superoxide dismutase (CuZnSOD), and the density of malondialdehyde (MDA) were also determined. EMP irradiation did not affect spermatozoon morphology, micronucleus formation rate, sperm number or viability, but the acrosin reaction rate decreased at 24 h and 48 h and recovered by 72 h after irradiation as compared to the controls. The ultrastructure of rat testis displayed more serious damage at 24 h than at other time points (6 h, 12 h, 48 h). Serum levels of luteotrophic hormone (LH) and testosterone (T) were elevated in irradiated rats as compared to controls. After irradiation, enzymatic activities of T-SOD and MnSOD were reduced by 24 h, consistent with the changes observed in MnSOD mRNA expression; MDA content increased at 6 h in turn. These studies have quantified the morphological damage and dysfunction in the rat reproductive system induced by EMP. The mechanism of EMP induced damage may be associated with the inhibition of MnSOD expression.

Primary frontoparietal lobe convexity germinoma with dural invasion mimics meningioma.

Intracranial germinomas are rare and account for only 0.4-3.4% of primary intracranial tumors. They develop mainly in the midline structures in adolescents. The pineal gland is the most common site of this tumor. Here, we describe an unusual case of a giant primary intracranial germinoma located in the intracranial hemisphere with radiological findings that mimicked a meningioma. The clinical diagnosis of the intracranial germinoma was difficult because of its unusual clinical presentation, the location of the lesion, and atypical imaging findings. Based on this case study, we suggest that germinoma might be a possible diagnosis when a tumor of the hemispheres with dura invasion mimics meningioma, especially in young patients. Furthermore, we recommend that frozen biopsy sections should be taken routinely during surgery to aid in rapid diagnosis and effective therapy.

Neuroprotective effect of osthole against acute ischemic stroke on middle cerebral ischemia occlusion in rats.

Osthole, a natural coumarin derivative, has taken considerable attention because of its diverse pharmacological functions. It has been reported to be useful in the treatment of chronic cerebral hypoperfusion and neuronal damage. In the present study, we examined the neuroprotective effect of osthole and its potential mechanisms against acute ischemic stroke induced by middle cerebral artery occlusion (MCAO) in rats. The rats were pretreated with osthole 10, 20 and 40 mg/kg 30 min before MCAO. The neuroprotective effect of osthole against acute ischemic stroke was evaluated by neurological deficit score (NDS), dry-wet weight and 2,3,5-triphenyltetrazolium chloride (TTC) staining. The contents of malondialdehyde (MDA) and glutathione (GSH), activity of myeloperoxidase (MPO) and the level of interleukin (IL)-1ß and IL-8 after 2h of MCAO in rats were detected to investigate its anti-oxidative action and anti-inflammatory property. Pretreatment with osthole significantly increased in GSH, and decreased the volume of infarction, NDS, edema, MDA, MPO, IL-1ß and IL-8 compared with rats in the MCAO group at 24h after MCAO. The study suggests the neuroprotective effect of osthole in the MCAO model of rats. The anti-oxidative action and anti-inflammatory property of osthole may contribute to a beneficial effect against stroke.

Beneficial effects of hydrogen gas in a rat model of traumatic brain injury via reducing oxidative stress.

Traumatic brain injury (TBI) is a leading cause of mortality and disability among the young population. It has been shown that hydrogen gas (H(2)) exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radical (OH, the most cytotoxic ROS). Recently, we have found that H(2) inhalation significantly improved the survival rate and organ damage of septic mice. In the present study, we investigated the effectiveness of H(2) therapy on brain edema, blood-brain barrier (BBB) breakdown, neurological dysfunction and injury volume in TBI-challenged rats. In addition, we investigated the effects of H(2) treatment on the changes of oxidative products and antioxidant enzymes in brain tissue of TBI-challenged rats. Hydrogen treatment was given by exposure to 2% H(2) from 5 min to 5h after sham or TBI operation, respectively. Here, we found that TBI-challenged rats showed significant brain injuries characterized by the increase of BBB permeability, brain edema and lesion volume as well as neurological dysfunction, which was significantly attenuated by 2% H(2) treatment. In addition, we found that the decrease of oxidative products and the increase of endogenous antioxidant enzymatic activities in the brain tissue may be associated with the protective effects of H(2) treatment in TBI-challenged rats. The present study supports that H(2) inhalation may be a more effective therapeutic strategy for patients with TBI.

Modified approach to construct a vascularized coral bone in rabbit using an arteriovenous loop.

The most important factor for the survival of thick three-dimensional tissues is the degree of vascularization. In this study, a modified arteriovenous loop (AVL) model was developed to prefabricate an axial vascularized tissue-engineered coral bone. In group A (n = 28), an arteriovenous fistula between rabbit femoral artery and vein was anastomosed to form an AVL. The AVL was placed in a coral block (6 x 8 x 10 mm (3)) as a vascular carrier. The complex was wrapped with polytetrafluoroethylene membrane and implanted subcutaneously. In group B (n = 20), there was no vascular carrier, and the same dimensional coral was directly implanted beneath inguinal skin. After 2, 4, 6, and 8 weeks, the rabbits were perfused with heparinized saline (for scanning electron microscopy), India ink (for histological examination), and ethylene perchloride (for vascular casts) via the abdominal aorta. In group A, histology showed that newly formed vasculature extended over the surfaces and invaded the entire coral blocks. The vascular density was significantly superior to that in group B. Vascular casts showed that new blood vessels robustly sprouted from the AVL. Scanning electron microscopy demonstrated that there were minute sprouting cavities in the vascular endangium. In this model, an axial vascularized coral bone could be effectively constructed.

[Exogenous nitric oxide inhibits the proliferation of mouse neural progenitor cells].

OBJECTIVE: To explore the inhibitive effect of exogenous nitric oxide (NO) on the proliferation of mouse neural progenitor cells (NPCs). METHODS: NPCs were cultured in medium containing EGF, and SNP was added as a donor of NO in vitro. The concentration of NO was measured by the Griess assay; The amount of living cells was measured by MTT assay. The NPCs were induced to differentiate in medium supplemented with serum. RESULT: The NO(-)2 concentrations in the supernatants of the experimental groups 1, 2, and 3 were 64.701 +/- 0.606, 82.659 +/- 0.394 and 93.648 +/- 0.394 micro mol/L respectively, 3.099 +/- 0.420 micro mol/L in th control group. After culture with SNP for 24 hours, MTT assay showed the A values of 0.546 +/- 0.016, 0.484 +/- 0.007, and 0.357 +/- 0.007 in the experimental groups 1, 2, and 3 respectively, 0.642 +/- 0.021 in th control group (all P < 0.01). After further culture in the medium without SNP for 24 hours, MTT assay showed the A values of 1.243 +/- 0.036, 1.064 +/- 0.097, and 0.834 +/- 0.031 in the experimental groups 1, 2, and 3 respectively, 1.581 +/- 0.072 in the control group (all P < 0.01). The differences between the A values of the supernatants in the same wells filled with the medium with and without SNP were all significant (P < 0.01). In the medium with serum the NPCs still proliferated actively and differentiated into neuron and glial cell after SNP was removed. CONCLUSION: Exogenous nitric oxide inhibits the proliferation of mice NPC in vitro.