Long noncoding RNA MALAT1 contributes to inflammatory response of microglia following spinal cord injury via the modulation of a miR-199b/IKKß/NF-κB signaling pathway.

Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was widely recognized to be implicated in human cancer, vascular diseases, and neurological disorders. This study was to explore the role and underlying mechanism of MALAT1 in acute spinal cord injury (ASCI). ASCI models in adult rats were established and demonstrated by a numerical decrease in BBB scores. Expression profile of MALAT1 and miR-199b following ASCI in rats and in vitro was determined using quantitative real-time PCR. RNA pull-down assays combined with RIP assays were performed to explore the interaction between MALAT1 and miR-199b. In the present study, MALAT1 expression was significantly increased (2.4-fold that of control) in the spinal cord of the rat contusion epicenter accompanied by activation of IKKß/NF-κB signaling pathway and an increase in the level of proinflammatory cytokines TNF-α and IL-1ß. Upon treatment with LPS, MALAT1 expression dramatically increased in the microglia in vitro, but knockdown of MALAT1 attenuated LPS-induced activation of MGs and TNF-α and IL-1ß production. Next, we confirmed that LPS-induced MALAT1 activated IKKß/NF-κB signaling pathway and promoted the production of proinflammatory cytokines TNF-α and IL-1ß through downregulating miR-199b. More importantly, MALAT1 knockdown gradually improved the hindlimb locomotor activity of ASCI rats as well as inhibited TNF-α, IL-1ß levels, and Iba-1 protein, the marker of activated microglia in injured spinal cords. Our study demonstrated that MALAT1 was dysregulated in ASCI rats and in LPS-activated MGs, and MALAT1 knockdown was expected to attenuate ASCI through repressing inflammatory response of MGs.

Downregulation of miR-199b promotes the acute spinal cord injury through IKKß-NF-κB signaling pathway activating microglial cells.

Inflammatory response played an important role in the progression of spinal cord injury (SCI). Several miRNAs were associated with the pathology of SCI. However, the molecular mechanism of miRNA involving in inflammatory response in acute SCI (ASCI) was poorly understood. Sprague-Dawley (SD) rats were divided into 2 groups: control group (n=6) and acute SCI (ASCI) group (n=6). The expression of miR-199b and IκB kinase ß-nuclear factor-kappa B (IKKß-NF-κB) signaling pathway were evaluated by quantitative reverse transcription-PCR (qRT-PCR) in rats with ASCI and in primary microglia activated by lipopolysaccharide (LPS). We found that downregulation of miR-199b and activation of IKKß/NF-κB were observed in rats after ASCI and in activated microglia. miR-199b negatively regulated IKKß by targeting its 3'- untranslated regions (UTR) through using luciferase reporter assay. Overexpression of miR-199b reversed the up-regulation of IKKß, p-p65, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in LPS-treated BV2 cells assessed by western blotting analysis. In addition, BMS-345541 reversed the up-regulation effects of miR-199b inhibitor on the expression of TNF-α and IL-1ß. In the SCI rats, overexpression of miR-199b attenuated ASCI and decreased the expression of IKKß-NF-κB signaling pathway and TNF-α and IL-1ß. These results indicated that miR-199b attenuated ASCI at least partly through IKKß-NF-κB signaling pathway and affecting the function of microglia. Our findings suggest that miR-199b may be employed as therapeutic for spinal cord injury.

'Ectopic' suprasellar type IIa PRL-secreting pituitary adenoma.

BACKGROUND: Ectopic pituitary adenomas (EPAs) are rare, and the suprasellar cistern seems to be the most common location. At this time, no detailed original classification, diagnosis, or treatment protocols for suprasellar pituitary adenomas (SPAs) have been described. CASE DESCRIPTION: A 19-year-old man showed visual disturbances and lack of libido for 3 years, he suffered a sharp decline in vision with only light perception in the last week. Magnetic resonance imaging scans revealed a large suprasellar cystic lesion with a normal pituitary in the sella turcica. Endocrinological findings showed an extremely high prolactin level of 1250 ng/mL. Because of the sharp decline in vision, the patient underwent total removal of the suprasellar lesion using a transfrontal interhemispheric approach. The tumor pedicle originated in the lower pituitary stalk without any connection to the anterior pituitary gland in the sella turcica, while the diaphragma sellae was incomplete. Clinical and endocrinological cure criteria were fulfilled and postoperative pathology confirmed a prolactin-secreting pituitary adenoma. CONCLUSION: Ectopic suprasellar pituitary adenomas (ESPAs) are extremely rare intracranial extracerebral tumors. SPAs can be classified into three types according to their origin and their relationship with surrounding tissue. Only type III is theoretically a true ectopic, based on previous reports. Thus, ESPAs are uncommon compared to other EPAs. Our case is the first reported case of a type IIa 'E'SPA and the first description of this subtype classification until now. The pars tuberalis may be different from the pars distalis, and each subtype of adenohypophyseal cells may have different migration characteristics, which leads to different proportions of each hormone-secreting subtype in SPAs and EPAs. Transsphenoidal surgery is minimally invasive, but transcranial surgery may remain a universal option for the treatment of suprasellar lesions.

Primary sellar melanocytic tumor mimicking hemorrhagic pituitary macroadenoma: Case report and literature review.

Primary melanocytic tumors of the central nervous system (CNS) are rare lesions, but primary sellar tumors are rarer. Only 10 cases have been reported, and they are often misdiagnosed as pituitary macroadenoma. We report the case of a 54-year-old Chinese man who developed progressive bitemporal hemianopsia and visual loss. Magnetic resonance imaging (MRI) revealed an intrasellar and suprasellar clouded lesion adhering to the optic chiasm, hypothalamus, and hypophyseal stalk that was suspected of being a hemorrhagic pituitary macroadenoma. Because of the atypically giant, hemorrhagic, and upward-growing lesion, an initial trans-sphenoidal approach failed, and subsequent transfrontal craniotomy was adopted to achieve macroscopically complete resection. Histopathologic findings revealed a benign melanocytic tumor. Despite an extensive search, no other primary or secondary site was found. Considering the relatively benign lesion, effective surgery, and potential significant consequences of radiotherapy, the patient received no further treatment and is still alive at the 7-year follow-up. Primary sellar melanocytic tumors are exceptional lesions that are difficult to diagnose before operating and/or obtaining pathological findings. The pathological classification and extent of surgical resection may play a key role in the prognosis. Once this type of lesion is suspected, the transfrontal approach may achieve preferable exposure and resection. Complete surgical resection may be sufficient for relatively benign lesions; otherwise, stereotactic fractionated radiotherapy is indicated. More cases should be reported to improve the treatment strategy.

lncRNA MEG3 restrained the M1 polarization of microglia in acute spinal cord injury through the HuR/A20/NF-κB axis.

The M1 polarization of microglia and neuroinflammation restrict the treatment of acute spinal cord injury (ASCI), and long non-coding ribonucleic acid (lncRNA) maternally expressed gene 3 (MEG3) expression is lessened in ASCI. However, the function and mechanism of lncRNA MEG3 in the M1 polarization of microglia and neuroinflammation in ASCI are unclear. The expressions of lncRNA MEG3 in ASCI mouse spinal cord tissues and lipopolysaccharide (LPS)-treated primary microglia and BV2 cells were quantified through a quantitative real-time polymerase chain reaction. In-vitro assays were conducted to explore the function of lncRNA MEG3 in the M1 polarization of microglia and neuroinflammation in ASCI. RNA degradation, RNA immunoprecipitation, RNA pull-down, cycloheximide-chase, and ubiquitination analyses were carried out to probe into the mechanism of lncRNA MEG3 in the M1 polarization of microglia and neuroinflammation in ASCI. The lncRNA MEG3 expression was lessened in the ASCI mouse spinal cord tissues and LPS-treated primary microglia and BV2 cells, and the overexpression of lncRNA MEG3 restrained the M1 polarization of microglia and the neuroinflammation by regulating the NF-κB signaling pathway. For the investigation of the potential mechanism of such, the overexpression of lncRNA MEG3 restrained the M1 polarization of microglia through the HuR/A20/NF-κB axis and boosted the motor function recovery and neuroinflammation relief in the mice with SCI. The overexpression of lncRNA MEG3 restrained the M1 polarization of microglia through the HuR/A20/NF-κB axis.

Clipping Ophthalmic Segment Artery Aneurysms Using a Modified Subdural Dolenc Approach: Classification and Experience Sharing.

BACKGROUND: Ophthalmic segment artery aneurysms (OSAs) are difficult to clip; therefore, improvement of the surgical method is of great significance to the prevention of complications, and the classification of the aneurysms is essential to formulate a reasonable surgical plan. OBJECTIVE: To explore the strategies and effects of surgery for OSAs using a modified subdural Dolenc approach. METHODS: The clinical data of 38 patients (12 men and 26 women, aged 48-73 years) with OSA were analyzed retrospectively. A total of 44 aneurysms were identified, 40 of which were OSAs. The 40 aneurysms were divided into types Ia1 (n = 2), Ia2 (n = 2), Ib (n = 6), IIa (n = 4), IIb (n = 4), IIIa (n = 0), IIIb (n = 4), IIIc (n = 16), and IV (n = 2) based on preoperative images. Thirty-nine OSAs were operated successfully through pterional craniotomy combined with the modified subdural Dolenc approach, and 1 aneurysm was clipped through the contralateral approach. Clinical outcomes were evaluated using the Glasgow Outcome Scale (GOS). RESULTS: Thirty-nine OSAs were clipped, and one was wrapped. Visual dysfunction, headache, and dizziness improved after the operation in 18 patients. One patient had new visual impairment, and there were no deaths. At discharge, the GOS score was 5 in 36 cases, 4 in 1 case, and 3 in 1 case. Thirty-seven patients had a GOS score of 5, and 1 patient had a score of 3 at 6 months after the operation. CONCLUSION: The modified subdural Dolenc approach (Zheng approach) for clipping OSAs may be associated with less trauma and good postoperative outcomes.

Successful Treatment of Severe Post-craniotomy Meningitis Caused by an Escherichia coli Sequence Type 410 Strain Coharboring bla NDM - 5 and bla CTX - M - 65.

Intracranial infections caused by multidrug-resistant Gram-negative bacterium have led to considerable mortality due to extremely limited treatment options. Herein, we firstly reported a clinical carbapenem-resistant Escherichia coli isolate coharboring bla NDM - 5 and bla CTX - M - 65 from a patient with post-craniotomy meningitis. The carbapenem-resistant Escherichia coli strain CNEC001 belonging to Sequence Type 410 was only susceptible to amikacin and tigecycline, both of which have poor penetration through the blood-brain barrier (BBB). The bla CTX - M - 65 gene was expressed on a 135,794 bp IncY plasmid. The bla NDM - 5 gene was located on a genomic island region of an IncX3-type plasmid pNDM5-CNEC001. Based on the characteristics of the strain, we presented the successful treatment protocol of intravenous (IV) tigecycline and amikacin combined with intrathecal (ITH) amikacin in this study. Intracranial infection caused by Escherichia coli coharboring bla NDM - 5 and bla CTX - M - 65 is rare and fatal. Continuous surveillance and infection control measures for such strain need critical attention in clinical settings.

Patients with supratentorial aneurysmal subarachnoid hemorrhage during the intermediate period: waiting or actively treating.

Perhaps the most difficult practical decision for neurosurgeons these days is whether to secure aneurysms during the intermediate period (4-10 days) after aneurysmal subarachnoid hemorrhage (SAH). We reviewed retrospectively a series of 115 patients with a Hunt-Hess grade I-III upon admission who were admitted 4-10 days after initial supratentorial aneurysmal SAH. Patients who underwent active treatment in the intermediate period were assigned to the intermediate group (n = 49), while those who accepted delayed obliteration of a ruptured aneurysm (11-30 days) were assigned to the late group (n = 66). The demographic characteristics, size and site of aneurysms, and clinical conditions were well balanced in the two groups. There was no difference in outcome between the two groups according to the Glasgow Outcome Scale (GOS) at discharge or a 6-month follow-up. Rebleeding before aneurysms obliteration was the leading factor resulting in poor outcome. In conclusion, for patients with supratentorial aneurysmal SAH who were in good clinical condition upon admission, active treatment during the intermediate period offered a good chance for a favorable outcome. An even larger number of patients from randomized clinical trials might be necessary to draw more reliable conclusions.

Patients with supratentorial aneurysmal subarachnoid hemorrhage during the intermediate period: waiting or actively treating.

Perhaps the most difficult practical decision for neurosurgeons these days is whether to secure aneurysms during the intermediate period (4-10 days) after aneurysmal subarachnoid hemorrhage (SAH). We retrospectively reviewed a series of 115 patients with a Hunt-Hess grade I-III upon admission who were admitted 4-10 days after initial supratentorial aneurysmal SAH. Patients who underwent active treatment in the intermediate period were assigned to the intermediate group (n = 49) while those who accepted delayed obliteration of a ruptured aneurysm (11-30 days) were assigned to the late group (n = 66). The demographic characteristics, size and site of aneurysms, and clinical conditions were well balanced in the two groups. There was no difference in outcome between the two groups according to the Glasgow Outcome Scale (GOS) at discharge or a six-month follow-up. Rebleeding before aneurysms obliteration was the leading factor resulting in poor outcome. In conclusion, for patients with supratentorial aneurysmal SAH who were in good clinical condition upon admission, active treatment during the intermediate period offered a good chance of a favorable outcome. An even larger number of patients from randomized clinical trials might be necessary to draw more reliable conclusions.

Elevation of neuron-specific enolase and S-100beta protein level in experimental acute spinal cord injury.

We evaluated the protein levels of neuron-specific enolase (NSE) and S-100beta in serum and cerebrospinal fluid (CSF) in an animal model of acute spinal cord injury and ascertained their relevance. Spinal cord injury was induced at the T8 level in rats. Enzyme-linked immunosorbent assay was used to measure the protein levels of NSE and S-100beta in both serum and CSF at different time points (30 min, 2 h, 6 h, 12 h and 24 h after induction of spinal cord injury). There existed a significant correlation between neurological deficits and the severity of spinal cord injury (p<0.05). Compared with the control group, the protein levels of NSE and S-100beta in serum and CSF significantly increased from 2 h after injury (p<0.05) and reached a maximum at 6 h. Within a certain time window, the protein levels of NSE and S-100beta in serum and CSF were closely related to the severity of injury level (p<0.05). The protein levels of NSE and S-100beta in serum and CSF significantly increased after experimental spinal cord injury in a time-dependent manner and thus may be considered specific biomarkers for acute spinal cord injury.

Efficacy of large decompressive craniectomy in severe traumatic brain injury.

OBJECTIVE: To investigate the role of large decompressive craniectomy (LDC) in the management of severe and very severe traumatic brain injury (TBI) and compare it with routine decompressive craniectomy (RDC). METHODS: The clinical data of 263 patients with severe TBI (GCS < or = 8) treated by either LDC or RDC in our department were studied retrospectively in this article. One hundred and thirty-five patients with severe TBI, including 54 patients with very severe TBI (GCS < or = 5), underwent LDC (LDC group). The other 128 patients with severe TBI, including 49 patients with very severe TBI, underwent RDC (RDC group). The treatment outcome and postoperative complications of the two treatment methods were compared and analyzed in a 6-month follow-up period. RESULTS: Ninety-six patients (71.7 %) obtained satisfactory treatment outcome in the LDC group, while only 75 cases (58.6 %) obtained satisfactory outcome in the RDC group (P < 0.05). Moreover, the efficacy of LDC in treating very severe TBI was higher than that of RDC (63.0 % vs. 36.7 %, P < 0.01). The chance of reoperation due to refractory intracranial pressure (ICP) in the LDC group was significantly lower than that of the RDC group (P < 0.05), while the incidences of delayed intracranial hematoma and subdural effusion were significantly higher than those of the RDC group ( P < 0.05). CONCLUSIONS: LDC is superior to RDC in improving the treatment outcome of severe TBI, especially the very severe ones. LDC can also efficiently reduce the chances of reoperation due to refractory ICP. However, it increases the incidences of delayed intracranial hematoma and contralateral subdural effusion.

[Diagnosis and micro-neurosurgery for the fourth cerebral ventricle tumors].

OBJECTIVE: To investigate the diagnostic method and analyze the result of microneurosurgical treatment for tumors of the fourth cerebral ventricle. METHODS: Tumor of the fourth ventricle was clinically diagnosed in 86 patients basing on the preliminary assessment of symptom and CT or MRI findings. Of these 86 patients treated with micro-neurosurgery, the tumors in 62 were totally removed, subtotally in 19, and partially in 5. Forty-two patients received postoperative radiotherapy. RESULTS: Three patients died postoperatively within ten days, and symptoms in 83 were improved after treatment. The average survival period was over 3 years. The pathology included 32 medulloblastomas, 23 ependymoma, 15 astrocytoma, 10 hemangiblastomas, 2 choroid plexus papillomas, and 4 epidermoid cysts. CONCLUSION: Medulloblastoma, astrocytoma and hemangiblastoma are suggested to be removed totally whenever technically possible according to the site, character and volume of the tumor. For ependymoma, if close to the brain stem, is recommended to be subtotally removed. Postoperative radiotherapy may be beneficial for malignant types.

Establishment of a mechanical injury model of rat hippocampal neurons in vitro.

OBJECTIVE: To establish a simple, reproducible, and practical mechanical injury model of hippocampal neurons of Sprague-Dawley rats in vitro. METHODS: Hippocampal neurons isolated from 1-2-day old rats were cultured in vitro. Mild, moderate and severe mechanical injuries were delivered to the neurons by syringe needle tearing, respectively. The control neurons were treated identically with the exception of trauma. Cell damage was assessed by measuring the Propidium Iodide (PI) uptaking at different time points (0.5, 1, 6, 12 and 24 hours) after injury. The concentration of neuron specific enolase was also measured at some time points. RESULTS: Pathological examination showed that degeneration, degradation and necrosis occurred in the injured cultured neurons. Compared with the control group, the ratio of PI-positive cells in the injured groups increased significantly after 30 minutes of injury (P<0.05). More severe the damage was, more PI-positive neurons were detected. Compared with the control group, the concentration of neuron specific enolase in the injured culture increased significantly after 1 hour of injury (P<0.05). CONCLUSIONS: The established model of hippocampal neuron injury in vitro can be repeated easily and can simulate the damage mechanism of traumatic brain injury, which can be used in the future research of traumatic brain injury.

[Symptomatic vasospasm after subarachnoid hemorrhage: study of 186 cases].

OBJECTIVE: To identify the risk factors associated with symptomatic vasospasm after aneurysmal subarachnoid hemorrhage (SAH). METHODS: The clinical data of 186 cases with SAH verified by radiology and lumbar puncture were reviewed retrospectively. RESULTS: Fifty-five of the 186 patients (29.6%) developed symptomatic vasospasm. The incidence of symptomatic vasospasm was significantly higher in the patients of Fisher grade III than in those of Fisher grade I and Fisher grade II, in the patients in poor clinical status at admission the in those in better clinical status, and in the patients with repeated reoccurrence of SAH then in those without reoccurrence (all P < 0.01). Sex, age, treatment modality, and use of antifibrinolytic drugs (AFD) did not influence the development of symptomatic vasospasm (all P > 0.05). Multivariate analysis showed that Fisher grade III [odds ratio (OR) 2.549, 95% confidence interval (CI) 1.406 - 4.517], poor clinical status at admission (OR 2.342, 95% CI 1.320 - 4.159) and repeated reoccurrence of SAH (OR 2.492, 95% CI 1.394 approximately 4.448) were associated with the increased risk of symptomatic vasospasm. CONCLUSION: Fisher grade III, poor clinical status at admission and repeated reoccurrence of SAH are significant independent risk factors of symptomatic vasospasm. The presence of symptomatic vasospasm can be independently predicted by the amount of subarachnoid hemorrhage, clinical status at admission, and times of SAH.

Correlation of cell apoptosis with brain edema and elevated intracranial pressure in traumatic brain injury.

OBJECTIVE: To study the correlation between brain edema, elevated intracranial pressure (ICP) and cell apoptosis in traumatic brain injury (TBI). METHODS: In this study, totally 42 rabbits in 7 groups were studied. Six of the animals were identified as a control group, and the remaining 36 animals were equally divided into 6 TBI groups. TBI models were produced by the modified method of Feeney. After the impact, ICP of each subject was recorded continuously by an ICP monitor until the animal was sacrificed at scheduled time. The apoptotic brain cells were detected by an terminal deoxynucleotide-transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay. Cerebral water content (CWC) was measured with a drying method and calculated according to the Elliott formula. Then, an analysis was conducted to determine the correlation between the count of apoptotic cells and the clinical pathological changes of the brain. RESULTS: Apoptotic cell count began to increase 2 h after the impact, and reached its maximum about 3 days after the impact. The peak value of CWC and ICP appeared 1 day and 3 days after the impact, respectively. Apoptotic cell count had a positive correlation with CWC and ICP. CONCLUSIONS: In TBI, occurrence of brain edema and ICP increase might lead to apoptosis of brain cells. Any therapy which can relieve brain edema and/or decrease ICP would be able to reduce neuron apoptosis, thereby to attenuate the secondary brain damage.

[Expression of PCNA and Bcl-2 in the traumatic brains implanted with embryonic brain tissue in rats].

OBJECTIVE: To investigate the expression of PCNA and Bcl-2 in the traumatic brain area transplanted with embryonic brain tissue in rats. METHODS: The cerebral contusion of rats was induced by dropping weight. The homogenates of embryonic brain tissue were transplanted into the traumatic brain area two weeks after injury. All rats were sacrificed 6 weeks after injury (4 weeks after transplantation), and their brains were examined histologically. The expressions of PCNA and Bcl-2 in the brains were analyzed by immunohistochemical methods. RESULTS: The histology of brain presented the capillary and glia proliferation, especially in the transplantation group. No significant difference was found in the expression of PCNA between two groups. However, Bcl-2 was overexpressed in the transplantation group. CONCLUSION: The transplantation of the embryonic brain tissue enhances the expression of Bcl-2, which may play a neuroprotective role following traumatic brain injury.

Solitary spinal dural syphilis granuloma mimicking a spinal meningioma.

Dural granuloma is extremely rare. To our knowledge, there has no case reported solitary spinal dural syphilis granuloma worldwide so far. Here we report our findings in a 49-year-old woman, who presented with 10-year progressive left lower-limb numbness and two weeks of right lower-limb numbness. Magnetic resonance imaging (MRI) suggested a homogeneous enhanced spindle-shaped lesion, 2.9 × 1.5 cm in size, occupying the spinal intradural extramedullary space, at the level of Thoracic (T)-2/3, which mimicked the appearance of spinal meningioma. The Treponema pallidum particle agglutination (TPPA) test titer of 1:8, and the venereal diseases research laboratory of cerebral spinal fluid (VDRL-CSF) was reactive, so confirmed neurosyphilis was considered. After formal anti-syphilis treatment, posterior laminectomy surgery was performed, and the lesion was completely separated and extirpated. Final histopathologic diagnosis of the lesion was confirmed as chronic granulomatous inflammation, combined with the neurosyphilis history, spinal dural syphilis granuloma was finally diagnosed. Postoperatively, the patient recovered without any further treatment.

Use of medical aural and encephalic glue-soaked gelfoam for frontal sinus repair: a single-centre experience.

BACKGROUND: Frontal sinus (FS) perforation is a common complication in frontal craniotomy. The primary goal of treatment is to seal the FS without destroying physiological function. OBJECTIVE: This article describes a new FS cavity reconstruction technique using medical aural and encephalic glue (EC glue)-soaked gelfoam. METHODS: Between 2007 and 2012, 118 patients underwent FS reconstruction using EC glue-soaked gelfoam. The FS cavity was reconstructed in all patients and no patient experienced intracranial infection, frontal sinusitis, or cerebrospinal fluid (CSF) leakage. RESULTS: Restoring physiological function is the primary goal of FS reconstruction. Difficulty often arises in sealing the sinus opening, especially when the mucosa is damaged. Mucosal border dissection and electric coagulation of the mucosal laceration can help to reconstruct the mucosal cavity. Sealing the sinus with autogenous or exogenous material, such as fascia, bone flap or gelfoam carries increased risks of intracranial infection, frontal sinusitis, and CSF leakage in the short term, and increased the occurrence of a FS mucocoele in the long term. Gelfoam saturated with EC glue obtained good results. CONCLUSION: We describe the application of gelfoam saturated with EC glue to treat an open FS with or without mucosal violation during frontal craniotomy. Gelfoam saturated with EC glue is a quick, effective, low-cost and reliable means of sealing the FS while preserving its physiological function.