NEAT1 Is a Novel Oncogenic LncRNA and Correlated with miR-143 in Pediatric Oligodendrogliomas.

INTRODUCTION: The noncoding RNAs (ncRNAs) play a role in biological processes of various cancers including gliomas. The majority of these transcripts are uniquely expressed in differentiated tissues or specific glioma types. Pediatric oligodendroglioma (POG) is a rare subtype of diffuse glioma and accounts for <1% of pediatric brain tumors. Because histologically POG resembles adult OG, the same treatment is applied as adults. However, the significance in predicting outcomes in POG patients is unclear. In this study, we aimed to investigate the prognostic significance of expression -profiles of microRNA (miRNA) and long noncoding RNA -(LncRNA) in POGs. METHODS: We investigated the levels of 13 known miRNAs and 6 LncRNAs in tumor samples from 9 patients with primary POG by using RT-PCR and analyzed their association with outcomes. RESULTS: The expression levels of miR-21, miR-106a, miR-10b, and LncRNA NEAT1 were higher, and the expression level of miR-143 was lower in POG tissues compared with normal brain tissues (p = 0.006, p = 0.032, p = 0.034, p = 0.002, and p = 0.001, respectively). High levels of NEAT1 and low expression of miR-143 were associated with decreased probability of short disease-free survival (p = 0.018 and p = 0.022, respectively). DISCUSSION: NEAT1 and miR-143 levels could serve as reciprocal prognostic predictors of disease progression in patients with POG. New treatment models to regulate the expression levels of NEAT1 and miR-143 will bring a new approach to the therapy of POG.

CT-Guided Percutaneous Trigeminal Tractotomy-Nucleotomy for Intractable Craniofacial Pain.

OBJECT: In this report, we aimed to analyze the outcome results of our patients who underwent percutaneous trigeminal tractotomy (TR) and nucleotomy (NC) procedures, which are defined as destructive procedures targeting the descending trigeminal tractus and nucleus caudalis of the spinal trigeminal nucleus, respectively, for intractable craniofacial pain. METHODS: The medical records of a total of 12 patients who underwent a total of 14 computed tomography (CT)-guided TR-NC procedures at our clinics between 2005 and 2017 were retrospectively reviewed. RESULTS: A significant increase in patients' performance status (p = 0.015) as well as a significant decrease in the VAS score (p < 0.001) were achieved. Grade I pain relief (VAS = 0, no pain) was established in 66.7% of the patients, whereas grade II pain relief was observed in the remaining patients. Two of the patients suffered from recurrent pain after the initial procedure. Both patients underwent a second trigeminal TR-NC procedure, and grade I pain relief was re-established. The mean VAS score at 3-month follow-up was 1.4 ± 1.1, whereas this score at 6-month follow-up was 2 ± 1.3. The trigeminal TR-NC procedure resulted in a significant decrease in patients' VAS scores at 3- and 6-month follow-up visits compared with preoperative VAS scores (p < 0.001). Transient ataxia was noted in only one patient (8.3%) early after the procedure. CONCLUSIONS: The results presented in the current study support the efficacy of the percutaneous CT-guided trigeminal TR-NC procedure in the management of intractable facial pain in selected patients. The use of CT guidance allows direct visualization of the target area, thereby enhancing the safety and success of the procedure.

Inhibition of mast cell tryptase attenuates neuroinflammation via PAR-2/p38/NFκB pathway following asphyxial cardiac arrest in rats.

BACKGROUND: Cardiac arrest survivors suffer from neurological dysfunction including cognitive impairment. Cerebral mast cells, the key regulators of neuroinflammation contribute to neuroinflammation-associated cognitive dysfunction. Mast cell tryptase was demonstrated to have a proinflammatory effect on microglia via the activation of microglial protease-activated receptor-2 (PAR-2). This study investigated the potential anti-neuroinflammatory effect of mast cell tryptase inhibition and the underlying mechanism of PAR-2/p-p38/NFκB signaling following asphyxia-induced cardiac arrest in rats. METHODS: Adult male Sprague-Dawley rats resuscitated from 10 min of asphyxia-induced cardiac arrest were randomized to four separate experiments including time-course, short-term outcomes, long-term outcomes and mechanism studies. The effect of mast cell tryptase inhibition on asphyxial cardiac arrest outcomes was examined after intranasal administration of selective mast cell tryptase inhibitor (APC366; 50 µg/rat or 150 µg/rat). AC55541 (selective PAR-2 activator; 30 µg/rat) and SB203580 (selective p38 inhibitor; 300 µg/rat) were used for intervention. Short-term neurocognitive functions were evaluated using the neurological deficit score, number of seizures, adhesive tape removal test, and T-maze test, while long-term cognitive functions were evaluated using the Morris water maze test. Hippocampal neuronal degeneration was evaluated by Fluoro-Jade C staining. RESULTS: Mast cell tryptase and PAR-2 were dramatically increased in the brain following asphyxia-induced cardiac arrest. The inhibition of mast cell tryptase by APC366 improved both short- and long-term neurological outcomes in resuscitated rats. Such behavioral benefits were associated with reduced expressions of PAR-2, p-p38, NFκB, TNF-α, and IL-6 in the brain as well as less hippocampal neuronal degeneration. The anti-neuroinflammatory effect of APC366 was abolished by AC55541, which when used alone, indeed further exacerbated neuroinflammation, hippocampal neuronal degeneration, and neurologic deficits following cardiac arrest. The deleterious effects aggregated by AC55541 were minimized by p38 inhibitor. CONCLUSIONS: The inhibition of mast cell tryptase attenuated neuroinflammation, led to less hippocampal neuronal death and improved neurological deficits following cardiac arrest. This effect was at least partly mediated via inhibiting the PAR-2/p-p38/NFκB signaling pathway. Thus, mast cell tryptase might be a novel therapeutic target in the management of neurological impairment following cardiac arrest.

Microsurgical Clipping of Giant P3 Segment Posterior Cerebral Artery Aneurysm: 2-Dimensional Operative Video.

Posterior cerebral artery (PCA) aneurysms comprise <2% of all intracranial aneurysms and are usually located on the P1 and P2 segments. Aneurysms of the P3 segment of the PCA are even rarer, and despite their proximity to the cerebral aqueduct, presentation with hydrocephalus is exceptional. This video demonstrates the case of a 28-year-old female patient who presented acute hydrocephalus due to a partially thrombosed, giant P3 segment PCA aneurysm. The patient was operated on in the semisitting position, and a right frontal ventricular drain was placed for brain relaxation. A U-shaped skin incision was made, and a left-sided, 6 cm × 6 cm parietooccipital craniotomy crossing the midline was performed. An interhemispheric approach was used to reach the aneurysm. The aneurysm was trapped via temporary clipping of the inflow and outflow arteries, thrombectomized, and then clipped using a right-angled fenestrated aneurysm clip. Postoperative computed tomography and magnetic resonance imaging revealed resolution of the hydrocephalus, and cerebral angiography confirmed total exclusion of the aneurysm from the circulation and occlusion of the P4 segment of the PCA, which was considered embolic. The patient made an excellent recovery, and she was discharged on postoperative day 3 (Video 1). This case demonstrates the efficacy of microsurgical clipping for a giant thrombotic P3 segment PCA aneurysm that caused a mass effect. Surgery excluded the aneurysm from the circulation and decompressed the cerebral aqueduct, obviating the need for a permanent ventriculoperitoneal shunt.

The Efficacy and Safety of Microvascular Decompression for Hemifacial Spasm: A Retrospective Analysis of Surgical Outcomes and Complications.

AIM: To determine the efficacy and safety of microvascular decompression (MVD) for hemifacial spasm (HFS) by retrospectively reviewing our results. MATERIAL AND METHODS: A total of 55 patients who underwent MVD in our clinic between 2003 and 2017 were retrospectively analyzed. Clinical outcome results, recurrence rates, and surgical complications were noted. RESULTS: Thirty-six patients were female (65%). The mean age of the patients was 51.3 years. The mean duration of the complaint was 46.4 months. In 45 patients (82%), HFS was completely resolved within the first 6 months after the surgery. Five patients (9%) with recurrent symptoms were reoperated within the first year of the surgery. HFS symptoms of five patients (9%) completely ceased initially, but started again and reoperation was required due to failure of alternative treatments. Delayed facial nerve palsy and hearing loss were noted in one patient for each (2%). Cerebrospinal fluid leak was observed in two patients (4%). No mortality was observed in this series. CONCLUSION: MVD is a safe and effective option for patients with HFS that is resistant to medical treatment.

FSLLRY-NH2 Improves Neurological Outcome After Cardiac Arrest in Rats.

AIM: To evaluate the effect of FSLLRY-NH2, a protease-activated receptor 2 (PAR2) inhibitor, on neurocognitive impairment and hippocampal neuronal degeneration in the setting of asphyxial cardiac arrest (ACA)-induced global cerebral ischemia (GCI) in rats. MATERIAL AND METHODS: A total of 43 Sprague-Dawley male rats were used. Shams and rats resuscitated from 9 minutes of ACA were randomized to two separate experiments including time course and short-term neurological outcomes. FSLLRY-NH2 (50 microgram [µg] per rat) was administered intranasally at 1 hour postresuscitation. Neurological function and hippocampal neuronal degeneration were evaluated after ACA. RESULTS: Significant neurological function decline and hippocampal neuron degeneration were observed in ACA animals as compared with the shams. Treatment with FSLLRY-NH2 significantly improved neurological outcome and reduced the number of degenerating hippocampal neurons after ACA. CONCLUSION: Targeting PAR2 may be a novel therapeutic approach in the management of neurological dysfunction after cardiac arrest-associated ischemic injury.

Overexpression of Mfsd2a attenuates blood brain barrier dysfunction via Cav-1/Keap-1/Nrf-2/HO-1 pathway in a rat model of surgical brain injury.

INTRODUCTION: Disruption of the blood brain barrier (BBB) and subsequent cerebral edema formation is one of the major adverse effects of brain surgery, leading to postoperative neurological dysfunction. Recently, Mfsd2a has been shown to have a crucial role for the maintenance of BBB functions. In this study, we aimed to evaluate the role of Mfsd2a on BBB disruption following surgical brain injury (SBI) in rats. MATERIALS AND METHODS: Rats were subjected to SBI by partial resection of the right frontal lobe. To evaluate the effect of Mfsd2a on BBB permeability and neurobehavior outcome following SBI, Mfsd2a was either overexpressed or downregulated in the brain by administering Mfsd2a CRISPR activation or knockout plasmids, respectively. The potential mechanism of Mfsd2a-mediated BBB protection through the cav-1/Nrf-2/HO-1 signaling pathway was evaluated. RESULTS: Mfsd2a levels were significantly decreased while cav-1, Nrf-2 and HO-1 levels were increased in the right frontal perisurgical area following SBI. When overexpressed, Mfsd2a attenuated brain edema and abolished neurologic impairment caused by SBI while downregulation of Mfsd2a expression further deteriorated BBB functions and worsened neurologic performance following SBI. The beneficial effect of Mfsd2a overexpression on BBB functions was associated with diminished expression of cav-1, increased Keap-1/Nrf-2 dissociation and further augmented levels of Nrf-2 and HO-1 in the right frontal perisurgical area, leading to enhanced levels of tight junction proteins following SBI. The BBB protective effect of Mfsd2a was blocked by selective inhibitors of Nrf-2 and HO-1. CONCLUSIONS: Mfsd2a attenuates BBB disruption through cav-1/Nrf-2/HO-1 signaling pathway in rats subjected to experimental SBI.

Insights into major facilitator superfamily domain-containing protein-2a (Mfsd2a) in physiology and pathophysiology. What do we know so far?

Major facilitator superfamily domain-containing protein-2a (Mfsd2a) which was considered as an orphan transporter has recently gained attention for its regulatory role in the maintenance of proper functioning of the blood-brain barrier. Besides the major role of Mfsd2a in maintaining the barrier function, increasing evidence has emerged with regard to the contributions of Mfsd2a to various biological processes such as transport, cell fusion, cell cycle, inflammation and regeneration, managing tumor growth, functioning of other organs with barrier functions or responses to injury. The purpose of this article is to review the different roles of Mfsd2a and its involvement in the physiological and pathophysiological processes primarily in the central nervous system and throughout the mammalian body under the lights of the current literature.

Retrosigmoid Transtentorial Resection of a Petroclival Meningioma: 2-Dimensional Operative Video.

In this video, we aimed to demonstrate retrosigmoid-transtentorial resection of a 4.5 × 4 × 4.5 cm3 left-sided petroclival meningioma compressing the brainstem in a 62-yr-old male who presented with decreased hearing on the left and imbalance. The patient was placed in park-bench position and a left-sided suboccipital craniotomy was performed. The mass was severely compressing the brainstem as well as the cranial nerves V, VI, VII, and VIII while IV was encased by the tumor. The circumferential dissection of the tumor was facilitated while the surgical corridor and exposure were enlarged by incising the tentorium. Uneventfully, the meningioma was resected in piecemeal fashion as it was not coming out easily with the ultrasonic aspirator. All relevant cranial nerves and adjacent vascular structures were protected. Early postoperative CT scan demonstrated changes due to the surgery and resolution of the compression on the brainstem. The patient made excellent recovery and he was discharged home on postoperative day 4 safely. Petroclival meningiomas are one of the most challenging tumors for neurosurgeons due to their close proximity to the vascular structures, cranial nerves as well as the brainstem. The retrosigmoid approach provides a direct route during microsurgical resection of these tumors. By incising the tentorium, the corridor can be widened while addressing the supratentorial portion of the tumor with relative ease.

The role of caveolin-1 in tumors of the brain - functional and clinical implications.

BACKGROUND: Caveolin-1 (cav-1) is the major structural protein of caveolae, the flask-shaped invaginations of the plasma membrane mainly involved in cell signaling. Today, cav-1 is believed to play a role in a variety of disease processes including cancer, owing to the variations of its expression in association with tumor progression, invasive behavior, metastasis and therapy resistance. Since first detected in the brain, a number of studies has particularly focused on the role of cav-1 in the various steps of brain tumorigenesis. In this review, we discuss the different roles of cav-1 and its contributions to the molecular mechanisms underlying the pathobiology and natural behavior of brain tumors including glial, non-glial and metastatic subtypes. These contributions could be attributed to its co-localization with important players in tumorigenesis within the lipid-enriched domains of the plasma membrane. In that regard, the ability of cav-1 to interact with various cell signaling molecules as well as the impact of caveolae depletion on important pathways acting in brain tumor pathogenesis are noteworthy. We also discuss conversant causes hampering the treatment of malignant glial tumors such as limited transport of chemotherapeutics across the blood tumor barrier and resistance to chemoradiotherapy, by focusing on the molecular fundamentals involving cav-1 participation. CONCLUSIONS: Cav-1 has the potential to pivot the molecular basis underlying the pathobiology of brain tumors, particularly the malignant glial subtype. In addition, the regulatory effect of cav-1-dependent and caveola-mediated transcellular transport on the permeability of the blood tumor barrier could be of benefit to overcome the restricted transport across brain barriers when applying chemotherapeutics. The association of cav-1 with tumors of the brain other than malignant gliomas deserves to be underlined, as well given the evidence suggesting its potential in predicting tumor grade and recurrence rates together with determining patient prognosis in oligodendrogliomas, ependymomas, meningiomas, vestibular schwannomas and brain metastases.

A Rare Complication of Endovascular Embolization: Extruded Onyx on Trigeminal Nerve.

Objectives To demonstrate a rare complication of endovascular tumor embolization with onyx. Design Operative video. Setting Department of neurological surgery in a university hospital. Participants A 39-year-old male who was diagnosed with a right sided hemangioblastoma. Main Outcome Measures Surgical resection of the tumor, preservation of the cranial nerves and extruded embolization material on trigeminal nerve. Results The tumor was embolized with onyx the day before surgery. Patient woke up with no sensation in the right side of his face. Diffusion magnetic resonance imaging (MRI) showed a small restricted diffusion area within the right superior cerebellar vermis. Microsurgical resection of the tumor was uneventful and complete resection was achieved (Fig. 1). After the resection was completed, the trigeminal nerve was identified. Some of the capillaries overlying the nerve as well as the cerebellum and brain stem had extruded onyx-embolic material (Fig. 2). Some of the onyx over the cerebellum was removed; however, the ones on the trigeminal nerve and brain stem were not removed due to the risk of injury to the nerve. Postoperative MRI confirmed total resection. Patient made excellent recovery except he continued to have no sensation in the right side of his face. Conclusion Preoperative embolization is an important adjunct to resection of large hemangioblastomas in selected cases because it may facilitate circumferential dissection and debulking of the tumor. Although extrusion of the embolization material is relatively common, immediate extrusion of onyx and its transfixion on a cranial nerve has not been reported before. Judicial selection of preoperative embolization is required in hemangioblastomas. The link to the Video can be found at: https://youtu.be/s0DjD26Xkas .

Facial nerve outcome and extent of resection in cystic versus solid vestibular schwannomas in radiosurgery era.

OBJECTIVE Cystic vestibular schwannomas (CVSs) are a subgroup of vestibular schwannomas (VSs) that are reported to be associated with unpredictable clinical behavior and unfavorable postoperative outcomes. The authors aimed to review their experience with microsurgical treatment of CVSs in terms of extent of resection and postoperative facial nerve (FN) function and compare these outcomes with those of their solid counterparts. METHODS Two hundred-eleven VS patients were treated surgically between 2006 and 2017. Tumors were defined as cystic when preoperative neuroimaging demonstrated cyst formation that was confirmed by intraoperative findings. Solid VS (SVSs) with similar classes were used for comparison. Clinical data of the patients were reviewed retrospectively, including clinical notes and images, as well as operative, pathology, and neuroradiology reports. RESULTS Thirty-two patients (20 males and 12 females) with a mean age of 52.2 years (range 17-77 years) underwent microsurgical resection of 33 CVSs (mean size 3.6 cm, range 1.5-5 cm). Forty-nine patients (26 males and 23 females) with a mean age of 49.9 years (range 21-75 years) underwent microsurgical resection of 49 SVSs (mean size 3 cm, range 2-4.5 cm). All operations were performed via either a retrosigmoid or a translabyrinthine approach. Gross-total resection was achieved in 30 cases in the CVS group (90.9%) and 37 in the SVS group (75.5%). The main reason for subtotal and near-total resection was adherence of the tumor to the brainstem and/or FN in both groups. None of the patients with subtotal or near-total resection in the CVS group demonstrated symptomatic regrowth of the tumor during the mean follow-up period of 41.6 months (range 18-82 months). The FN was anatomically preserved in all patients in both groups. Good FN outcomes were achieved in 15 of CVS (grade I-II; 45.5%) and 35 of SVS (71.4%) surgeries at discharge. Good and fair FN functions were noted in 22 (grade I-II; 81.5%) and 5 (grade III only; 18.5%) of the CVS patients, respectively, at the 1-year follow-up; none of the patients showed poor FN function. CONCLUSIONS Surgery of CVSs does not necessarily result in poor outcomes in terms of the extent of resection and FN function. Special care should be exercised to preserve anatomical continuity of the FN during surgery, since long-term FN function outcomes are much more satisfactory than short-term results. High rates of gross-total resection and good FN outcomes in our study may also suggest that microsurgery stands as the treatment of choice in select cases of large CVSs and SVSs in the era of radiosurgery.

Investigation of topographical anatomy of Broca's area: an anatomic cadaveric study.

PURPOSE: The sulci constituting the structure of the pars triangularis and opercularis, considered as 'Broca's area', present wide anatomical and morphological variations between different hemispheres. The boundaries are described differently from one another in various studies. The aim of this study was to explore the topographical anatomy, confirm the morphological asymmetry and highlight anatomical variations in Broca's area. METHODS: This study was performed with 100 hemispheres to investigate the presence, continuity, patterns and connections of the sulcal structures that constitute the morphological asymmetry of Broca's area. RESULTS: Considerable individual anatomical and morphological variations between the inferior frontal gyrus and related sulcal structures were detected. Rare bilateralism findings supported the morphological asymmetry. The inferior frontal sulcus was identified as a single segment in 54 % of the right and two separate segments in 52 % of the left hemispheres, which was the most common pattern. The diagonal sulcus was present in 48 % of the right and 54 % of the left hemispheres. It was most frequently connected to the ascending ramus on both sides. A 'V' shape was observed in 42.5 % of the right hemispheres and a 'Y' shape in 38.3 % of the left hemispheres, which was the most common shape of the pars triangularis. Moreover, the full results are specified in detail. CONCLUSIONS: Knowledge of the anatomical variations in this region is indispensable for understanding the functional structure and performing safe surgery. However, most previously published studies have aimed to determine the anatomical asymmetry of the motor speech area without illuminating the topographical anatomy encountered during surgery.