Insights into neuroinflammatory mechanisms of deep brain stimulation in Parkinson's disease.

Parkinson's disease, a progressive neurodegenerative disorder, involves gradual degeneration of the nigrostriatal dopaminergic pathway, leading to neuronal loss within the substantia nigra pars compacta and dopamine depletion. Molecular factors, including neuroinflammation, impaired protein homeostasis, and mitochondrial dysfunction, contribute to the neuronal loss. Deep brain stimulation, a form of neuromodulation, applies electric current through stereotactically implanted electrodes, effectively managing motor symptoms in advanced Parkinson's disease patients. Deep brain stimulation exerts intricate effects on neuronal systems, encompassing alterations in neurotransmitter dynamics, microenvironment restoration, neurogenesis, synaptogenesis, and neuroprotection. Contrary to initial concerns, deep brain stimulation demonstrates antiinflammatory effects, influencing cytokine release, glial activation, and neuronal survival. This review investigates the intricacies of deep brain stimulation mechanisms, including insertional effects, histological changes, and glial responses, and sheds light on the complex interplay between electrodes, stimulation, and the brain. This exploration delves into understanding the role of neuroinflammatory pathways and the effects of deep brain stimulation in the context of Parkinson's disease, providing insights into its neuroprotective capabilities.

The interplay between neuroinflammatory pathways and Parkinson's disease.

Parkinson's disease, a progressive neurodegenerative disorder predominantly affecting elderly, is marked by the gradual degeneration of the nigrostriatal dopaminergic pathway, culminating in neuronal loss within the substantia nigra pars compacta (SNpc) and dopamine depletion. At the molecular level, neuronal loss in the SNpc has been attributed to factors including neuroinflammation, impaired protein homeostasis, as well as mitochondrial dysfunction and the resulting oxidative stress. This review focuses on the interplay between neuroinflammatory pathways and Parkinson's disease, drawing insights from current literature.

Co-loading of Temozolomide with Oleuropein or rutin into polylactic acid core-shell nanofiber webs inhibit glioblastoma cell by controlled release.

Glioblastoma (GB) has susceptibility to post-surgical recurrence. Therefore, local treatment methods are required against recurrent GB cells in the post-surgical area. In this study, we developed a nanofiber-based local therapy against GB cells using Oleuropein (OL), and rutin and their combinations with Temozolomide (TMZ). The polylactic acid (PLA) core-shell nanofiber webs were encapsulated with OL (PLAOL), rutin (PLArutin), and TMZ (PLATMZ) by an electrospinning process. A SEM visualized the morphology and the total immersion method determined the release characteristics of PLA webs. Real-time cell tracking analysis for cell growth, dual Acridine Orange/Propidium Iodide staining for cell viability, a scratch wound healing assay for migration capacity, and a sphere formation assay for tumor spheroid aggressiveness were used. All polymeric nanofiber webs had core-shell structures with an average diameter between 133 ± 30.7-139 ± 20.5 nm. All PLA webs promoted apoptotic cell death, suppressed cell migration, and spheres growth (p < 0.0001). PLAOL and PLATMZ suppressed GB cell viability with a controlled release that increased over 120 h, while PLArutin caused rapid cell inhibition (p < 0.0001). Collectively, our findings suggest that core-shell nano-webs could be a novel and effective therapeutic tool for the controlled release of OL and TMZ against recurrent GB cells.

Hemorrhagic presentation of previously silent brain tumors / Presentación hemorrágica de tumores cerebrales anteriormente silenciosos

Introduction and objectives Acute presentation with intracranial hemorrhage owing to a previously silent brain tumor (BT) is rare. Although any BT can bleed, the frequency and type of bleeding varies across tumor types. Materials and methods We aimed to retrospectively review our experience with 55 patients with BTs presenting with ICH. Results Signs of increased intracranial pressure were the most common symptoms. The temporal lobe was the most common lesion site (n=22). Hemorrhages were mainly confined to the tumor margins (HCTs) (n=34). Extensive intraparenchymal hemorrhages (EIHs) were mainly associated with moderately/severely decreased levels of consciousness (LOCs) (n=15/16). High-grade glioma (HGGT) (n=25) was the leading pathological diagnosis followed by metastasis (MBT) (n=16/55). The hemorrhage type was associated with the pathological diagnosis of the tumor. Patients with HGGT (n=19/25) and MBT (n=9/16) mainly presented with HCTs, whereas low-grade gliomas (LGGT) primarily caused EIHs (n=6/7). Conclusions Hemorrhagic presentation is a rare occurrence in BTs. Among all, MBT and HGGT are responsible for majority of the cases. Importantly, despite their relatively benign characteristics, LGGTs mainly result in extensive parenchymal destruction once they bleed. Maximum surgical resection of hemorrhagic BTs and decompression of the affected brain regions followed by histological confirmation of the diagnosis should be the main goals of treatment in cases with hemorrhagic BTs (AU)

Introducción y objetivos La presentación aguda con hemorragia intracraneal debida a un tumor cerebral (BT) anteriormente silencioso es rara. A pesar de que cualquier BT puede sangrar, la frecuencia y el tipo de sangrado varían según el tipo de tumor. Materiales y métodos Nuestro objetivo fue reexaminar retrospectivamente nuestra experiencia con 55 pacientes con los BT que presentaban HIC. Resultados Los síntomas más comunes fueron signos de aumento de la presión intracraneal. El lóbulo temporal fue el sitio de lesión más común (n=22). Las hemorragias se limitaron especialmente a los márgenes tumorales (HCT) (n=34). Las hemorragias intraparenquimatosas extensas (HIE) se asociaron mayormente con niveles de conciencia moderada/severamente disminuidos (LOC) (n=15/16). El glioma de alto grado (HGGT) (n=25) fue el principal diagnóstico patológico después de la metástasis (MBT) (n=16/55). El tipo de hemorragia se asoció con el diagnóstico patológico del tumor. Los pacientes con HGGT (n=19/25) y MBT (n=9/16) presentaron mayormente con HCT, mientras que los gliomas de bajo grado (LGGT) causaron principalmente HIE (n=6/7). Conclusiones La presentación hemorrágica es una ocurrencia rara en los BT. Entre todos, MBT y HGGT son responsables de la mayoría de los casos. Más importante aún, pese a sus características relativamente benignas, los LGGT resultan mayormente una destrucción extensa del parénquima una vez que sangran. La resección quirúrgica máxima de BT hemorrágicos y la descompresión de las regiones cerebrales afectadas con la confirmación histológica del diagnóstico deben ser los objetivos principales del tratamiento en casos con BT hemorrágicos (AU)

Diabetes Mellitus-Mediated MALAT1 Expression Induces Glioblastoma Aggressiveness.

AIM: To describe the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in glioblastoma (GB) progression in patients concurrently diagnosed with diabetes mellitus (DM). MATERIAL AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor samples of 47 patients diagnosed with GB only and 13 patients diagnosed with GB and DM (GB-DM) were enrolled in this study. Data for p53 and Ki67 immunohistochemical staining of the tumors and blood HbA1c levels of patients with DM were retrospectively collected. MALAT1 expression was assessed using quantitative real-time polymerase chain reaction. RESULTS: The coexistence of GB and DM induced the nuclear expression of p53 and Ki67 compared with GB only. MALAT1 expression was higher in GB-DM tumors than in GB only tumors. The expression of MALAT1 and HbA1c levels were positively correlated. Additionally, MALAT1 was positively correlated with tumoral p53 and Ki67. The disease-free survival of patients with GB-DM with high MALAT1 expression was shorter than that of those diagnosed with GB only and with a lower MALAT1 expression. CONCLUSION: Our findings suggest that one of the mechanisms of the facilitating effect of DM on GB tumor aggressiveness is via MALAT1 expression.

Hemorrhagic presentation of previously silent brain tumors.

INTRODUCTION AND OBJECTIVES: Acute presentation with intracranial hemorrhage owing to a previously silent brain tumor (BT) is rare. Although any BT can bleed, the frequency and type of bleeding varies across tumor types. MATERIALS AND METHODS: We aimed to retrospectively review our experience with 55 patients with BTs presenting with ICH. RESULTS: Signs of increased intracranial pressure were the most common symptoms. The temporal lobe was the most common lesion site (n=22). Hemorrhages were mainly confined to the tumor margins (HCTs) (n=34). Extensive intraparenchymal hemorrhages (EIHs) were mainly associated with moderately/severely decreased levels of consciousness (LOCs) (n=15/16). High-grade glioma (HGGT) (n=25) was the leading pathological diagnosis followed by metastasis (MBT) (n=16/55). The hemorrhage type was associated with the pathological diagnosis of the tumor. Patients with HGGT (n=19/25) and MBT (n=9/16) mainly presented with HCTs, whereas low-grade gliomas (LGGT) primarily caused EIHs (n=6/7). CONCLUSIONS: Hemorrhagic presentation is a rare occurrence in BTs. Among all, MBT and HGGT are responsible for majority of the cases. Importantly, despite their relatively benign characteristics, LGGTs mainly result in extensive parenchymal destruction once they bleed. Maximum surgical resection of hemorrhagic BTs and decompression of the affected brain regions followed by histological confirmation of the diagnosis should be the main goals of treatment in cases with hemorrhagic BTs.

Olea europaea Leaf Phenolics Oleuropein, Hydroxytyrosol, Tyrosol, and Rutin Induce Apoptosis and Additionally Affect Temozolomide against Glioblastoma: In Particular, Oleuropein Inhibits Spheroid Growth by Attenuating Stem-like Cell Phenotype.

The effects of Olea europaea leaf extract (OLE) phenolics, including oleuropein (OL), hydroxytyrosol (HT), tyrosol (TYR), and rutin against glioblastoma (GB), independently and in combination with temozolomide (TMZ), were investigated in T98G and A172 cells. Cell growth was assessed by WST-1, real-time cell analysis, colony formation, and cell cycle distribution assays. A dual acridine orange propidium iodide (AO/PI) staining and annexin V assay determined cell viability. A sphere-forming assay, an intracellular oxidative stress assay, and the RNA expression of CD133 and OCT4 investigated the GB stem-like cell (GSC) phenotype. A scratch wound-healing assay evaluated migration capacity. OL was as effective as OLE in terms of apoptosis promotion (p < 0.001) and GSC inhibition (p < 0.001). HT inhibited cell viability, GSC phenotype, and migration rate (p < 0.001), but its anti-GB effect was less than the total effect of OLE alone. Rutin decreased reactive oxygen species production and inhibited colony formation and cell migration (p < 0.001). TYR demonstrated the least effect. The additive effects of OL, HT, TYR and rutin with TMZ were significant (p < 0.001). Our data suggest that OL may represent a novel therapeutic approach against GB cells, while HT and rutin show promise in increasing the efficacy of TMZ therapy.

A clinical evaluation of gelastic and dacrystic seizures: a multicenter study.

BACKGROUND: Gelastic seizures are extremely rare, short-lasting, unprovoked, and uncontrollable laughing attacks. We conducted this retrospective evaluation to determine whether these symptoms, manifesting in different forms, such as cheerful laughter, laughing, smiling, and sobbing had any value in terms of etiology or localization. METHODS: A total of 31 patients who exhibited bouts of laughing or crying and who were under follow-up between 2000 and 2019 at tertiary epilepsy centers were included in the study. Laughing seizures were divided into three groups in terms of semiology (i.e., laughter with mirth, laughter without mirth, and smile). Dacrystic seizures were accompanied by some gelastic seizures and were divided into two groups in terms of semiology (i.e., weeping loudly [motor and voice-sobbing] and crying). RESULTS: Of the 27 patients with laughing seizures, 12 had seizures that manifested with smiling, 7 had seizures that manifested with laughing and mirth, and 8 had seizures that manifested with laughter without mirth. Dacrystic-gelastic seizures were observed in four patients, among whom 2 patients had crying and laughter without mirth and 2 patients had weeping loudly and laughter without mirth episodes. CONCLUSION: Gelastic and dacrystic seizures often suggest hypothalamic hamartomas, in the literature. This rare ictal behavior can originate from different cortical locations and lesions of a different nature. However, we found that gelastic seizures with smiling were a more homogenous group with regard to location in the temporal lobe, which we aimed to show by evaluating the patients included in this study.

ANTECEDENTES: Crises gelásticas são ataques de riso extremamente raros, de curta duração, não provocados e incontroláveis. Realizamos esta avaliação retrospectiva para determinar se esses sintomas, manifestando-se de diferentes formas, como riso alegre, riso, sorriso e soluço, tinham algum valor em termos de etiologia ou localização. MéTODOS: Foram incluídos no estudo 31 pacientes que apresentavam crises de riso ou choro e que estavam em acompanhamento entre 2000 e 2019 em centros terciários de epilepsia. As crises de riso foram divididas em três grupos em termos de semiologia (ou seja, riso com alegria, riso sem alegria e sorriso). As crises dacrísticas foram acompanhadas por algumas crises gelásticas e foram divididas em dois grupos em termos de semiologia (ou seja, choro alto [motor e soluçar a voz] e choro). RESULTADOS: Dos 27 pacientes com crises de riso, 12 tiveram crises que se manifestaram com sorriso, 7 tiveram crises que se manifestaram com riso e alegria e 8 tiveram crises que se manifestaram com riso sem alegria. Crises dácristico-gelásticas foram observadas em quatro pacientes, sendo 2 pacientes com choro e riso sem alegria e 2 pacientes com choro alto e riso sem alegria. CONCLUSãO: Crises gelásticas e dacrísticas frequentemente sugerem hamartomas hipotalâmicos, na literatura. Este comportamento ictal raro pode ter origem em diferentes localizações corticais e lesões de natureza diversa. No entanto, verificamos que as crises gelásticas com sorriso foram um grupo mais homogêneo quanto à localização no lobo temporal, o que buscamos evidenciar avaliando os pacientes incluídos neste estudo.

A clinical evaluation of gelastic and dacrystic seizures: a multicenter study / Uma avaliação clínica das crises gelásticas e dacrísticas: um estudo multicêntrico

Abstract Background Gelastic seizures are extremely rare, short-lasting, unprovoked, and uncontrollable laughing attacks. We conducted this retrospective evaluation to determine whether these symptoms, manifesting in different forms, such as cheerful laughter, laughing, smiling, and sobbing had any value in terms of etiology or localization. Methods A total of 31 patients who exhibited bouts of laughing or crying and who were under follow-up between 2000 and 2019 at tertiary epilepsy centers were included in the study. Laughing seizures were divided into three groups in terms of semiology (i.e., laughter with mirth, laughter without mirth, and smile). Dacrystic seizures were accompanied by some gelastic seizures and were divided into two groups in terms of semiology (i.e., weeping loudly [motor and voice-sobbing] and crying). Results Of the 27 patients with laughing seizures, 12 had seizures that manifested with smiling, 7 had seizures that manifested with laughing and mirth, and 8 had seizures that manifested with laughter without mirth. Dacrystic-gelastic seizures were observed in four patients, among whom 2 patients had crying and laughter without mirth and 2 patients had weeping loudly and laughter without mirth episodes. Conclusion Gelastic and dacrystic seizures often suggest hypothalamic hamartomas, in the literature. This rare ictal behavior can originate from different cortical locations and lesions of a different nature. However, we found that gelastic seizures with smiling were a more homogenous group with regard to location in the temporal lobe, which we aimed to show by evaluating the patients included in this study.

Resumo Antecedentes Crises gelásticas são ataques de riso extremamente raros, de curta duração, não provocados e incontroláveis. Realizamos esta avaliação retrospectiva para determinar se esses sintomas, manifestando-se de diferentes formas, como riso alegre, riso, sorriso e soluço, tinham algum valor em termos de etiologia ou localização. Métodos Foram incluídos no estudo 31 pacientes que apresentavam crises de riso ou choro e que estavam em acompanhamento entre 2000 e 2019 em centros terciários de epilepsia. As crises de riso foram divididas em três grupos em termos de semiologia (ou seja, riso com alegria, riso sem alegria e sorriso). As crises dacrísticas foram acompanhadas por algumas crises gelásticas e foram divididas em dois grupos em termos de semiologia (ou seja, choro alto [motor e soluçar a voz] e choro). Resultados Dos 27 pacientes com crises de riso, 12 tiveram crises que se manifestaram com sorriso, 7 tiveram crises que se manifestaram com riso e alegria e 8 tiveram crises que se manifestaram com riso sem alegria. Crises dácristico-gelásticas foram observadas em quatro pacientes, sendo 2 pacientes com choro e riso sem alegria e 2 pacientes com choro alto e riso sem alegria. Conclusão Crises gelásticas e dacrísticas frequentemente sugerem hamartomas hipotalâmicos, na literatura. Este comportamento ictal raro pode ter origem em diferentes localizações corticais e lesões de natureza diversa. No entanto, verificamos que as crises gelásticas com sorriso foram um grupo mais homogêneo quanto à localização no lobo temporal, o que buscamos evidenciar avaliando os pacientes incluídos neste estudo.

A Rare Cause of Epilepsy: Ulegyria Revisited in a Series of 10 Patients.

Introduction. Ulegyria results from perinatal hypoxic-ischemic brain injury in term infants. The specific mushroom-shaped configuration of ulegyria results from small atrophic circumvolutions at the bottom of a sulcus underlying an intact gyral apex. Clinically, ulegyria is generally associated with epilepsy. Here, we aimed to delineate the characteristics of patients with ulegyria and the epileptic seizures they experience. Material and methods. Medical records including radiology and pathology reports, video-electroencephalographic (EEG) analysis, operative notes, hospital progress and outpatient clinic notes were reviewed retrospectively in a total of 10 ulegyria patients. Results. Patients ages ranged between 24 and 58 years (mean, 32 ± 9.8 years). Past medical history was confirmed for neonatal asphyxia in 2 (20%). Neurological examination was remarkable for spastic hemiparesis in 1 (10%) patient with perisylvian ulegyria and for visual field deficits in 2 patients (20%) with occipital ulegyria. Ulegyria most commonly involved the temporoparietal region (n = 5, 50%) followed by the perisylvian area (n = 2, 20%). Except the one with bilateral perisylvian ulegyria, all patients had unilateral lesions (n = 9, 90%). Hippocampal sclerosis accompanied ulegyria in 2 patients (20%). All patients experienced epileptic seizures. Mean age at seizure onset was 8.8 ± 5.4 years (range, 2-20 years). Interictal scalp EEG and EEG-video monitoring records demonstrated temporoparietal and frontotemporal activities in 5 (50%) and 2 (20%) patients, respectively. The seizures were successfully controlled by antiepileptic medication in 8 patients (n = 8, 80%). The remaining 2 patients (%20) with concomitant hippocampal sclerosis required microsurgical resection of the seizure foci due to medically resistant seizures. Discussion. Ulegyria is easily recognized with its unique magnetic resonance imaging characteristics and clinical presentation in the majority of cases. It is highly associated with either medically resistant or medically controllable epileptic seizures. The treatment strategy depends on the age at onset and extends of the lesion that has a significant impact on the severity of the clinical picture.

Long non-coding RNAs as a predictive markers of group 3 medulloblastomas.

ObjectiveThe appropriate treatments for the different molecular subgroups of medulloblastomas are challenging to determine. Hence, this study aimed to examine the expression profiles of long non-coding RNAs (LncRNAs) to determine a marker that may be important for treatment selection in these subgroups.MethodsChanges in the expression of LncRNAs in the tissues of patients with medulloblastoma, which are classified into four subgroups according to their clinical characteristics and gene expression profiles, were examined via reverse transcription polymerase chain reaction. Moreover, there association with patient prognosis was evaluated.ResultsThe expression levels of MALAT1 and SNGH16 were significantly higher in patients with group 3 medulloblastoma than in those with other subtypes. Patients with high expression levels of MALAT1 and SNGH16 had a relatively shorter overall survival than those with low expression levels.ConclusionsPatients with group 3 medulloblastoma have a high MALAT1 level, which is associated with poor prognosis. Therefore, MALAT1 can be a new therapeutic target in medulloblastoma.

Coexistence of TERT C228T mutation and MALAT1 dysregulation in primary glioblastoma: new prognostic and therapeutic targets.

Objective: This study was designed to conduct molecular classification based on IDH1/2, TERT, ATRX, and DAXX changes in pediatric and adult primary glioblastoma (GB) and to analyze the potential interaction of LncRNA MALAT1 in the determined homogeneous subgroups.Methods: We analyzed the expression profiles of ATRX/DAXX and MALAT1 using the qRT-PCR method and IDH and TERT mutation status using DNA sequencing analysis in 85 primary pediatric and adult GB patients.Results: IDH1 mutation was observed in 5 (5.88%) and TERT mutation in 65 (76.47%) primary pediatric and adult GB patients. ATRX and DAXX were detected in 18 (21.18%) and 7 (8.24%) patients. TERT mutation and loss of ATRX/DAXX were associated with short overall survival (p < 0.001, p < 0.001, respectively). Patients carrying especially TERT C228T mutation had worse prognosis (p < 0.001). Six subgroups were obtained from the genetic analysis. Among the subgroups, MALAT1 was highly expressed in group A that had a single TERT mutation as compared to that in groups D and E (p = 0.001 and p < 0.001, respectively); further, high MALAT1 expression was associated with worse prognosis in patients with C228T mutation (p < 0.001).Conclusions: Our findings highlight that the presence of TERT C228T mutation and expression of MALAT1 can be used as primary targets during the follow-up of primary GB patients and in the development of new treatment strategies.

Comparison of Clinical and Molecular Wnt and SHH Subgroups in Medulloblastoma Tumor Cases.

AIM: To determine the Wnt and SHH subtypes at the molecular level, and to compare them clinically by examining the changes in CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression in the medulloblastoma of a Turkish population determined according to patient selection criteria. In this context, the clinical distinction between Wnt and SHH groups are realized by considering the age, gender, survival time, location of the lesion, and radiological features of the patients. MATERIAL AND METHODS: Molecular separation was performed by RT-PCR analysis of CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression changes. RESULTS: About 17.8% and 22.2% of the cases were included in the Wnt and the SHH group, respectively. When comparing group differences based on clinical and molecular data, 72.7% and 66.6% of matches were observed in the Wnt and the SHH group, respectively. CONCLUSION: It has been revealed that molecular analysis and grouping of patients with medulloblastoma can provide support for clinically determined subgroups.

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.

Anti-Apoptotic and Anti-Oxidant Effects of Systemic Uridine Treatment in an Experimental Model of Sciatic Nerve Injury.

AIM: To investigate the anti-apoptotic and anti-oxidant effects of systemic uridine treatment in a rat model of sciatic nerve injury. MATERIAL AND METHODS: Thirty-two adult male rats were equally randomized to Sham, Control, U100, and U500 groups. Sham rats received a sham operation by exposing the right sciatic nerve without transection, while those in the Control, U100, and U500 groups underwent right sciatic nerve transection followed by immediate primary anostomosis. Sham and Control groups received saline (0.9% NaCl) injections intraperitoneally (i.p.), while U100 and U500 groups received 100 mg/kg and 500 mg/kg uridine injections (i.p.), respectively, once a day for 7 days after the surgery. Rats in all the groups were sacrificed on the eighth day; sciatic nerve samples were analyzed for apoptosis by Western Blotting and for oxidation parameters including myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Uridine treatment at the dose of 500 mg/kg significantly decreased as apoptosis determined by Caspase-3/Actin ratio and exhibited significant anti-oxidant effects as determined by decreased levels of MPO and MDA as well as increased levels of SOD, GPx, and CAT compared to controls. Uridine at 100 mg/kg was only found to decrease the Caspase-3/Actin ratio, although it significantly decreased MDA and increased CAT levels compared to controls. CONCLUSION: Treatment with uridine reduces apoptosis and oxidation in a rat model of sciatic nerve injury dose-dependently. Thus, uridine may be beneficial in peripheral nerve regeneration by exhibiting anti-apoptotic and anti-oxidant effects.

Uridine treatment improves nerve regeneration and functional recovery in a rat model of sciatic nerve injury.

AIM: Peripheral nerve regeneration remains an issue, and novel therapeutic approaches are required for functional recovery. This study investigated the regenerative potential and long-term functional effects of Uridine treatment in a rat model of sciatic nerve injury. MATERIAL AND METHODS: Male Sprague-Dawley rats were randomized to receive sham surgery plus saline (Sham group), right sciatic nerve transection and primary repair plus saline (Control group), right sciatic nerve transection, and primary repair plus 500 mg/kg Uridine (Uridine group). Saline or Uridine was injected intraperitoneally (i.p.) for seven days, and the rats were monitored for 12 weeks after surgery. We evaluated electrophysiological and functional recovery using electromyography (EMG) and sciatic functional index (SFI) at six and 12 weeks, respectively. At 12 weeks, rats were decapitated and their right sciatic nerves were examined in macroscopic and histomorphologic manners. RESULTS: Functional evaluation by SFI and sciatic nerve conduction velocity analyzed by EMG both decreased in the Control group but recovered in the Uridine group 12 weeks after surgery. Additionally, upon experiment completion, Uridine treatment was observed to enhance nerve adherence, separability scores, and the number of myelinated axons. CONCLUSION: These results reveal that short-term Uridine treatment provides morphological and electrophysiological benefits, which are represented by long-term functional improvement in a rat model of sciatic nerve injury. These findings validate and extend our knowledge on Uridine's regenerative effects in peripheral nerve injuries.

The Evaluation of Survivin and Bcl-2 Expression on the Medical Radiation Doses for Neural Tube Defect Development.

AIM: To investigate the effects of different radiation doses on the development of the neural tube defect in chick embryos using computed tomography (CT), and assess its correlation with survivin and Bcl-2 expressions. MATERIAL AND METHODS: A total of 150 chicken eggs were used and grouped into five categories. In Group 1 (n=30), the embryos were not exposed to radiation. In Group 2 (n=30), the embryos were irradiated using lung cancer screening chest CT protocol. In Groups 3 and 4 (n=30 each), the abdominopelvic and adult routine head CT protocols, respectively, were used to irradiate the embryos. In Group 5 (n=30), the embryos were irradiated using adult brain perfusion CT protocol. Subsequently, the embryos were examined under a stereomicroscope to assess the presence of neural tube developmental abnormalities. Moreover, immunohistochemical staining was performed to determine the survivin and Bcl-2 expression levels. RESULTS: The risk of developing neural tube defect increased with the amount of exposed radiation. Moreover, no significant correlation was observed between the survivin and Bcl-2 expression levels and the radiation dose. CONCLUSION: Overall, the results of this study indicate that the radiation from CT may cause neural tube defect in chicken embryos.

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.

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.

Long noncoding RNA MALAT1 may be a prognostic biomarker in IDH1/2 wild-type primary glioblastomas.

Primary glioblastoma (GB) is the most aggressive type of brain tumors. While mutations in isocitrate dehydrogenase (IDH) genes are frequent in secondary GBs and correlate with a better prognosis, most primary GBs are IDH wild-type. Recent studies have shown that the long noncoding RNA metastasis associated lung adenocarcinoma transcript-1 (MALAT1) is associated with aggressive tumor phenotypes in different cancers. Our aim was to clarify the prognostic significance of MALAT1 in IDH1/2 wild-type primary GB tumors. We analyzed IDH1/2 mutation status in 75 patients with primary GB by DNA sequencing. The expression of MALAT1 was detected in the 75 primary GB tissues and 5 normal brain tissues using reverse transcription quantitative PCR (RT-qPCR). The associations between MALAT1 expression, IDH1/2 mutation status, and clinicopathological variables of patients were determined. IDH1 (R132H) mutation was observed in 5/75 primary GBs. IDH2 (R172H) mutation was not detected in any of our cases. MALAT1 expression was significantly upregulated in primary GB vs. normal brain tissues (p = 0.025). Increased MALAT1 expression in IDH1/2 wild-type primary GBs correlated with patient age and tumor localization (p = 0.032 and p = 0.025, respectively). A multivariate analysis showed that high MALAT1 expression was an unfavorable prognostic factor for overall survival (p = 0.034) in IDH1/2 wild-type primary GBs. High MALAT1 expression may have a prognostic role in primary GBs independent of IDH mutations.