Aquaporin 2 in Cerebral Edema: Potential Prognostic Marker in Craniocerebral Injuries.

Despite continuous medical advancements, traumatic brain injury (TBI) remains a leading cause of death and disability worldwide. Consequently, there is a pursuit for biomarkers that allow non-invasive monitoring of patients after cranial trauma, potentially improving clinical management and reducing complications and mortality. Aquaporins (AQPs), which are crucial for transmembrane water transport, may be significant in this context. This study included 48 patients, with 27 having acute (aSDH) and 21 having chronic subdural hematoma (cSDH). Blood plasma samples were collected from the participants at three intervals: the first sample before surgery, the second at 15 h, and the third at 30 h post-surgery. Plasma concentrations of AQP1, AQP2, AQP4, and AQP9 were determined using the sandwich ELISA technique. CT scans were performed on all patients pre- and post-surgery. Correlations between variables were examined using Spearman's nonparametric rank correlation coefficient. A strong correlation was found between aquaporin 2 levels and the volume of chronic subdural hematoma and midline shift. However, no significant link was found between aquaporin levels (AQP1, AQP2, AQP4, and AQP9) before and after surgery for acute subdural hematoma, nor for AQP1, AQP4, and AQP9 after surgery for chronic subdural hematoma. In the chronic SDH group, AQP2 plasma concentration negatively correlated with the midline shift measured before surgery (Spearman's ρ -0.54; p = 0.017) and positively with hematoma volume change between baseline and 30 h post-surgery (Spearman's ρ 0.627; p = 0.007). No statistically significant correlation was found between aquaporin plasma levels and hematoma volume for AQP1, AQP2, AQP4, and AQP9 in patients with acute SDH. There is a correlation between chronic subdural hematoma volume, measured radiologically, and serum AQP2 concentration, highlighting aquaporins' potential as clinical biomarkers.

Preoperative embolisation of head and neck paragangliomas - a single-centre experience.

INTRODUCTION: Paragangliomas are neuroendocrine tumours commonly located in the abdomen, thorax, head and neck. The definitive treatment for these tumours is surgical resection, which in some cases can be very challenging due to the involvement of critical neurovascular structures and their high vascularity. Therefore, pre-operative embolisation may be performed to reduce the risk of complications. This study aimed to present our experience with endovascular embolisation of head and neck paragangliomas (HNP). MATERIAL AND METHODS: In this single-centre study, we reviewed data from consecutive patients with HNP who underwent pre-operative embolisation from 2017 to 2023. The efficacy of embolisation, the method of embolisation, as well as the rate of complications, were noted. RESULTS: A total of 27 patients (15 females) with an average age of 47 years underwent selective embolisation of HNP. Satisfactory embolisation, defined as occlusion of > 75% of the blood supply, was achieved in 22/27 cases (81.5%). The most commonly used embolic agents included coils and microspheres. With the exception of minor vessel dissections in two patients and embolic agent migration in two patients causing reversible occlusion of the intracranial vessels, there were no other complications associated with embolisation. No neurological deficits occurred in relation to the endovascular procedure. CONCLUSIONS: The results of our study indicate that endovascular embolisation of HNP prior to surgical resection is a safe and efficacious procedure, with a relatively low complication rate and associated morbidity.

Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury.

Traumatic Brain Injury (TBI) represents a significant health concern, necessitating advanced therapeutic interventions. This detailed review explores the critical roles of astrocytes, key cellular constituents of the central nervous system (CNS), in both the pathophysiology and possible rehabilitation of TBI. Following injury, astrocytes exhibit reactive transformations, differentiating into pro-inflammatory (A1) and neuroprotective (A2) phenotypes. This paper elucidates the interactions of astrocytes with neurons, their role in neuroinflammation, and the potential for their therapeutic exploitation. Emphasized strategies encompass the utilization of endocannabinoid and calcium signaling pathways, hormone-based treatments like 17ß-estradiol, biological therapies employing anti-HBGB1 monoclonal antibodies, gene therapy targeting Connexin 43, and the innovative technique of astrocyte transplantation as a means to repair damaged neural tissues.

Conoidin A, a Covalent Inhibitor of Peroxiredoxin 2, Reduces Growth of Glioblastoma Cells by Triggering ROS Production.

Compounds that cause oxidative stress have recently gained considerable interest as potential anticancer treatment modalities. Nevertheless, their efficiency may be diminished by the antioxidant systems often upregulated in cancer cells. Peroxiredoxins (PRDXs) are antioxidant enzymes that scavenge peroxides and contribute to redox homeostasis. They play a role in carcinogenesis and are upregulated in several cancer types. Here, we assessed the expression pattern of PRDX1 and PRDX2 in glioblastoma (GBM) and examined the efficacy of their inhibitors in GBM cell lines and patient-derived GBM cells. Both PRDX1 and PRDX2 were upregulated in GBM compared to non-tumor brain tissues and their considerable amounts were observed in GBM cells. Adenanthin, a compound inhibiting PRDX1 activity, slightly decreased GBM cell viability, while conoidin A (CONA), a covalent PRDX2 inhibitor, displayed high toxicity in GBM cells. CONA elevated the intracellular reactive oxygen species (ROS) level. Pre-treatment with an ROS scavenger protected cells from CONA-induced death, indicating that ROS accumulation plays a crucial role in this phenomenon. Menadione or celecoxib, both of which are ROS-inducing agents, potentiated the anticancer activity of CONA. Collectively, our results unveil PRDX1 and PRDX2 as potential targets for GBM therapy, and substantiate the further exploration of their inhibitors.

Endovascular embolisation as minimally-invasive treatment for spinal dural arteriovenous fistulas - evaluation of long-term results.

AIM OF STUDY: Spinal dural arteriovenous fistulas (sDAVF) are rare spinal cord lesions formed between a radicular artery and medullary vein leading to venous hypertension resulting in neurological impairment. Endovascular embolisation is a minimally-invasive method aiming to interrupt the shunt between the artery and vein. We report our experience with sDAVF treated endovascularly. MATERIAL AND METHODS: Clinical and procedural data of 16 consecutive patients diagnosed with sDAVF was reviewed. Pre- and post-operative neurological condition was evaluated using both the Aminoff and Logue disability scale and the VAS scale. Rates of complete occlusions, technical difficulties, and procedural complications were noted. RESULTS: Four of the patients were female and 12 were male; mean age was 62.4 years. Mean interval between symptom onset and treatment was 13.3 months. Complete occlusion was achieved in 88% (14/16 patients). Significant or moderate clinical improvement in long-term follow-up was observed in eight patients (50%). Recurrence was observed in two cases (13%). CONCLUSIONS AND CLINICAL IMPLICATIONS: While endovascular methods are being refined and thus achieving an increasing percentage of successful occlusions, patients should be closely monitored since this condition is recurrent and the clinical consequences of myelopathy can persist despite complete occlusion of the shunt.

Pro- vs. Anti-Inflammatory Features of Monocyte Subsets in Glioma Patients.

Monocytes constitute a heterogenous group of antigen-presenting cells that can be subdivided based on CD14, CD16 and SLAN expression. This division reflects the functional diversity of cells that may play different roles in a variety of pathologies including gliomas. In the current study, the three monocyte subpopulations: classical (CD14+ CD16+ SLAN-), intermediate (CD14dim CD16+ SLAN-) and non-classical (CD14low/- CD16+ SLAN+) in glioma patients' peripheral blood were analysed with flow cytometry. The immune checkpoint molecule (PD-1, PD-L1, SIRPalpha, TIM-3) expression along with pro- and anti-inflammatory cytokines (TNF, IL-12, TGF-beta, IL-10) were assessed. The significant overproduction of anti-inflammatory cytokines by intermediate monocytes was observed. Additionally, SLAN-positive cells overexpressed IL-12 and TNF when compared to the other two groups of monocytes. In conclusion, these results show the presence of different profiles of glioma patient monocytes depending on CD14, CD16 and SLAN expression. The bifold function of monocyte subpopulations might be an additional obstacle to the effectiveness of possible immunotherapies.

Menadione Potentiates Auranofin-Induced Glioblastoma Cell Death.

Glioblastoma (GBM) is the most aggressive primary brain tumor. Recently, agents increasing the level of oxidative stress have been proposed as anticancer drugs. However, their efficacy may be lowered by the cytoprotective activity of antioxidant enzymes, often upregulated in neoplastic cells. Here, we assessed the mRNA and protein expression of thioredoxin reductase 1 (TrxR1), a master regulator of cellular redox homeostasis, in GBM and non-tumor brain tissues. Next, we examined the influence of an inhibitor of TrxR1, auranofin (AF), alone or in combination with a prooxidant menadione (MEN), on growth of GBM cell lines, patient-derived GBM cells and normal human astrocytes. We detected considerable amount of TrxR1 in the majority of GBM tissues. Treatment with AF decreased viability of GBM cells and their potential to form colonies and neurospheres. Moreover, it increased the intracellular level of reactive oxygen species (ROS). Pre-treatment with ROS scavenger prevented the AF-induced cell death, pointing to the important role of ROS in the reduction of cell viability. The cytotoxic effect of AF was potentiated by treatment with MEN. In conclusion, our results identify TrxR1 as an attractive drug target and highlights AF as an off-patent drug candidate in GBM therapy.

Low-Cost Cranioplasty-A Systematic Review of 3D Printing in Medicine.

The high cost of biofabricated titanium mesh plates can make them out of reach for hospitals in low-income countries. To increase the availability of cranioplasty, the authors of this work investigated the production of polymer-based endoprostheses. Recently, cheap, popular desktop 3D printers have generated sufficient opportunities to provide patients with on-demand and on-site help. This study also examines the technologies of 3D printing, including SLM, SLS, FFF, DLP, and SLA. The authors focused their interest on the materials in fabrication, which include PLA, ABS, PET-G, PEEK, and PMMA. Three-dimensional printed prostheses are modeled using widely available CAD software with the help of patient-specific DICOM files. Even though the topic is insufficiently researched, it can be perceived as a relatively safe procedure with a minimal complication rate. There have also been some initial studies on the costs and legal regulations. Early case studies provide information on dozens of patients living with self-made prostheses and who are experiencing significant improvements in their quality of life. Budget 3D-printed endoprostheses are reliable and are reported to be significantly cheaper than the popular counterparts manufactured from polypropylene polyester.

Continuous Ingestion of Lacticaseibacillus rhamnosus JB-1 during Chronic Stress Ensures Neurometabolic and Behavioural Stability in Rats.

The intestinal microbiome composition and dietary supplementation with psychobiotics can result in neurochemical alterations in the brain, which are possible due to the presence of the brain-gut-microbiome axis. In the present study, magnetic resonance spectroscopy (MRS) and behavioural testing were used to evaluate whether treatment with Lacticaseibacillus rhamnosus JB-1 (JB­1) bacteria alters brain metabolites' levels and behaviour during continuous exposure to chronic stress. Twenty Wistar rats were subjected to eight weeks of a chronic unpredictable mild stress protocol. Simultaneously, half of them were fed with JB-1 bacteria, and the second half was given a daily placebo. Animals were examined at three-time points: before starting the stress protocol and after five and eight weeks of stress onset. In the elevated plus maze behavioural test the placebo group displayed increased anxiety expressed by almost complete avoidance of exploration, while the JB-1 dietary supplementation mitigated anxiety which resulted in a longer exploration time. Hippocampal MRS measurements demonstrated a significant decrease in glutamine + glutathione concentration in the placebo group compared to the JB-1 bacteria-supplemented group after five weeks of stress. With the progression of stress the decrease of glutamate, glutathione, taurine, and macromolecular concentrations were observed in the placebo group as compared to baseline. The level of brain metabolites in the JB-1-supplemented rats were stable throughout the experiment, with only the taurine level decreasing between weeks five and eight of stress. These data indicated that the JB-1 bacteria diet might stabilize levels of stress-related neurometabolites in rat brain and could prevent the development of anxiety/depressive-like behaviour.

Analysis of Factors Affecting 5-ALA Fluorescence Intensity in Visualizing Glial Tumor Cells-Literature Review.

Glial tumors are one of the most common lesions of the central nervous system. Despite the implementation of appropriate treatment, the prognosis is not successful. As shown in the literature, maximal tumor resection is a key element in improving therapeutic outcome. One of the methods to achieve it is the use of fluorescent intraoperative navigation with 5-aminolevulinic acid. Unfortunately, often the level of fluorescence emitted is not satisfactory, resulting in difficulties in the course of surgery. This article summarizes currently available knowledge regarding differences in the level of emitted fluorescence. It may depend on both the histological type and the genetic profile of the tumor, which is reflected in the activity and expression of enzymes involved in the intracellular metabolism of fluorescent dyes, such as PBGD, FECH, UROS, and ALAS. The transport of 5-aminolevulinic acid and its metabolites across the blood-brain barrier and cell membranes mediated by transporters, such as ABCB6 and ABCG2, is also important. Accompanying therapies, such as antiepileptic drugs or steroids, also have an impact on light emission by tumor cells. Accurate determination of the factors influencing the fluorescence of 5-aminolevulinic acid-treated cells may contribute to the improvement of fluorescence navigation in patients with highly malignant gliomas.

Profiling Glioblastoma Cases with an Expression of DCX, OLIG2 and NES.

Glioblastoma (GBM) remains the leading cause of cancer-related deaths with the lowest five-year survival rates among all of the human cancers. Multiple factors contribute to its poor outcome, including intratumor heterogeneity, along with migratory and invasive capacities of tumour cells. Over the last several years Doublecortin (DCX) has been one of the debatable factors influencing GBM cells' migration. To resolve DCX's ambiguous role in GBM cells' migration, we set to analyse the expression patterns of DCX along with Nestin (NES) and Oligodendrocyte lineage transcription factor 2 (OLIG2) in 17 cases of GBM, using immunohistochemistry, followed by an analysis of single-cell RNA-seq data. Our results showed that only a small subset of DCX positive (DCX+) cells was present in the tumour. Moreover, no particular pattern emerged when analysing DCX+ cells relative position to the tumour margin. By looking into single-cell RNA-seq data, the majority of DCX+ cells were classified as non-cancerous, with a small subset of cells that could be regarded as glioma stem cells. In conclusion, our findings support the notion that glioma cells express DCX; however, there is no clear evidence to prove that DCX participates in GBM cell migration.

Saturation transfer MRI is sensitive to neurochemical changes in the rat brain due to chronic unpredictable mild stress.

Chemical exchange saturation transfer (CEST) MRI was performed for the evaluation of cerebral metabolic changes in a rat model of depressive-like disease induced by chronic unpredictable mild stress (CUMS). CEST Z-spectra were acquired on a 7 T MRI with two saturation B1 amplitudes (0.5 and 0.75 µT) to measure the magnetization transfer ratio (MTR), CEST and relayed nuclear Overhauser effect (rNOE). Cerebral cortex and hippocampus were examined in two groups of animals: healthy control (n = 10) and stressed (n = 14), the latter of which was exposed to eight weeks of the CUMS protocol. The stressed group Z-spectrum parameters, primarily MTRs, were significantly lower than in controls, at all selected frequency offsets (3.5, 3.0, 2.0, - 3.2, - 3.6 ppm) in the cortex (the largest difference of ~ 3.5% at - 3.6 ppm, p = 0.0005) and the hippocampus (MTRs measured with a B1 = 0.5 µT). The hippocampal rNOE contributions decreased significantly in the stressed brains. Glutamate concentration (assessed using ELISA) and MTR at 3 ppm correlated positively in both brain regions. GABA concentration also correlated positively with CEST contributions in both cerebral areas, while such correlation with MTR was positive in hippocampus, and nonsignificant in cortex. Results indicate that CEST is sensitive to neurometabolic changes following chronic stress exposure.

The implications of nitric oxide metabolism in the treatment of glial tumors.

Glial tumors are the most common intracranial malignancies. Unfortunately, despite such a high prevalence, patients' prognosis is usually poor. It is related to the high invasiveness, tendency to relapse and the resistance of tumors to traditional methods of treatment. An important link in the aspect of these issues may be nitric oxide (NO) metabolism. It is a very complex mechanism with multidirectional effects on the neoplastic process. Depending on the concentration axis, it can both exert pro-tumor action as well as contribute to the inhibition of tumorigenesis. The latest observations show that the control of its metabolism can be very helpful in the development of new methods of treating gliomas, as well as in increasing the effectiveness of the agents currently used. The influence of nitric oxide and nitric oxide synthase (NOS) activity on glioma stem cells seem to be of particular importance. The use of specific inhibitors may allow the reduction of tumor growth and its tendency to relapse. Another important feature of GSCs is their conditioning of glioma resistance to traditional forms of treatment. Recent studies have shown that modulation of NO metabolism can suppress this effect, preventing the induction of radio and chemoresistance. Moreover, nitric oxide is involved in the regulation of a number of immune mechanisms. Adequate modulation of its metabolism may contribute to the induction of an anti-tumor response in the patients' immune system.

Probiotics, Prebiotics and Postbiotics on Mitigation of Depression Symptoms: Modulation of the Brain-Gut-Microbiome Axis.

The brain-gut-microbiome axis is a bidirectional communication pathway between the gut microbiota and the central nervous system. The growing interest in the gut microbiota and mechanisms of its interaction with the brain has contributed to the considerable attention given to the potential use of probiotics, prebiotics and postbiotics in the prevention and treatment of depressive disorders. This review discusses the up-to-date findings in preclinical and clinical trials regarding the use of pro-, pre- and postbiotics in depressive disorders. Studies in rodent models of depression show that some of them inhibit inflammation, decrease corticosterone level and change the level of neurometabolites, which consequently lead to mitigation of the symptoms of depression. Moreover, certain clinical studies have indicated improvement in mood as well as changes in biochemical parameters in patients suffering from depressive disorders.

Lensoside Aß as an Adjuvant to the Anti-Glioma Potential of Sorafenib.

AIM: The anti-glioma effect of lensoside Aß alone and in combination with sorafenib (pro-survival Raf kinase inhibitor) was evaluated for the first time in terms of programmed cell death induction in anaplastic astrocytoma and glioblastoma multiforme cell lines as an experimental model. Apoptosis, autophagy, and necrosis were identified microscopically (fluorescence and scanning microscopes) and confirmed by flow cytometry (mitochondrial membrane potential MMP and cell death). The expression of apoptotic (caspase 3) and autophagic markers (beclin 1) as well as Raf kinase were estimated by immunoblotting. The FTIR method was used to determine the interaction of the studied drugs with lipid and protein groups within cells, while the modes of drug action within the cells were assessed with the FLIM technique. RESULTS: Lensoside Aß itself does not exhibit anti-glioma activity but significantly enhances the anti-cancer potential of sorafenib, initiating mainly apoptosis of up to 90% of cells. It was correlated with an increased level of active caspase 3, a reduced MMP value, and a lower level of Raf kinase. The interaction with membrane structures led to morphological changes typical of programmed death. CONCLUSIONS: Our results indicate that lensoside Aß plays an important role as an adjuvant in chemotherapy with sorafenib and may be a potential candidate in anti-glioma combination therapy.

Prophylactic use of dural tenting sutures in elective craniotomies in adults-is it necessary? A study protocol for a multicentre, investigator- and participant-blinded randomised, parallel-group, non-inferiority trial.

BACKGROUND: In the early days of neurosurgery, extradural haemorrhages (EDHs) contributed to a high mortality rate after craniotomies. Almost a century ago, Walter Dandy reported dural tenting sutures as an effective way to prevent postoperative EDH. Over time, his technique gained in popularity and significance to finally become a neurosurgical standard. Yet, several retrospective reports and one prospective report have questioned the ongoing need for dural tenting sutures. Dandy's explanation that the haemostasis observed under hypotensive conditions is deceiving and eventually causes EDH may be obsolete. Today, proper intra- and postoperative care, including maintenance of normovolemia and normotension and the use of modern haemostatic agents, may be sufficient for effective haemostasis. Thus, there is a fundamental need to evaluate the necessity of dural tenting sutures in a solid, unbiased, evidence-based manner. METHODS: This study is designed as a randomised, multicentre, double-blinded, controlled interventional trial with 1:1 allocation. About one half of the participants will undergo craniotomy without dural tenting sutures and will be considered an intervention group. The other half will undergo craniotomy with these sutures. Both groups will be followed clinically and radiologically. The primary outcome is reoperation due to extradural haematoma. Secondary outcomes aim to evaluate the impact of dural tenting sutures on mortality, readmission risk, postoperative headaches, size of extradural collection, cerebrospinal fluid leak risk and the presence of any new neurological deficit. The study protocol follows the SPIRIT 2013 statement. DISCUSSION: It is possible that many neurosurgeons around the globe are tenting the dura in elective craniotomies which brings no benefit and only extends the operation. Unfortunately, there is not enough data to support or reject this technique in modern neurosurgery. This is the first study that may produce strong, evidence-based recommendations on using dural tenting sutures. TRIAL REGISTRATION, ETHICS AND DISSEMINATION: The Bioethics Committee of the Medical University of Warsaw approved the study protocol (KB/106/2018). The trial is registered at http://www.clinicaltrials.gov ( NCT03658941 ) on September 6, 2018. The findings of this trial will be submitted to a peer-reviewed neurosurgical journal. Abstracts will be submitted to relevant national and international conferences. TRIAL STATUS: Protocol version and date: version 1.5, 14.01.2020 First recruitment: September 7, 2018 Estimated recruitment completion: September 1, 2021.

Epidermal Growth Factor Receptor and its Oncogenic EGFRvIII Variant in Benign and Malignant Brain Tumors.

BACKGROUND/AIM: Tumorigenesis and cancer progression might be driven by abnormal activation of growth factor receptors. Importantly, molecular changes in EGFR-dependent signaling is one of the most common characteristics of brain tumors. PATIENTS AND METHODS: HER1 and EGFRvIII variants in meningiomas and glioblastomas were evaluated at the RNA level. RESULTS: EGFRvIII was found in 18.6% of glioblastomas (GBM), whereas 25% of EGFRvIII positive tumors express wild-type EGFR as well. HER1 was over-expressed in benign meningiomas compared to glioblastomas, whereas HER1 expression in meningiomas differed significantly between sub-types of meningiomas. EGFRvIII and HER1 where positively correlated in glioblastomas. Yet, the patient overall survival did not differ between high- and low-HER1 expressing glioblastomas or between EGFRvIII positive and negative GBMs. CONCLUSION: HER1 may be considered as an independent factor for classification of benign meningiomas. The mRNA levels of HER1 or EGFRvIII should not be used as independent prognostic factors for patients with gliomas.

Factors with the strongest prognostic value associated with in-hospital mortality rate among patients operated for acute subdural and epidural hematoma.

INTRODUCTION: Traumatic brain injury (TBI) still remains a serious health problem and is called a "silent epidemic". Each year in Europe 262 per 100,000 individuals suffer from TBI. The most common consequence of severe head injuries include acute subdural (SDH) and epidural hematomas (EDH), which usually require immediate surgically treatment. The aim of our study is to identify factors which have the strongest prognostic value in relation to in-hospital mortality rate among of patients undergoing surgery for EDH and SDH. PATIENTS AND METHODS: Cohort included 128 patients with isolated craniocerebral injuries who underwent surgery for EDH (28 patients) and SDH (100 patients) in a single, tertiary care Department of Neurosurgery. The data were collected on admission of patients to the Emergency Department and retrospectively analyzed. The following factors were analyzed: demographic data, physiological parameters, laboratory variables, computed tomography scan characteristics and the time between trauma and surgery. Likewise, we have investigated the in-hospital mortality of patients at the time of discharge. RESULTS: We found that the factors with the strongest prognostic values were: the initial GCS score, respiratory rate, glycaemia, blood saturation, systolic blood pressure, midline shift and type of hematoma. Additionally, we proved that a drop by one point in the GCS score almost doubles the risk of in-hospital death while the presence of coagulopathy increases the risk of in-hospital death almost six times. CONCLUSION: Most of the factors with the strongest prognostic value are factors that the emergency team can treat prior to the hospital admission. Coagulopathy, however that has the strongest influence on in-hospital death rate can only be efficiently treated in a hospital setting.

Characteristics of Fluorescent Intraoperative Dyes Helpful in Gross Total Resection of High-Grade Gliomas-A Systematic Review.

Background: A very important aspect in the treatment of high-grade glioma is gross total resection to reduce the risk of tumor recurrence. One of the methods to facilitate this task is intraoperative fluorescence navigation. The aim of the study was to compare the dyes used in this technique fluorescent intraoperative navigation in terms of the mechanism of action and influence on the treatment of patients. Methods: The review was carried out on the basis of articles found in PubMed, Google Scholar, and BMC search engines, as well as those identified by searched bibliographies and suggested by experts during the preparation of the article. The database analysis was performed for the following phrases: "glioma", "glioblastoma", "ALA", "5ALA", "5-ALA", "aminolevulinic acid", "levulinic acid", "fluorescein", "ICG", "indocyanine green", and "fluorescence navigation". Results: After analyzing 913 citations identified on the basis of the search criteria, we included 36 studies in the review. On the basis of the analyzed articles, we found that 5-aminolevulinic acid and fluorescein are highly effective in improving the percentage of gross total resection achieved in high-grade glioma surgery. At the same time, the limitations resulting from the use of these methods are marked-higher costs of the procedure and the need to have neurosurgical microscope in combination with a special light filter in the case of 5-aminolevulinic acid (5-ALA), and low specificity for neoplastic cells and the dependence on the degree of damage to the blood-brain barrier in the intensity of fluorescence in the case of fluorescein. The use of indocyanine green in the visualization of glioma cells is relatively unknown, but some researchers have suggested its utility and the benefits of using it simultaneously with other dyes. Conclusion: The use of intraoperative fluorescence navigation with the use of 5-aminolevulinic acid and fluorescein allows the range of high-grade glioma resection to be increased.

Design, synthesis and biological evaluation of novel 1,3,4-thiadiazole derivatives as anti-glioblastoma agents targeting the AKT pathway.

In spite of progress in understanding biology of glioblastoma (GBM), this tumor remains incurable with a median survival rate of 15 months. Previous studies have shown that 2-(4-fluorophenyloamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (FPDT) and 2-(3-chlorophenyloamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (CPDT) diminished viability of cancer cell lines of different origin. In the current study, we have examined activity of these compounds in several GBM cell lines and patient-derived GBM cells. We have also designed, synthesized and evaluated anti-GBM activity of novel 1,3,4-thiadiazole derivatives containing additional Cl or CH2CH3 substitute at C5-position of 2,4-dihydroxyphenyl. The tested compounds presented a considerable cytotoxicity against all GBM cell lines examined as well as patient-derived GBM cells. They were 15-110 times more potent than temozolomide, the first-line chemotherapeutic agent for GBM. Notably, in anticancer concentrations three of the derivatives were not toxic to human astrocytes. FPDT appeared to be the most promising compound with IC50 values between 45 µM and 68 µM for GBM cells and >100 µM for astrocytes. It augmented activity of temozolomide and inhibited proliferation migration and invasion of GBM cells. Treatment with FPDT diminished phosphorylation level of GSK3ß and AKT. Pretreatment with PDGF-BB, an AKT activator, partially protected cells from death caused by FPDT, indicating that FPDT-mediated decrease in cell viability is causatively related to the inhibition of the AKT pathway.