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The emerging arena of space exploration has created opportunities to study cancer cell biology in the environments of microgravity and hypergravity. Studying cellular behavior in altered gravity conditions has allowed researchers to make observations of cell function that would otherwise remain unnoticed. The patient-derived QNS108 brain tumor initiating cell line (BTIC), isolated from glioblastoma (GBM) tissue, was launched on a suborbital, parabolic rocket flight conducted by EXOS Aerospace Systems & Technologies. All biologicals and appropriate ground controls were secured post-launch and transported back to our research facility. Cells from the rocket-flight and ground-based controls were isolated from the culture containers and expanded on adherent flasks for two weeks. In vitro migration, proliferation, and stemness assays were performed. Following cell expansion, male nude mice were intracranially injected with either ground-control (GC) or rocket-flight (RF) exposed cells to assess tumorigenic capacity (n = 5 per group). Patient-derived QNS108 BTICs exposed to RF displayed more aggressive tumor growth than the GC cells in vitro and in vivo. RF cells showed significantly higher migration (p < 0.0000) and stemness profiles (p < 0.01) when compared to GC cells. Further, RF cells, when implanted in vivo in the brain of rodents had larger tumor-associated cystic growth areas (p = 0.00029) and decreased survival (p = 0.0172) as compared to those animals that had GC cells implanted.

Cerebrovascular diseases are considered to be amongst the most serious public health issues,since they are the third leading cause of death（WHO,2014）and the most common cause of disability worldwide.Its monetary significance is evidenced by the economic burden imposed on health care systems,given that the cost of medical care for a patient that has suffered a stroke is around$25,741US dollars every 5 years（Luengo-Fernandez et al.,2012）.A stroke occurs as a result of a disturbance or interruption of cerebral blood flow that significantly reduces the supply of oxygen and glucose to the neural tissue. Consequently, several cell death mechanisms （secondary lesion mechanisms） such as necrosis, excitotoxicity, free radical production and inflammation are triggered （Castillo, 2000）.

There is a general lack of consensus on both anatomic definition and function of Broca’s area, often localized to the pars triangularis (pT) and pars opercularis (pOp) of the left inferior frontal gyrus (IFG). Given the belief that this region plays a critical role in expressive language functions, resective surgery is often avoided to preserve function. However, the putative role of Broca’s area in speech production has been recently challenged. The current study aims to investigate the plausibility of glioma resection and neurological outcomes in “Broca’s area”. We report a single-surgeon, consecutive case series feasibility study describing the resection of gliomas within the IFG. Presentation, mapping, functional outcome, and extent of resection variables were considered for analysis. All included patients had tumors located in the traditional “Broca’s area”, eight (53.33 %) additionally extending into the insular and subinsular regions. All patients except for one, presented with speech-language deficits preoperatively. Awake brain surgery for tumor resection with direct cortical and subcortical stimulation and intraoperative neuropsychological evaluation was carried out in all individuals. During stimulation, positive speech-language sites within the IFG were identified in ten patients. Two patients (13.33 %) experienced a decline in naming during intraoperative cognitive monitoring and thirteen (86.66 %) had a stable performance throughout surgery. At two-week follow-up, all patients had recovery of language functions compared to initial presentation. Overall extent of resection (EOR) was 60.35 % ( ± 29.60) with residual tumor being the greatest within the insular and subinsular areas. EOR was stratified in anatomical regions within the IFG, being the pOr the area with the greatest EOR (97.4 %), followed by the pT (84.1 %), pOp (83.8 %), and vPMC (80 %). The belief that Broca’s area is not safe to resect is challenged. Adequate mapping and careful patient selection allow maximum safe resection of tumors located in the traditional “Broca’s area”, with low risk of postoperative morbidity. •Tumor surgery in the dominant inferior frontal gyrus is feasible in a carefully selected subset of patients.•Awake brain surgery with speech and language mapping are fundamental during surgery of the dominant inferior frontal gyrus.•Extent of resection in the cortical component of tumors within the IFG, ranged between 80 % and 97 %, which validated the notion that surgery within Broca’s area is feasible.•Extent of resection was limited by functional speech areas detected intraoperatively.

Background Immunization with neural derived peptides (INDP) as well as scar removal—separately—have shown to induce morphological and functional improvement after spinal cord injury (SCI). In the present study, we compared the effect of INDP alone versus INDP with scar removal on motor recovery, regeneration-associated and cytokine gene expression, and axonal regeneration after chronic SCI. Scar removal was conducted through a single incision with a double-bladed scalpel along the stump, and scar renewal was halted by adding α,α′-dipyridyl. Results During the chronic injury stage, two experiments were undertaken. The first experiment was aimed at testing the therapeutic effect of INDP combined with scar removal. Sixty days after therapeutic intervention, the expression of genes encoding for TNFα, IFNγ, IL4, TGFβ, BDNF, IGF1, and GAP43 was evaluated at the site of injury. Tyrosine hydroxylase and 5-hydroxytryptamine positive fibers were also studied. Locomotor evaluations showed a significant recovery in the group treated with scar removal + INDP. Moreover; this group presented a significant increase in IL4, TGFβ, BDNF, IGF1, and GAP43 expression, but a decrease of TNFα and IFNγ. Also, the spinal cord of animals receiving both treatments presented a significant increase of serotonergic and catecholaminergic fibers as compared to other the groups. The second experiment compared the results of the combined approach versus INDP alone. Rats receiving INDP likewise showed improved motor recovery, although on a lesser scale than those who received the combined treatment. An increase in inflammation and regeneration-associated gene expression, as well as in the percentage of serotonergic and catecholaminergic fibers was observed in INDP-treated rats to a lesser degree than those in the combined therapy group. Conclusions These findings suggest that INDP, both alone and in combination with scar removal, could modify the non-permissive microenvironment prevailing at the chronic phase of SCI, providing the opportunity of improving motor recovery.

Intracerebral haemorrhage (ICH) describes haemorrhage into the brain parenchyma that may result in a decline of the patient’s neurological function. ICH is a common cause of morbidity and mortality worldwide. Aggressive surgical treatment for ICH has remained controversial as clinical trials have failed to demonstrate substantial improvement in patient outcome and mortality. Recently, promising mechanical and pharmacological minimally invasive surgery (MIS) techniques for the treatment of ICH have been described. MIS was designed with the objective of reducing morbidity due to complications of surgical manipulation. Mechanical MIS includes the use of tubular retractors and small diameter instruments for ICH removal. Pharmacological methods consist of catheter placement inside the haematoma cavity for the passive drainage of the haematoma over the course of several days. One of the most favourable approaches for MIS is the use of natural corridors for reaching the lesion, such as the transsulcal parafascicular approach. This approach provides an anatomical dissection of the subjacent white matter tracts, causing the least amount of damage while evacuating the haematoma. A detailed description of the currently known MIS techniques and devices is presented in this review. Special attention is given to the transsulcal parafascicular approach, which has particular benefits to provide a less traumatic MIS with promising overall patient outcome.

In recent years, the endoscopic endonasal approach (EEA) for craniopharyngiomas has proven to be a safe option for extensive tumor resection, with minimal or no manipulation of the optic nerves and excellent visualization of the superior hypophyseal branches when compared to the Transcranial Approach (TCA). However, there is an ongoing debate regarding the criteria for selecting different approaches. To explore the current results of EEA and discuss its role in the management of craniopharyngiomas, we performed MEDLINE, Embase, and LILACS searches from 2012 to 2022. Baseline characteristics, the extent of resection, and clinical outcomes were evaluated. Statistical analysis was performed through an X2 and Fisher exact test, and a comparison between quantitative variables through a Kruskal–Wallis and verified with post hoc Bonferroni. The tumor volume was similar in both groups (EEA 11.92 cm3, -TCA 13.23 cm3). The mean follow-up in months was 39.9 for EEA and 43.94 for TCA, p = 0.76). The EEA group presented a higher visual improvement rate (41.96% vs. 25% for TCA, p < 0.0001, OR 7.7). Permanent DI was less frequent with EEA (29.20% vs. 67.40% for TCA, p < 0.0001, OR 0.2). CSF Leaks occurred more frequently with EEA (9.94% vs. 0.70% for TCA, p < 0.0001, OR 15.8). Recurrence rates were lower in the EEA group (EEA 15.50% vs. for TCA 21.20%, p = 0.04, OR 0.7). Our results demonstrate that, in selected cases, EEA for resection of craniopharyngiomas is associated with better results regarding visual preservation and extent of tumor resection. Postoperative CSF leak rates associated with EEA have improved compared to the historical series. The decision-making process should consider each person’s characteristics; however, it is noticeable that recent data regarding EEA justify its widespread application as a first-line approach in centers of excellence for skull base surgery.

Metabolic rewiring in glioblastoma (GBM) is linked to intra- and extracellular pH regulation. In this study, we sought to characterize the role of melatonin on intracellular pH modulation and metabolic consequences to identify the mechanisms of action underlying melatonin oncostatic effects on GBM tumor initiating cells. GBM tumor initiating cells were treated at different times with melatonin (1.5 and 3.0 mM). We analyzed melatonin’s functional effects on GBM proliferation, cell cycle, viability, stemness, and chemo-radiosensitivity. We then assessed the effects of melatonin on GBM metabolism by analyzing the mitochondrial and glycolytic parameters. We also measured the intracellular and extracellular pH. Finally, we tested the effects of melatonin on a mouse subcutaneous xenograft model. We found that melatonin downregulated LDHA and MCT4, decreasing lactate production and inducing a decrease in intracellular pH that was associated with an increase in ROS and ATP depletion. These changes blocked cell cycle progression and induced cellular death and we observed similar results in vivo. Melatonin’s cytotoxic effects on GBM were due, at least in part, to intracellular pH modulation, which has emerged as a newly identified mechanism, providing new insights into the oncostatic effect of melatonin on GBM.

IntroductionDespite aggressive treatment with chemoradiotherapy and maximum surgical resection, survival in patients with glioblastoma (GBM) remains poor. Ongoing efforts are aiming to prolong the lifespan of these patients; however, disparities exist in reported survival values with lack of clear evidence that objectively examines GBM survival trends. We aim to describe the current status and advances in the survival of patients with GBM, by analyzing median overall survival through time and between treatment modalities.MethodsA systematic review was conducted according to PRISMA guidelines to identify articles of newly diagnosed glioblastoma from 1978 to 2018. Full-text glioblastoma papers with human subjects, ≥ 18 years old, and n ≥ 25, were included for evaluation.ResultsThe central tendency of median overall survival (MOS) was 13.5 months (2.3–29.6) and cumulative 5-year survival was 5.8% (0.01%–29.1%), with a significant difference in survival between studies that predate versus postdate the implementation of temozolomide and radiation, [12.5 (2.3–28) vs 15.6 (3.8–29.6) months, P < 0.001]. In clinical trials, bevacizumab [18.2 (10.6–23.0) months], tumor treating fields (TTF) [20.7 (20.5–20.9) months], and vaccines [19.2 (15.3–26.0) months] reported the highest central measure of median survival.ConclusionCoadministration with radiotherapy and temozolomide provided a statistically significant increase in survival for patients suffering from glioblastoma. However, the natural history for GBM remains poor. Therapies including TTF pooled values of MOS and provide means of prolonging the survival of GBM patients.

Purpose of ReviewPatients with brain and spine tumors are at high risk of presenting cancer-related complications at disease presentation or during active treatment and are usually related to the type and location of the lesion. Here, we discuss presentation and management of the most common emergencies affecting patients with central nervous system neoplastic lesions.Recent FindingsTumor-related emergencies encompass complications in patients with central nervous system neoplasms, as well as neurologic complications in patients with systemic malignancies. Brain tumor patients are at high risk of developing multiple complications such as intracranial hypertension, brain herniation, intracranial bleeding, spinal cord compression, and others.SummaryNeuro-oncologic emergencies require immediate attention and multi-disciplinary care. These emergent situations usually need rapid decision-making and management on an inpatient basis.

The efficacy of stem cell therapy is greatly influenced by their secretory properties. Evidence suggests that there is a high concentration of growth factors such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and glial cell line-derived neurotrophic factor (GDNF) after stem cell transplantation. Also, the presence of therapeutic molecules and cytokines such as stem cell factor (SCF), stromal cell-derived factor-1α (SDF-1α), RNAs, nuclear enriched abundant transcript 1 (NEAT1), and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is consistent throughout several studies. Apart from modulating the homeostasis of the surrounding tissues, these factors have pleiotropic properties over the host tissue, among which are angiogenic, anti-inflammatory, antiapoptotic, and neurogenic effects. In the present manuscript, we discuss the different secretion factors and their beneficial activity after stem cell transplantation. Recent developments in emerging technologies for coadjunctive therapies that may aid in stem cell transplantation into the central nervous system, such as cell encapsulation, molecular Trojan horses, and viral vectors, are also presented in this article.