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Neurology International
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Glioblastoma: Mechanics of Development, Progression and New Surgical and Clinical...
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Glioblastoma: Mechanics of Development, Progression and New Surgical and Clinical Management

A special issue of Neurology International (ISSN 2035-8377).

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 10003

Special Issue Editor

Dr. Nicola Montemurro

E-Mail Website
Guest Editor
Department of Neurosurgery, Azienda Ospedaliero Universitaria Pisana (AOUP), University of Pisa, 56100 Pisa, Italy
Interests: brain tumor; glioblastoma; low-grade glioma; meningioma; neuro-oncology; augmented reality; virtual reality; tractography; spine tumor; traumatic brain injury; hydrocephalus
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Glioblastoma is a diffusely infiltrative malignant brain tumor that leads to significant morbidity and mortality among affected patients. The new 2021 WHO Classification of Tumors of the Central Nervous System opened new horizons in molecular changes and in clinical and surgical practice.

Due to the extremely poor prognosis, it is imperative to investigate new and altered molecular mechanisms that may be involved in glioblastoma pathogenesis. Despite recent new studies and technologies, due to unfavorable prognosis, it is essential to look for novel, potentially change molecular processes involved in the disease's etiology and progression that may lead to the creation of more effective therapeutic strategies. Research on novel adjuvant agents, advanced personalized molecular diagnostics and response to novel targeted molecular therapies for the treatment of glioblastoma is promising.

This special issue covers all aspects of glioblastoma, including surgical innovations, original research on current and experimental treatment options, studies on molecular characteristics of glioblastoma, as well as mechanisms underlying growth inhibition: apoptosis, autophagy, necrosis.

The aim of this special issue will be to contribute to a better understanding of tumor heterogeneity/microenvironment, the different molecular signature in GBM subtypes and the relative contributions of glioma stem cells. Original papers, systematic reviews, meta-analyses and quality-of-life focused stereotactic radiosurgery, brain surgery, interstitial laser thermotherapy and oncology studies on this topic of interest are welcome.

Dr. Nicola Montemurro
Guest Editor

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Keywords

  • glioblastoma cell line
  • target therapy
  • grosso-total resection
  • molecular markers
  • glioblastoma
  • signalling pathways
  • epigenomics
  • tumor heterogeneity
  • oncogenes
  • exosomes
  • tumor microenvironment

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Published Papers (4 papers)

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Research

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30 pages, 14321 KiB  
Article
Differential Effects of Extracellular Vesicles from Two Different Glioblastomas on Normal Human Brain Cells
by Mary Wang, Arin N. Graner, Bryne Knowles, Charlotte McRae, Anthony Fringuello, Petr Paucek, Michael Gavrilovic, McKenna Redwine, Caleb Hanson, Christina Coughlan, Stacey Grimaldo-Garcia, Brooke Metzger, Vince Bolus, Timothy J. Kopper, Marie Smith, Wenbo Zhou, Morgan Lenz, Aviva Abosch, Steven Ojemann, Kevin O. Lillehei, Xiaoli Yu and Michael W. Graneradd Show full author list remove Hide full author list
Neurol. Int. 2024, 16(6), 1355-1384; https://doi.org/10.3390/neurolint16060103 - 6 Nov 2024
Viewed by 1588
Abstract
Background/Objectives: Glioblastomas (GBMs) are dreadful brain tumors with abysmal survival outcomes. GBM extracellular vesicles (EVs) dramatically affect normal brain cells (largely astrocytes) constituting the tumor microenvironment (TME). We asked if EVs from different GBM patient-derived spheroid lines would differentially alter recipient brain cell [...] Read more.
Background/Objectives: Glioblastomas (GBMs) are dreadful brain tumors with abysmal survival outcomes. GBM extracellular vesicles (EVs) dramatically affect normal brain cells (largely astrocytes) constituting the tumor microenvironment (TME). We asked if EVs from different GBM patient-derived spheroid lines would differentially alter recipient brain cell phenotypes. This turned out to be the case, with the net outcome of treatment with GBM EVs nonetheless converging on increased tumorigenicity. Methods: GBM spheroids and brain slices were derived from neurosurgical patient tissues following informed consent. Astrocytes were commercially obtained. EVs were isolated from conditioned culture media by ultrafiltration, concentration, and ultracentrifugation. EVs were characterized by nanoparticle tracking analysis, electron microscopy, biochemical markers, and proteomics. Astrocytes/brain tissues were treated with GBM EVs before downstream analyses. Results: EVs from different GBMs induced brain cells to alter secretomes with pro-inflammatory or TME-modifying (proteolytic) effects. Astrocyte responses ranged from anti-viral gene/protein expression and cytokine release to altered extracellular signal-regulated protein kinase (ERK1/2) signaling pathways, and conditioned media from EV-treated cells increased GBM cell proliferation. Conclusions: Astrocytes/brain slices treated with different GBM EVs underwent non-identical changes in various omics readouts and other assays, indicating “personalized” tumor-specific GBM EV effects on the TME. This raises concern regarding reliance on “model” systems as a sole basis for translational direction. Nonetheless, net downstream impacts from differential cellular and TME effects still led to increased tumorigenic capacities for the different GBMs. Full article
(This article belongs to the Special Issue Glioblastoma: Mechanics of Development, Progression and New Surgical and Clinical Management)
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14 pages, 3274 KiB  
Article
Multiple Administration of Dexamethasone Possesses a Deferred Long-Term Effect to Glycosylated Components of Mouse Brain
by Stanislav D. Aladev, Dmitry K. Sokolov, Anastasia V. Strokotova, Galina M. Kazanskaya, Alexander M. Volkov, Svetlana V. Aidagulova and Elvira V. Grigorieva
Neurol. Int. 2024, 16(4), 790-803; https://doi.org/10.3390/neurolint16040058 - 22 Jul 2024
Cited by 1 | Viewed by 1144
Abstract
Glucocorticoids are used during glioblastoma treatment to prevent the cerebral edema effect surrounding normal brain tissue. The aim of our study was to investigate the long-term effects of multiple administrations of glucocorticoids onto the glycosylated components (proteoglycans and glycosaminoglycans) of normal brain extracellular [...] Read more.
Glucocorticoids are used during glioblastoma treatment to prevent the cerebral edema effect surrounding normal brain tissue. The aim of our study was to investigate the long-term effects of multiple administrations of glucocorticoids onto the glycosylated components (proteoglycans and glycosaminoglycans) of normal brain extracellular matrix and the glucocorticoid receptor (GR, Nr3c1) in an experimental model in vivo. Two-month-old male C57Bl/6 mice (n = 90) were injected intraperitoneally with various doses of dexamethasone (DXM) (1; 2.5 mg/kg) for 10 days. The mRNA levels of the GR, proteoglycans core proteins, and heparan sulfate metabolism-involved genes were determined at the 15th, 30th, 60th, and 90th days by a real-time RT–PCR. The glycosaminoglycans content was studied using dot blot and staining with Alcian blue. A DXM treatment increased total GAG content (2-fold), whereas the content of highly sulfated glycosaminoglycans decreased (1.5–2-fold). The mRNA level of the heparan sulfate metabolism-involved gene Hs3St2 increased 5-fold, the mRNA level of Hs6St2 increased6–7-fold, and the mRNA level of proteoglycan aggrecan increased 2-fold. A correlation analysis revealed an association between the mRNA level of the GR and the mRNA level of 8 of the 14 proteoglycans-coding and 4 of the 13 heparan sulfate metabolism-involved genes supporting GR involvement in the DXM regulation of the expression of these genes. In summary, multiple DXM administrations led to an increase in the total GAG content and reorganized the brain extracellular matrix in terms of its glycosylation pattern. Full article
(This article belongs to the Special Issue Glioblastoma: Mechanics of Development, Progression and New Surgical and Clinical Management)
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Review

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14 pages, 1173 KiB  
Review
Macrophages in Recurrent Glioblastoma as a Prognostic Factor in the Synergistic System of the Tumor Microenvironment
by Nicola Montemurro, Bhavya Pahwa, Anish Tayal, Anushruti Shukla, Manuel De Jesus Encarnacion, Issael Ramirez, Renat Nurmukhametov, Vishal Chavda and Antonella De Carlo
Neurol. Int. 2023, 15(2), 595-608; https://doi.org/10.3390/neurolint15020037 - 23 Apr 2023
Cited by 40 | Viewed by 4277
Abstract
Glioblastoma (GBM) is a common and highly malignant primary tumor of the central nervous system in adults. Ever more recent papers are focusing on understanding the role of the tumor microenvironment (TME) in affecting tumorigenesis and the subsequent prognosis. We assessed the impact [...] Read more.
Glioblastoma (GBM) is a common and highly malignant primary tumor of the central nervous system in adults. Ever more recent papers are focusing on understanding the role of the tumor microenvironment (TME) in affecting tumorigenesis and the subsequent prognosis. We assessed the impact of macrophages in the TME on the prognosis in patients with recurrent GBM. A PubMed, MEDLINE and Scopus review was conducted to identify all studies dealing with macrophages in the GBM microenvironment from January 2016 to December 2022. Glioma-associated macrophages (GAMs) act critically in enhancing tumor progression and can alter drug resistance, promoting resistance to radiotherapy and establishing an immunosuppressive environment. M1 macrophages are characterized by increased secretion of proinflammatory cytokines, such as IL-1ß, tumor necrosis factor (TNF), IL-27, matrix metalloproteinase (MMPs), CCL2, and VEGF (vascular endothelial growth factor), IGF1, that can lead to the destruction of the tissue. In contrast, M2 is supposed to participate in immunosuppression and tumor progression, which is formed after being exposed to the macrophage M-CSF, IL-10, IL-35 and the transforming growth factor-ß (TGF-β). Because there is currently no standard of care in recurrent GBM, novel identified targeted therapies based on the complex signaling and interactions between the glioma stem cells (GSCs) and the TME, especially resident microglia and bone-marrow-derived macrophages, may be helpful in improving the overall survival of these patients in the near future. Full article
(This article belongs to the Special Issue Glioblastoma: Mechanics of Development, Progression and New Surgical and Clinical Management)
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Other

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8 pages, 2720 KiB  
Case Report
Astrocytoma Mimicking Herpetic Meningoencephalitis: The Role of Non-Invasive Multimodal Monitoring in Neurointensivism
by Uri Adrian Prync Flato, Barbara Cristina de Abreu Pereira, Fernando Alvares Costa, Marcos Cairo Vilela, Gustavo Frigieri, Nilton José Fernandes Cavalcante and Samantha Longhi Simões de Almeida
Neurol. Int. 2023, 15(4), 1403-1410; https://doi.org/10.3390/neurolint15040090 - 29 Nov 2023
Viewed by 1765
Abstract
Neuromonitoring is a critical tool for emergency rooms and intensive care units to promptly identify and treat brain injuries. The case report of a patient with status epilepticus necessitating orotracheal intubation and intravenous lorazepam administration is presented. A pattern of epileptiform activity was [...] Read more.
Neuromonitoring is a critical tool for emergency rooms and intensive care units to promptly identify and treat brain injuries. The case report of a patient with status epilepticus necessitating orotracheal intubation and intravenous lorazepam administration is presented. A pattern of epileptiform activity was detected in the left temporal region, and intravenous Acyclovir was administered based on the diagnostic hypothesis of herpetic meningoencephalitis. The neurointensivist opted for multimodal non-invasive bedside neuromonitoring due to the complexity of the patient’s condition. A Brain4care (B4C) non-invasive intracranial compliance monitor was utilized alongside the assessment of an optic nerve sheath diameter (ONSD) and transcranial Doppler (TCD). Based on the collected data, a diagnosis of intracranial hypertension (ICH) was made and a treatment plan was developed. After the neurosurgery team’s evaluation, a stereotaxic biopsy of the temporal lesion revealed a grade 2 diffuse astrocytoma, and an urgent total resection was performed. Research suggests that monitoring patients in a dedicated neurologic intensive care unit (Neuro ICU) can lead to improved outcomes and shorter hospital stays. In addition to being useful for patients with a primary brain injury, neuromonitoring may also be advantageous for those at risk of cerebral hemodynamic impairment. Lastly, it is essential to note that neuromonitoring technologies are non-invasive, less expensive, safe, and bedside-accessible approaches with significant diagnostic and monitoring potential for patients at risk of brain abnormalities. Multimodal neuromonitoring is a vital tool in critical care units for the identification and management of acute brain trauma as well as for patients at risk of cerebral hemodynamic impairment. Full article
(This article belongs to the Special Issue Glioblastoma: Mechanics of Development, Progression and New Surgical and Clinical Management)
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