Peritumoral Microenvironment in High-Grade Gliomas: From FLAIRectomy to Microglia–Glioma Cross-Talk

Altieri, Roberto; Barbagallo, Davide; Certo, Francesco; Broggi, Giuseppe; Ragusa, Marco; Pietro, Cinzia Di; Caltabiano, Rosario; Magro, Gaetano; Peschillo, Simone; Purrello, Michele; Barbagallo, Giuseppe

doi:10.3390/brainsci11020200

Cited by 38 publications

(27 citation statements)

References 100 publications

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“…Apart from the most common glial tumors,[ 2 , 3 , 10 ] the central nervous system (CNS) can be the primary site of onset of different types of neoplasms, including neuroepithelial, neuronal, embryonal, and mesenchymal tumors. [ 1 , 27 ] Primary CNS tumors exhibit a large series of signs and symptoms, largely dependent on the specific brain location, including seizures or other neurological deficits.…”

Section: Discussionmentioning

confidence: 99%

A “polymorphous low-grade neuroepithelial tumor of the young (PLNTY)” diagnosed in an adult. Report of a case and review of the literature

Broggi

Certo

Altieri

et al. 2021

Surgical Neurology International

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Background: Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a rare neuropathological entity, recently introduced in neuro-oncology. These tumors, histologically similar to oligodendrogliomas, cause epilepsy, occurring in children and young adults. Only few cases of PLNTY have been described in literature and all reported cases invariably focused on the onset of these tumors in children and young adults. Case Description: We report the case of a 50-year-old woman suffering from epilepsy since the 1st year of her life. Computed tomography scan and magnetic resonance imaging of the brain documented the presence of a calcified mass involving left temporal lobe. The tumor was surgically excised and the histological examination showed a hypocellular and massively calcified neoplasm with morphological and immunohistochemical features consistent with the diagnosis of “PLNTY.” Conclusion: A review of the literature revealed that there are 31 cases of PLNTY reported in literature, most of which are children or young adults. The present case represents the second PLNTY diagnosed in a middle-aged adult to the best of our knowledge, suggesting that PLNTY should always be included in the differential diagnosis of low-grade brain tumors, also in adult patients.

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Section: Discussionmentioning

confidence: 99%

A “polymorphous low-grade neuroepithelial tumor of the young (PLNTY)” diagnosed in an adult. Report of a case and review of the literature

Broggi

Certo

Altieri

et al. 2021

Surgical Neurology International

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“…Activation of microglia will not only cause damage to the central nervous system but also affect the occurrence and development of glioma ( Altieri et al, 2021 ). As the most common inducer of the inflammatory response, LPS interacts with TLRs on the cell surface to induce dimerization of TLR4 on the cell membrane.…”

Section: Discussionmentioning

confidence: 99%

RRx-001 Exerts Neuroprotection Against LPS-Induced Microglia Activation and Neuroinflammation Through Disturbing the TLR4 Pathway

et al. 2022

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Neuroinflammation plays an important role in the pathogenesis of many central nervous system diseases. Here, we investigated the effect of an anti-cancer compound RRx-001 on neuroinflammation and its possible new applications. BV2 cells and primary microglia cells were used to evaluate the role of RRx-001 in LPS-induced microglial activation and inflammatory response in vitro. And, we found that the increase in the synthesis and release of cytokines and the up-regulation of pro-inflammatory factors in LPS-treated microglial cells were significantly reduced by RRx-001 pretreatment. As the most classical inflammatory pathways, NF-κB and MAPK signaling pathways were activated by LPS, but were inhibited by RRx-001. Transcription of NLRP3 was also reduced by RRx-001. In addition, LPS induced oxidative stress by increasing the expression of Nox mediated by transcription factors NF-κB and AP-1, while RRx-001 pretreatment ameliorated Nox-mediated oxidative stress. LPS-induced activation of TAK1, an upstream regulator of NF-κB and MAPK pathways, was significantly inhibited by RRx-001 pretreatment, whereas recruitment of MyD88 to TLR4 was not affected by RRx-001. LPS-primed BV2 condition medium induced injury of primary neurons, and this effect was inhibited by RRx-001. Furthermore, we established a neuroinflammatory mouse model by stereotactic injection of LPS into the substantia nigra pars compacta (SNpc), and RRx-001 dose-dependently reduced LPS-induced microglial activation and loss of TH + neurons in the midbrain. In conclusion, the current study found that RRx-001 suppressed microglia activation and neuroinflammation through targeting TAK1, and may be a candidate for the treatment of neuroinflammation-related brain diseases.

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“…In addition, studies have shown that the grade of glioma is proportional to the number of infiltrating "M2"-type microglia in the microenvironment. Therefore, glioma-associated microglia and macrophages are also one of the research hotspots in the microenvironment of glioma [24]. Microglia can be activated and recruited to the lesion site within a few hours.…”

Section: Discussionmentioning

confidence: 99%

The Synergistic Effect of TRPV1 on Oxidative Stress-Induced Autophagy and Apoptosis in Microglia

Huang

Lin

Pang

et al. 2021

Analytical Cellular Pathology

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Stroke mostly including ischemic stroke is the second leading mortality and disability worldwide. Oxidative stress injury occurred during ischemic stroke treatment generally. A high amount of reactive oxygen species (ROS) is involved in oxidative stress induction. Transient receptor potential vanilloid 1 (TRPV1) has been shown to regulate oxidative stress and apoptosis in microglia; however, the detailed mechanisms remain unclear. We aimed to explore whether autophagy-regulated oxidative stress and apoptosis are associated with TRPV1. The model of oxygen and glucose deprivation (OGD/R) in microglia was established. The siRNA of Atg5 and inhibitors and agonists of both autophagy and TRPV1 were involved in our study. Autophagy-related markers Atg5, LC3II/LC3I, and Beclin-1 were measured, and the autophagosome was observed under a transmission electron microscope (TEM). Caspase 3 was detected using ELISA. ROS and JC-1 were detected using flow cytometry. Apoptosis was observed by TUNEL. The results indicated that oxidative stress-induced injury and apoptosis may be impeded by the increasing autophagy, and TRPV1 inhibition could suppress the OGD/R-induced autophagy of microglia. However, the effect of TRPV1’s inhibitor on oxidative stress and apoptosis was not obvious when the autophagy was blocked. These findings suggested that TRPV1 may exhibit antioxidative and antiapoptosis effect on OGD/R-induced microglia. However, the experimental results do not fully demonstrate that the TRPV1-mediated antioxidative and antiapoptosis effect is through the affecting autophagy entirely.

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Peritumoral Microenvironment in High-Grade Gliomas: From FLAIRectomy to Microglia–Glioma Cross-Talk

Cited by 38 publications

References 100 publications

A “polymorphous low-grade neuroepithelial tumor of the young (PLNTY)” diagnosed in an adult. Report of a case and review of the literature

A “polymorphous low-grade neuroepithelial tumor of the young (PLNTY)” diagnosed in an adult. Report of a case and review of the literature

RRx-001 Exerts Neuroprotection Against LPS-Induced Microglia Activation and Neuroinflammation Through Disturbing the TLR4 Pathway

The Synergistic Effect of TRPV1 on Oxidative Stress-Induced Autophagy and Apoptosis in Microglia

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