A major malignant trait of gliomas is their remarkable infiltration capacity. When glioma develops, the tumor cells have already reached the distant part. Therefore, complete removal of the glioma is impossible. Recently, research on the involvement of the tumor microenvironment in glioma invasion has advanced. Local hypoxia triggers cell migration as an environmental factor. The transcription factor hypoxia-inducible factor (HIF) -1α, produced in tumor cells under hypoxia, promotes the transcription of various invasion related molecules. The extracellular matrix surrounding tumors is degraded by proteases secreted by tumor cells and simultaneously replaced by an extracellular matrix that promotes infiltration. Astrocytes and microglia become tumor-associated astrocytes and glioma-associated macrophages/microglia, respectively, in relation to tumor cells. These cells also promote glioma invasion. Interactions between glioma cells actively promote infiltration of each other. Surgery, chemotherapy, and radiation therapy transform the microenvironment, allowing glioma cells to invade. These findings indicate that the tumor microenvironment may be a target for glioma invasion. On the other hand, because the living body actively promotes tumor infiltration in response to the tumor, it is necessary to reconsider whether the invasion itself is friend or foe to the brain.

4Results. All nine patients had complete or substantial resolution of their formerly intractable headache after TSS. Headaches consisted of ocular pain ipsilateral to the adenoma localization within the sella in four cases and bifrontal headache in five.Magnetic resonance imaging of these patients revealed small diaphragmatic foramen, which were so narrow that only the pituitary stalk could pass. Computed tomography scans showed ossification beneath the sellar floor in the sphenoid sinus, presellar type in six cases, and choncal type in three. The adenomas included cysts in seven cases.There was no cavernous sinus invasion. Intrasellar pressure measurements averaged 41.5 ± 8.5 mmHg, range 34-59, significantly higher than in control patients without headache (n = 12), namely 22.2 ± 10.6 mmHg (16-30).Conclusion. In this study, the authors demonstrated the validity of TSS in the treatment of intractable headache associated with pituitary adenoma. The presence of ocular pain, especially ipsilateral to the adenoma, integrity of the diaphragm sella, and ossification in the sphenoid sinus, cyst or hemorrhage and the absence of cavernous sinus invasion were the indications for TSS for patients complaining of intractable headache and having pituitary adenomas. 5

Glioma persists as one of the most aggressive primary tumors of the central nervous system. Glioma cells are known to communicate with tumor-associated macrophages/microglia via various cytokines to establish the tumor microenvironment. However, how extracellular vesicles (EVs), emerging regulators of cell–cell communication networks, function in this process is still elusive. We report here that glioma-derived EVs promote tumor progression by affecting microglial gene expression in an intracranial implantation glioma model mouse. The gene expression of thrombospondin-1 (Thbs1), a negative regulator of angiogenesis, was commonly downregulated in microglia after the addition of EVs isolated from different glioma cell lines, which endogenously expressed Wilms tumor-1 (WT1). Conversely, WT1-deficiency in the glioma-derived EVs significantly attenuated the Thbs1 downregulation and suppressed the tumor progression. WT1 was highly expressed in EVs obtained from the cerebrospinal fluid of human patients with malignant glioma. Our findings establish a novel model of tumor progression via EV-mediated WT1–Thbs1 intercellular regulatory pathway, which may be a future diagnostic or therapeutic target.

From the embarrassing character commonly infiltrating eloquent brain regions, the surgical resection of glioma remains challenging. Owing to the recent development of in vivo visualization techniques for the human brain, white matter regions can be delineated using diffusion tensor imaging (DTI) as a routine clinical practice in neurosurgery. In confirmation of the results of DTI tractography, a direct electrical stimulation (DES) substantially influences the investigation of cortico-subcortical networks, which can be identified via specific symptoms elicited in the concerned white matter tracts (eg., the arcuate fascicle, superior longitudinal fascicles, inferior fronto-occipital fascicle, inferior longitudinal fascicle, frontal aslant tract, sensori-motor tracts, optic radiation, and so forth). During awake surgery for glioma using DES, it is important to identify the anatomo-functional structure of white matter tracts to identify the surgical boundaries of brain regions not only to achieve maximal resection of the glioma but also to maximally preserve quality of life. However, the risk exists that neurosurgeons may be misled by the inability of DTI to visualize the actual anatomy of the white matter fibers, resulting in inappropriate decisions regarding surgical boundaries. This review article provides information of the critical neuronal network that is necessary to identify and understand in awake surgery for glioma, with special references to white matter tracts and the author’s experiences.