The Pathophysiology of Post-Traumatic Glioma

Malignant glioma is a brain tumor with a very high mortality rate resulting from the specific morphology of its infiltrative growth and poor early detection rates. The causes of one of its very specific types, i.e., post-traumatic glioma, have been discussed for many years, with some studies providing evidence for mechanisms where the reaction to an injury may in some cases lead to the onset of carcinogenesis in the brain. In this review of the available literature, we discuss the consequences of breaking the blood–brain barrier and consequences of the influx of immune-system cells to the site of injury. We also analyze the influence of inflammatory mediators on the expression of genes controlling the process of apoptosis and the effect of chemical mutagenic factors on glial cells in the brain. We present the results of experimental studies indicating a relationship between injury and glioma development. However, epidemiological studies on post-traumatic glioma, of which only a few confirm the conclusions of experimental research, indicate that any potential relationship between injury and glioma, if any, is indirect

Epidemiology of Glioblastoma Multiforme–Literature Review

Glioblastoma multiforme (GBM) is one of the most aggressive malignancies, with a median overall survival of approximately 15 months. In this review, we analyze the pathogenesis of GBM, as well as epidemiological data, by age, gender, and tumor location. The data indicate that GBM is the higher-grade primary brain tumor and is significantly more common in men. The risk of being diagnosed with glioma increases with age, and median survival remains low, despite medical advances. In addition, it is difficult to determine clearly how GBM is influenced by stimulants, certain medications (e.g., NSAIDs), cell phone use, and exposure to heavy metals

Perineuronal Nets and Their Role in Synaptic Homeostasis

Extracellular matrix (ECM) molecules that are released by neurons and glial cells form perineuronal nets (PNNs) and modulate many neuronal and glial functions. PNNs, whose structure is still not known in detail, surround cell bodies and dendrites, which leaves free space for synapses to come into contact. A reduction in the expression of many neuronal ECM components adversely affects processes that are associated with synaptic plasticity, learning, and memory. At the same time, increased ECM activity, e.g., as a result of astrogliosis following brain damage or in neuroinflammation, can also have harmful consequences. The therapeutic use of enzymes to attenuate elevated neuronal ECM expression after injury or in Alzheimer’s disease has proven to be beneficial by promoting axon growth and increasing synaptic plasticity. Yet, severe impairment of ECM function can also lead to neurodegeneration. Thus, it appears that to ensure healthy neuronal function a delicate balance of ECM components must be maintained. In this paper we review the structure of PNNs and their components, such as hyaluronan, proteoglycans, core proteins, chondroitin sulphate proteoglycans, tenascins, and Hapln proteins. We also characterize the role of ECM in the functioning of the blood-brain barrier, neuronal communication, as well as the participation of PNNs in synaptic plasticity and some clinical aspects of perineuronal net impairment. Furthermore, we discuss the participation of PNNs in brain signaling. Understanding the molecular foundations of the ways that PNNs participate in brain signaling and synaptic plasticity, as well as how they change in physiological and pathological conditions, may help in the development of new therapies for many degenerative and inflammatory diseases of the brain

Glioblastoma Multiforme Tumors in Women Have a Lower Expression of Fatty Acid Elongases <em>ELOVL2</em>, <em>ELOVL5</em>, <em>ELOVL6</em>, and <em>ELOVL7</em> than in Men

One line of research on the possible ways of inhibiting the growth of glioblastoma multiforme (GBM), a brain tumor with a very poor prognosis, is the analysis of its metabolism, such as fatty acid synthesis by desaturases and elongases. This study examines the expression of elongases ELOVL1, ELOVL2, ELOVL3, ELOVL4, ELOVL5, ELOVL6, and ELOVL7 in GBM tumor samples from 28 patients (16 men and 12 women), using a quantitative real-time polymerase chain reaction (qRT-PCR). To demonstrate the influence of the tumor microenvironment on the tested elongases, U-87 MG cells were cultured in nutrient-deficient conditions and with cobalt chloride (CoCl2) as a hypoxia-mimetic agent. The results showed that the expression of ELOVL1 and ELOVL7 in the GBM tumor was lower than in the peritumoral area. The expression of six of the seven studied elongases differed between the sexes. Hypoxia increased the expression of ELOVL5 and ELOVL6 and decreased the expression of ELOVL1, ELOVL3, ELOVL4, and ELOVL7 in U-87 MG cells. These results indicate that the synthesis of fatty acids, especially polyunsaturated fatty acids (PUFA), in GBM tumors may be higher in men than in women. In contrast, the synthesis of saturated fatty acids (SFA) may be higher in women than in men

Epidemiology of Anthropometric Factors in Glioblastoma Multiforme—Literature Review

Although glioblastoma multiforme (GBM) is a widely researched cancer of the central nervous system, we still do not know its full pathophysiological mechanism and we still lack effective treatment methods as the current combination of surgery, radiotherapy, and chemotherapy does not bring about satisfactory results. The median survival time for GBM patients is only about 15 months. In this paper, we present the epidemiology of central nervous system (CNS) tumors and review the epidemiological data on GBM regarding gender, age, weight, height, and tumor location. The data indicate the possible influence of some anthropometric factors on the occurrence of GBM, especially in those who are male, elderly, overweight, and/or are taller. However, this review of single and small-size epidemiological studies should not be treated as definitive due to differences in the survey methods used. Detailed epidemiological registers could help identify the main at-risk groups which could then be used as homogenous study groups in research worldwide. Such research, with less distortion from various factors, could help identify the pathomechanisms that lead to the development of GBM

Epidemiology of Anthropometric Factors in Glioblastoma Multiforme—Literature Review

Although glioblastoma multiforme (GBM) is a widely researched cancer of the central nervous system, we still do not know its full pathophysiological mechanism and we still lack effective treatment methods as the current combination of surgery, radiotherapy, and chemotherapy does not bring about satisfactory results. The median survival time for GBM patients is only about 15 months. In this paper, we present the epidemiology of central nervous system (CNS) tumors and review the epidemiological data on GBM regarding gender, age, weight, height, and tumor location. The data indicate the possible influence of some anthropometric factors on the occurrence of GBM, especially in those who are male, elderly, overweight, and/or are taller. However, this review of single and small-size epidemiological studies should not be treated as definitive due to differences in the survey methods used. Detailed epidemiological registers could help identify the main at-risk groups which could then be used as homogenous study groups in research worldwide. Such research, with less distortion from various factors, could help identify the pathomechanisms that lead to the development of GBM

Atypical Pupil Reactions in Brain Dead Patients

Background: During routine diagnosis of brain death, changes in pupil diameter in response to the stimulation of peripheral nerves are sometimes observed. For example, pupillary dilation after diagnosed brain death is described in the literature as the ciliospinal reflex. However, pupil constriction creates diagnostic doubts. Objective: The pupillometric analysis of pupil response to stimulation of the cervicothoracic spinal cord in patients with diagnosed brain death. Methods: Instrumental tests to confirm the arrest of cerebral circulation were performed in 30 adult subjects (mean age 53.5 years, range 26–75 years) with diagnosed brain death. In addition, a pupillometer was used to measure the change in pupil diameter in response to neck flexion. Intervention: Flexion of the neck and measuring the response in change of the pupil with the use of the pupillometer. Results: The change in the pupil was observed in the examined group of patients. Difference in pupil size ≥ 0.2 mm was observed in 14 cases (46%). In five cases (17%), pupil constriction was found (from 0.2 to 0.7 mm). Measurement error was +/− 0.1 mm. Conclusions: Both pupillary constriction and dilatation may occur due to a ciliospinal reflex in patients with brain death. This phenomenon needs further research in order to establish its pathophysiology

CCL18 Expression Is Higher in a Glioblastoma Multiforme Tumor than in the Peritumoral Area and Causes the Migration of Tumor Cells Sensitized by Hypoxia

Glioblastoma multiforme (GBM) is a brain tumor with a very poor prognosis. For this reason, researchers worldwide study the impact of the tumor microenvironment in GBM, such as the effect of chemokines. In the present study, we focus on the role of the chemokine CCL18 and its receptors in the GBM tumor. We measured the expression of CCL18, CCR8 and PITPNM3 in the GMB tumor from patients (16 men and 12 women) using quantitative real-time polymerase chain reaction. To investigate the effect of CCL18 on the proliferation and migration of GBM cells, experiments were performed using U-87 MG cells. The results showed that CCL18 expression was higher in the GBM tumor than in the peritumoral area. The women had a decreased expression of PITPNM3 receptor in the GBM tumor, while in the men a lower expression of CCR8 was observed. The hypoxia-mimetic agent, cobalt chloride (CoCl2), increased the expression of CCL18 and PITPNM3 and thereby sensitized U-87 MG cells to CCL18, which did not affect the proliferation of U-87 MG cells but increased the migration of the test cells. The results indicate that GBM cells migrate from hypoxic areas, which may be important in understanding the mechanisms of tumorigenesis

Androgen Receptor Expression in the Various Regions of Resected Glioblastoma Multiforme Tumors and in an In Vitro Model

Glioblastoma multiforme (GBM) is a malignant glioma, difficult to detect and with the lowest survival rates among gliomas. Its greater incidence among men and its higher survival rate among premenopausal women suggest that it may be associated with the levels of androgens. As androgens stimulate the androgen receptor (AR), which acts as a transcription factor, the aim of this study was the investigate the role of AR in the progression of GBM. The study was conducted on tissues collected from three regions of GBM tumors (tumor core, enhancing tumor region, and peritumoral area). In addition, an in vitro experiment was conducted on U-87 cells under various culture conditions (necrotic, hypoxic, and nutrient-deficient), mimicking the conditions in a tumor. In both of the models, androgen receptor expression was determined at the gene and protein levels, and the results were confirmed by confocal microscopy and immunohistochemistry. AR mRNA expression was higher under nutrient-deficient conditions and lower under hypoxic conditions in vitro. However, there were no differences in AR protein expression. No differences in AR mRNA expression were observed between the tested tumor structures taken from patients. No differences in AR mRNA expression were observed between the men and women. However, AR protein expression in tumors resected from patients was higher in the enhancing tumor region and in the peritumoral area than in the tumor core. In women, higher AR expression was observed in the peritumoral area than in the tumor core. AR expression in GBM tumors did not differ significantly between men and women, which suggests that the higher incidence of GBM in men is not associated with AR expression. In the group consisting of men and women, AR expression varied between the regions of the tumor: AR expression was higher in the enhancing tumor region and in the peritumoral area than in the tumor core, showing a dependence on tumor conditions (hypoxia and insufficient nutrient supply)

Expression of SCD and FADS2 Is Lower in the Necrotic Core and Growing Tumor Area than in the Peritumoral Area of Glioblastoma Multiforme

The expression of desaturases is higher in many types of cancer, and despite their recognized role in oncogenesis, there has been no research on the expression of desaturases in glioblastoma multiforme (GBM). Tumor tissue samples were collected during surgery from 28 patients (16 men and 12 women) diagnosed with GBM. The effect of necrotic conditions and nutritional deficiency (mimicking conditions in the studied tumor zones) was studied in an in vitro culture of human brain (glioblastoma astrocytoma) U-87 MG cells. Analysis of desaturase expression was made by qRT-PCR and the immunohistochemistry method. In the tumor, the expression of stearoyl&ndash;coenzyme A desaturase (SCD) and fatty acid desaturases 2 (FADS2) was lower than in the peritumoral area. The expression of other desaturases did not differ in between the distinguished zones. We found no differences in the expression of SCD, fatty acid desaturases 1 (FADS1), or FADS2 between the sexes. Necrotic conditions and nutritional deficiency increased the expression of the studied desaturase in human brain (glioblastoma astrocytoma) U-87 MG cells. The obtained results suggest that (i) biosynthesis of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) in a GBM tumor is less intense than in the peritumoral area; (ii) expressions of SCD, SCD5, FADS1, and FADS2 correlate with each other in the necrotic core, growing tumor area, and peritumoral area; (iii) expressions of desaturases in a GBM tumor do not differ between the sexes; and (iv) nutritional deficiency increases the biosynthesis of MUFA and PUFA in GBM cells