Browsing by Author "Akyol, Mehmet Edip"

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Effects of Vitamin D and Memantine on Repetitive Mild Traumatic Brain Injury Via Mtor, Trpm2, and Gaba Expression Levels on Juvenile Rats
(Turkish Neurosurgical Soc, 2024) Gulsen, Ismail; Ak, Hakan; Akyol, Mehmet Edip; Ozmen, Ozlem; Alp, Hamit Hakan; Arabaci, Ozkan
AIM: To investigate the effects of vitamin D and memantine on the healing process in juvenile rats with repetitive brain injury (rTBI) and to elucidate the mechanisms underlying these potential therapeutic effects. MATERIAL and METHODS: Juvenile rats were randomly allocated into seven groups, with eight rats per group: sham-operated (Group I), trauma (Group II), memantine supplementation (10 mg/kg) pre-trauma (Group III), vitamin D supplementation (5 mu g/kg) pre-trauma (Group IV), vitamin D supplementation post-trauma (Group V), memantine and vitamin D supplementation post-trauma (Group VI), and vitamin D supplementation pre- and post-trauma with post-trauma memantine supplementation (Group VII). A modified repeated weight drop model was employed to induce rTBI. Brain tissues and blood samples were collected for analysis. Expressions of the mammalian target of rapamycin (mTOR), temporary receptor potential (TRPM2), and GABA receptors were assessed via immunohistochemistry. Levels of 8-hydroxy-2-deoxyguanine (8-OHdG) were determined using high-performance liquid chromatography (HPLC). Matrix metalloproteinases -2 and -9, tissue inhibitors of metalloproteinases-1 and-2, and NADPH oxidation-4 levels were determined using commercially available enzyme-linked immunosorbent Test kits. Immunohistochemistry analyses were performed on the brain cortex and hippocampus. RESULTS: The levels of 8OHdG/106dG, MMP-2, MMP-9, TIMP-1, -TIMP2, and NOX-4 were significantly higher in the trauma group than in the other groups. No difference was found between the control and Pre Vit D+Mem+Post Vit D groups regarding 8OHdG/106dG, MMP-2, -9 and NOX-4 levels. Normalized expressions of mTOR and TRPM2 were observed in Groups VI and VII. Conversely, GABA expression levels decreased in Group II, with the most pronounced therapeutic effects observed in Group VII. CONCLUSION: Memantine and vitamin D positively affected rTBI when used alone. Their combined use exhibited greater therapeutic outcomes. These effects are mediated by mTOR mRNA, TRPM2 mRNA, and GABA mRNA expressions.
Ghrelin Ameliorates Neuronal Damage, Oxidative Stress, Inflammatory Parameters, and Gfap Expression in Traumatic Brain Injury
(Taylor & Francis Ltd, 2024) Erkec, Ozlem Ergul; Acikgoz, Eda; Huyut, Zubeyir; Akyol, Mehmet Edip; Ozyurt, Enver Onat; Keskin, Siddik
ObjectiveThis study investigated the effects of ghrelin on oxidative stress, working memory, inflammatory parameters, and neuron degeneration.MethodsTBI was produced with the weight-drop technique. Rats in the G+TBI and TBI+G groups received ghrelin for 7 days. The control group received saline. On the 8th day of the study, the brain and blood tissue were taken under anesthesia.ResultsA significant increase in brain GSH-PX, MDA, IL-1 beta, TGF-beta 1, and IL-8 levels and a significant decrease in CAT levels were found in the TBI group compared to the control. Serum MDA, GSH, IL-1 beta, and IL-8 levels were increased with TBI. Ghrelin treatment after TBI significantly increased the serum GSH, CAT, GSH-PX, and brain GSH and CAT levels, while it significantly decreased the serum MDA, IL-1 beta, and brain MDA, TGF-beta 1, and IL-8 levels. Histological evaluations revealed that ghrelin treatment led to a reduction in inflammation, while also significantly ameliorating TBI-induced neuron damage and vascular injuries. Immunohistochemistry staining showed that GFAP staining intensity was significantly increased in the cortex and hippocampus in TBI, and GFAP immunoreactivity was decreased with ghrelin treatment.ConclusionThe results from this study suggested that ghrelin may have curative effects on TBI.
Histopathological and Immunohistochemical Investigation of the Effect of Shilajit in Rats With Experimental Spinal Cord Injury
(Turkish Assoc Trauma Emergency Surgery, 2023) Cetin, Eyup; Sancak, Tunahan; Keles, Omer Faruk; Unlu, Ilker; Akyol, Mehmet Edip; Arabaci, Ozkan
BACKGROUND: This experimental study was designed to investigate the histopathological and immunohistochemical effects of Shilajit in rats with experimentally induced spinal cord injury (SCI). METHODS: The rats were divided into three groups: Control group: The group in which spinal cord damage was created but no drug was administered. Low-dose group: This is the group in which intraperitoneal Shilajit is given at a dose of 150 mg/kg at the 1st h, 1st day, 2nd day, and 3rd day after spinal cord damage was induced. High-dose group: This is the group in which intraperitoneal Shilajit is given at a dose of 250 mg/kg at the 1st h, 1st day, 2nd day, and 3rd day after spinal cord damage was induced. Thin sections taken from the spinal cord after euthanasia were sent for histopathological and immunohistochemical examination. RESULTS: Histopathological examination of the high-dose group showed lower amounts of morphological findings compared to the low-dose group and control group. While a significant CD68 immune reaction was observed in the control group of rats with spinal injury, the positive immune reaction was found to be significantly decreased in the Shilajit-applied groups. CONCLUSION: It is thought that the use of Shilajit in SCI will reduce the effects of secondary damage in SCI and that its administration to such patients will have positive effects on the results.
Investigation of Oxidative Stress Level and Antioxidant Enzyme Activities in Operated and Nonoperated Patients With Spontaneous Intracerebral Hematoma
(Thieme Medical Publ inc, 2024) Akyol, Mehmet Edip; Demir, Canan; Gorken, Gokhan
Background Complex underlying mechanisms consisting of cytotoxic, excitotoxic, and inflammatory effects of intraparenchymal hemorrhage (ICH) are responsible for the highly detrimental effects on brain tissue. Oxidative stress also plays a significant role in brain damage after ICH; however, it is less important than other factors. In this study, we aimed to evaluate the oxidative stress parameters malondialdehyde (MDA) and antioxidant-reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CT) activities in operated and nonoperated patients with spontaneous ICH. Methods One hundred patients with spontaneous ICH and 100 healthy controls were included in this study. Within the indication, 50 of the 100 patients underwent decompressive surgery. MDA, GSH, SOD, and CT activities were measured in the serum obtained from the patients. Results SOD and CT levels were lower in the nonoperated group than in the operated and control groups. GSH was similar in the operated and nonoperated groups, but it was lower in the control group. However, MDA was higher in those who did not undergo surgery than in the other groups. Conclusions In our study, MDA, an indicator of oxidative stress, was found to be lower, and CT and SOD activities were found to be higher in ICH patients who underwent decompression than in those who did not. This is the first study to present the correlations of MDA, SOD, CT, and GSH in operated and nonoperated patients with spontaneous ICH.
A New Approach in the Treatment of Traumatic Brain Injury: the Effects of Levosimendan on Necrosis, Apoptosis, and Oxidative Stress
(Elsevier Science inc, 2022) Aycan, Abdurrahman; Oksuz, Ersoy; Gonullu, Edip; Kume, Tuncay; Ergur, Bekir; Akyol, Mehmet Edip; Kuyumcu, Fetullah
- OBJECTIVE: Traumatic brain injury (TBI) is an essential and common health problem worldwide. Levosimendan is an inotropic and vasodilator drug used to treat heart failure. Moreover, it exerts pleiotropic effects and, thus, protective effects on many organs. The present study aimed to investigate the effect of levosimendan on necrosis, apoptosis, and reactive oxygen species in rats with TBI. - METHODS: The study included 28 female Wistar-Albino rats weighing 200-250 g. The rats were divided into 4 groups with 7 rats each as follows: Group 1: No trauma group (Control), Group 2: Traumatized, untreated group (T), Group 3: Levosimendan was administered at a dose of 12 mg/kg intraperitoneally 1 hour after the trauma (L1), Group 4: Levosimendan was administered at a dose of 12 mg/kg intraperitoneally 2 hours after the concussion (L2). After the experiment, the rats were decapitated, and the brain tissue was removed. Necrosis was assessed with Cresyl violet staining, apoptosis was assessed with immunohistochemical analysis, superoxide dismutase and catalase levels were measured with the spectrophotometric method, and malondialdehyde (MDA) levels were assessed by High-Performance Liquid Chromatography. - RESULTS: The number of necrotic cells in the L1 and L2 groups was significantly lower than in the K and T groups (P = 0.015 and P = 0.03, respectively). Although the active caspase-3 level was signified considerably in the T, L1, and L2 groups compared to the K group, no significant difference was found among these 3 groups (P > 0.05). The results of superoxide dismutase levels were similar to those of active caspase-3. catalase level was significantly higher in the K group than in the T and L2 groups (P = 0.045). Malondialdehyde activity was considerably higher in the L1 and L2 groups compared to the K group (P = 0.023). - CONCLUSIONS: Our results indicated that levosimendan may exert a neuroprotective effect by reducing necrosis in TBI and that levosimendan does not affect apoptosis and antioxidant levels in TBI. Comprehensive studies are needed to elucidate the effect of levosimendan on TBI fully.
A New Approach in the Treatment of Traumatic Brain Injury: the Effects of Levosimendan on Necrosis, Apoptosis, and Oxidative Stress (Vol 168, Pg E432, 2022)
(Elsevier Science inc, 2023) Aycan, Abdurrahman; Oksuz, Ersoy; Gonullu, Edip; Kume, Tuncay; Ergur, Bekir; Akyol, Mehmet Edip; Kuyumcu, Fetullah
Operative and Prognostic Parameters Associated With Elective Versus Emergency Surgery in a Retrospective Cohort of Elderly Patients
(Springer, 2019) Soyalp, Celaleddin; Yuzkat, Nureddin; Kilic, Mehmet; Akyol, Mehmet Edip; Demir, Canser Yilmaz; Gulhas, Nurcin
AimTo evaluate operative and prognostic parameters associated with elective versus emergency surgery in a retrospective cohort of elderly patients.MethodsA total of 533 geriatric patients (aged65 years, median age: 73.0 years, 50.7% were females) who underwent either elective surgery (n=285) or emergency surgery (n=248) were included in this study. Data on patient demographics, co-morbid disorders, type of surgery and anesthesia, American Society of Anesthesiologists (ASA) physical status (PS) classification, length of hospital stay, length of ICU stay, hospitalization outcome, prognosis (survivor, non-survivor) were obtained from medical records.ResultsEmergency surgery group was associated with higher prevalence of ASA-PS III (48.8 vs. 25.6%, p<0.001) and ASA-PS IV (19.0 vs. 0.4%, p<0.001) categories and higher mortality rates (20.6 vs. 4.9% vs. p<0.001) when compared to the elective surgery group. ASA-PS IV category was associated with oldest patient age (median 82.0 vs. 71.0years for ASA-PS I and II, p<0.001 for each and versus 75.0years for ASA-PS III, p<0.05) and highest mortality rate (35.4 vs. 3.4% for ASA-PS I, 6.0% for ASA-PS II and 16.5% for ASA-PS III, p<0.001) as compared with other categories.ConclusionIn conclusion, our findings in a retrospective cohort of elderly surgical patients revealed high prevalence of co-morbidities, predominance of ASA-PS II or ASA-PS III classes and an overall in-hospital mortality rate of 12.2%. Emergency as compared with elective surgery seems to be associated with older age, male gender, ASA-PS III and IV classes, higher likelihood of postoperative ICU transfer and higher mortality rates.
Prolidase Activity in Meningomyelocelo Defect and Ichemia Modified Albumin Levels Research
(2023) Zengin, İrfan; Akyol, Mehmet Edip
Amaç: Bu çalışmada, meningomyelosel nedeniyle tedavi almakta olan çocuklarda ve kontrol grubunda serum prolidaz aktivitesi ve serum iskemi modifiye albümin (İMA) düzeylerinin araştırılması ve meningomyelosel patogenezindeki rolünü araştırmayı amaçladık. Yöntem: Çalışmaya nöral tüp defekti (NTD) tanısı ile takip edilen 45 hasta ve NTD hastalığı olmadığı bilinen 45 kontrol dahil edildi. Seçilen hastalardan ailenin onamı alınarak kan örneği alınarak serum prolidaz aktivitesi ve serum iskemi modifiye albümin çalışıldı. Ayrıca hastalarda, NTD tipi, lezyon seviyesi, klinik bulgu ve hidrosefali cerrahisi varlığıyla birlikte, serum B12 vitamini, folat ve kalsiyum düzeylerine ilişkin bilgiler toplandı. Bulgular: Takip edilen NTD hastalarının 20‟si (%44,4) erkek ve 25‟i kız (%55,6) idi. Bu hastaların yaş ortalaması 21,71±33,53 aydı. Hastaların 34‟ünde (%75,6) meningomyelosel mevcut iken 5‟inde (%11,1) meningosel, 6‟sında ise (%13,3) myeloşizis bulunuyordu. Serum İMA ve serum prolidaz aktivitesi için hasta ve kontrol grup ortalamaları arasındaki fark istatistiksel olarak önemli bulundu (her iki analiz için; p=0,001). Ayrıca, meningomyelosel, meningosel, myeloşizis hastalarında prolidaz aktivitesi açısından istatistiksel olarak anlamlı fark bulunmadığı görüldü. Sonuç: Oksidatif stres için iyi bir belirteç olan serum İMA düzeyi ve kolajen metabolizmasında önemli rol oynayan serum prolidaz aktivitesinin meningomyelosel hastalarında yüksek olduğu saptandı. Bu sonuçlar, meningomyelosel hastalarında serum prolidaz aktivitesinin ve serum İMA düzeyinin süreğen yüksekliğinin nedenlerinin incelenmesinin, NTD'lerin patogenezinin aydınlatılmasına katkıda bulunabileceğini göstermektedi
Relationship Between Hydrocephalus Etiology and Ventriculoperitoneal Shunt Infection in Children and Review of Literature
(Pakistan Medical Assoc, 2018) Arslan, Mehmet; Aycan, Abdurrahman; Gulsen, Ismail; Akyol, Mehmet Edip; Kuyumcu, Fetullah
Objective: The purpose of this retrospective study was to clarify the relationship of shunt infection to childhood hydrocephalus etiology Methods: We analyzed 1021 patients with childhood hydrocephalus who underwent V-P shunting over a period of approximately 15 years. The etiology of 1021 patients include myelomeningocele (794 patient), congenital (165 patient) and intraventricular haemorrhage (62 patient). Results: Of the 1021 patients who underwent V-P shunting, 19.32% exhibited shunt infection. Shunt infection developed in 180 (22.67%) of 794 patients with myelomeningocele, 9 (5.45%) of 165 patients with congenital obstructive hydrocephalus, and 9 (14.51%) of 62 patients with intraventricular haemorrhage. Recurrent shunt infection was detected in 54 (27.27%) of 198 patients with a previous shunt infection. Conclusions: Patients with previous shunt infection as well as those with shunts associated with myelomeningocele were observed to be at a greater risk for shunt infection. Results indicated that patients with congenital obstructive hydrocephalus may be less prone to shunt infections.
Role of Matrix Metalloproteinases on the Development of Neural Tube Defect
(2018) Akyol, Mehmet Edip; Arslan, Mehmet
Nöral Tüp Defekti (NTD) en yaygın ve en ağır klinik özelliklere sahip konjenital malfarmasyonlardan biridir. Embriyogenez sırasında nöral plağın nöral tüpü oluşturamaması sonucu NTD oluşur. NTD'nin birbirinden faklı özellik gösteren birçok tipi vardır. NTD gelişiminde genetik ve çevresel faktörler rol oynamaktadır. Beslenme (folik asit ve B vitaminleri eklenmesi) gibi çevresel faktörlerle NTD oluşumu engellenmeye çalışılsa da bu yaklaşım yeterli olamamaktadır. NTD'nin önlenmesi için prognostik, prediktif ve/veya terapötik genetik faktörlerin belirlenmesine ihtiyaç vardır. NTD gelişimini ve oluşumunu gösteren biobelirteç bulunmamaktadır. NTD gelişiminde ektstraselüler matriksin (ECM) oluşumu, nöral krest hücrelerinin göçü önemli rol oynamaktadır. Matriks metalloproteinazlar (MMP) ECM yapılanmasında, hücre göçünde, hücre invazyonunda ve diğer hücresel davranışların belirlenmesinde majör rol oynamaktadır. MMP ekspresyonlarının ve aktivasyonunun NTD'deki rolü bilinmemektedir. Bu çalışmanın amacı insan NTD gelişimindeki MMP-1, -2 ve -9 genlerinin ekspresyonlarının rolünün araştırılması amaçlanmıştır. NTD tanısı konan yeni doğan 40 bebek hastadan periferik kan ve NTD dokusu ile sağlıklı doğan 4 bebekten periferik kan alınmıştır. Periferik kan ve dokulardan total RNA izolasyonu ve kantitatif Gerçek Zamanlı Polimeraz Zincir Reaksiyonu (Q-RT-PZR) ile MMP-1, -2 ve -9 gen ekspresyonları araştırılmıştır. İstatistiksel analiz için SPSS 20.0 kullanılmıştır. MMP-1,-2 ve -9 gen ekspresyonları açısından hasta ile sağlıklı bireylerin kan örnekleri arasında ekspresyon farklılıkları saptanmıştır. NTD dokularındaki MMP'lerin ve özellikle MMP-1 ve MMP-9 gen ekspresyonlarının periferik kan örneklerine göre ortalama 2 ile 5000 kat yüksek olduğu saptanmıştır. NTD'nin alt tipleri arasında MMP-2 ekspresyonu açısından anlamlı farklılık saptanmıştır (p=0,012) Hastaların Ca+2, B12 ve Folat seviyeleri ile NTD gelişimi ve MMP genlerinin ekspresyonları arasında anlamlı bir ilişki saptanamamıştır (p>0,05). Bu çalışmada NTD araştırmalarında periferik kan yerine NTD dokusu kullanılması gerekliliği ortaya çıkmıştır. Ayrıca, bu çalışma NTD gelişiminde MMP'lerin önemli rollerinin olabileceğini ve MMP-1, -2 ve -9 genlerinin ekspresyonlarının NTD' patogenezinde rol oynayabileceğini gösteren literatürdeki ilk çalışmadır.
Serum Prolidase and Ischemia-Modified Albumin Levels in Neural Tube Defects: a Comparative Study of Myelomeningocele, Meningocele, and Myeloschisis
(int Scientific information, inc, 2025) Zengin, Irfan; Akyol, Mehmet Edip; Arslan, Mustafa; Arabaci, Ozkan; Yurekturk, Eyyup; Cetin, Eyup; Demir, Halit
Background: Neural tube defects (NTDs) are congenital malformations resulting from incomplete neural tube closure, leading to severe neurological impairments. Despite advances in prenatal screening and surgical interventions, the biochemical mechanisms underlying NTDs remain unclear. Prolidase, an enzyme involved in collagen metabolism, and ischemia-modified albumin (IMA), a marker of oxidative stress, may play roles in NTD pathogenesis. This study aimed to compare serum prolidase and IMA levels in infants with NTDs and healthy controls to assess their potential contribution to NTD development. Material/Methods: A case-control study was conducted, including 45 infants diagnosed with NTDs (myelomeningocele, meningocele, and myeloschisis) and 45 age-and sex-matched healthy controls. Serum prolidase and IMA levels were measured using validated spectrophotometric methods. Statistical analyses were performed to compare biomarker levels between groups and among NTD subtypes. Results: Serum prolidase levels were significantly elevated in NTD patients (2.21 +/- 0.06 IU/L) compared to controls (1.07 +/- 0.04 IU/L, p<0.001). Similarly, serum IMA levels were higher in NTD patients (0.40 +/- 0.01 ABSU) than in controls (0.22 +/- 0.01 ABSU, p<0.001). No significant differences were observed in biomarker levels among the different NTD subtypes (p>0.05). Conclusions: Elevated prolidase and IMA levels in NTD patients suggest a potential role in NTD pathogenesis, possibly through impaired collagen metabolism and oxidative stress. Further research is needed to explore their diagnostic and therapeutic implications in neural tube defect management.
Spinal Metastasis of Unknown Primary Accompanied by Neurologic Deficit or Vertebral Instability
(Elsevier Science inc, 2018) Aycan, Abdurrahman; Celik, Sebahattin; Kuyumcu, Fetullah; Akyol, Mehmet Edip; Arslan, Mehmet; Dogan, Erkan; Arslan, Harun
BACKGROUND AND OBJECTIVE: Spinal bone metastases are common. They are mostly localized to the lumbar, thoracic, and cervical spine. The most common primaries to result in spinal metastases include lung, breast, and prostate carcinomas in adults as opposed to leukemia, Ewing sarcoma, rhabdomyosarcoma, and neuroblastoma in children. In patients diagnosed with cancer, bone metastases are found in 40% and spinal metastases in 10%. In this study, we reviewed 25 patients diagnosed with a spinal metastasis of unknown primary who presented with low back pain or acute-onset neurologic deficits and underwent operative treatment. METHODS: The retrospective study included 25 patients with a spinal metastasis of unknown primary who presented to our clinic with acute-onset vertebral fracture or neurologic deficit. Statistical descriptions were obtained for each patient. Survival analysis was performed using the Kaplan-Meier method. RESULTS: The 25 patients included 17 men (68%) and 8 women (32%), with a mean age of 55 years (range, 14-81 years). Eleven patients (44%) presented with varying degrees of motor deficits ranging from flaccid paralysis to paraplegia. Motor deficits were completely reversed in 4 patients postoperatively. The tumors were localized to the upper thoracic spine (T1-4) in 2 patients, in the midthoracic spine (T5-8) in 2 patients, in the lower thoracic spine (T9-12) in 8 patients, in the cervical 7 in 1 patient, and in the lumbar spine in 12 patients. In 10 patients, the tumor affected multiple spinal regions. Nonosseous tumors were not present in 10 patients. Ten patients had an extradural tumor. Costal involvement was detected in 2 patients. The tumors were pathologically identified as lung cancer (n = 3), lymphoma (n = 5), breast cancer (n = 3), gastric cancer (n = 2), liver cancer (n = 2), prostate cancer (n = 2), renal cell carcinoma (n = 2), malignant melanoma (n = 1), plasmacytoma (n = 1), bladder cancer (n = 1), paraganglioma (n = 1), Ewing sarcoma (n = 1), and yolk sac carcinoma (n = 1). Posterior instrumentation was performed in patients with instability. In addition, decompression was performed in patients with neurologic deficit. CONCLUSIONS: Considering that 10% of patients with cancer are diagnosed by vertebral metastasis, presence of malignancy should be suspected and a detailed examination should be performed in patients presenting with vertebral fractures caused by no or minor trauma. Moreover, in patients presenting with neurologic deficit, soft tissue metastases leading to spinal cord compression should be kept inmind and further examinations should be promptly administered.
Tissue Expressions of Regulatory Enzymes of the Krebs Cycle in Low- and High-Grade Gliomas
(Turkish Neurosurgical Soc, 2023) Tahmazoglu, Burak; Kemerdere, Rahsan; Akyol, Mehmet Edip; Orhan, Bagnu; Ince, Merve; Serin, Huriye; Tanriverdi, Taner
AIM: To compare tissue levels of the regulatory enzymes related to the Krebs cycle between low, and high-grade supratentorial gliomas. MATERIAL and METHODS: Forty patients who underwent surgery for supratentorial gliomas (19 with low-grade and 21 with high-grade gliomas) were evaluated. The regulatory enzymes directly involved in the Krebs cycle, namely pyruvate dehydrogenase, citrate synthase, alpha-ketoglutarate dehydrogenase, and isocitrate dehydrogenase, and two enzymes that indirectly regulate the Krebs cycle, namely glutamate dehydrogenase and glutaminase, were quantitatively studied in tumor tissues using ELISA. The results were compared between the two groups. RESULTS: The levels of all enzymes were higher in the high-grade glioma group but only pyruvate dehydrogenase, citrate synthase, and isocitrate dehydrogenase levels showed statistical significance. Moreover, all enzymes showed higher tissue levels in grade -II compared to grade-I gliomas, but only two enzymes, glutamate dehydrogenase and glutaminase, reached significantly higher levels. In the high-grade glioma group, all enzymes again showed higher tissue levels in grade-IV gliomas than in grade-III gliomas, but none showed statistical significance. CONCLUSION: Regulatory enzymes of the Krebs cycle are increased in high-grade gliomas compared to low-grade gliomas. Glutaminolysis enzymes, namely glutamate dehydrogenase and glutaminase, which are required for resupplying the Krebs cycle, are also increased in order to meet the high energy demand in high-grade gliomas.