Glutamate Excitotoxicity and Its Role in Glioblastoma Biology

Role of Glutamate-mediate Excitotoxicity in Invasion and Progression Processes of Glioblastoma Multiforme

Gliomas are the most frequent type of primary brain tumors in adults; among them glioblastoma multiforme (GBM) is the most malignant, being associated with the worst prognosis. Glutamate (Glu) is an aminoacid, responsible for essential functions in the Central Nervous System (CNS), acting both as metabolite and neurotransmitter. It is essential for regulating cellular metabolism and developmental synaptogenesis, cellular migration, differentiation and death. Recent scientific evidences have demonstrated alteration in Glu synthesis and signaling being directly involved in GBM growth and invasion

Glu and its scavenger's levels are measurable both in serum and in the cerebral-spinal fluid (CSF), thus making them ideal markers for tumor aggressiveness and disease activity as well as a potential target for new therapeutic approaches.

Serum and CSF levels of glutamic oxaloacetic transaminase (GOT1), Glutamate Pyruvate Transaminase (GPT) and glutamate and aspartate levels of a total of 40 patients will be collected.

Molecular biology analyses will be conducted and oncological and imaging data will be collected during follow-up in patients enrolled in the present studies. MRI imaging as well as blood sampling will be performed at definite timepoints (baseline and 3, 6 and 9 months follow-up).

Inclusion Criteria:

• Adult patients with a brain lesion suspected for GBM, candidate to gross total tumor resection (GTR), followed by radiotherapy and chemotherapy (concomitant and adjuvant).
• Patient able to provide informed consent.

Exclusion Criteria:

• Age < 18 years
• Liver disease
• Severe anemia (Hb <8mg/dl)
• Pregnancy