OSR Journal of Student Research

Article Title

Characterizing the Effect of Combined Temozolomide-Irradiation Therapy on Cognitive Function and Investigating Neural Stem Cells and Extracellular Vesicles as Translational Therapies


Each year, approximately 240,000 cancer patients are diagnosed with brain tumors. Following cessation of radiation therapy treatment, 50% of these patients experience delayed adverse cognitive effects. Although difficulty to quantify, these treatment associated effects on mood, memory, concentration, and executive functions are persistent and have a major negative impact on quality of life. Despite acknowledgment of the cognitive problems, differences in disease status, treatment regiment, and baseline cognitive reserve between patients makes it difficult to study the mechanisms underlying effects on cognition. Therefore, it is critical to conduct controlled animal studies to define the neurotoxicity of irradiation and chemotherapy and the mechanisms underlying their toxic effects. In this study, we aim to characterize the effects of temozolomide (an adjuvant chemotherapeutic agent used in clinical protocols) and radiation therapy, and to investigate whether temozolomide (TMZ) exacerbates cognitive impairments. Further, past work in our lab has demonstrated the benefit conferred by both intrahippocampal stem cell transplantations and stem cell-derived extracellular vesicle transplantations in ameliorating neurocognitive deficits associated with cranial irradiation (IRR). Thus, we also aim to investigate the efficacy of these grafting interventions on ameliorating neurocognitive deficits associated with combined TMZ+IRR treatment. Ultimately, these experiments will provide the foundation for elucidating the causes of radiation- and chemotherapy-induced cognitive impairment and will be instrumental in developing a translational strategy for the long-term resolution of these unintended cognitive side effects.

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