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dc.contributor.authorLucas, Antigone
dc.date.accessioned2019-06-14
dc.date.available2019-06-14
dc.date.issued2018-12-14
dc.identifier.urihttp://hdl.handle.net/2123/20561
dc.description.abstractChemotherapy has prolonged the survival rates of cancer patients. However, chemotherapy causes peripheral neuropathies and cognitive impairments. Isolating which chemotherapy agents are responsible for these behavioural changes is difficult. Patients are given regimens that contain several agents alongside hormone therapy and radiation. Animal models are useful to elucidate which class of agents have the most neurotoxic effect and can determine which neural mechanisms are vulnerable to chemotherapy. Animal models can also determine which pharmacological agents reduce neurotoxic side effects to restore normal functioning. The first aim of this thesis was to compose a systematic review of chemobrain in animal models. The second aim was to explore the effects of oxaliplatin (OXP) on cognition in rodents. The third aim was to determine whether ibudilast (IBU), a proven immune therapy and nicotinamide mononucleotide (NMN), a permeable nicotinamide adenine dinucleotide precursor can reduce OXP-induced neurotoxicity. The systematic review showed that across all chemotherapy regimens short term memory (STM) was profoundly impaired. Impairments were associated with disrupted neurogenesis, oxidative stress, inflammation and altered neuronal morphology. The most cytotoxic regimens were cisplatin and methotrexate + 5-fluorouracil with or without cyclophosphamide. These regimens produced impairments in STM, long term memory and executive control. Experiments demonstrated that one injection of IBU or consumption of NMN for 7 days reduced OXP-induced object recognition memory impairments in acute and chronic pre-clinical models of OXP-induced neurotoxicity. Furthermore, OXP-treated rats showed intact object recognition memory at least 7 days post NMN treatment cessation. One injection of IBU also prevented OXP-induced tactile allodynia. These experiments highlight the therapeutic potential of IBU and NMN in reducing the neurotoxic side effects of platinum chemotherapy agents.en_AU
dc.publisherUniversity of Sydneyen_AU
dc.publisherFaculty of Scienceen_AU
dc.publisherDiscipline of Psychologyen_AU
dc.rightsThe author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.en_AU
dc.subjectChemotherapyen_AU
dc.subjectCognitionen_AU
dc.subjectNeuroimmuneen_AU
dc.subjectRodenten_AU
dc.titleChemotherapy-Induced Cognitive Impairments: Targeting Neuroimmune Processes as Potential Treatmentsen_AU
dc.typeMasters Thesisen_AU
dc.type.pubtypeMaster of Philosophy M.Philen_AU
dc.description.disclaimerAccess is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.en_AU


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