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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/33749

Title: A Comparative Study of the Impact of Sustained and Intermittent Docetaxel Chemotherapy in Brain in a Mouse Model
Authors: Zhang, Ji
Advisor: Piquette-Miller, Micheline
Department: Pharmaceutical Sciences
Keywords: Docetaxel
Chemotherapy
Cognitive impairment
Neurotoxicity
Autophagy
Astrocyte
Apoptosis
Neuronal Calcium Sensor-1
Issue Date: 4-Dec-2012
Abstract: Title: “A comparative study of the impact of sustained and intermittent docetaxel chemotherapy in brain in a mouse model” Ji Zhang Master of Science Graduate Department of Pharmaceutical Sciences, University of Toronto November, 2011 Abstract A subset of patients suffers cognitive impairment during or long after chemotherapy. This may result from chemotherapeutic agents crossing the blood brain barrier (BBB). This thesis examined the effects of docetaxel (DTX) on brain toxicity, and the effects of different dosing schedules on brain DTX concentrations and neurotoxicity. Examination of DTX treated mice (total dose of 32mg/kg) revealed appreciable amounts of DTX crossed the BBB after either intermittent (four weekly doses) or sustained (one injection of DTX-PoLigel) administration despite differences in peak drug concentrations and overall exposure profiles. Measurements of autophagy and astrocytes activation not only provided evidence of DTX caused neurotoxicity in the central nervous system, but also revealed a link between dosing schedule and neurotoxicity. Furthermore, the discovery suggested connections between DTX brain exposure, diverse biological events (such as BBB permeability and reactive oxygen species activity), and the microenvironment at synapse-neuron junctions, which should be further explored.
URI: http://hdl.handle.net/1807/33749
Appears in Collections:Master

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