Cisplatin induced sensory neuropathy is prevented by vascular endothelial growth factor-A

Vencappa, Samanta and Donaldson, Lucy F. and Hulse, Richard P. (2015) Cisplatin induced sensory neuropathy is prevented by vascular endothelial growth factor-A. American Journal of Translational Research, 7 (6). pp. 1032-1044. ISSN 1943-8141

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Abstract

Increased patient survival is a mark of modern anti-cancer therapy success. Unfortunately treatment side-effects such as neurotoxicity are a major long term concern. Sensory neuropathy is one of the common toxicities that can arise during platinum based chemotherapy. In many cases the current poor understanding of the neurological degeneration and lack of suitable analgesia has led to high incidences of patient drop out of treatment. VEGF-A is a prominent neuroprotective agent thus it was hypothesised to prevent cisplatin induced neuropathy. Systemic cisplatin treatment (lasting 3 weeks biweekly) resulted in mechanical allodynia and heat hyperalgesia in mice when compared to vehicle control. PGP9.5 sensory nerve fibre innervation was reduced in the plantar skin in the cisplatin treated group versus vehicle control mice. The cisplatin induced sensory neurodegeneration was associated with increased cleaved caspase 3 expression as well as a reduction in Activating Transcription Factor 3 and panVEGF-A expression in sensory neurons. VEGF-A165b expression was unaltered between vehicle and cisplatin treatment. rhVEGF-A165a and rhVEGF-A165b both prevented cisplatin induced sensory neurodegeneration. Cisplatin exposure blunts the regenerative properties of sensory neurons thus leading to sensory neuropathy. However, here it is identified that administration of VEGF-A isoform subtypes induce regeneration and prevent cell death and are therefore a possible adjunct therapy for chemotherapy induced neuropathy.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Cancer and Stem Cells
University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
Depositing User: Donaldson, Lucy
Date Deposited: 21 Mar 2018 09:49
Last Modified: 23 Mar 2018 04:50
URI: http://eprints.nottingham.ac.uk/id/eprint/50551

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