Cytokine-mediated blood brain barrier disruption as a conduit for cancer/chemotherapy-associated neurotoxicity and cognitive dysfunction

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dc.contributor.authorWardill, H.
dc.contributor.authorMander, K.
dc.contributor.authorVan Sebille, Y.
dc.contributor.authorGibson, R.
dc.contributor.authorLogan, R.
dc.contributor.authorBowen, J.
dc.contributor.authorSonis, S.
dc.date.issued2016
dc.description.abstractNeurotoxicity is a common side effect of chemotherapy treatment, with unclear molecular mechanisms. Clinical studies suggest that the most frequent neurotoxic adverse events affect memory and learning, attention, concentration, processing speeds and executive function. Emerging preclinical research points toward direct cellular toxicity and induction of neuroinflammation as key drivers of neurotoxicity and subsequent cognitive impairment. Emerging data now show detectable levels of some chemotherapeutic agents within the CNS, indicating potential disruption of blood brain barrier integrity or transport mechanisms. Blood brain barrier disruption is a key aspect of many neurocognitive disorders, particularly those characterized by a proinflammatory state. Importantly, many proinflammatory mediators able to modulate the blood brain barrier are generated by tissues and organs that are targets for chemotherapy-associated toxicities. This review therefore aims to explore the hypothesis that peripherally derived inflammatory cytokines disrupt blood brain barrier permeability, thereby increasing direct access of chemotherapeutic agents into the CNS to facilitate neuroinflammation and central neurotoxicity.
dc.description.statementofresponsibilityHannah R. Wardill, Kimberley A. Mander, Ysabella Z.A. Van Sebille, Rachel J. Gibson, Richard M. Logan, Joanne M. Bowen, and Stephen T. Sonis
dc.identifier.citationInternational Journal of Cancer, 2016; 139(12):2635-2645
dc.identifier.doi10.1002/ijc.30252
dc.identifier.issn0020-7136
dc.identifier.issn1097-0215
dc.identifier.orcidWardill, H. [0000-0002-6613-3661]
dc.identifier.orcidGibson, R. [0000-0002-4796-1621]
dc.identifier.orcidLogan, R. [0000-0002-9331-1814]
dc.identifier.orcidBowen, J. [0000-0003-0876-0031]
dc.identifier.urihttp://hdl.handle.net/2440/104783
dc.language.isoen
dc.publisherWliey
dc.rights© 2016 UICC
dc.source.urihttps://doi.org/10.1002/ijc.30252
dc.subjectblood brain barrier
dc.subjectchemotherapy-induced gut toxicity
dc.subjectcognitive dysfunction
dc.subjectinflammation
dc.subjectneurotoxicity
dc.titleCytokine-mediated blood brain barrier disruption as a conduit for cancer/chemotherapy-associated neurotoxicity and cognitive dysfunction
dc.typeJournal article
pubs.publication-statusPublished

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