Skip to main content
. Author manuscript; available in PMC: 2015 Sep 1.
Published in final edited form as: Free Radic Biol Med. 2014 Jul 1;0:157–174. doi: 10.1016/j.freeradbiomed.2014.06.006

Figure 11.

Figure 11

Model for CICI (“chemobrain”) based on demonstrated results from our laboratory. Dox (ADR), as a prototypical ROS-generating agent that does not cross the BBB, causes oxidation of ApoA1 in plasma, which leads to increased levels of TNFα. This cytokine crosses the BBB to enter glia and neurons, generating even more TNFα. Subsequent biochemical events lead to brain mitochondrial dysfunction and resultant apoptosis as explained more in the text. Mesna, which does not interfere with cancer chemotherapy, blocks Dox-mediated oxidation of ApoA1 and elevation of TNFα. Anti- TNFα antibody blocks elevated TNFα from crossing the BBB. Both treatments inhibit the biochemical events that otherwise cause neuronal death. See text and [169-171, 174, 176, 181, 182] for more details.