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Mapping Chemobrain (CRCI) and
Peripheral neuropathy (CIPN) after Doxorubicin
Newsletter # 135
Animal models
Developing effective co-therapies requires robust preclinical models that capture both central and peripheral damage simultaneously.
Unlike many chemotherapy neurotoxicity models that focus on either cognitive dysfunction or peripheral neuropathy alone, this protocol captures both CRCI and CIPN within a single rapid 14-day study, providing an efficient platform for therapeutic screening.
of mice
at day 14
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The temporal divergence between behavioral recovery and persistent NfL elevation suggests that doxorubicin induces two distinct neurotoxic mechanisms. Because doxorubicin poorly penetrates the blood-brain barrier, the transient cognitive deficit likely results from treatment-induced peripheral inflammation that triggers temporary neuroinflammation and synaptic dysfunction, peaking around Day 10 and resolving by Day 14. Conversely, the persistent elevation of sNfL reflects ongoing injury within the peripheral nervous system, particularly the dorsal root ganglia and sensory axons, resulting in cumulative neurotoxicity and structural degeneration. These findings demonstrate that behavioral recovery alone may not reflect resolution of underlying neuronal injury.
This optimized model provides a valuable platform for drug discovery. An effective neuroprotective candidate should both restore cognitive performance at Day 10 and reduce the sustained peripheral axonal injury evidenced by elevated sNfL at Day 14.
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