Comparison of Young and Adult Rat Models of Chemotherapy-Induced Alopecia

Background: Chemotherapy-induced alopecia (CIA) is a common side effect of cancer treatment with profound psychosocial repercussions. Several young (before day 14) and adult (after 3 weeks) murine models for CIA have been developed, yet no study thus far has compared these models. Young models are naturally synchronized in anagen while adult models require synchronization into anagen. Here, we compared the gross and histological features of the young versus adult models of CIA in pigmented rats. Additionally, we determined the effectiveness of heat shock treatment to prevent CIA; heat shock has not been tested before in pigmented young or adult rats. Methods: To induce synchronized anagen, adult rats were clipped during early telogen. To induce alopecia, young and adult rats received intraperitoneal injections of etoposide or cyclophosphamide. Rats from each model were randomized to receive heat shock preceding chemotherapy. Alopecia was observed 10 days post-chemotherapy, and dorsal skin biopsies were analyzed for histology. Results: Upon chemotherapy, young rats developed total alopecia, whereas adult rats developed alopecia restricted to the clipped area. Histologically, equivalent hair follicle dystrophy wasobserved in each model 10 days post-chemotherapy. Moreover, both the young and adult rats demonstrated areas of protection from CIA corresponding to localized heat shock pretreatment. Conclusions: Both the young and adult rat models mimic clinical and microscopic findings of CIA. However, the young rat model, with naturally synchronized anagen, develops total alopecia upon chemotherapy, and may be a more suitable model to screen protective compounds.