Abstract

Peripheral nerve injury (PNI) triggers a complex cellular response in the nervous system, involving both neurons and supporting glial cells, where the balance between survival and death pathways dictates functional recovery. The tumor suppressor protein p53 is a critical regulator of cell fate, mediating responses to cellular stress, including DNA damage and oxidative stress, which are hallmarks of PNI. This study investigates the specific role of p53-dependent signaling in modulating the survival and apoptotic cascades in both neuronal and glial populations following PNI. Using a rodent model of sciatic nerve crush injury, we analyzed the temporal expression and activation of p53 and its downstream targets, such as Bax, Puma, and p21, in the dorsal root ganglia and the distal nerve stump. Our findings indicate a differential activation of p53 pathways: early p53 activation in neurons correlates with increased apoptosis, while delayed, moderate p53 signaling in Schwann cells appears to promote a pro-survival and regenerative phenotype. These results highlight the dual, context-dependent role of p53 in the post-injury environment and suggest that targeting p53 signaling could be a viable therapeutic strategy to enhance nerve regeneration and functional outcome.