Abstract: Acrolein in spinal cord injury: The propensity of reactive aldehydes such as acrolein to both initiate and perpetuate tissue damage after spinal cord injury (SCI) is well established. Formed primarily from lipid peroxidation, acrolein is known to be one of the most reactive aldehydes. Acrolein will quickly overwhelm endogenous clearance mechanisms and antioxidants, and form adducts with lipids, proteins, and DNA. Acrolein is pro-inflammatory and contributes significantly to cellular stress, eventually leading to cell death of neurons (Figure 1). After a neurotrauma, acrolein forms immediately and remains significantly elevated for at least 2 weeks (Burcham, 2017). When injected at physiologically relevant concentrations, acrolein-induced pathologies mirror those seen in trauma (Burcham, 2017). On the other hand, when acrolein is successfully sequestered, significant benefits including reduction of pain, increased locomotion, and restoration of cord tissue structure are observed. Yet, more complete removal of acrolein proves challenging given the high concentrations of acrolein that are generated after injury. There are currently no Food and Drug Administration (FDA)-approved medications for SCI patients that remove acrolein, and promote recovery, despite the known benefits. One of the main challenges of establishing an effective anti-acrolein based therapy for clinical usage is the need for small molecule aldehyde scavengers to cross the blood-brain barrier and do so at concentrations that will remove acrolein effectively without harmful side effects.