The assessment of acrolein changes in CNS traumas and diseases to determine its pathological role and therapeutic value

Acrolein is a highly reactive alpha, beta-unsaturated aldehyde produced both in the environment and endogenously by lipid peroxidation. Initial evidence from previous studies implies causal relationships between acrolein exposure and pathological progression of a number of CNS disorders. In this study, existing acrolein measurement methods were validated and improved before being used to measure acrolein changes in CNS disorders. Among the methods validated, the immunoblotting based method and the 3-HPMA based method produced the most promising results. Additionally, acrolein scavengers such as hydralazine were identified and used to determine the pathological role of acrolein and the value of targeting this species in CNS disorders. With the assistance of these acrolein study tools, acrolein was shown to increase significantly but was also able to be reduced by hydralazine in spinal cord injury, traumatic brain injury, Parkinson\u27s disease and multiple sclerosis animal models. Additionally, in vivo reduction of acrolein by hydralazine correlated strongly with the improvement of the symptoms associated with the CNS disorders, confirming the pathological role of acrolein in CNS disorders. Potential acrolein mediated pathological pathways were also briefly studied. Acrolein was shown to induce alpha-synuclein oligomerization, demyelination and pain sensations. Lastly, pilot clinical studies with patient urine samples were facilitated with the clinically applicable 3-HPMA based method. Elevations of acrolein levels were observed in both dogs with acute spinal cord injury and in human multiple sclerosis patients. Collectively, these data confirmed the pathological role of acrolein and the therapeutic value of acrolein scavengers in CNS disorders