Carbonyl Scavenging as an Antioxidant Neuroprotective Strategy for Acute Traumatic Brain Injury

Reactive oxygen-induced lipid peroxidation (LP) has been documented to play a critical role in pathophysiology, neurodegeneration, and neurological disability that follows acute traumatic brain injury (TBI) and spinal cord injury (SCI). Consistent with that fact, a number of antioxidant compounds that either scavenges reactive oxygen species or directly inhibit LP have been shown to be protective in preclinical models of TBI and SCI. Although LP is able to damage neural cellular and intracellular membranes, much of the damage is caused by the generation of neurotoxic aldehydic end products derived from peroxidized polyunsaturated fatty acids such as arachidonic acid. Most notably, these reactive compounds, 4-hydroxynonenal (4-HNE) and 2-propenal (acrolein), induce further reactive oxygen species formation and LP. This chapter reviews a relatively new antioxidant strategy involving the pharmacological scavenging of 4-HNE and acrolein referred to as "carbonyl scavenging" that is neuroprotective in SCI and TBI animal models. The prototypes of this class are hydralazine and phenelzine (PZ) that contain hydrazine moieties that can covalently react with the carbonyl function groups of 4-HNE or acrolein thus intercepting them and thus preventing their ability of exacerbate posttraumatic oxidative neurodegeneration.