Acrolein scavengers as potential therapy for spinal cord injury
Abstract
The pathophysiology of traumatic spinal cord injury (SCI) is characterized by the initial, primary injury, as well as a number of secondary injury mechanisms that occur not only at the initial injury site, but in adjacent tissue as well. In particular, it has long been established that oxidative stress plays a critical role in secondary injury and promotes the spreading of the injury to the adjacent, otherwise uninjured tissue. Thus, oxidative stress represents an important target of therapeutic intervention following the initial trauma. However, free radical scavengers have been largely ineffective at promoting improved recovery in clinical trials of SCI, and as such a novel target to attenuate oxidative stress is highly warranted. In addition to free radicals, peroxidation of lipid membranes following SCI produces reactive aldehydes such as acrolein. Acrolein is capable of depleting endogenous antioxidants such as glutathione, generating free radicals, promoting oxidative stress, and damaging proteins and DNA. Acrolein has a significantly longer half-life than the transient free radicals, and thus may represent a potentially better target of therapeutic intervention to attenuate oxidative stress. There is growing evidence to suggest that reactive aldehydes such as acrolein play a critical role in oxidative stress and SCI. As such, acrolein scavenging may be a novel means of therapy to attenuate oxidative stress and improve recovery following SCI. The purpose of these experiments is to further evaluate the role of acrolein in SCI, and furthermore evaluate the ability of acrolein scavengers to attenuate secondary injury following compression.
Degree
Ph.D.
Advisors
Shi, Purdue University.
Subject Area
Neurosciences
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