Project 15

Carbonyl scavenging agents and their effects in neuronal viability and axonal growth after exposure to Acrolein or carbonyl stress

The broad hypothesis underlying this work is that carbonyl-scavenging compounds that block cell damage by acrolein and related electrophilic carbonyls will protect against spinal neurodegeneration following traumatic spinal cord injury (SCI). This hypothesis is based on a growing body of literature showing a role for acrolein, a reactive & highly toxic endogenous electrophile, as well as other reactive carbonyls in SCI pathogenesis. A subsidiary hypothesis is that exposure to mixtures of reactive carbonyl compounds, as occurs in the damaged spinal cord, is more toxic to neuronal cells than exposure to individual compounds. These hypotheses will be tested using a combination of in vitro approaches:

Aim: Using primary neuronal cells comprising dorsal root ganglia from rat embryos or adults, to explore the effect of acrolein and “carbonyl stress” on neuronal viability and axonal growth, and establish whether carbonyl-scavenging agents attenuate any disruption of axon extension