Exogenous Bcl-XLFusion Protein SparesNeurons After Spinal Cord Injury

Document Type



Brain and Mind Institute


Spinal cord injury (SCI) induces neuronal death, includingapoptosis, which is completed within 24 hr at and aroundthe impact site. We identified early proapoptotic tran-scriptional changes, including upregulation of proapop-totic Bax and downregulation of antiapoptotic Bcl-xL,Bcl-2, and Bcl-w, using Affymetrix DNA microarrays. Be-cause Bcl-xLis the most robustly expressed antiapop-totic Bcl-2 molecule in adult central nervous system, wedecided to characterize better the effect of SCI on Bcl-xLexpression. We found Bcl-xLexpressed robustlythroughout uninjured spinal cord in both neurons and gliacells. We also found Bcl-xLlocalized in different cellularcompartments: cytoplasmic, mitochondrial, and nuclear.Bcl-xLprotein levels decreased in the cytoplasm andmitochondria 2 hr after SCI and persisted for 24 hr. Totest the contribution of proapoptotic decreases in Bcl-xLto neuronal death, we augmented endogenous Bcl-xLlevels by administering Bcl-xLfusion protein (Bcl-xLFP)into injured spinal cords. Bcl-xLFP significantly in-creased neuronal survival, suggesting that SCI-inducedchanges in Bcl-xLcontribute considerably to neuronaldeath. Because Bcl-xLFP increases survival of dorsalhorn neurons and ventral horn motoneurons, it couldbecome clinically relevant in preserving sensory and mo-tor functions after SCI.©2005 Wiley-Liss, Inc


his work was published before the author joined Aga Khan University.


Journal of Neuroscience Research