FAS deficiency reduces apoptosis, spares axons and improves function after spinal cord injury

• Published in: Experimental neurology 2005-12, Vol.196 (2), p.390-400
• Main Authors: Casha, S., Yu, W.R., Fehlings, M.G.
• Format: Article
• Language: English
• Subjects: 2',3'-Cyclic-Nucleotide Phosphodiesterases - metabolism; Analysis of Variance; Animals; Apoptosis; Apoptosis - genetics; Axons - physiology; Behavior, Animal; Blotting, Western - methods; Caspase 3; Caspase 8; Caspases - metabolism; Cell Count - methods; Disease Models, Animal; FAS; fas Receptor - genetics; fas Receptor - metabolism; Female; Functional Laterality; Glial Fibrillary Acidic Protein - metabolism; Heat-Shock Proteins - metabolism; In Situ Nick-End Labeling - methods; In Vitro Techniques; Indoles - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity - physiology; Muscle Proteins - metabolism; Neuroprotection; Oligodendrocyte; Phosphopyruvate Hydratase - metabolism; Propidium; Recovery of Function - genetics; Spinal Cord Injuries - genetics; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - physiopathology; Spinal cord injury; Stilbamidines - metabolism; Time Factors
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2005.08.020

After spinal cord injury (SCI), apoptosis of neurons and oligodendrocytes is associated with axonal degeneration and loss of neurological function. Recent data have suggested a potential role for FAS death receptor-mediated apoptosis in the pathophysiology of SCI. In this study, we examined the effect of FAS deficiency on SCI in vitro and in vivo. FAS Lpr/lpr mutant mice and wildtype background-matched mice were subjected to a T5–6 clip compression SCI, and complementary studies were done in an organotypic slice culture model of SCI. Post-traumatic apoptosis in the spinal cord, which was seen in neurons and oligodendrocytes, was decreased in the FAS-deficient mice both in vivo and in vitro particularly in oligodendrocytes. FAS deficiency was also associated with improved locomotor recovery, axonal sparing and preservation of oligodendrocytes and myelin. However, FAS deficiency did not result in a significant increase in surviving neurons in the spinal cord at 6 weeks after injury, likely reflecting the importance of other cell death mechanisms for neurons. We conclude that inhibition of the FAS pathway may be a clinically attractive neuroprotective strategy directed towards oligodendroglial and axonal preservation in the treatment of SCI and neurotrauma.