The central nervous system (CNS) is a major dose-limiting organ in clinical …

• Abstract
• Introduction
• Specific cell types in the central nervous system and their function
• Clinical radiation therapy
• Histopathologic changes
• Early gene induction
• Apoptosis
• Inhibition of neurogenesis
• Hypoxia, barrier disruption, and necrosis of the white matter
• ICAM-1
• Cell replacement
• Reducing apoptotic cell death
• Reducing secondary cell death
• Conclusion
• References
• Figure

Biology Articles » Biophysics » Medical Biophysics » Mechanisms of radiation injury to the central nervous system: implications for neuroprotection » Reducing apoptotic cell death

Reducing apoptotic cell death

- Mechanisms of radiation injury to the central nervous system: implications for neuroprotection

Protection against radiation injury may be achieved by reducing apoptotic endothelial cell death. Intravenous administration of bFGF immediately prior to XRT inhibits endothelial cell apoptosis in the murine CNS (3). Further study of key elements of the apoptotic pathway in this system may suggest growth factor –based (or other) approaches directed at reducing endothelial apoptosis. Inhibiting acid sphingomyelinase activity might provide a highly specific approach to reduce radiation-induced endothelial cell apoptosis. Indeed, acid sphingomyelinase inhibitors are currently being developed (99). It remains to be seen whether the challenge of modifying apoptosis in the important normal tissue compartments can be achieved without adversely impacting the ability to target and kill tumor cells.

Other growth factors that warrant further investigations include platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF) (100). When PDGF was intrathecally administered concomitant with irradiation of the rat spinal cord, modest but significant protection was observed (101). Whether this was mediated through reduction of apoptotic cell death remains to be investigated.