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 » Histopathologic changes

Histopathologic changes

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

Although few gross histopathologic changes are observed immediately after XRT, there are profound early changes at the cell and molecular level as discussed below. The histopathologic changes of late radiation-induced CNS injury include glial atrophy, demyelination and necrosis confined to white matter, and varying degrees of vascular changes in both white and gray matter (23). In the human CNS, these changes are typically described in the patients with the most severe injury (24), and human studies are also limited by confounding effects of many unknown host, treatment, and tumor factors. In clinical XRT, the radiation dose is typically given in a number of daily fractions over five to seven weeks. The influence of dose, fractionation treatment, time, and other treatment parameters on late functional and histopathological changes has been derived from studies in rodent models. For example, in XRT-associated paralysis of rats that occurs within seven months of XRT administration, necrosis and/or demyelination of the white matter occurs in the absence of apparent vascular abnormalities (23). Glial atrophy and vascular changes were observed much later and after lower doses. Late radiation-induced morphological changes in CNS microvessels include telangiectasias, dilatation, and vessel wall hyalinization and thickening with fibrinoid necrosis (25, 26). In the rodent spinal cord, these vascular changes are associated with no or very minor neurological deficits. In the brain, these vascular changes are associated with impairment of spatial learning and working memory, and were observed at doses below the threshold of necrosis (27). These histopathological studies provide important clues to the target cells of damage. For decades, a debate occurred regarding the role of the oligodendrocyte versus the vascular endothelial cell in the white matter lesions observed after XRT. With the availability of molecular tools and new insight in neurobiology, there has been a paradigm shift away from the target cell theory. Instead, the damage response is now increasingly viewed as a continuous, dynamic and interacting process.