%0 Journal Article
%T Experimental concepts for toxicity prevention and tissue restoration after central nervous system irradiation
%A Carsten Nieder
%A Nicolaus Andratschke
%A Sabrina T Astner
%J Radiation Oncology
%D 2007
%I BioMed Central
%R 10.1186/1748-717x-2-23
%X The risk of permanent central nervous system (CNS) toxicity, which typically becomes detectable after an asymptomatic latency period, continues to influence clinical treatment decisions. Interindividual differences in sensitivity result in a certain variability of the threshold dose and preclude administration of a guaranteed safe dose, even in the current era of high-precision image-guided radiotherapy. The easiest and most effective way of avoiding CNS side effects is to minimize the dose of radiation. This does, however, not solve the problem of normal tissue present within the target volume, for example due to diffuse microscopic spread, which escapes current imaging technology. For certain groups of patients, further progress can only be expected from efforts directed at widening the therapeutic window between tumor and normal tissue through specific modulation of their responses to radiotherapy (e.g., toxicity prevention) or from delayed intervention such as tissue regeneration strategies. Both prevention and treatment of side effects have their specific advantages and disadvantages. Importantly, they are not standard clinical options at this time. To exploit potential targets for intervention, we will discuss the pathogenesis of radiation-induced CNS toxicity and review preclinical data on prevention and tissue regeneration. We focus on two types of damage, i.e. neurocognitive decline and radiation necrosis. The latter is relevant to treatment of the brain and the spinal cord.Initial evaluations of radiation-induced CNS toxicity date back at least 70 years ago. These historical data have been summarized in previous reviews, for example by van der Kogel [1] and Schultheiss et al. [2]. In brief, previous experimental studies indicated that signs of diffuse demyelination develop in animals 2 weeks after CNS radiotherapy. After approximately 2 months, remyelination processes were observed. These early changes correspond to clinical symptoms such as Lhermitte's si
%U http://www.ro-journal.com/content/2/1/23