Radiation-induced brain injury: a review
- 1 Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA
- 2 Brain Tumor Center of Excellence, Wake Forest School of Medicine, Winston-Salem, NC, USA
- 3 Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, USA
Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their integration at clinically relevant doses and schedules. Recently developed techniques in neuroscience and neuroimaging provide not only an opportunity to accomplish this, but they also offer the opportunity to identify new biomarkers and new targets for interventions to prevent or ameliorate these late effects.
Keywords: brain injury, hippocampal changes, metastatic brain tumor, pathogenesis, radiation-induced
Citation: Greene-Schloesser D, Robbins ME, Peiffer AM, Shaw EG, Wheeler KT and Chan MD (2012) Radiation-induced brain injury: a review. Front. Oncol. 2:73. doi: 10.3389/fonc.2012.00073
Received: 25 May 2012; Paper pending published: 09 June 2012;
Accepted: 26 June 2012; Published online: 19 July 2012.
Edited by:Michael L. Freeman, Vanderbilt University School of Medicine, USA
Reviewed by:Michael L. Freeman, Vanderbilt University School of Medicine, USA
Eddy S. Yang, Comprehensive Cancer Center, University of Alabama-Birmingham School of Medicine, USA
Copyright: © 2012 Greene-Schloesser, Robbins, Peiffer, Shaw, Wheeler and Chan. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Mike E. Robbins, Department of Radiation Oncology, Wake Forest School of Medicine, Medical Center Boulevard, Room 412C NRC, Mail Box #571059, Winston-Salem, NC 27157, USA. e-mail: firstname.lastname@example.org
†Dana Greene-Schloesser and Mike E. Robbins have contributed equally to this article.