Radiation-induced brain injury: A review
Dana Greene-Schloesser,Mike E. Robbins,Ann M. Peiffer,Edward G. Shaw,Kenneth T. Wheeler,Michael D. Chan +5 more
TLDR
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.Abstract:
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.read more
Citations
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疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Journal ArticleDOI
Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours
TL;DR: Evidence of acute radiation-triggered CNS inflammation, injury to neuronal lineages, accessory cells and their progenitors, and loss of supporting structure integrity is presented, which could synergistically alter the signalling microenvironment in progenitor cell niches in the brain and the hippocampus, which is a structure critical to memory and cognition.
Journal ArticleDOI
Molecular Pathways: Radiation-Induced Cognitive Impairment
TL;DR: Clinically prescribed drugs, including PPARα and PPARγ agonists, as well as RAS blockers, prevent radiation-induced neuroinflammation and cognitive impairment independent of improved neurogenesis, and offers the promise of improving the quality of life of brain tumor patients who receive radiotherapy.
Journal ArticleDOI
Cranial irradiation compromises neuronal architecture in the hippocampus
TL;DR: Findings are unique in demonstrating dose-responsive changes in dendritic complexity, synaptic protein levels, spine density and morphology, alterations induced in hippocampal neurons by irradiation that persist for at least 1 mo, and that resemble similar types of changes found in many neurodegenerative conditions.
Journal ArticleDOI
Cancer-treatment-induced neurotoxicity—focus on newer treatments
TL;DR: Familiarity with the neurological syndromes associated with cancer treatments enables clinicians to use the appropriate treatment for the underlying malignancy while minimizing the risk of neurological damage, which might preserve patients' quality of life.
References
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疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Journal ArticleDOI
Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Roger Stupp,Warren P. Mason,Martin J. van den Bent,Michael Weller,Barbara Fisher,Martin J.B. Taphoorn,Karl Belanger,Alba A. Brandes,Christine Marosi,Ulrich Bogdahn,Jürgen Curschmann,Robert C. Janzer,Samuel K. Ludwin,Thierry Gorlia,Anouk Allgeier,Denis Lacombe,J. Gregory Cairncross,Elizabeth Eisenhauer,René O. Mirimanoff +18 more
TL;DR: The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.
Journal ArticleDOI
Diffusion tensor imaging: Concepts and applications
D. Le Bihan,J.-F. Mangin,Cyril Poupon,Chris A. Clark,Sabina Pappatà,Nicolas Molko,Hugues Chabriat +6 more
TL;DR: The concepts behind diffusion tensor imaging are reviewed and potential applications, including fiber tracking in the brain, which, in combination with functional MRI, might open a window on the important issue of connectivity.
Journal ArticleDOI
Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols.
Paul S. Tofts,Gunnar Brix,David L. Buckley,Jeffrey L. Evelhoch,Elizabeth Henderson,Michael V. Knopp,Henrik Larsson,Ting-Yim Lee,Nina A. Mayr,Geoffrey J. M. Parker,Ruediger E. Port,June S. Taylor,Robert M. Weisskoff +12 more
TL;DR: A standard set of quantity names and symbols related to the estimation of kinetic parameters from dynamic contrast‐enhanced T1‐weighted magnetic resonance imaging data, using diffusable agents such as gadopentetate dimeglumine (Gd‐DTPA), are described.