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radiation cognition neurogenesis

Terry C Burns, Ahmed J Awad, Matthew D Li, Gerald A Grant
Brain radiation is a fundamental tool in neurooncology to improve local tumor control, but it leads to profound and progressive impairments in cognitive function. Increased attention to quality of life in neurooncology has accelerated efforts to understand and ameliorate radiation-induced cognitive sequelae. Such progress has coincided with a new understanding of the role of CNS progenitor cell populations in normal cognition and in their potential utility for the treatment of neurological diseases. The irradiated brain exhibits a host of biochemical and cellular derangements, including loss of endogenous neurogenesis, demyelination, and ablation of endogenous oligodendrocyte progenitor cells...
May 2016: Neurosurgical Focus
Maki K Yamada
Whole brain radiation therapy for the treatment of tumors can sometimes cause cognitive impairment. Memory deficits were noted in up to 50% of treated patients over a short period of several months. In addition, an increased rate of dementia in young patients has been noted over the longer term, i.e. years. A deficit in neurogenesis after irradiation has been postulated to be the main cause of cognitive decline in patients, but recent data on irradiation therapy for limited parts of the brain appear to indicate other possibilities...
2016: Drug Discoveries & Therapeutics
Arianna Casciati, Katalin Dobos, Francesca Antonelli, Anett Benedek, Stefan J Kempf, Montserrat Bellés, Andrea Balogh, Mirella Tanori, Luis Heredia, Michael J Atkinson, Christine von Toerne, Omid Azimzadeh, Anna Saran, Geza Sáfrány, Mohammed A Benotmane, M Victoria Linares-Vidal, Soile Tapio, Katalin Lumniczky, Simonetta Pazzaglia
Therapeutic irradiation of pediatric and adult patients can profoundly affect adult neurogenesis, and cognitive impairment manifests as a deficit in hippocampal-dependent functions. Age plays a major role in susceptibility to radiation, and younger children are at higher risk of cognitive decay when compared to adults. Cranial irradiation affects hippocampal neurogenesis by induction of DNA damage in neural progenitors, through the disruption of the neurogenic microenvironment, and defective integration of newborn neurons into the neuronal network...
May 10, 2016: Oncotarget
Anggraeini Puspitasari, Noriko Koganezawa, Yuta Ishizuka, Nobuhiko Kojima, Natsume Tanaka, Takashi Nakano, Tomoaki Shirao
Cranial X irradiation can severely impair higher brain function, resulting in neurocognitive deficits. Radiation-induced brain injury is characterized by acute, early and late delayed changes, and morbidity is evident more than 6 months after irradiation. While the acute effects of radiation exposure on the brain are known, the underlying mechanisms remain unclear. In this study, we examined the acute effect of X radiation on synaptic function using behavioral analysis and immunohistochemistry. We found that 10 Gy whole-brain irradiation immediately after conditioning (within 30 min) impaired the formation of fear memory, whereas irradiation 24 h prior to conditioning did not...
April 2016: Radiation Research
Nicole N Chmielewski, Chongshan Caressi, Erich Giedzinski, Vipan K Parihar, Charles L Limoli
Growing evidence suggests that radiation-induced oxidative stress directly affects a wide range of biological changes with an overall negative impact on CNS function. In the past we have demonstrated that transgenic mice over-expressing human catalase targeted to the mitochondria (MCAT) exhibit a range of neuroprotective phenotypes following irradiation that include improved neurogenesis, dendritic complexity, and cognition. To determine the extent of the neuroprotective phenotype afforded by MCAT expression in different hippocampal regions, we analyzed subiculum neurons for changes in neuronal structure and synaptic integrity after exposure to low dose (0...
June 2016: Environmental and Molecular Mutagenesis
Phillip Yang, David Leu, Keqiang Ye, Chandra Srinivasan, John R Fike, Ting-Ting Huang
Brain radiotherapy is frequently used successfully to treat brain tumors. However, radiotherapy is often associated with declines in short-term and long-term memory, learning ability, and verbal fluency. We previously identified a downregulation of the brain-derived neurotrophic factor (BDNF) following cranial irradiation in experimental animals. In the present study, we investigated whether targeting the BDNF high affinity receptor, tropomysin receptor kinase B (TrkB), could mitigate radiation-induced cognitive deficits...
May 2016: Experimental Neurology
Eliedonna Cacao, Francis A Cucinotta
Radiation impairment of neurogenesis in the hippocampal dentate gyrus is one of several factors associated with cognitive detriments after treatment of brain cancers in children and adults with radiation therapy. Mouse models have been used to study radiation-induced changes in neurogenesis, however the models are limited in the number of doses, dose fractions, age and time after exposure conditions that have been studied. The purpose of this study is to develop a novel predictive mathematical model of radiation-induced changes to neurogenesis using a system of nonlinear ordinary differential equations (ODEs) to represent the time, age and dose-dependent changes to several cell populations participating in neurogenesis as reported in mouse experiments exposed to low-LET radiation...
March 2016: Radiation Research
Sona Balentova, Marian Adamkov
Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain and may lead to molecular, cellular and functional changes. Given its central role in memory and adult neurogenesis, the majority of studies have focused on the hippocampus. These findings suggested that hippocampal avoidance in cranial radiotherapy prevents radiation-induced cognitive impairment of patients...
2015: International Journal of Molecular Sciences
J Dietrich, M Prust, J Kaiser
Cancer therapies can be associated with significant central nervous system (CNS) toxicity. While radiation-induced brain damage has been long recognized both in pediatric and adult cancer patients, CNS toxicity from chemotherapy has only recently been acknowledged. Clinical studies suggest that the most frequent neurotoxic adverse effects associated with chemotherapy include memory and learning deficits, alterations of attention, concentration, processing speed and executive function. Preclinical studies have started to shed light on how chemotherapy targets the CNS both on cellular and molecular levels to disrupt neural function and brain plasticity...
November 19, 2015: Neuroscience
Ting-Ting Huang, David Leu, Yani Zou
Hippocampal-dependent cognitive functions rely on production of new neurons and maintenance of dendritic structures to provide the synaptic plasticity needed for learning and formation of new memories. Hippocampal formation is exquisitely sensitive to patho-physiological changes, and reduced antioxidant capacity and exposure to low dose irradiation can significantly impede hippocampal-dependent functions of learning and memory by reducing the production of new neurons and alter dendritic structures in the hippocampus...
June 15, 2015: Archives of Biochemistry and Biophysics
Yeonghoon Son, Miyoung Yang, Sohi Kang, Sueun Lee, Jinwook Kim, Juhwan Kim, Seri Park, Joong-Sun Kim, Sung-Kee Jo, Uhee Jung, Taekyun Shin, Sung-Ho Kim, Hongbing Wang, Changjong Moon
The brain can be exposed to ionizing radiation in various ways, and such irradiation can trigger adverse effects, particularly on learning and memory. However, the precise mechanisms of cognitive impairments induced by cranial irradiation remain unknown. In the hippocampus, brain-derived neurotrophic factor (BDNF) plays roles in neurogenesis, neuronal survival, neuronal differentiation, and synaptic plasticity. The significance of BDNF transcript variants in these contexts is becoming clearer. In the present study, both object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice were assessed 1 month after a single exposure to cranial irradiation (10 Gy) to evaluate hippocampus-related behavioral dysfunction following such irradiation...
May 2015: Neurobiology of Learning and Memory
Yeonghoon Son, Miyoung Yang, Hongbing Wang, Changjong Moon
Cranial irradiation (IR) is commonly used for the treatment of brain tumors but may cause disastrous brain injury, especially in the hippocampus, which has important cognition and emotional regulation functions. Several preclinical studies have investigated the mechanisms associated with cranial IR-induced hippocampal dysfunction such as memory defects and depression-like behavior. However, current research on hippocampal dysfunction and its associated mechanisms, with the ultimate goal of overcoming the side effects of cranial radiation therapy in the hippocampus, is still very much in progress...
March 2015: Brain, Behavior, and Immunity
Natália Kokošová, Lenka Tomášová, Terézia Kisková, Beňadik Šmajda
The intrauterinal development in mammals represents a very sensitive period of life in relation to many environmental factors, including ionizing radiation (IR). The developing nervous system is particularly vulnerable to IR, and the consequences of exposure are of importance because of its potential health risks. The aim of our work was to assess whether prenatal irradiation of rats on the 17th day of embryonic development with a dose of 1 Gy would affect the formation of new cells and the number of mature neurons in the hippocampus and the selected forms of behaviour in the postnatal period...
January 2015: Cellular and Molecular Neurobiology
Stefan J Kempf, Arianna Casciati, Sonja Buratovic, Dirk Janik, Christine von Toerne, Marius Ueffing, Frauke Neff, Simone Moertl, Bo Stenerlöw, Anna Saran, Michael J Atkinson, Per Eriksson, Simonetta Pazzaglia, Soile Tapio
BACKGROUND/PURPOSE OF THE STUDY: Epidemiological evidence suggests that low doses of ionising radiation (≤1.0 Gy) produce persistent alterations in cognition if the exposure occurs at a young age. The mechanisms underlying such alterations are unknown. We investigated the long-term effects of low doses of total body gamma radiation on neonatally exposed NMRI mice on the molecular and cellular level to elucidate neurodegeneration. RESULTS: Significant alterations in spontaneous behaviour were observed at 2 and 4 months following a single 0...
2014: Molecular Neurodegeneration
Liyuan Zhang, Kun Li, Rui Sun, Yuan Zhang, JianFeng Ji, Peigeng Huang, Hongying Yang, Ye Tian
BACKGROUND: It has been long recognized that cranial irradiation used for the treatment of primary and metastatic brain tumor often causes neurological side-effects such as intellectual impairment, memory loss and dementia, especially in children patients. Our previous study has demonstrated that whole-brain irradiation (WBI) can cause cognitive decline in rats. Minocycline is an antibiotic that has shown neuroprotective properties in a variety of experimental models of neurological diseases...
2014: Radiation Oncology
Xiaorong Dong, Ming Luo, Guodong Huang, Jian Zhang, Fan Tong, Yanlei Cheng, Qian Cai, Jihua Dong, Gang Wu, Jing Cheng
PURPOSE: Radiation-induced brain injury (RIBI) is the most common side-effect after cranial radiation therapy (CRT). In the present study, the RIBI mice model was established and the changes in the expression of tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β) mRNA, and the related signal pathways in the hippocampus of this model were investigated. MATERIALS AND METHODS: 10 Gy CRT or sham-irradiation was given to the three-week old mice. The water maze test was used to test the RIBI model in mice...
March 2015: International Journal of Radiation Biology
Antiño R Allen, Kirsten Eilertson, Sourabh Sharma, Jennifer Baure, Barrett Allen, David Leu, Susanna Rosi, Jacob Raber, Ting-Ting Huang, John R Fike
Radiation exposure due to radiological terrorism and military circumstances are a continuing threat for the civilian population. In an uncontrolled radiation event, it is likely that there will be other types of injury involved, including trauma. While radiation combined injury is recognized as an area of great significance, overall there is a paucity of information regarding the mechanisms underlying the interactions between irradiation and other forms of injury, or what countermeasures might be effective in ameliorating such changes...
November 2014: Radiation Research
Albert Attia, Brandi R Page, Glenn J Lesser, Michael Chan
Radiation-induced cognitive decline in cancer survivors who have received brain radiotherapy is an insidious problem with worsening severity over time. Because of improved survival with modern therapies, an increasing number of long term survivors are affected with limited options for treatment once diagnosed. Recently there has been enthusiasm for evaluating new approaches to prevent the onset of radiation-induced cognitive decline. Clinical trials have assessed the role of pharmaceuticals such as memantine and donepezil in ameliorating the cognitive effects of brain irradiation...
December 2014: Current Treatment Options in Oncology
Nathan A DeCarolis, Phillip D Rivera, Francisca Ahn, Wellington Z Amaral, Junie A LeBlanc, Shveta Malhotra, Hung-Ying Shih, David Petrik, Neal Melvin, Benjamin P C Chen, Amelia J Eisch
The high-LET HZE particles from galactic cosmic radiation pose tremendous health risks to astronauts, as they may incur sub-threshold brain injury or maladaptations that may lead to cognitive impairment. The health effects of HZE particles are difficult to predict and unfeasible to prevent. This underscores the importance of estimating radiation risks to the central nervous system as a whole as well as to specific brain regions like the hippocampus, which is central to learning and memory. Given that neurogenesis in the hippocampus has been linked to learning and memory, we investigated the response and recovery of neurogenesis and neural stem cells in the adult mouse hippocampal dentate gyrus after HZE particle exposure using two nestin transgenic reporter mouse lines to label and track radial glia stem cells (Nestin-GFP and Nestin-CreER(T2)/R26R:YFP mice, respectively)...
July 1, 2014: Life Sciences in Space Research
Shengjun Ji, Ye Tian, Yi Lu, Rui Sun, Jianfeng Ji, Liyuan Zhang, Shumin Duan
Radiotherapy is often employed for the treatment of head and neck cancer. Unfortunately, its neurotoxic effects on normal brain tissue often compromise the quality of life (QOL) for survivors. Particularly, acute cognitive deficit (ACD), which can occur several days to one month after irradiation, limits its therapeutic use. Impairment of neurogenesis in the hippocampus plays a key role in the development of radiation-induced cognitive deficit, and brain-derived neurotrophic factor (BDNF) may be involved. In the present study, we re-evaluated the effects of different doses of radiation on the development of ACD in Sprague Dawley rats...
August 19, 2014: Brain Research
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