scholarly journals Effects of 5-Ion Beam Irradiation and Hindlimb Unloading on Metabolic Pathways in Plasma and Brain of Behaviorally Tested WAG/Rij Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Jacob Raber ◽  
Sarah Holden ◽  
Reetesh Sudhakar ◽  
Reed Hall ◽  
Breanna Glaeser ◽  
...  
Keyword(s):  
Total Body Irradiation ◽  
Metabolic Pathways ◽  
Ion Beam ◽  
Cognitive Testing ◽  
Hindlimb Unloading ◽  
Ion Beam Irradiation ◽  
Behavioral Measures ◽  
Mixed Beam ◽  
Total Body

A limitation of simulated space radiation studies is that radiation exposure is not the only environmental challenge astronauts face during missions. Therefore, we characterized behavioral and cognitive performance of male WAG/Rij rats 3 months after sham-irradiation or total body irradiation with a simplified 5-ion mixed beam exposure in the absence or presence of simulated weightlessness using hindlimb unloading (HU) alone. Six months following behavioral and cognitive testing or 9 months following sham-irradiation or total body irradiation, plasma and brain tissues (hippocampus and cortex) were processed to determine whether the behavioral and cognitive effects were associated with long-term alterations in metabolic pathways in plasma and brain. Sham HU, but not irradiated HU, rats were impaired in spatial habituation learning. Rats irradiated with 1.5 Gy showed increased depressive-like behaviors. This was seen in the absence but not presence of HU. Thus, HU has differential effects in sham-irradiated and irradiated animals and specific behavioral measures are associated with plasma levels of distinct metabolites 6 months later. The combined effects of HU and radiation on metabolic pathways in plasma and brain illustrate the complex interaction of environmental stressors and highlights the importance of assessing these interactions.

scholarly journals The Burden of Survivorship on Hematological Patients—Long-Term Analysis of Toxicities after Total Body Irradiation and Allogeneic Stem Cell Transplantation

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5640
Author(s):  
Michael Oertel ◽  
Jonas Martel ◽  
Jan-Henrik Mikesch ◽  
Sergiu Scobioala ◽  
Christian Reicherts ◽  
...  
Keyword(s):  
Stem Cell ◽  
Side Effects ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Total Body Irradiation ◽  
Whole Body ◽  
Total Body

Total body irradiation is an effective conditioning modality before autologous or allogeneic stem cell transplantation. With the whole body being the radiation target volume, a diverse spectrum of toxicities has been reported. This fact prompted us to investigate the long-term sequelae of this treatment concept in a large patient cohort. Overall, 322 patients with acute leukemia or myelodysplastic syndrome with a minimum follow-up of one year were included (the median follow-up in this study was 68 months). Pulmonary, cardiac, ocular, neurological and renal toxicities were observed in 23.9%, 14.0%, 23.6%, 23.9% and 20.2% of all patients, respectively. The majority of these side effects were grades 1 and 2 (64.9–89.2% of all toxicities in the respective categories). The use of 12 Gray total body irradiation resulted in a significant increase in ocular toxicities (p = 0.013) and severe mucositis (p < 0.001). Renal toxicities were influenced by the age at transplantation (relative risk: 1.06, p < 0.001) and disease entity. In summary, total body irradiation triggers a multifaceted, but manageable, toxicity profile. Except for ocular toxicities and mucositis, a 12 Gray regimen did not lead to an increase in long-term side effects.

scholarly journals Long-Term Quantitative Biodistribution and Side Effects of Human Mesenchymal Stem Cells (hMSCs) Engraftment in NOD/SCID Mice following Irradiation

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Sabine François ◽  
Benoit Usunier ◽  
Luc Douay ◽  
Marc Benderitter ◽  
Alain Chapel
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Side Effects ◽  
Total Body Irradiation ◽  
Human Mesenchymal Stem Cells ◽  
Scid Mice ◽  
Human Mscs ◽  
Long Term Treatment ◽  
Total Body

There is little information on the fate of infused mesenchymal stem cells (MSCs) and long-term side effects after irradiation exposure. We addressed these questions using human MSCs (hMSCs) intravenously infused to nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice submitted to total body irradiation (TBI) or local irradiation (abdominal or leg irradiation). The animals were sacrificed 3 to 120 days after irradiation and the quantitative and spatial distribution of hMSCs were studied by polymerase chain reaction (PCR). Following their infusion into nonirradiated animals, hMSCs homed to various tissues. Engraftment depended on the dose of irradiation and the area exposed. Total body irradiation induced an increased hMSC engraftment level compared to nonirradiated mice, while local irradiations increased hMSC engraftment locally in the area of irradiation. Long-term engraftment of systemically administered hMSCs in NOD/SCID mice increased significantly in response to tissue injuries produced by local or total body irradiation until 2 weeks then slowly decreased depending on organs and the configuration of irradiation. In all cases, no tissue abnormality or abnormal hMSCs proliferation was observed at 120 days after irradiation. This work supports the safe and efficient use of MSCs by injection as an alternative approach in the short- and long-term treatment of severe complications after radiotherapy for patients refractory to conventional treatments.

scholarly journals Long-term remission of Philadelphia chromosome–positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractionated total body irradiation–etoposide regimen

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 903-909 ◽  
Author(s):  
Ginna G. Laport ◽  
Joseph C. Alvarnas ◽  
Joycelynne M. Palmer ◽  
David S. Snyder ◽  
Marilyn L. Slovak ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Total Body Irradiation ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Disease Status ◽  
Matched Sibling ◽  
Total Body

Abstract Allogeneic hematopoietic cell transplantation (HCT) is the only known curative modality for patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). Sixty-seven patients with HLA-matched sibling donors received fractionated total body irradiation (FTBI) and high-dose VP16, whereas 11 patients received FTBI/VP16/cyclophosphamide, and 1 patient received FTBI/VP16/busulfan. The median age was 36 years. At the time of HCT, 49 patients (62%) were in first complete remission (CR1) and 30 patients (38%) were beyond CR1 (> CR1). The median follow-up was 75 months (range, 14-245 months). The 10-year overall survival for the CR1 and beyond CR1 patients was 54% and 29% (P = .01), respectively, and event-free survival was 48% and 26% (P = .02), respectively. There was no significant difference in relapse incidence (28% vs 41%, P = .28), but nonrelapse mortality was significantly higher in the beyond CR1 patients, (31% vs 54%, P = .03, respectively). By univariate analysis, factors affecting event-free and overall survival were white blood cell count at diagnosis (< 30 × 109/L vs > 30 × 109/L) and disease status (CR1 vs > CR1). The median time to relapse for CR1 and for beyond CR1 patients was 12 months and 9 months, respectively. Our results indicate that FTBI/VP16 with or without cyclophosphamide confers long-term survival in Ph+ ALL patients and that disease status at the time of HCT is an important predictor of outcome.

Long-term complications of total body irradiation in adults

2001 ◽  
Vol 49 (1) ◽  
pp. 125-131 ◽  
Author(s):  
Olivier Thomas ◽  
Marc-André Mahé ◽  
Loı̈c Campion ◽  
Sylvain Bourdin ◽  
Noël Milpied ◽  
...  
Keyword(s):  
Total Body Irradiation ◽  
Total Body

scholarly journals Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner

Blood ◽  
2014 ◽  
Vol 123 (20) ◽  
pp. 3105-3115 ◽  
Author(s):  
Lijian Shao ◽  
Wei Feng ◽  
Hongliang Li ◽  
David Gardner ◽  
Yi Luo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Total Body Irradiation ◽  
Bone Marrow Suppression ◽  
Premature Senescence ◽  
Independent Manner ◽  
Telomere Shortening ◽  
Key Points ◽  
Total Body

Key Points Total body irradiation causes long-term bone marrow suppression by selectively inducing HSC senescence. The induction of HSC senescence is independent of telomere shortening and p16Ink4a and Arf.

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