scholarly journals Rescue of cognitive function following fractionated brain irradiation in a novel preclinical glioma model

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Xi Feng ◽  
Sharon Liu ◽  
David Chen ◽  
Susanna Rosi ◽  
Nalin Gupta
Keyword(s):  
Tumor Growth ◽  
Cognitive Deficits ◽  
Memory Deficits ◽  
Cognitive Outcomes ◽  
Whole Brain Irradiation ◽  
Clinical Model ◽  
Brain Irradiation ◽  
Reliable Assessment ◽  
Radiation Induced

More than half of long-term brain tumor survivors develop irreversible cognitive decline that severely affect their quality of life. However, there is no pre-clinical model that allows long-term assessment of cognition, and there is no treatment which ameliorates cognitive deficits in patients. Here, we report a novel glioma mouse model that offers manageable tumor growth and reliable assessment of cognitive functions in a post-treatment manner. Using this model, we found that fractionated whole-brain irradiation (fWBI), but not tumor growth, results in memory deficits. Transient inhibition of CSF-1R during fWBI prolongs survival of glioma-bearing mice and fully prevents fWBI-induced memory deficits. This result suggests that CSF-1R inhibition during radiotherapy can be explored as an approach to improve both survival and cognitive outcomes in patients who will receive fWBI. Taken together, the current study provides a proof of concept of a powerful tool to study radiation-induced cognitive deficits in glioma-bearing animals.

scholarly journals Role of PPARs in Radiation-Induced Brain Injury

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Sriram Ramanan ◽  
Weiling Zhao ◽  
David R. Riddle ◽  
Mike E. Robbins
Keyword(s):  
Brain Injury ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Whole Brain Irradiation ◽  
Brain Irradiation ◽  
Ppar Agonists ◽  
The Usa ◽  
Radiation Induced

Whole-brain irradiation (WBI) represents the primary mode of treatment for brain metastases; about 200 000 patients receive WBI each year in the USA. Up to 50% of adult and 100% of pediatric brain cancer patients who survive >6 months post-WBI will suffer from a progressive, cognitive impairment. At present, there are no proven long-term treatments or preventive strategies for this significant radiation-induced late effect. Recent studies suggest that the pathogenesis of radiation-induced brain injury involves WBI-mediated increases in oxidative stress and/or inflammatory responses in the brain. Therefore, anti-inflammatory strategies can be employed to modulate radiation-induced brain injury. Peroxisomal proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the steroid/thyroid hormone nuclear receptor superfamily. Although traditionally known to play a role in metabolism, increasing evidence suggests a role for PPARs in regulating the response to inflammation and oxidative injury. PPAR agonists have been shown to cross the blood-brain barrier and confer neuroprotection in animal models of CNS disorders such as stroke, multiple sclerosis and Parkinson's disease. However, the role of PPARs in radiation-induced brain injury is unclear. In this manuscript, we review the current knowledge and the emerging insights about the role of PPARs in modulating radiation-induced brain injury.

scholarly journals EXTH-08. REPLACEMENT OF MICROGLIA BY BRAIN-ENGRAFTED MACROPHAGES PREVENTS MEMORY DEFICITS AFTER THERAPEUTIC WHOLE-BRAIN IRRADIATION

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi83-vi84
Author(s):  
Xi Feng ◽  
Sonali Gupta ◽  
David Chen ◽  
Zoe Boosalis ◽  
Sharon Liu ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Memory Deficits ◽  
Protective Effects ◽  
Whole Brain Irradiation ◽  
Synaptic Loss ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Brain Radiotherapy ◽  
The Brain ◽  
Therapeutic Avenue

Abstract Microglia have a distinct origin compared to blood circulating myeloid cells. Under normal physiological conditions, microglia are maintained by self-renewal, independent of hematopoietic progenitors. Following genetic or pharmacologic depletion, newborn microglia derive from the local residual pool and quickly repopulate the entire brain. The depletion of brain resident microglia during therapeutic whole-brain irradiation fully prevents irradiation-induced synaptic loss and recognition memory deficits but the mechanisms driving these protective effects are unknown. Here, we demonstrate that after CSF-1R inhibitor-mediated microglia depletion and therapeutic whole-brain irradiation, circulating monocytes engraft into the brain and replace the microglia pool. These monocyte-derived brain-engrafted macrophages have reduced phagocytic activity compared to microglia from irradiated brains, but similar to locally repopulated microglia without brain irradiation. Transcriptome comparisons reveal that brain-engrafted macrophages have both monocyte and embryonic microglia signatures. These results suggest that monocyte-derived brain-engrafted macrophages represent a novel therapeutic avenue for the treatment of brain radiotherapy-induced cognitive deficits.

scholarly journals SCIDOT-04. REPLACEMENT OF MICROGLIA BY BRAIN-ENGRAFTED MACROPHAGES PREVENTS MEMORY DEFICITS AFTER THERAPEUTIC WHOLE-BRAIN IRRADIATION

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi273-vi273
Author(s):  
Xi Feng ◽  
Sonali Gupta ◽  
David Chen ◽  
Zoe Boosalis ◽  
Sharon Liu ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Memory Deficits ◽  
Protective Effects ◽  
Whole Brain Irradiation ◽  
Synaptic Loss ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Brain Radiotherapy ◽  
The Brain ◽  
Therapeutic Avenue

Abstract Microglia have a distinct origin compared to blood circulating myeloid cells. Under normal physiological conditions, microglia are maintained by self-renewal, independent of hematopoietic progenitors. Following genetic or pharmacologic depletion, newborn microglia derive from the local residual pool and quickly repopulate the entire brain. The depletion of brain resident microglia during therapeutic whole-brain irradiation fully prevents irradiation-induced synaptic loss and recognition memory deficits but the mechanisms driving these protective effects are unknown. Here, we demonstrate that after CSF-1R inhibitor-mediated microglia depletion and therapeutic whole-brain irradiation, circulating monocytes engraft into the brain and replace the microglia pool. These monocyte-derived brain-engrafted macrophages have reduced phagocytic activity compared to microglia from irradiated brains, but similar to locally repopulated microglia without brain irradiation. Transcriptome comparisons reveal that brain-engrafted macrophages have both monocyte and embryonic microglia signatures. These results suggest that monocyte-derived brain-engrafted macrophages represent a novel therapeutic avenue for the treatment of brain radiotherapy-induced cognitive deficits.

scholarly journals Radiation-Induced Cognitive Dysfunction After Different Schemes of Fractionated Whole Brain Irradiation

2014 ◽  
Vol 5 (2) ◽  
pp. 26-35
Author(s):  
Zorkina Yana Аlexandrovna ◽  
Zubkov Еugene Аndreevich ◽  
Yusubalieva Gaukhar Maratovna ◽  
Gorlachev Gennadiy Efimovich ◽  
Golanov Andrey Vladimirivich ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Radiation Induced

Radiation-Induced Primary Brain Lymphoma: A Case Report

1995 ◽  
Vol 81 (3) ◽  
pp. 204-207 ◽  
Author(s):  
Moshe E. Stein ◽  
Nissim Haim ◽  
Menachem Ben-Shachar ◽  
Dorith Goldsher ◽  
Zvi Bernstein ◽  
...  
Keyword(s):  
Latency Period ◽  
High Dose ◽  
Low Grade ◽  
Whole Brain Irradiation ◽  
Brain Lymphoma ◽  
Brain Irradiation ◽  
Long Latency ◽  
Primary Brain Lymphoma ◽  
Radiation Induced ◽  
Acquired Immunodeficiency

A patient who developed primary brain lymphoma 6 years following whole brain irradiation due to a low-grade glioma is described. The patient had no evidence of congenital or acquired immunodeficiency state and achieved a good and prompt response to aggressive chemotherapy, including high-dose methotrexate. The previous radiation therapy is implicated in the etiology of the lymphoma because of the geometric coincidence, the relatively long latency period and the different histology. A brief review of current literature is reported.

scholarly journals An Updated Review on Memantine Efficacy in Reducing Cognitive Dysfunction of Whole-brain Irradiation for Adult Patients with Brain metastasis

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Anya jafari ◽  
Zahra Siavashpour ◽  
Mohammad Houshyari
Keyword(s):  
Brain Metastasis ◽  
Verbal Learning ◽  
Whole Brain Radiotherapy ◽  
Protective Effects ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Brain Radiotherapy ◽  
Delayed Recognition

Context: Increased survival of patients with cancer raises the need to pay attention to long-term side effects. Patients with brain metastasis experienced cognition failure after whole-brain radiotherapy. This review aimed at concluding the efficacy of Memantine in preserving cognitive function by reducing the brain toxicity of whole-brain radiotherapy for metastatic brain cancers. Evidence Acquisition: Published studies evaluating memantine protective effects during brain metastasis radiotherapy were searched for in scientific databases (e.g., Embase, PubMed, Cochrane database, Google Scholar, Scopus) using keywords including whole-brain radiotherapy and Memantine. Results: A total of 4 prospective clinical trials were included in the review. Effects of Memantine on cognition tests were evaluated in these trials. A significantly better Hopkins Verbal Learning Test-Revised (HVLT-R) delayed recognition at months 6 was achieved in RTOG 0614 and NRG CC001. Longer time to cognitive decline was found in the memantine arm of the RTOG trial and was statistically significant. Memantine effects were not statistically significant before 2 months. Conclusions: It seems reasonable to consider Memantine during radiation to prevent long-term cognitive failure in patients with brain metastasis due to the current results. Memantine improves cognition function during whole-brain radiotherapy (WBRT) without adding irreparable complications.

Brain sarcoma of meningeal origin after cranial irradiation in childhood acute lymphocytic leukemia

1984 ◽  
Vol 61 (4) ◽  
pp. 772-776 ◽  
Author(s):  
Pascal Tiberin ◽  
Esther Maor ◽  
Rina Zaizov ◽  
Ian J. Cohen ◽  
Menachem Hirsch ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Childhood Leukemia ◽  
Multimodality Treatment ◽  
Cranial Irradiation ◽  
Lymphocytic Leukemia ◽  
Whole Brain Irradiation ◽  
Content Type ◽  
Brain Irradiation ◽  
Low Dosage

✓ The authors report their experience with an unusual case of intracerebral sarcoma of meningeal cell origin in an 8½-year-old girl. This tumor occurred 6½ years after cranial irradiation at relatively low dosage (2200 rads) had been delivered to the head in the course of a multimodality treatment for acute lymphocytic leukemia. The tumor recurred approximately 10 months after the first surgical intervention. Macroscopic total excision of the recurrent growth followed by whole-brain irradiation (4500 rads) failed to eradicate it completely and local recurrence prompted reoperation 18 months later. This complication of treatment in long-term childhood leukemia survivors is briefly discussed, as well as the pathology of meningeal sarcomas.

Sign in / Sign up

Export Citation Format

Share Document